Leronlimab - CytoDyn
Alternative Names: Leronlimab-PRO 140; leronlimab-PRO140; PA-14; PRO-140; Vyrologix®Latest Information Update: 07 Mar 2024
At a glance
- Originator Progenics Pharmaceuticals
- Developer Albert Einstein Israelite Hospital; CytoDyn; Progenics Pharmaceuticals
- Class Antineoplastics; Antiretrovirals; Antivirals; Hepatoprotectants; Immunotherapies; Monoclonal antibodies; Vascular disorder therapies
- Mechanism of Action CCR5 receptor antagonists; Virus internalisation inhibitors
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Orphan Drug Status
Yes - Graft-versus-host disease
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
Highest Development Phases
- Registered Triple negative breast cancer
- Preregistration COVID 2019 infections; HIV infections
- Phase III COVID-19 pneumonia
- Phase II Graft-versus-host disease; Non-alcoholic steatohepatitis; Post acute COVID 19 syndrome; Solid tumours
- Preclinical Multiple sclerosis; Stroke; Traumatic brain injuries
- Discontinued HIV-1 infections
Most Recent Events
- 29 Feb 2024 U.S. FDA has lifted the clinical hold on the a pre-exposure prophylaxis (PrEP) clinical trial of Leronlimab in HIV infections
- 06 Feb 2024 Cytodyn in partnership with Albert Einstein College of Medicine and Montefiore Medical Center plans a preclinical trial for Glioblastoma in USA in 2024
- 01 Feb 2024 Cytodyn in collaboration with Albert Einstein College of Medicine has submitted its revised HIV clinical trial protocol to the FDA
Development Overview
Introduction
Leronlimab (formerly PRO 140) is a humanised IgG4 monoclonal antibody that blocks the HIV co-receptor, CCR5, being developed by CytoDyn, for the treatment and prevention of HIV-1 infections, graft-versus-host disease (GvHD), breast cancer, solid tumours, COVID-2019 infections, post-acute-COVID-19-syndrome, metabolic dysfunction-associated steatohepatitis (MASH) formerly non-alcoholic steatohepatitis (NASH), and in traumatic brain injury and stroke recovery. Leronlimab blocks the predominant HIV (R5) subtype entry into T cells by masking CCR5 without interfering with the normal function of CCR5 in mediating immune responses. CCR5 may play a role in tumour invasion, metastases, and tumor microenvironment control. CCR5 has also gained importance as a target for neural repair in stroke and traumatic brain injury. As leronlimab crosses the blood-brain barrier with 70-75% receptor occupancy of the CCR5 receptors in the brain, it is anticipated to help treat patients with traumatic brain injuries and strokes. Blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. Candidate received emergency use authorization from Health Canada for metastatic triple-negative breast cancer (mTNBC). The drug is under regulatory review for HIV infections in the US. Candidate is under regulatory review for COVID-2019 infections in Canada. Clinical development for breast cancer, solid tumours, HIV infections, non-alcoholic steatohepatitis (NASH), COVID-2019 infections, post-acute-COVID-19-syndrome, COVID-2019 pneumonia, graft versus host is underway in Brazil, USA, Philippines and the UK. Preclinical development is underway in the US for autoimmune disorders like multiple sclerosis, prevention of HIV infections as an intravenous formulation, stroke, and traumatic brain injuries.
CytoDyn discontinued the development of intravenous formulation of lernolimab in HIV-1 infections in the US.
Leronlimab was originally discovered and developed by Progenics Pharmaceuticals (a subsidiary of Lantheus Holding) through phase II clinical trials. Progenics was seeking to develop leronlimab as a new HIV therapy that combined infrequent dosing and a more favourable adverse effect profile than existing therapies, with the goal of developing a long-acting, self-administered therapy for HIV infection. However, the company discontinued development of leronlimab and sold it to CytoDyn in 2012 [1] .
In June 2020, Progenics Pharmaceuticals was acquired by Lantheus Holdings [2] .
Company Agreements
In December 2023, Cytodyn entered into a partnership with Albert Einstein College of Medicine and Montefiore Medical Center. The company will be providing leronlimab to support a preclinical trial evaluating the efficacy of leronlimab independently and in combination with temozolomide in treating glioblastoma multiforme, also known as grade IV astrocytoma in infected humanized mice. Upon completion of the study, the academic institutions will provide the Company with a research report outlining the study results, and they will have the right to publish and present the study results. GBM is the most common type of primary malignant brain tumor and is aggressive and fast-growing. This study is expected to take place in the 2024 calendar year. [3]
In Januery 2022, Regnum, CytoDyn and SevenScore Pharmaceuticals entered into a assignment of the commercialization and license agreement and a related supply agreement to commercialize leronlimab (PRO 140) in the US for the treatment of HIV from SevenScore to Regnum. The CLA was signed between Vyera Pharmaceuticals and CytoDyn on December 2019 and assigned to SevenScore on October 2020. Under the terms of the commercialization and license agreement, Regnum has been granted an exclusive license to market and distribute leronlimab in the US for the treatment of HIV and CytoDyn will maintain responsibility for the development and FDA approval of leronlimab for all HIV-related and other indications. In exchange for such exclusive license, Regnum has agreed to pay regulatory and sales-based milestone payments, as well as a royalty of 50 percent on net sales. [4]
In May 2021, CytoDyn enterted into an exclusive supply and distribution agreement with Macleods Pharmaceuticals in India. The commercial agreement will enable Macleods to sell leronlimab in India, following regulatory clearance. [5]
In May 2021, CytoDyn entered into a research and development agreement with Academic Research Organization (ARO) Albert Einstein Israelite Hospital to evaluate leronlimab in two phase III COVID-19 trials including a small trial in critically ill and a large trial in severe populations in Brazil. The trials are intended to provide the Brazilian regulatory authority, ANVISA, with the requisite data to consider advancing the availability of leronlimab to Brazilians infected with COVID-2019 infections. Other details of the agreement were not disclosed. [6]
In April 2021, CytoDyn entered into a distribution and supply agreement with Biomm S.A. for the supply of leronlimab for the treatment of COVID-19 and all other leronlimab indications in Brazil. [7]
In November 2020, CytoDyn entered an agreement with amfAR to test the ability of leronlimab to mediate a functional HIV cure. CytoDyn’s partnership with amfAR will advance clinical studies to incorporate leronlimab to mimic a CCR5-deficient stem cell donor and attempt to functionally cure an HIV+ person receiving a stem cell transplant from a donor expressing CCR5. [8]
In July 2020, CytoDyn entered into a distribution and supply agreement with American Regent for the distribution of leronlimab for the treatment of COVID-19 in the US. Under the terms of the agreement, CytoDyn will supply leronlimab for the treatment of COVID-19 for distribution by American Regent and receive quarterly payments based on a profit-sharing arrangement. [9]
In June 2020, CytoDyn and the Coordinating Commission of the National Institutes of Health and High Specialty Hospitals of Mexico (NIH)entered into a Memorandum of Understanding (MOU) to conduct a phase III trial with leronlimab for COVID-2019 infections in severe and critically ill patients, with the potential to collaborate on additional COVID-19 trials. Under the terms of MOU, CytoDyn will supply leronlimab at its expense to the NIH and both parties are proceeding forward expeditiously to complete the mutually agreed protocol for trial. [10]
In February 2020, CytoDyn signed a nonbinding letter of intent (LOI) for the joint development and licensing of leronlimab in China with Longen China Group. CytoDyn and Longen will be exploring opportunities for leronlimab for the treatment of the 2019 novel coronavirus (2019-nCoV) and cancer. Financial details were not disclosed. [11]
In December 2019, CytoDyn and Vyera Pharmaceuticals entered into a commercialisation, licensing and supply agreement in the US for HIV infections. Under the terms of agreement, CytoDyn will maintain responsibility for the development and the US FDA approval of leronlimab for all HIV-related and other indications and Vyera will be responsible for exclusively market and distribute leronlimab in the US for the treatment of HIV. CytoDyn will receive upfront and regulatory and sales-based milestone payments of up to $US87.5 million, along with a royalty of 50 percent on net sales. Vyera will also make an investment in CytoDyn of $US4 million in the form of registered CytoDyn common stock. [12]
In July 2019, CytoDyn entered into an exclusive worldwide licensing agreement with IncellDX to sell non-commercial grade quantities of leronlimab for use in the development and commercialization of immunoassays for quantitative measurement of CCR5 levels on human cells. Under the terms of the agreement, IncellDX will be responsible for all aspects of assay development, regulatory clearance, including leronlimab labeling, packaging and commercialization. At the end of each month during the term of the agreement, IncellDX will provide to CytoDyn demand forecasts for leronlimab for the subsequent 3-month period. [13]
In June 2019, CytoDyn signed a Memorandum of Understanding (MOU) with Thai Red Cross AIDS Research Centre (TRCARC) for the design and conduct of a pre-exposure prophylaxis (PrEP) clinical trial of leronlimab in volunteers who are at high risk of HIV infection. Under the terms of the collaboration, CytoDyn is obliged to provide leronlimab without any other financial support whereas TRCARC will assume responsibilities for all necessary regulatory permissions and conduct of the trial under mutually agreed protocol. No additional financial terms were disclosed. [14]
In April 2019, CytoDyn signed a contract manufacturing deal with Samsung Biologics, for the manufacture of the former's bio-drugs, including leronlimab. The deal is worth $US31 million and may be increased up to $US246 million by 2027, provided that CytoDyn concludes its product development efforts and initiates commercialization. [15]
In October 2012, CytoDyn completed the acquisition of leronlimab from Progenics by paying the $US3.5 million for the transfer of ownership of the technology and related intellectual property as well as approximately 25 million mg of bulk drug substance. Progenics will be eligible for two milestone payments following initiation of a phase III trial ($US1.5 million) and the first NDA approval ($US5 million), as well as royalties on sale upon commercialisation [1] . CytoDyn had entered into an asset purchase agreement with Progenics to acquire leronlimab in July 2012. Under the terms of the agreement, an initial payment was to be made to Progenics in the amount of $US3.5 million, as well as subsequent potential milestone and royalty payments. The transaction was subject to the satisfaction of a number of closing conditions, including: (i) Progenics having received all required authorizations, consents and approvals of government authorities; (ii) Progenics having entered into and delivered intellectual property assignments; (iii) the Company and Progenics having entered into a transition services agreement; (iv) the Company having obtained the financing and raising of capital it needs in order to consummate the transactions contemplated by the Agreement; and (v) the Company having completed and been satisfied with its continuing due diligence investigation of leronlimab [16] .
As part of an agreement with Progenics, Protein Design Labs humanised leronlimab. Progenics had agreed to pay a licensing and signing fee and was also liable for milestone payments and royalties on any future sales. In February 2002, Progenics announced that a humanised form of leronlimab had been selected for clinical testing. Humanised leronlimab is designed to be non-immunogenic, making it suitable for long-term therapy of patients with HIV infections [17] . In January 2006, Protein Design Labs changed its name to PDL BioPharma [18] .
In July 2002, Progenics announced that it had signed an agreement to use ViroLogic's proprietary HIV resistance testing technology (PhenoSense™ HIV entry assay) in the development of leronlimab and PRO 542 [see Adis Insight drug profile 800005801]. The assay will be used to assess viral susceptibility to leronlimab and PRO 542 [19] . In September 2005, ViroLogic changed its name to Monogram Biosciences [20] .
Manufacturing agreement
In April 2019, CytoDyn and Samsung BioLogics entered into a manufacturing agreement of 1$ billion worth of Leronlimab to meet expected demand for future revenues post approval. Effective from 29 July 2015, CytoDyn entered into a license agreement with Lonza Sales, covering Lonza’s “system know-how” technology with respect to CytoDyn’s use of proprietary cell lines to manufacture new leronlimab material. Under the terms of agreement CytoDyn is required to pay £600 000 by 15 December 2015, and a second payment of up to an additional £600 000 by 30 June 2016, in each case excluding certain value added taxes and similar amounts (CytoDyn, Form S-1, February 2016).
Key Development Milestones
Glioblatoma: As of February 2024,
Cytodyn in partnership with Albert Einstein College of Medicine and Montefiore Medical Center plans a preclinical trial for Glioblastoma in USA in 2024 [3] .
Solid tumours
In November 2021, CytoDyn received emergency use authorization from Health Canada for treatment of a patient with metastatic triple-negative breast cancer [21] .
In November 2021, CytoDyn completed the phase II basket trial of leronlimab for the treatment of approximately 22 different solid tumour, including melanoma, brain-glioblastoma, throat, lung, stomach, colon carcinoma, breast, testicular, ovarian, uterine, pancreas, bladder, among other indications (NCT04504942; CD09_Basket). The open label trial initiated in February 2020 and enrolled 30 patients in the US, with locally advanced or metastatic solid tumours. Leronlimab will be administered subcutaneously as a weekly dose of 350 mg. In April 2020, first patient from the trial was treated [22] . The primary endpoint of the basket trial is progression-free survival. CytoDyn received central Institutional Review Board (IRB) approval to initiate a phase II basket trial to evaluate subcutaneous leronlimab for the multiple locally advanced or metastatic solid tumours in the US.Earlier, the company filed a protocol for the basket trial with the US FDA under its cancer IND. Based on outcome, CytoDyn intended to file for Breakthrough Therapy designation for all solid tumour cancers [23] [24] [25] [26] [27] [28] .
In November 2021, CytoDyn has submitted an application for breakthrough therapy designation to the US FDA for leronlimab as a treatment for metastatic triple-negative breast cancer (mTNBC). This application was based on the data analysis from the compassionate use study, the phase Ib/II study, and the Basket study, released by the company [29] . In January 2020, the company had filed of breakthrough therapy designation with the US FDA for the use of leronlimab as an adjuvant therapy for the treatment of mTNBC. In August 2019, under emergency Investigational New Drug a(IND) application of the US FDA, first patient with metastatic triple-negative breast cancer was treated with leronlimab. The company plans to seek Accelerated approval with the US FDA for the use of leronlimab, based upon the results of phase II trial [30] [31] [32] .
In November 2019, the Institutional Review Board approved the compassionate use (expanded access programme) of leronlimab for treatment of patients with triple-negative breast cancer (TNBC). This programme will allow access to TNBC patients who are not eligible to receive leronlimab under the ongoing phase II trial [33] .
Prior to September 2019, CytoDyn dosed the the first patient with leronlimab to treat metastatic triple-negative breast cancer through the expanded access program. Earlier in May 2019 the company announced its intention to initiate an expanded-access programme for patients with serious or life-threatening illnesses. In May 2019, the US FDA granted Fast Track Designation to leronlimab for use in combination with carboplatin for the treatment of patients with CCR5-positive metastatic triple-negative breast cancer (mTNBC). Further, in the same month, . In February 2019, CytoDyn announced that it has applied for Orphan drug status for triple-negative breast cancer. The application was based on positive results obtained in preclinical studies [34] [35] [36] [37] .
In September 2019, the US FDA completed the safety review of the application (Protocol number CD08_mCRC) approved the conduct of a phase II trial of leronlimab in combination with regorafenib in patients with metastatic colorectal cancer. Earlier in August 2019, CytoDyn filed a phase II protocol with the US FDA [34] [38] .
As of February 2023, CytoDyn withdrew a phase II trial prior to enrolment. The open, prospective study intended to investigate leronlimab in combination with regorafenib [See AdisInsight Drug profile 800024225] in patients with CCR5+, microsatellite Stable (MSS) metastatic colorectal cancer (mCRC) (NCT05730673; CD08_mCRC) [39]
In November 2021, CytoDyn completed a phase Ib/II trial of leronlimab for the treatment of patients with metastatic triple-negative breast cancer (CD07TNBC; NCT03838367). The open label trial initiated in January 2019 and enrolled 48 patients in the US [23] . Earlier in November 2018, the US FDA approved the IND application submitted by CytoDyn for initiation of the trial. As of September 2019, the phase II portion was initiated and first patient was given injection of leronlimab. CytoDyn intends to utilise results form this trial for regulatory pathway, including potential Breakthrough Therapy Designation and accelerated approval by the US FDA for the use of leronlimab in mTNBC. As at 13 February 2020, total seven patients were treated in the trial and screening for additional patients was underway [40] [34] [41] [42] [43] [44] . In December 2019, CytoDyn released the early results from the two patients of the trial demonstrating the sustained response to leronlimab. The results demonstrated shrinkage of tumour (via MRI) after three weeks of treatment with leronlimab in an emergency IND protocol. Additionally, the results from the patient enrolled at stage 4 metastatic breast cancer (MBC) demonstrated shrinkage of the tumours following the first leronlimab injection, reduction in brain edema, and remarkably, disappearance of several metastatic tumors. There were no serious adverse events reported [45] [31] . In January 2020, similar positive data was released by CytoDyn from the two patients after 15 weeks of treatment with leronlimab in combination with carboplatin.No severe adverse events were reported [46] . In February 2020, updated interim efficacy data from the trial were released by CytoDyn [26] . In March 2020, the company announced the first mTNBC patient is in remission and that her oncologist suggested a termination of treatment with carboplatin and to continue leronlimab only as monotherapy [47] . In July 2021, CytoDyn announced that the trial has successfully advanced from the phase Ib part to phase II part, and the company also confirmed that the phase II part will be assessed using 700 mg dose [48] . In July 2021, CytoDyn released preliminary interim efficacy data from a trial [49] . The safety and efficacy data presented at the 44th Annual San Antonio Breast Cancer Symposium (SABCS-2022) [50] .
In October 2022, CytoDyn released efficacy data from a pooled analysis of phase Ib/II, the compassionate trial, the Basket trial [51] In April 2022, CytoDyn presented efficacy data from a pooled analysis of phase Ib/II, phase II basket trial and compassionate use trial at the 113th annual meeting of the American Association for Cancer Research (AACR-2022) [28] [44] [52] [53] .
In October 2021, CytoDyn announced a study in collaboration with The University of Texas MD Anderson Cancer Center for treating triple-negative breast cancer (TNBC) of leronlimab in combination with immune checkpoint blockade in a humanised TNBC xenograft model [54] .
Leronlimab binds to CCR5 in human breast cancer, blocks cytokines induced CCR5 signaling and human breast cancer cell invasion [55] .
In January 2020, CytoDyn released the preclinical data from macaques which showed that the leronlimab prevented the intrarectal transmission of Simian-Human Immunodeficiency Virus (SHIV) [56] .
In March 2019, CytoDyn announced that its has filed application with the USFDA for Fast Track Designation for leronlimab in Metastatic-Triple Negative Breast Cancer (mTNBC) on the basis of positive preclinical data in murine xenograft models. Data showed showed significant reduction in the volume of human breast cancer tumor metastasis. The metastatic tumor volume was reduced by more than 98% after 7 weeks [57] .
In February 2019, preclinical data from mouse xenograft models for breast and prostate cancer showed that it reduced the incidence of human breast cancer metastasis by more than 98% during the six week treatment. Based on these results, CytoDyn is planning to expand pre-clinical animal studies into eight cancer indications [37] .
In August 2019, CytoDyn announced that leronlimab treatment in mice models suppressed growth of colon carcinoma in both low and high CCR5 expression tumours [58] . In August 2018, CytoDyn released the preclinical data for leronlimab in human colorectal cancer. Leronlimab was in preclinical development for colorectal cancer since 2017 [59] .
In preclinical studies, leronlimab inhibited metastasis and invasion of cancer into healthy cells, following a surrogate assay for metastatic breast cancer. Treatment with CCR5 inhibitors can inhibit metastasis and invasion of prostate, breast and colon cancers, including patients with treatment-resistant colon cancer. Leronlimab detected CCR5 on metastatic human breast cancer cells and blocked their invasiveness [60] [61] .
COVID-2019 infections
In March 2022, U.S. Food and Drug Administration (FDA) suspended the company's COVID-19 program and placed a full clinical hold on it in the US. Additionally, the company decided to suspend its Brazil COVID-19 trial while awaiting results from the previously scheduled data safety monitoring committee meeting and is reevaluating the timing of its HIV BLA resubmission [62] [63] .
In December 2021, CytoDyn received positive response from the US FDA to conduct a phase III trial to evaluate the efficacy and safety of leronlimab in combination with standard of care for critically ill patients with COVID-19 pneumonia with need for Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) [64] . Earlier, in the same month, CytoDyn submitted an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (“FDA”) for phase III trial to evaluate the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO) [65]
In April 2022, CytoDyn suspended a phase III trial that was designed to assess the safety and efficacy of leronlimab plus standard of care in critically ill patients hospitalized with COVID-19 pneumonia who are requiring mechanical ventilation or extracorporeal oxigenation (ECMO) (NCT04901689; ARO_21_018_002). The double-blind, parallel, placebo controlled and randomised trial was initiated in October, 2021 and enrolled 316 patients in Brazil [66] .
In April 2022, CytoDyn suspended the CD17 phase III trial that was designed to assess the safety and efficacy of leronlimab plus standard of care in patients hospitalized with COVID-19 pneumonia who are not requiring mechanical ventilation or extracorporeal oxygenation (ECMO) (ARO21_018_001; NCT04901676). The double-blind, parallel and randomised trial was initiated in September, 2019 and enroledl 612 patients in Brazil [67] .
As of March 2022, CytoDyn suspended the CD16 phase III that focused on hospitalised critically ill COVID-19 patients who required mechanical and invasive ventilation or Extracorporeal Membrane Oxygenation (ECMO). The trial was initiated in October 2021. Leronlimab was administered via intravenous therapy (IV) in four doses or 700 mg per week. The trial was conducted across 29 research centers (hospitals) with 316 patients in Brazil. The first patient was dosed in trial [68] [69] . In December 2021, CytoDyn received agreement from the Brazilian Health Regulatory Agency (ANVISA) to modify the CD16 trial and authorised CytoDyn to submit the requested changes. CytoDyn will submit the revised protocol for CD16 trial providing for a reduction in total enrollment from 330 to 126 patients, with interim efficacy analysis by DSMB after 40% of patients (51 patients) are enrolled and have completed follow-up to Day 28 [70] .
In September 2021, Brazil’s regulatory authority ANVISA (Agência Nacional de Vigilância Sanitária) approved the start of an additional phase III CD16 trial of leronlimab for 316 critically ill COVID-19 patients who are requiring mechanical and invasive ventilation or extracorporeal membrane oxygenation (ECMO) [71] . Earlier, ANVISA had cleared the trial with a condition of providing more information about CMC, which the company intended to submit [72] . Earlier in August 2021, CytoDyn announced that ANVISA approved the clinical trial protocol to commence patient enrollment in the trial for severe COVID-19 patients. The trial is intended to provide ANVISA with the requisite data to consider advancing the availability of leronlimab to Brazilians infected with COVID-19 [73] [67] .
Before May 2021, CytoDyn announced that the the CD12 trial did not meet mITT endpoints. The company will soon provide an update on ongoing work with the US FDA and other regulatory agencies on using sub-population data to ensure future adequate trial design, in order to continue to further its clinical development of leronlimab in the treatment of patients with COVID-19 [74] .Previously, In December 2020, CytoDyn completed the enrolment in the phase III portion of a phase IIb/III trial in patients with severe-to-critical COVID-2019, under the granted emergency IND. The randomised, double blind, placebo controlled, adaptive, multi-centre trial is evaluating the safety and efficacy of leronlimab, and was initiated in April 2020(NCT04347239; CD12_COVID-19). The primary outcome is all-cause mortality at day 28. The study enrolled 394 patients in the US and UK [75] [76] [77] . Earlier in April 2020, the company had filed a second clinical trial protocol for leronlimab with the US FDA for COVID-2019. Phase III portion of the trial was initiated in July 2020. In August 2020, CytoDyn received positive Data Safety Monitoring Committee (DSMC) recommendation for leronlimab for the treatment of COVID-19 infections. The DSMC did not raise any safety concerns from the data reviewed from 149 patients and recommended to continue the trial. In October 2020, CytoDyn reached the required enrolment of 195 patients in the phase III trial to perform an interim analysis and is expected to occur again after enrolment reaches 293 patients. In November 2020, CytoDyn announced that it has reached enrollment of 293 patients in the phase III trial for COVID-19 infections, thereby meeting the requested criteria for a second interim efficacy analysis by the Data Safety Monitoring Committee (DSMC). After the first interim analysis, the DSMC requested a second interim analysis of all data after enrollment had reached 293 patients or 75% of the total patients for the trial. Trial showed 82% reduction in critically ill, mechanically ventilated patients with statistically significant p value. In December 2020, CytoDyn concluded that it will be far more time efficient to forego the second interim analysis and to analyse the results of the phase III portion of the trial with the data on 390 patients, and to provide final data to the US Food and Drug Administration, Health Canada, MHRA, and Philippines FDA. In February 2021, CytoDyn unblinded the data of the trial and reported that the company has concluded its ongoing discussion with the Medicines and Healthcare products Regulatory Agency (MHRA) of the UK, Health Canada and the US FDA regarding the outcome of the trial [78] [79] [80] [81] [82] [83] [84] [85] [86] [87] [88] [89] . In March 2021, CytoDyn released initial results from the trial and also announced the submission of results to US FDA, MHRA and Health Canada. In March 2021, updated efficacy data from the trial were released by CytoDyn. In April 2021, top line efficacy data from the trial were released by the CytoDyn. In December 2021, updated data from this trial were released by CytoDyn [90] [91] [92] [93] [65]
In April 2021, CytoDyn submitted manufacturing section (CMC) of interim order application to Health Canada for COVID-2019 infection under rolling review. CytoDyn also announced that company's manufacturing practices are in compliance with GMP requirements. The company will submit remaining sections in near future [94] .
In April 2021, CytoDyn announced that the first Compassionate Special Permit (CSP) patient in the Philippines improved significantly 35 hours after receiving a 700 mg injection of leronlimab under a licensed physician’s request for CSP to treat COVID-19 patients [95] . Earlier in December 2020, CytoDyn announced the intention to file for Emergency Use Authorisation (EUA) for leronlimab as a treatment for severe-to-critical COVID-2019 patients with the Food and Drug Administration in the Philippines. Earlier in October 2020, CytoDyn had announced that it had conducted a meeting with Chiral Pharma Corporation (a subsidiary of Philippine New Marketlink Pharmaceutical Corporation), to register leronlimab (PRO 140) for potential approval from the Food and Drug Administration in the Philippines, for the treatment of patients with COVID-19 infections [79] [96] .
In March 2021, CytoDyn announced intention to file Accelerated Rolling Review with MHRA for COVID-2019 infections [97] .
In March 2021, CytoDyn initiated the process to submit an interim order with Health Canada [97] .
In March 2021, CytoDyn announced that based upon a discussion with the US FDA, MHRA, and Health Canada for the determination the best path forward for approval of leronlimab, CytoDyn intends to conduct another study of 140 patients for the treatment of COVID-2019 infections in critically ill population with the same sites as the CD12 and/or more sites added [93] . CytoDyn also announced that, it concurrently filed an additional protocol with the US FDA using the existing sites from its CD12 trial to quickly enroll patients in this population during the ongoing regulatory discussions. Also, CytoDyn is underway other regulatory authorities for the worldwide expansion of the trial [92] . In December 2020, CytoDyn announced that the US FDA provided guidance for addition of an open-label extension to the phase III CD12_COVID-19 trial [see below] and specific criteria for the continuation of eINDs for patients meeting the inclusion/exclusion criteria of this trial. The company will amend changes in the trial design and submit it to the US FDA and upon approval, all the trial sites will have option to enroll additional qualified patients with all receiving leronlimab. The US FDA also provided specific guidance to enable physicians seeking eIND for patients with COVID-2019 infections [98] .
In December 2020, CytoDyn reported that the US FDA granted approval to administer leronlimab for severe-to-critical COVID-19 infection patients under emergency IND (eIND) in the US [99] .
In May 2020, CytoDyn announced that it will collaborate with the of Mexican National Institutes of Health and provide leronlimab for a trial for the treatment of severe and critically ill patients COVID-19 patients in Mexico. The small phase III trial intends to enrol approximately 25 patients in Mexico [10] [100] .
In May 2020, CytoDyn announced intention to submit a protocol to the US FDA for a factorial design of phase III trial to compare effectiveness of leronlimab versus remdesivir and in combination with remdesivir for the treatment of COVID-19 [101] .
In August 2020, CytoDyn provided its top-line report from its recently completed phase II clinical trial [see below] for patients with mild-to-moderate COVID-19 symptoms to the Medicines and Healthcare Products Regulatory Agency (MHRA), UK. Later, in the same month, it was reported that after several months of providing requested information about manufacturing and safety of leronlimab, the MHRA of the UK Government authorised the company to enrol for its ongoing trial for severe-to-critical COVID-19 patients [see below], in the UK. The company requested the regulatory pathway for Fast Track approval noting the efficacy and safety results from the phase II trial [102] [77] .
In July 2020, CytoDyn completed phase II trial that evaluated the safety and efficacy of leronlimab in patients with mild-to-moderate COVID-2019 infections (CD10_COVID-19; NCT04343651) [82] . The randomized, double-blind, placebo controlled trial was initiated in April 2020 and enrolled approximately 86 patients in the US. In June 2020, enrolment in the trial was completed. In July 2020, CytoDyn announced its intention to lock and unblind the trial data later in the week [83] [103] [104] [9] [85] . Efficacy results from the trial were released by the company in July 2020 [105] [106] . In August 2020, adverse events and efficacy data from a phase II trial in COVID-2019 infections released by CytoDyn [107] .
CytoDyn in April 2020, reported that 12 severely ill COVID-2019 patients were treated in a phase II trial in the US under emergency IND approval by the US FDA. Earlier, the company released favourable data from eight patients treated in the study. A preliminary laboratory evaluation of the first four patients treated with leronlimab revealed that the immune profile in these patients approached normal levels and the levels of cytokines involved in the cytokine storm (including IL-6 and TNF alpha) were much improved. Regarding the trial, CytoDyn clarified that the treatment was not a part of the company’s proposed phase II protocol recently submitted to the US FDA. Earlier in March 2020, CytoDyn submitted an IND application to the US FDA for the conduct of the trial. Subsequently, as per US FDA suggestions, CytoDyn filed another round of modifications to its IND and protocol for the trial [85] [108] [109] [86] [87] [110] [111] [112] [113] [114] [115] [116] [104] .
In May 2020, CytoDyn reported of its request submission to the US FDA for granting 'compassionate use' expanded access, for extending leronlimab availability to patients ineligible for participation in two ongoing clinical trials for coronavirus infections [see below]. At this time, the company also reported that the FDA had approved 60 emergency INDs (eINDs) for leronlimab use for treating COVID-2019 infections [100] [117] .
In May 2020, CytoDyn released the efficacy data from compassionate care treatment in critically ill patients with COVID-19 infections [118] .
In March 2020, CytoDyn announced that the company will request a preliminary Breakthrough Therapy designation meeting based on the recommendations by the US FDA [47] .
HIV infections
In February 2024, The US FDA lifts the clincal hold on leronlimab. The company can now proceed with its proposed HIV clinical trial exploring leronlimab and its effects on chronic inflammation [119] . Earlier, in April 2022, CytoDyn has suspended a pre-exposure prophylaxis (PrEP) clinical trial of leronlimab in HIV infections in Thailand as the US FDA has placed a partial clinical hold on the trial [120] . In February 2024, CytoDyn announced that it has submitted its revised HIV clinical trial protocol to the FDA. The Company believes this submission will lead to the removal of the clinical hold currently in effect [3] . Earlier in March 2022, U.S. Food and Drug Administration (FDA) suspended the company's HIV program and placed a partial clinical hold on it in the US . As a result, the patients who were involved in these trials will now have access to other therapeutic opportunities, and no clinical trials will begin or resume until the partial clinical hold is resolved [62] .
In October 2022, CytoDyn announced that the company has voluntarily withdrawn its pending Biologics License Application (BLA) for leronlimab as a combination therapy in persons living with HIV with resistance to highly active antiretroviral therapy (HAART) in the HIV multi-drug resistant population (HIV-MDR) [51] Earlier, in November 2021, CytoDyn initiated the resubmission of its Biologics License Application (BLA) for HIV infections under rolling review consistent with guidance from the US FDA and in December 2021 completed the submission of all the major sections of CMC modules to the US FDA. The company plans to submit the clinical section in the first quarter of 2022 [121] [122] . Earlier in October 2021, CytoDyn announced that the US FDA accepted the Company’s revised “Rolling Review” timeline for the Company’s upcoming resubmission of its Biologics License Application (“BLA”) for leronlimab as a combination therapy for highly treatment experienced HIV patients [123] . In August 2021, CytoDyn received comments from the US FDA on its dose justification report for resubmission of its Biologics License Application (BLA) for HIV. The company expects to fully resubmit CMC and non-clinical Sections as early as September 2021 [124] . In July 2021, CytoDyn submitted a dose justification report to the US FDA to advance its BLA filing seeking FDA approval for leronlimab as a combination therapy for HIV patients. In July 2020, CytoDyn received a Refusal to File letter from the US FDA for its BLA that sought approval of leronlimab as a combination therapy with HAART for treatment experienced HIV-infected patients. The US FDA informed that the BLA did not contain certain information needed to complete a substantive review, due to which the BLA cannot be filed. In June 2020, CytoDyn received the BLA Acknowledgment Letter from the US FDA advising the company could receive PDUFA date on July 10, 2020, subject to the ongoing review. CytoDyn had also filed a request to the US FDA for a Priority Review designation for the BLA. In May 2020, CytoDyn submitted all remaining requested clinical datasets to the US FDA. In April 2020, the company filed its BLA with the US FDA. The BLA submission was initiated in March 2019 with the filing of the non-clinical portion of BLA with the US FDA. The non-clinical portion constitutes the first of three sections of the BLA submission for leronlimab as a combination therapy with HAART for HIV-infected patients. The clinical datasets were updated to tackle FDA comments for mock datasets in March 2020. Earlier, the US FDA had reviewed and accepted CytoDyn’s request to submit on a rolling basis its Biologics License Application (BLA) in March 2019. The company also plans to file for a label expansion for leronlimab as a monotherapy based on its registration-directed study [see below] [125] [126] [127] [128] [102] [83] [103] [129] [130] [131] [117] [132] [133] [134] [135] .
In October 2020, Medicines & Healthcare product Regulatory Agency (MHRA) of the UK government has cleared CytoDyn to file its Biologics License Application (BLA) for leronlimab as a combination therapy for multi-drug resistance HIV patients in the UK. The MHRA’s clearance for the BLA filing included a treatment regimen of one injection per week of 350 mg of the Company’s product leronlimab, as contrasted to the dosage used in the phase III clinical trial conducted in the US for this indication of two consecutive injections of 175 mg per week [136] .
As of April 2022, CytoDyn has suspended a phase III trial of leronlimab in combination with remdesivir for the treatment of COVID-2019 infections as the US FDA placed a full clinical hold on the trial [137] .
In April 2022, CytoDyn announced that the phase III trial has been suspended as the US FDA has placed a partial clinical hold on the HIV program. Before April 2022, CytoDyn had plannned to initiate a registration-directed phase III trial of leronlimab monotherapy in patients with HIV infections, to support a label extension [96] [138] [139] [140] [141] [142] .
In December 2021, CytoDyn filed a request with the US FDA for approval of expanded access use of leronlimab for multi-drug resistance (MDR) HIV patients. Earlier the company had sought FDA approval to charge for leronlimab used in the HIV patients and plans to file the last portion of this request [143] [96] [138] [139] [140] [141] [142] .
In February 2019, the company conducted a follow-up meeting with the US FDA regarding its BLA submission for leronlimab combination therapy and positive interim data of its 700 mg monotherapy trial. In the meeting, the FDA agreed to accept safety data from 100 patients in the monotherapy trial with the 700mg dose after recognising that the higher dosage of 700mg in the monotherapy trial had a much higher response rate than the 350 mg dose used in the combination therapy trial. The company has enrolled 45 patients in leronlimab monotherapy with 700mg dose, 29 additional patients who have switched from lower doses to the 700mg dose and over 40 patients currently in screening to initiate 700mg dose arm of monotherapy trial. The FDA also permitted the company to upgrade all ongoing patients who are currently on 350mg in the combination therapy to 700mg dose [144] [134] [145] [146] .
CytoDyn, in April 2020, reported conditional acceptance by the US. FDA of the proprietary name Vyrologix for leronlimab as a combination therapy for highly treatment experienced HIV patients. The final approval of proprietary name is contingent on the USFDA approval of Biologics License Application (BLA) [147] .
In June 2019, CytoDyn announced that the US FDA has requested for an in-person meeting to discuss and finalise the earlier submitted protocol of a pivotal monotherapy trial of leronlimab in patients with HIV. Previously in May 2019, CytoDyn had filed with the US FDA the planned pivotal trial protocol for leronlimab as a monotherapy for HIV patients [148] [149] . Earlier, in October 2018, CytoDyn reported its plan to conduct a registration-directed trial of leronlimab monotherapy for HIV-infected patients, which if successful, could support a BLA for label extension [140] .
As of April 2022, CytoDyn announced the phase II/III trial has been suspended and that the US FDA has placed a partial clinical hold on the trial. In April 2019, CytoDyn initiated phase II/III trial of leronlimab to assess the efficacy, clinical safety and tolerability parameters of PRO 140 in combination with falling ART for the initial one-week treatment period, and in combination with optimized background therapy during the subsequent 24-week treatment period (PRO 140_CD02_OpenLabel; NCT03902522). Approximately, 25 patients with HIV-1 infections are to be enrolled in the USA [150] .
In August 2017, CytoDyn initiated an extension protocol phase II/III trial for virologically suppressed subjects who successfully completed PRO140_CD03 trial [see below] (NCT05271370; PRO 140_CD03 Extension). The trial is designed to assess the long term antiviral activity, safety, and tolerability of of PRO 140 350mg, 525mg, or 700mg as single-agent maintenance therapy for the chronic suppression of CCR5-tropic HIV-1 infection. The open-label trial intends to enroll approximately 56 patients in the US.
In November 2020, CytoDyn completed a phase IIb/III study that evaluated the safety and efficacy of once weekly leronlimab SC maintenance therapy in virologically suppressed patients with CCR5-tropic HIV-1 infection (NCT02859961; PRO140CD03). The randomised study was initiated in October 2016, and enrolled 500 patients in the US, who was shifted from suppressive combination antiretroviral therapy to leronlimabsingle agent maintenance therapy for 48 weeks. As of August 2017, more than 100 patients were enrolled in the trial. In July 2018, CytoDyn received clearance from the independent Institutional Review Board (IRB) to increase the weekly leronlimab dose from 525mg to 700mg for newly enrolled patients. Participants in the trial who failed to maintain suppressed HIV viral load on a lower dose of the drug was permitted to continue in the trial with a higher dose. In November 2018, efficacy data were released by the company. CytoDyn has planned to submit a pivotal monotherapy trial protocol for leronlimab as a single-agent maintenance therapy with the intention of filing for a label expansion, subject to combination therapy’s first approval. In March 2019, CytoDyn presented the interim efficacy and safety results at the 26th Conference on Retroviruses and Opportunistic Infections (CROI-2019). In August 2019, CytoDyn released updated efficacy results from the trial. Earlier, in October 2019, the phase III portion of the trial was initiated [151] [152] [153] [154] [155] [141] [156] [157] [158] .
In July 2018, CytoDyn completed a phase III trial that evaluated the efficacy, safety, and tolerability of leronlimab in conjunction with existing ART (failing regimen) for one week and Optimized Background Therapy (OBT) for 24 weeks respectively as a component of HAART (highly active antiretroviral therapy) (PRO140CD02; NCT02483078) [159] [160] . The double-blind, randomised trial was initiated in June 2015 and enrolled 52 patients in the US and Puerto Rico [161] [162] [163] [164] [165] [166] [167] . In February 2018, CytoDyn reported that leronlimab met the primary endpoint of the trial, which was the proportion of patients with ≥0.5 log10 reduction in HIV-1 RNA viral load from baseline at the end of the one-week treatment period (p˂0.01). In November 2021, CytoDyn also announced its plan to file for expanded access use of leronlimab for a fee to MDR HIV patients who might need leronlimab urgently [122] . In June 2018, updated results from the trial were presented at the at the American Society for Microbiology's Microbe 2018 (ASMM-2018) and further released in July 2018 [168] [169] [161] [170] [171] [146] [172] [173] [174] .
In February 2015, CytoDyn reported that its first phase IIb trial achieved 98% success with four weeks of treatment with leronlimab in HIV patients (NCT02175680). This US based 14 week trial evaluated the efficacy of once-weekly leronlimab monotherapy as treatment substitution for the maintenance of viral suppression in 43 HIV patients who were stable on combination HAART, but needed or wished to discontinue HAART therapy temporarily. The trial was completed in September 2016. Earlier, in July 2014, the company reported positive interim data from the trial, based on which, DSMB recommended the recruitment of second cohort in the trial [175] [176] [177] [178] . The company was also conducting the CD01 extension study, in which patients from the phase IIb trial were allowed to continue on the monotherapy (PRO 140_CD 01-Extension; NCT02355184). Positive interim data from this extension study were released in July 2015, followed by updated data in September 2015. In May 2018, the company reported that patients, who had successfully reached the trial endpoint, will continue to the extension study [179] [135] . In August 2017, CytoDyn completed another CD02_EA extension study, that provided continued access to leronlimabto patients who had completed participation in PRO140_CD02 (NCT02759042; PRO140CD02EA) and continued to receive clinical benefit and would require leronlimab to form a viable regimen (NCT02990858; PRO 140 _CD02 Extension). In September 28, 2021, the extension trial completed enrolment 44 patients in the US [180] [174] [181] [166] [182] [183] . In April 2022, the company released results of this extension study [184] .
In September 2014, Drexel University, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) initiated a phase IIa trial to evaluate leronlimab monotherapy in adult patients infected with CCR5-tropic HIV-1 (PRO 140 2103; 1210001606; 5U01AI095085-03; NCT02257788). The randomised, open-label trial is intended to enrol 40 patients in the US [185] .
CytoDyn in June 2015 announced that the company has signed a new contract with Amarex to manage the first phase III trial of leronlimab. In January 2014, CytoDyn announced that it was preparing protocols for two phase IIb trials of leronlimab in two additional therapeutic indications. The company is collaborating with the contract research organisation Amarex Clinical Research to prepare the protocols; the first trial protocol was submitted to the FDA in February 2014, and the second was scheduled for completion in the second quarter of 2014. The study drug manufacturing and quality (CMC) of leronlimab in regard to use in other clinical trials had earlier been approved by the FDA [164] [176] [186] .
CytoDyn entered into a clinical trial agreement with the Drexel University College of Medicine, in November 2012, in relation to two phase IIb studies that the University intends to conduct with leronlimab. The trials will be funded by approximately $US10 million from the National Institutes of Health (NIH). CytoDyn will supply 5000 doses of leronlimab to the University and in return, CytoDyn is entitled to use the data from these trials to maintain its IND application for leronlimab in order to support future clinical trial applications to the US FDA [187] . Subsequently, the two organisations entered into a contract with Ajinomoto Althea to formulate leronlimab through a "fill and finish" process; the resulting clinical-ready vials will be used in the NIH-funded phase IIb trials that are expected to begin in 2014.
In February 2013, CytoDyn entered into a collaboration with an investigator at The Scripps Research institute to conduct a preclinical study of leronlimab in an animal pre-exposure prophylaxis model of HIV infection [188] .
Progenics announced, in February 2009, that it had selected the subcutaneous (SC) formulation of leronlimabfor further development, subject to funding, for which Progenics applied to government agencies. The decision followed positive results from a completed phase II trial, which were presented at the 16th Conference on Retroviruses and Opportunistic Infections (CROI-2009). The company planned to meet with the US FDA to discuss registration studies of the SC formulation [189] . The company has since discontinued development on programmes outside of its core focus of oncology, as reported in its Form 10-K (filed 15 March 2012).
In February 2017, Progenics withdrew a phase IIb trial prior to enrollment due to lack of enrollment, that was designed to evaluate the efficacy of leronlimab as an adjunct to a new, optimised, oral antiretroviral regimen in HIV-1-infected injection drug users with viral rebound and documented poor adherence to the previous antiretroviral regimen. The primary endpoint was percentage of patients without virologic failure at week 24 (NCT01272258) [190] . The trial was halted previously based on strategic business reasons. Following the acquisition, CytoDen had submitted a revised protocol to the US FDA in October 2013 and the company had received approval to commence patients screening in January 2014 [191] [192] .
The phase II clinical programme of Progenics for leronlimab comprised two US-based clinical trials in a total of 70 patients with HIV-1 infection. One trial was investigating intravenous (IV) administration and the other, SC administration of the drug. Both studies were in patients with early-stage HIV infection who had not received antiretroviral therapy in the previous 3 months. In the IV administration study, initiated in December 2007, approximately 30 patients with HIV-1 infection were randomised to receive one 10 mg/kg dose, or one 5 mg/kg dose of leronlimab, or placebo (NCT00613379) [193] . The SC administration study was initiated in April 2008 (NCT00642707) [194] . Patients with HIV-1 infection were randomised to one of four treatment arms: leronlimab (162mg) for three single SC doses on days 1, 8, and 15 (Arm 1); leronlimab(324mg) for three single SC doses on days 1, 8, and 15 (Arm 2); leronlimab (324mg) for two single SC doses on days 1 and 15 plus one SC dose of placebo on day 8 (Arm 3); or placebo for three single SC doses on days 1, 8 and 15. Results from the two trials showed that both IV and SC forms of leronlimab exhibited potent and prolonged activity and were generally well tolerated. These data supported the feasibility of two treatment options: monthly IV and weekly SC dosing [195] [196] [197] [198] .
In March 2017, Drexel University and National Institute on Drug Abuse (NIDA) withdrew a phase IIb trial prior to enrolment that was designed to evaluate the efficacy of leronlimab as an adjunct to a new, optimised, oral antiretroviral regimen in HIV-infected injection drug users with viral rebound and documented poor adherence to the previous antiretroviral regimen (PRO 140 2102; NCT02438345). This randomised, double-blind, placebo-controlled trial planned to enrol approximately 76 patients in the US [199] .
Progenics completed enrolment and dosing of 39 patients with HIV infection in a phase Ib trial of leronlimab during December 2006. The trial evaluated the tolerability, pharmacology and antiviral activity of the antibody in this patient population. This double-blind, placebo-controlled, dose-escalation study was conducted in patients who had not taken any antiretroviral therapy within the previous 3 months and who had HIV plasma concentrations ≥5000 copies/mL. Patients received a single IV dose of leronlimab (0.5, 2 or 5 mg/kg) or placebo. Leronlimab blood concentrations and CCR5 coating were determined and compared with antiviral effects. Positive preliminary results were reported, which the company believed support the initiation of multi dose studies of the drug in combination with other agents. Detailed analysis of the phase Ib trial indicated that leronlimab was generally well tolerated and no dose-limiting toxicity was observed [197] [200] [201] [202] [203] [204] .
Leronlimab (IV administration) was well tolerated and had favourable pharmacodynamic profile in a double-blind, placebo-controlled, phase Ia study in 20 healthy male subjects (NCT00110591) [205] [206] . This study was conducted under the auspices of the US National Institute of Allergy and Infectious Diseases (NIAID), which provided funding for the development of leronlimab [198] .
Leronlimab was granted fast track status by the US FDA in February 2006, for the treatment of HIV infection as a combination therapy with HAART [207] .
In January 2022, pharmacodynamics data from in-vitro study was released by CytoDyn [208]
Preclinical evaluation was conducted in collaboration with Aaron Diamond AIDS Research Center in the US. In laboratory tests, leronlimab blocked the entry and replication of multiple strains of HIV. In the mouse model, the monoclonal antibody effectively blocked replication of HIV and reduced viral levels to nearly undetectable amounts in all animals treated.
Graft-versus-host disease
(GvHD): In October 2017, the US FDA granted orphan drug designation to leronlimab for the prevention of GvHD. The application for the orphan drug designation was filed in December 2015 [209] (CytoDyn, Form S-1, February 2016).
In December 2020, CytoDyn reported terminated a phase II trial due to the lack of patients during the COVID-19 pandemic [99] . CytoDyn, in November 2016, initiated a phase II trial to evaluate the safety, efficacy and feasibility of the use of leronlimab as an add-on therapy to standard graft-versus-host disease (GVHD) prophylaxis of acute GVHD in adult patients undergoing reduced intensity conditioning allogeneic stem-cell transplantation (NCT02737306; 140CD03GVHD; PRO 140_CD 03_GVHD). The randomised, double-blind trial was designed to enrol approximately 60 patients in the US. Previously, in October 2015, CytoDyn had reported that it had filed an IND application with the US FDA to conduct a phase II clinical trial of leronlimab in patients with GvHD, and in December 2015, received clearance from the FDA to conduct the trail. CytoDyn reported in June 2015 that leronlimab is effective in treatment of GvHD and believes that it has favourable dosing and pharmacokinetics, less toxicity and side effects and no direct stimulation (agonist activity) of the CCR5 receptor [210] [159] [211] . In March 2020, the company announced treatment of first patient in the trial under the amended trial protocol. The protocol includes reduced intensity conditioning (RIC) patients and an open-label design under which all patients receive leronlimab. The Independent Data Monitoring Committee (iDMC) had completed the interim analysis of the data from 10 patients enrolled in the trial in March 2018. Based on the analysis the company had decided to make amendments in the trial protocol and obtain concordance for it from the US FDA [212] [213] . The amendments included switching the pre-treatment conditioning regimen from aggressive myeloablative conditioning to a reduced intensity conditioning, and switching from a blinded one-for-one randomised placebo-controlled design to an open-label design, under which all enrollees received leronlimab. The amendments also provided for a 50% increase in the dose of leronlimab to more closely mimic preclinical dosing. Further in June 2018, CytoDyn reported that the central Institutional Review Board (IRB) has approved the trial for GvHD and triggered the initiation of patient enrolment in five clinical sites. At that time, the company also reported that the next review of data by the iDMC will occur following enrolment of 10 patients under the amended protocol after each patient has been dosed for 30 days [214] .
In the near future, CytoDyn expects to file the Breakthrough Therapy designation for the treatment of GvHD in patients requiring bone marrow transplants [210] .
Non-alcoholic Steatohepatitis (NASH)
In November 2021, CytoDyn announced that, plans to proceed to file a phase III protocol with the FDA and request accelerated approval for leronlimab in patients with non-alcoholic steatohepatitis (NASH) [23] .
In January 2023, CytoDyn completed a phase II trial which was designed to evaluate safety and efficacy of leronlimab in patients with non-alcoholic steatohepatitis (NASH) (CDI-NASH-01; NCT04521114) The randomised, double-blind, placebo-controlled trial was initiated in June 2020 and intended to enrol 90 patients in the US. The trial is designed to assess if leronlimab may control the devastating liver fibrosis associated with NASH. In December 2020, the first patient was enrolled in the trial. Later in March 2021, 20 patients were enrolled in the trial. In November 2021, CytoDyn released efficacy data from the trial [215] [216] [217] [103] [80] [218] . In November 2021, the company released updated data from a open label arm of the trial. The company announced that, 60 participants in double-blinded arm (700 mg) will be unblinded by early December 2021 [23] . In December 2021, additional preliminary data from the trial were released by the company [219] . In January 2022, updated efficacy and safety data released by the company [220] . In June 2022, results from the trial were presented at The International Liver Congress 2022 (ILC-2022) [221] . In November 2022, updated efficacy data from the trial were presented at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD-2022) [222] .
In October 2019, the US FDA granted approval to CytoDyn to initiate enrolment in a phase II trial for non-alcoholic steatohepatitis. Earlier in September 2019, CytoDyn submitted an Investigational New Drug (IND) application with the US FDA seeking approval to conduct a trial [152] [223] .
In October 2019, CytoDyn initiated a phase II trial to evaluate leronlimab for the prevention of devastating liver fibrosis associated with non-alcoholic steatohepatitis (NASH). The protocol for this double-blind, prospective, randomised trial intended to enrol 60 participants, has been approved by US FDA [152] [218] .
As of December 2021, in preclinical studies, leronlimab is shown to reduce fibrosis in animal models of NASH liver fibrosis [219]
Results from a preclinical study of leronlimab in the treatment of NASH were released by CytoDyn, in November 2019. [224] .
In May 2019, CytoDyn entered into a collaboration with an investigator at The Cleveland Clinic and initiated a preclinical study of leronlimab in humanised murine NASH models [225] .
Post-acute-COVID-19-syndrome
In July 2021, CytoDyn completed a phase II trial to evaluate the safety and efficacy of Vyrologix™ (leronlimab) in the treatment of patients with prolonged COVID-19 symptoms, a condition now known as Post-Acute COVID Syndrome (PACS), suffering from long-hauler symptoms (NCT04678830; CD15COVID19). The trial was initiated in March 2021 and in the same month, 20 patients were enrolled and dosed in the first 10 days of the trial for COVID-2019 long-haulers symptoms [216] [226] . The randomised, double-blind, placebo controlled trial enrolled 56 patients in USA. Earlier in November 2020, CytoDyn had filed a protocol with the US FDA for the trial. The study will have an interim analysis after half of the patients are enrolled and will allow the company to report the results [151] . Patient enrolment was completed in April 2021. CytoDyn announced that, final treatment for the last enrolled patient will be in early June with results expected in July [227] . Later, in June 2021, preliminary results after unblinding the data from the trial were released by CytoDyn [228] .
Traumatic brain injuries and stroke
In October 2020, CytoDyn announced that two patients - one with brain injury and second with stroke and partial paralysis during breast cancer treatment, were administered leronlimab under the recently expanded Right to Try statute. These patients had demonstrated noticeable signs of improvement and recovery upon treatment [229] .
Autoimmune disorders
As of October 2022, Leronlimab was still in preclinical development for autoimmune disorders like multiple sclerosis (CytoDyn pipeline, October 2022).
Financing information
In November 2020, CytoDyn completed a second non-dilutive convertible note of $US28.5 million immediately available capital. The company intends to use the capital to file BLAs in Canada and the UK for leronlimab as a combination therapy for HIV patients [230] .
In March 2020, CytoDyn completed a new non-dilutive convertible debt offering with an institutional investor, which provides $US15 million of immediately available capital. The company intends to use the capital to bring leronlimab to market [231] .
In October 2013, CytoDyn raised $US14 million through a private offering. The proceeds are intended to be used to fund operating expenses in order to continue development of PRO 140 in HIV [232] .
Patent Information
In July 2021, the US Patent and Trademark Office (USPTO) granted a patent number 11 045 546, claiming the method of treating hyperinflammation in patients with COVID-2019 infections. The patent covers methods of facilitating normalisation of the CD4+ T cell/CD8+ T cell ratios or increasing CD8+ T cell frequency with leronlimab or a binding fragment in SARS-CoV-2 infected subjects, include those having mild, moderate, or severe COVID-19, exhibiting no symptoms associated with COVID-2019, or having cytokine release syndrome, acute respiratory distress syndrome (ARDS), hemophagocytic lymphohistiocytosis (HLH), or macrophage activation syndrome. The patent also claim use of leronlimab in combination with other agents, including an antiviral agent, a non-CCR5 immunomodulatory agent, a CCL5 binding agent, an immune checkpoint molecule inhibitor, or any combination thereof. The patent is valid till 15 June 2040 [233] .
CytoDyn, in April 2020, CytoDyn received a notice of allowance from the United States Patent and Trademark Office (USPTO) for the Vyrologix mark [147] .
CytoDyn reported in its form S-1 (February 2016), that it has 12 issued US patents and 27 issued international patents for leronlimab, which are expected to expire between 2016 and 2031. CytoDyn also has 7 US patent applications and 16 international patent applications for leronlimab(CytoDyn, Form S-1, February 2016).
Drug Properties & Chemical Synopsis
- Route of administration IV, Parenteral, SC
- Formulation Infusion, Injection, unspecified
- Class Antineoplastics, Antiretrovirals, Antivirals, Hepatoprotectants, Immunotherapies, Monoclonal antibodies, Vascular disorder therapies
- Target CCR5 receptor; Virus internalisation
- Mechanism of Action CCR5 receptor antagonists; Virus internalisation inhibitors
-
WHO ATC code
A05B-A (Liver therapy)
J05A-X (Other antivirals)
L01F (Monoclonal antibodies and antibody drug conjugates)
L03 (Immunostimulants)
N (Nervous System)
R07 (Other Respiratory System Products)
-
EPhMRA code
A5B (Hepatic Protectors, Lipotropics)
J5C (HIV antivirals)
L1G (Monoclonal Antibody Antineoplastics)
L3 (Immunostimulating Agents)
N (Nervous System)
R7 (Other Respiratory System Products)
- Chemical name Immunoglobulin G4, anti-(human Chemokine receptor CCR5) (humanized monoclonal PRO 140 γ4-chain), disulfide with humanized monoclonal PRO 140 κ-chain, dimer
- Molecular formula C6534 H10036 N1720 O2040 S42
- CAS Registry Number 674782-26-4
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
advanced breast cancer |
Outcome Measure |
PD-L1/CD274 calcium modulating ligand C-C chemokine receptor type 5 (CCR5) |
|
|
advanced breast cancer |
Brief Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
advanced breast cancer |
Detailed Description |
solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19 coiled-coil domain containing 6 C-C chemokine receptor type 5 (CCR5) |
|
|
advanced breast cancer |
Eligibility Criteria |
PD-L1/CD274 HER2/ERBB2 C-C chemokine receptor type 5 (CCR5) |
|
|
advanced breast cancer |
Official Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
advanced breast cancer |
Brief Summary |
solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19 coiled-coil domain containing 6 C-C chemokine receptor type 5 (CCR5) |
|
|
cognition disorders |
Outcome Measure |
Transforming growth factor-beta (TGF-beta) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 C-reactive protein (CRP) C-C chemokine receptor type 5 (CCR5) B3GNTL1 |
|
|
cOVID 2019 infections |
Outcome Measure |
T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 CD3 gamma chain (CD3G) C-C chemokine receptor type 5 (CCR5) |
|
|
COVID-19 respiratory infection |
Outcome Measure |
Transforming growth factor-beta (TGF-beta) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 C-reactive protein (CRP) C-C chemokine receptor type 5 (CCR5) B3GNTL1 |
|
|
dyspnoea |
Outcome Measure |
Transforming growth factor-beta (TGF-beta) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 C-reactive protein (CRP) C-C chemokine receptor type 5 (CCR5) B3GNTL1 |
|
|
fatigue |
Outcome Measure |
Transforming growth factor-beta (TGF-beta) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 C-reactive protein (CRP) C-C chemokine receptor type 5 (CCR5) B3GNTL1 |
|
|
graft-versus-host disease |
Eligibility Criteria |
RNA binding motif protein 45 MHC class I antigen HLA-A heavy chain (HLA-A) major histocompatibility complex, class II, DR beta 1 HLA-A Breakpoint cluster region protein (BCR/NY-REN-26) |
|
|
hepatic fibrosis |
Eligibility Criteria |
Thyroid stimulating hormone beta (TSH) |
|
|
hepatic fibrosis |
Outcome Measure |
Tumor necrosis factor alpha (TNF-alpha) TNF-beta Interleukin-6 (IL-6) Interleukin 1 Beta (IL-1β) Interleukin 1 alpha (IL-1α) GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase 2 Cytokeratin 18 C-reactive protein (CRP) C-C motif chemokine 5 (CCL5 |
|
|
HIV infections |
Eligibility Criteria |
T-cell surface antigen CD4 CXCR4 C-C chemokine receptor type 5 (CCR5) |
|
|
HIV infections |
Official Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
HIV-1 infections |
ArmGroup Description |
C-C chemokine receptor type 5 (CCR5) |
|
|
HIV-1 infections |
Outcome Measure |
T-cell surface antigen CD4 Granulocyte-macrophage colony-stimulating factor (GM-CSF) CXCR4 C-C chemokine receptor type 5 (CCR5) |
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|
HIV-1 infections |
Brief Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
HIV-1 infections |
Detailed Description |
C-C chemokine receptor type 5 (CCR5) |
|
|
HIV-1 infections |
Eligibility Criteria |
T-cell surface antigen CD4 CXCR4 C-C chemokine receptor type 5 (CCR5) |
|
|
HIV-1 infections |
Official Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
HIV-1 infections |
Brief Summary |
C-C chemokine receptor type 5 (CCR5) |
|
|
non-alcoholic steatohepatitis |
Eligibility Criteria |
Thyroid stimulating hormone beta (TSH) |
|
|
non-alcoholic steatohepatitis |
Outcome Measure |
Tumor necrosis factor alpha (TNF-alpha) TNF-beta Interleukin-6 (IL-6) Interleukin 1 Beta (IL-1β) Interleukin 1 alpha (IL-1α) GGTLC5P GGTLC4P GGT gamma-glutamyltransferase light chain 3 gamma-glutamyltransferase 2 Cytokeratin 18 C-reactive protein (CRP) C-C motif chemokine 5 (CCL5 |
|
|
respiratory insufficiency |
Outcome Measure |
T-cell surface antigen CD4 T-cell receptor T3 delta chain (CD3d) T-cell receptor CD3-epsilon (CD3e) T-Cell differentiation antigen CD8 CD3 gamma chain (CD3G) C-C chemokine receptor type 5 (CCR5) |
|
|
sleep disorders |
Outcome Measure |
Transforming growth factor-beta (TGF-beta) T-cell surface antigen CD4 T-Cell differentiation antigen CD8 C-reactive protein (CRP) C-C chemokine receptor type 5 (CCR5) B3GNTL1 |
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|
solid tumours |
Outcome Measure |
C-C chemokine receptor type 5 (CCR5) |
|
|
solid tumours |
Brief Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
solid tumours |
Arm Group Description |
C-C chemokine receptor type 5 (CCR5) |
|
|
solid tumours |
Eligibility Criteria |
C-C chemokine receptor type 5 (CCR5) |
|
|
solid tumours |
Official Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
solid tumours |
Brief Summary |
C-C chemokine receptor type 5 (CCR5) |
|
|
triple negative breast cancer |
Outcome Measure |
PD-L1/CD274 calcium modulating ligand C-C chemokine receptor type 5 (CCR5) |
|
|
triple negative breast cancer |
Brief Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
triple negative breast cancer |
Arm Group Description |
C-C chemokine receptor type 5 (CCR5) |
|
|
triple negative breast cancer |
Detailed Description |
solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19 coiled-coil domain containing 6 C-C chemokine receptor type 5 (CCR5) |
|
|
triple negative breast cancer |
Eligibility Criteria |
PD-L1/CD274 HER2/ERBB2 C-C chemokine receptor type 5 (CCR5) |
|
|
triple negative breast cancer |
Official Title |
C-C chemokine receptor type 5 (CCR5) |
|
|
triple negative breast cancer |
Brief Summary |
solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19 coiled-coil domain containing 6 C-C chemokine receptor type 5 (CCR5) |
Biomarker
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| COVID 2019 infections | Interim order application (rolling review) | - | Preregistration | Canada | SC / Injection | CytoDyn | 23 Mar 2021 |
| COVID 2019 infections | - | - | Phase II/III | United Kingdom | SC / Injection | CytoDyn | 20 Aug 2020 |
| COVID 2019 infections | under Compassionate Special Permit | - | Clinical Phase Unknown | Philippines | SC / Injection | CytoDyn | 05 Apr 2021 |
| COVID 2019 infections | - | - | Suspended (III) | Brazil | IV / unspecified | CytoDyn | 30 Mar 2022 |
| COVID 2019 infections | - | - | Suspended (III) | USA | SC / Injection | CytoDyn | 30 Mar 2022 |
| COVID-19 pneumonia | - | - | Phase III | Brazil | SC / unspecified | Albert Einstein Israelite Hospital, CytoDyn | 09 Sep 2021 |
| Graft-versus-host disease | - | Prevention | Phase II | USA | SC / Injection | CytoDyn | 01 Nov 2016 |
| HIV infections | Rolling submission | Combination therapy, Treatment-experienced | Preregistration | USA | SC / Injection | CytoDyn | 03 Dec 2021 |
| HIV infections | maintenance therapy | Monotherapy, Treatment-experienced | Phase III | USA | SC / Injection | CytoDyn | 01 Oct 2019 |
| HIV infections | In adult patients with AML or MDS undergoing allogeneic stem-cell transplantation | Prevention | Phase II | USA | SC / Injection | CytoDyn | 01 Nov 2016 |
| HIV-1 infections | - | - | Discontinued (II) | USA | IV / Infusion | Progenics Pharmaceuticals | 11 Feb 2009 |
| Multiple sclerosis | - | - | Preclinical | USA | unspecified / unspecified | CytoDyn | 12 Oct 2022 |
| Non-alcoholic steatohepatitis | - | - | Phase II | USA | Parenteral / unspecified | CytoDyn | 01 Oct 2019 |
| Post acute COVID 19 syndrome | suffering from long-hauler symptoms | - | Phase II | USA | SC / Injection | CytoDyn | 01 Mar 2021 |
| Solid tumours | - | Late-stage disease, Metastatic disease | Phase II | USA | SC / Injection | CytoDyn | 17 Feb 2020 |
| Stroke | with partial paralysis | - | Preclinical | USA | Parenteral / unspecified | CytoDyn | 26 Oct 2020 |
| Traumatic brain injuries | - | - | Preclinical | USA | Parenteral / unspecified | CytoDyn | 26 Oct 2020 |
| Triple negative breast cancer | Emergency Use Authorization | Metastatic disease | Registered | Canada | SC / Injection | CytoDyn | 10 Nov 2021 |
| Triple negative breast cancer | triple-negative | Combination therapy, Late-stage disease, Metastatic disease, Recurrent | Phase II | USA (fast track) | SC / Injection | CytoDyn | 12 Jul 2021 |
Priority Development Status
| Type | Region | Indication |
|---|---|---|
| Fast Track | USA | Triple negative breast cancer |
Orphan Status
| Indication | Patient Segment | Country | Organisation | Event Date |
|---|---|---|---|---|
| Graft-versus-host disease | Prevention | USA | CytoDyn | 05 Oct 2017 |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| Progenics Pharmaceuticals | Originator | USA |
| CytoDyn | Owner | USA |
| American Regent | Market Licensee | USA |
| Vyera Pharmaceuticals | Market Licensee | USA |
| Biomm | Market Licensee | Brazil |
| CytoDyn | Market Licensee | Brazil |
| Regnum | Market Licensee | USA |
| IncellDx | Licensee | USA |
| Monogram Biosciences | Technology Provider | USA |
| PDL BioPharma | Technology Provider | USA |
| National Institute of Allergy and Infectious Diseases | Funder | USA |
| The Scripps Research Institute | Collaborator | USA |
| Albert Einstein Israelite Hospital | Collaborator | Brazil |
| Cleveland Clinic | Collaborator | USA |
| Montefiore Medical Center | Collaborator | USA |
| Drexel University College of Medicine | Collaborator | USA |
| University of Texas M. D. Anderson Cancer Center | Collaborator | USA |
| Thai Red Cross AIDS Research Centre | Collaborator | Thailand |
Scientific Summary
Pharmacokinetics
Pooled results from studies of single IV or multiple (n = 3) SC doses of leronlimab in patients with HIV-1 infections, demonstrated that patients who achieved an AUC of at least 0.2 exhibited maximal viral load reduction (MVLR). The terminal half-life of leronlimab was 3.5 days for both IV and SC administration. Mean AUC increased as a function of dose for IV (Studies 1302 and 2301 combined; 0.0104-0.003, 0.0733-0.024, 0.244-0.099, and 0.425-0.171 for 0.5, 2, 5 and 10 mg/kg, respectively; n = 49) and SC (Study 2101; 0.0209-0.01 and 0.0537-0.034 for 162 mg and 324 mg, respectively; n = 33) administration. The relationship between MVLR versus AUC was asymptotic, with MVLR observed at an AUC of 0.2. Furthermore, magnitude and time course of mean viral load suppression following a single IV dose of 5, 10 mg/kg or 3 SC doses of 324 mg were qualitatively similar over the treatment period [242] .
Leronlimab had a favourable pharmacokinetic profile in a double-blind, placebo-controlled, phase Ia study. A total of 20 healthy male subjects were treated with a single dose of leronlimab 0.1, 0.5, 2.0 or 5.0 mg/kg, or a placebo, administered by IV infusion. Serum concentrations of leronlimab increased proportionally with dose, and decreased with a serum half-life of approximately 2 weeks [205] [252] .
Adverse Events
Phase II
No adverse events or side effects were observed in HIV patients after three weeks of therapy with leronlimab, in a phase IIb trial (NCT02175680). Patients were treated with normal drug regimen plus leronlimab for one week followed by up to 12 weeks of therapy with leronlimab alone [177] . According to data from the related extension study, leronlimab monotherapy was well tolerated in all treated patients [180] .
Updated results from phase II trial in patients with non-alcoholic steatohepatitis showed that leronlimab was generally safe and well tolerated. There were no significant differences in treatment emergent adverse events between leronlimab and placebo groups. There was no grade 3 or higher drug related treatment emergent adverse event. Injection site reaction and mild diarrhea occurred more frequently with leronlimab than placebo but were not associated with discontinuation [221] [220] [218] .
Interim data from the phase II/III CD03 trial (n=147) showed that, a single-agent maintenance therapy of leronlimab was generally well tolerated at all dose levels. The frequency and severity of injection site reactions were comparable between the three dose groups and the incidence or severity of injection site reactions was not increased in patients receiving higher doses [154] [158] .
In the phase II/III CD02 pivotal trial, serious adverse events (SAEs) associated with leronlimab, were not experienced by any patient, during the entire 25-week course of trial duration [169] [161] [160] .
Interim analysis of a phase II trial showed that an intravenous (IV) formulation of leronlimab was well tolerated by patients with HIV infection who had not taken any antiretroviral therapy within the previous 3 months and who had HIV plasma concentrations ≥ 5000 copies/mL [196] .
According to data from the phase IIb extension trial, leronlimab subcutaneous monotherapy was well tolerated with no-drug-related major adverse events or treatment discontinuation reported in 16 of the 17 evaluable patients, for nearly two years, until documentation. One patient discontinued at week 47 (with VL <40 c/mL) due to relocation and 5 patients experienced virologic failure (VF) (2 consecutive viral load ≥ 400 c/mL). The mean time to VF was 329 days (106 - 691) [241] [180] [182] .
Final data from the phase II trial of the SC formulation of leronlimab have shown that in patients with HIV infections who were treatment naive or had discontinued therapy for ≥3 months, leronlimab was generally well tolerated in comparison with placebo, with mild and transient local reactions at the site of infusion occurring in a minority of subjects. There were no drug-related serious adverse events and no study discontinuations related to leronlimab [189] [244] . These results were consistent with previously reported interim results [196] .
Phase I
In a phase Ib trial (n = 39), leronlimab was generally well tolerated in patients with HIV infections and did not significantly affect RANTES (regulated upon activation, normal T cell expressed and secreted) levels [200] .
Leronlimab was well tolerated in a phase Ib trial in 39 patients with HIV infection who had not taken any antiretroviral therapy within the previous 3 months and who had HIV plasma concentrations ≥ 5000 copies/mL. No serious adverse events were reported [201] .
In a phase Ib/II study among 15 patients had archived tumor tissue assessed for CCR5 expression, the most common treatment-emergent adverse events (TEAEs) by any grade were: fatigue (6/10), headache (4/10), constipation (3/10), and nausea (3/10). The following grade ≥3 TEAEs were reported: neutropenia, anemia, thrombocytopenia, hyponatremia, hypertension, diarrhea and headache. Serious adverse events were reported in 2 patients (grade 2 sepsis and grade 3 headache). The following leronlimab treatment related adverse events (TRAEs) occurred (all grade 1): injection site reaction in cohort 1, fatigue (n=2) and headache in cohort 2. Three carboplatin TRAEs ≥3 were reported in one patient in cohort 1: thrombocytopenia, anemia and leukopenia [50] .
Pooled analyses:
Pooled analyses of three blinded prospective clinical drug studies - phase Ib/II dose escalation (n = 10, Compassionate Use (n = 16), and Basket Study (n = 2) - of leronlimab in metastatic triple negative breast cancer (mTNBC) patients (n = 28) demonstrated a total of n=68 TEAEs, with n = 7 grade I/II and n = 1 grade III related to leronlimab [234] [44] [53] [28] .
Leronlimab was generally well tolerated at all dose levels in a double-blind, placebo-controlled phase Ia study in healthy male subjects. All 20 subjects received the full dose of the drug, and no infusion-related toxicities were observed. No clinically meaningful drug-related side effects or changes in electrocardiograms were observed during follow-up [205] .
Covid-2019 infections
Phase III:
In a phase III trial, leronlimab demonstrated continued safety for the treatment of severe-to-critical patients with COVID-2019 infections [92] [89] .
Phase II:
In a phase II trial that enrolled 84 patients with COVID-19 infections, leronlimab treatment was well tolerated. In leronlimab group, 34% (19 of 56 patients) at least one AE was reported, compared to 50% (14 of 28 patients) treated with placebo. During the trial, total 19 serious adverse events (SAEs) were observed. Eleven (11) SAEs were reported in six patients (6/28; 21.4%) receiving placebo compared to eight SAEs in five patients (5/56; 8.9%) receiving leronlimab. SAEs noted in the leronlimab arm were not drug related. One death was reported following 33 days of enrolment out from the 84 patients treated which was noted to be treatment unrelated [105] [106] [104] .
Results from phase II trial showed that the incidence, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs) were lower in the leronlimab group compared to the placebo group. Patients treated with placebo were more than twice as likely to experience SAEs or AEs compared to patients treated with leronlimab. Treatment with leronlimab demonstrated reductions in both serious adverse events, as well as predictors of pulmonary collapse in patients with mild-to-moderate COVID-19 infections. The results also demonstrated that CCR5 blockade by leronlimab given as a weekly subcutaneous injection is reasonably safe and associated with fewer adverse events than when compared to placebo [107] [104] .
Post-acute-COVID-19-syndrome
In a phase II trial in patients with post-acute-COVID-19-syndrome, no adverse safety signals were noted [226] [228] .
Pharmacodynamics
Summary
Preclinical study in macaques demonstrated that the leronlimab prevented the intrarectal transmission of Simian-Human Immunodeficiency Virus (SHIV) [56] .
In a mouse model, leronlimab significantly decreased in tumour growth of the human colon carcinoma cell line (SW480) greater than 50%, when compared with the control mice. All the results were dose dependent. Leronlimab also extended the life of treated mice [59] .
Preclinical data showed that leronlimab inhibited a human colon carcinoma cell line, SW480 cells, metastases to liver and lung in a mouse model. After four weeks, the mice were sacrificed and the lungs and livers removed for analysis of invasion of the colon cancer cells. Leronlimab produced statistically significant inhibition of metastases to lung and liver in this mouse model [237] .
In vitro results demonstrated that the leronlimab maintained full activity in the presence of extensive resistance to the four main antiviral classes. Leronlimab IC50 did not appear significantly altered by previous or current exposure to maraviroc. In vitro, leronlimab and maraviroc have been reported to have synergistic activity. In vitro susceptibility to leronlimab is not affected by extensive drug resistance and exposure to maraviroc. Leronlimab have some advantages over maraviroc as a clinically valuable CCR5 antagonist, including lower toxicity, less drug-drug interaction issue and less frequent dosing [208]
In rhesus macaques acutely infected with simian human immunodeficiency virus (SHIV) were treated with high intravenous doses of leronlimab for 12 weeks observed reduced SHIV viral loads by 10 000 fold. Leronlimab was found within all anatomical compartments analysed, including mucosal and lymphatic tissues, sites of early viral replication after transmission and latency, respectively [184] .
Pooled analyses:
Pooled analyses of three blinded prospective clinical drug studies - phase Ib/II dose escalation (n = 10, Compassionate Use (n = 16), and Basket Study (n = 2) - of leronlimab in metastatic triple negative breast cancer (mTNBC) patients (n = 28) demonstrated a drop in circulating TACs was identified in 75% (n = 21/28) patients and predicted for significantly better clinical outcomes, mPFS = 6.2 and mOS >12 months [234] [44] [53] [28] .
In a preclinical study involving immunodeficient, NOD-scid gamma (NSG) mice, leronlimab treatment led to an effective inhibition of fatty liver development, which is an early indication of non-alcoholic steatohepatitis (NASH). Earlier data showed that leronlimab effectively blocked xenogeneic graft-versus-host disease (Xeno-GvHD) in these humanised mice. Thus, the potential for treatment of non-alcoholic fatty liver disease (a precursor of NASH) was displayed. The immunodeficient, NOD-scid gamma (NSG) mice were fed a high fat, NASH-inducing diet, transplanted with human stem cells to repopulate the deficient immune system, prior to treatment with leronlimab [224] .
Clinical studies
no resistance to leronlimab was observed in pooled results from 84 subjects treated with either single IV or 2-3 SC doses, suggesting a high genetic barrier for viral resistance to leronlimab. A total of 79/84 (94%) subjects treated with leronlimab maintained R5 viruses on-study. Of the 5 subjects that experienced a tropism shift, 3 had pre-existing minor variants of CXCR4. The median fold-change (FC) IC50 was 1.76 (range 0.26-4.99) at baseline and no significant changes were observed at viral rebound, with a 1.7-fold increase for all subjects. Maximum percent inhibition of R5 virus for all subjects was 98% at baseline, viral rebound and end-of-study timepoints [243] .
According to data from the phase IIb extension trial, post treatment IC50, IC90 and fold change values showed no significant change compared with baseline results in virologic failure and non-virologic failure patients treated with leronlimab, maraviroc and AMD 3100 [241] [180] [182] .
Leronlimab had favourable pharmacodynamic profile in a double-blind, placebo-controlled, phase Ia study. A total of 20 healthy male subjects were treated with a single dose of leronlimab 0.1, 0.5, 2.0 or 5.0 mg/kg, or a placebo, administered by IV infusion. At doses of leronlimab 5 mg/kg, CCR5 lymphocytes were coated with leronlimab for > 60 days, and the study was extended to monitor these subjects for an additional 60 days [205] .
Initial results from a phase Ia study, in which leronlimab was administered to healthy male volunteers, showed that serum concentration of leronlimab increased dose-dependently and the rate of clearance was similar to that of other humanised monoclonal antibodies. Leronlimab did not deplete CCR5 lymphocyte levels, but did mask the leronlimab epitope. Plasma RANTES levels were unchanged by treatment and anti-leronlimab antibodies were not generated. Higher dose levels are planned [252] . Further results from this study demonstrated that there was dose-dependent binding of leronlimab to CCR5 cells. The volunteer who received the highest dose showed significant masking of CCR5 throughout the 60-day follow-up period and the trial was extended to allow for continued monitoring of the individual. The double-blind, randomised, placebo-controlled, dose-escalation trial evaluated IV infusion of leronlimab at doses of 0.1, 0.5, 2.0 and 5.0 mg/kg or placebo in 5 volunteers [251] .
Updated results from a phase Ib trial in 39 patients with HIV infection, showed that there was a positive trend towards increased numbers of CD4+ T cells in patients who received a single 5 mg/kg dose of intravenously administered leronlimab. At day 8, there was an average increase from baseline of 129 cells/mm3. Levels remained elevated for 3 weeks post-treatment [246] .
Preclinical studies
Leronlimab exhibited activity against HIV-1 and HIV-2 isolates in vitro. The HIV-2 panel comprised five R5 and two R5X4 viruses. Each of the R5 HIV-2 isolates was efficiently inhibited by leronlimab. The median IC50 was < 0.2 µg/mL, similar to that observed for HIV-1 in this study and previous trials. Leronlimab were equipotent against the HIV-1 and HIV-2 isolates examined. Replication of R5X4 HIV-2 was not measurably affected by leronlimab [245] .
Leronlimab inhibited HIV by blocking virus to cell fusion at concentrations that did not affect the regular function of the CCR5 co-receptor in vitro [264] .
A single IP dose of leronlimab (1mg) reduced plasma HIV 1 viral loads to below detectable limits (< 400 copies/mL) in infected SCID mice. Viral load reductions persisted for 6-9 days post-dose. In comparison, control antibody had no effect on viral loads [257] .
Leronlimab effectively controls established HIV-1 infection in vivo. In this animal study, CB-17 SCID mice were reconstituted with peripheral blood mononuclear cells and infected with the R5 isolate of HIV-1JR-CSF. When viral steady state was reached, the animals were treated intraperitoneally with leronlimab or control antibody, initially as a single 1mg dose and then in multi-doses in the range 0.1-1.0mg, every 3 days for 3 weeks. The mice were monitored for viral burden. Viral load reductions of up to 1.8 log10 were seen in all animals treated with the single and multi-dose leronlimab. The single injection of leronlimab resulted in a transitory control of viral replication, and prolonged control was seen with multiple injections. Treatment with leronlimab did not lead to lymphocyte depletion, indicating that viral load reduction was solely due to CCR5 blockage. Viral rebound did not occur during therapy, and dose-dependent differences were observed in the kinetics of the leronlimab-mediated reductions in viral load [255] .
Leronlimab blocked HIV-1 entry through CCR5 without affecting the receptors normal activity. Leronlimab was assessed in vitro for its effects on human immune cells. Complete suppression of HIV replication was achieved at leronlimab concentrations that had little or no effect on CC-chemokine signalling through CCR5 and other immunologic activities [254] .
In vivo,
both murine leronlimab and humanised leronlimab, when administered as multiple injections, effectively controlled viral replication in SCID mice which had been infected with the R5 isolate HIV-1JR-CSF. In 12 mice, a single injection of murine leronlimab (1mg) reduced plasma HIV-1 RNA to non-detectable levels; however, in three mice, escape mutants emerged, causing a rebound in viral replication. The role of each mutation in co-receptor usage was analysed by site-directed mutagenesis; this showed that the escape variant switched to X4 via dual tropic R5X4 viruses. The escape variant showed high in vitro sensitivity to neutralisation by antibodies, patient sera and viral entry inhibitors. The authors of the study suggested that co-receptor usage should be closely monitored during anti-CCR5 therapy [253] .
Antimicrobial Activity
Summary
Leronlimab escape mutants continued to require CCR5 for entry and remained susceptible to small-molecule CCR5 antagonists (vicriviroc). Leronlimab was active against viruses resistant to small-molecule CCR5 antagonists, which suggests that leronlimab and CCR5 antagonists may represent distinct subclasses of CCR5 inhibitors. In the in vitro preclinical study, leronlimab inhibited vicriviroc escape mutants and vicriviroc inhibited leronlimab escape mutants. The primary HIV-1 JR-FL and Case C 1/85 drug resistant variants were generated in the presence of leronlimab and vicriviroc, and were passaged weekly in vitro on peripheral blood mononuclear cells [250] .
Leronlimab also exhibits potent and reproducible synergy in vitro with another HIV entry inhibitor, maraviroc [249] .
Leronlimab was the most potent inhibitor of HIV entry to target cells out of 6 inhibitory monoclonal antibodies investigated in an in vitro study. Potent and synergistic antiviral activity was observed when CCR5-targeting agents were combined with other HIV entry inhibitors [259] .
Leronlimab potently inhibited a diverse group of clinically relevant HIV isolates that represent major subclasses of HIV, including isolates from 24 South African viruses from a genetic subtype that accounts for half of all new infections worldwide. Compared with RANTES, the molecule that normally binds to the CCR5 receptor in humans, leronlimab effectively protected both primary T cells and macrophages from HIV infection, whereas RANTES acted on T cells only. Additional investigation demonstrated that viruses failed to develop resistance and remained sensitive to leronlimab despite prolonged exposure to the drug [258] [262] .
A synergistic antiviral effect was detected for the triple combination of leronlimab + PRO 542 + pentafuside in an in vitro study. The concentration necessary to achieve 95% HIV inhibition was reduced 24-fold for PRO 542, 17-fold for leronlimab, and 7-fold for pentafuside when the 3 drugs were administered together [260] .
Leronlimab demonstrated potent and sustained antiviral activity against primary virus. In in vitro studies, viral sensitivity to leronlimab was evaluated following prolonged exposure to the agent in peripheral blood mononuclear cells (PBMC), using the R5 biological clone HIV-1Case C1/85 and a p24 read out. In vivo studies employed SCID mice reconstituted with normal human PBMCs and later infected with the R5 isolate HIV-1JR-CSF. The mice were treated with single and multiple intraperitoneal injections of leronlimab and monitored for plasma viral RNA. Both in vitro and in vivo, virus remained sensitive to leronlimab following prolonged exposure. Single and multiple doses of leronlimab reduced viral loads to undetectable levels [256] .
Leronlimab inhibited all 31 test viruses in a study examining the compound as a function of HIV-1 subtype. There was no obvious dependence on genetic subtype or protease/reverse transcriptase/enfuvirtide resistance. Mean EC50 and FC values were 0.50 and 1.5, respectively. Mean FC values were 1.0, 1.5, 0.94, 1.4, 1.5, 1.8, and 1.2 for subtypes A-D, F, G, and J, respectively [248] .
Therapeutic Trials
Phase Ib/II: In the phase Ib/II study, among fifteen patients had archived tumor tissue assessed for CCR5 expression, two out of seven patients eligible for response achieved a confirmed partial response, and 4 patients stable disease [50] . Preliminary interim data from the patient with metastatic triple-negative breast cancer (MTNBC) showed 72% of patients had a decrease in cancer-associated macrophage-like cells (CAMLs ) ~30 days after induction of leronlimab. The decrease in CAMLs were associated with a ~300% increase in mean progression-free survival (mPFS), a significant ~450% increase in overall survival (OS) at 12 months [49] . In phase Ib/II trial, data from the first patient with metastatic triple-negative breast cancer (MTNBC) showed that circulating tumour cells (CTC) were dropped to zero in two weeks of treatment. Total CTC and EMT (Epithelial Mesenchymal Transition in Tumour Metastasis) dropped to zero after about one month of treatment with leronlimab, 350mg, once-a-week. There were no detectable circulating tumor cells (CTC) or putative metastatic tumor cells in the peripheral blood following 15 weeks of treatment with leronlimab in combination with carboplatin. CT scan analysis showed a 20% tumour shrinkage within the first few weeks of treatment with leronlimab. Data from the second patient showed 50% shrinkage of the primary tumor. No new metastasis in the brain were reported after treatment with leronlimab monotherapy. The follow up brain scan demonstrated that the largest brain lesion had a greater than 4-fold reduction (56%) in size. No change was reported in the size of smaller brain lesions. Also, cerebral edema remained unchanged. In the patients, total CTC and EMT were dropped to zero. The patient was previously treated with pertuzumab and trastuzumab for over a year and a half. The patient has been dosed by leronlimab since November 25, 2019 with one 700 mg dose each week. Data from the third patient, CAML counts post leronlimab treatment were reduced from 45 to 30. CTC+EMT counts were stable and there has been no change in the total number. In fourth patient, total CTC+EMT dropped by 75% in the first two weeks of treatment with leronlimab [26] [46] [31] [44]
Pooled analysis:
Pooled results from 19 subjects dosed between 525 mg and 700 mg (4 subjects increased dose from 350 mg to 525 mg and were included in the higher dose cohort). The median PFS (mPFS) for the 525 mg – 700 mg cohort was 6.2 months (95% CI 2.6 months - 7.5 months). There were 9 subjects dosed at 350 mg, mPFS was 2.2 months (95% CI 0.7 months - 12+ months). There was a meaningful PFS advantage at the higher doses when compared with the lower, 350 mg dose cohort. Furthermore, the preliminary results of the leronlimab studies also showed similarity in the PFS outcomes of mTNBC patients treated with leronlimab + carboplatin compared to overall leronlimab treated population. Of the 28 subjects enrolled, 13 subjects received leronlimab + carboplatin treatment. The mPFS for leronlimab + carboplatin population was 3.9 months (95% CI 2.3 months - 6.0 months). The subgroup analysis of PFS based on the individual subjects in each study was also reviewed. The mPFS for phase Ib/II study was 3.9 months (95% CI 2.3 months – 6.2 months), mPFS for the Compassionate Use study was 3.3 months (95% CI 1.3 months – 7.5 months), and mPFS for the Basket Study was 2.8 months (95% CI N/A). Combined, the overall mPFS for all 28 patients treated with leronlimab in the population of mTNBC patients regardless of dosage, conjunction therapy type, brain or bone metastases that have failed more than one line of previous therapy was 4.1 months (95% CI 2.5 months – 7.0 months). The mean PFS was 3.7 ± 2.93 standard deviation (SD). The impact of leronlimab in the mTNBC patients' disease progression, Overall Survival (OS) was analyzed in the same 28 subjects. The median OS (mOS) for leronlimab + carboplatin population was 12+ months (95% CI 5.4 months - 12+ months). The mOS for the 350 mg cohort was 4.6 months (95% CI 1.1 months -12+ months). The mOS for the 525-700 mg cohort was 12+ months (95% CI 5.5 months – 12+ months). The overall median OS for leronlimab treated population of mTNBC patients regardless of brain or bone metastases that have failed more than one line of previous therapy was 6.5 months (95% CI 5.0 months – 12+ months). The mean value for OS was 5.5 ±4.31 standard deviation (SD) [51] Results from pooled analysis of a phase Ib/II (n=10), compassionate use (n =16), and Basket trial (n=2) demonstrated that, after administration of leronlimab, circulating tumor cells (CTCs) were found in 29% (n=8/28) of patients at BL, and cancer associated macrophage-like cells (CAMLS) were found in 96% (n=27/28) in patients with metastatic triple negative breast cancer (mTNBC). Evaluating CTC change was found to be limited, as only 5 patients had any CTC increase, although the absence or drop of CTCs at T1 was significant for better PFS (HR=13.7 CI 95% 2.0-93.8, p=0.0296) and better OS (HR=397.7 CI 95% 19.3-100+, p=0.0019). By comparison, CAMLs or CTCs were evaluable in 100% of patients, with an increases of either population at T1 also significantly predicting for worse PFS (HR=5.8 CI 95% 1.4-23.6, p=0.0354) and worse OS (HR=36.0 CI 95% 6.2-207.6, p=0.0004) [44] [28] [52] [53] .
Pooled analyses of three blinded prospective clinical drug studies - phase Ib/II dose escalation (n = 10, Compassionate Use (n = 16), and Basket Study (n = 2) - of leronlimab in metastatic triple negative breast cancer (mTNBC) patients (n = 28) demonstrated high clinical benefit of the therapy. At 12 months, patients had a mPFS = 3.8 months (95%CI 2.3-6.2) and mOS = 6.6 months (CI95% 4.9-12+). However, patients treated with 525-700 mg doses (n = 19) had a >75% improved mPFS = 6.1 months (95%CI 2.3-7.5) and mOS 12+ months (95%CI 5.5-12+) [234] [44] [53] [28] .
Pooled analysis of 28 patients with CCR5+ Metastatic Triple-Negative Breast Cancer (mTNBC), who had failed at least two lines of previous therapy showed that 75% of the patients who exhibited a lower level of circulating cells after leronlimab (86%) or at baseline (14%) exhibited a 3600% increase in 12-month overall survival (OS) (p = 0.0004), as compared with a 980% increase in OS previously reported in August 2021. The updated analysis also suggested a 580% increase in 12-month progression free survival (PFS) (p = 0.0354), as compared with up to a 660% increase in PFS previously reported in August 2021. Of the 28 pooled patients, 16 are from compassionate use study, 10 from the phase Ib/II trial, and 2 from the Basket trial. The median overall survival (mOS) for patients that received leronlimab plus carboplatin (n = 13) was 12+ months (95% CI, 5.4 – 12+ months). The median progression-free survival (mPFS) for patients that received higher doses (525 mg) of leronlimab plus chemotherapy was 6.2 months (95% CI, 2.6 – 7.5 months), which is significantly longer compared to SOC chemotherapy (2.3 months) or SG (4.8 months). Out of 12 subjects with measurable lesions by PET/CT scans at baseline and after start of leronlimab induction, showed that 11 (92%) patients exhibited stable or partial response to leronlimab, with 3 (25%) PRs, 8 (66.7%) SDs and 1 (8%) having progressive disease after the first follow up scan. The 75% of the patients who exhibited lower level of circulating cells after leronlimab or at baseline exhibited statistically significant improvement in mOS (Hazard Ratio (HR): 36.0 (95% CI, 6.2 – 207.6, p=0.0004)) and in mPFS (HR: 5.8 (95% CI, 1.4 – 23.6, p=0.0354)), respectively. [44] [28] [235] [29] .
Updated results in an open-label part 2 of phase II NASH01 trial, showed the mean percent changes from baseline PDFF and cT1 to week 14 were both significantly reduced (-5.94% vs +9.85%, p = 0.008 and-24.38 msvs +27.64 ms, p = 0.021) respectively in the leronlimab350 mg group (n = 22) compared with placebo (n = 28). Favorable increases in apolipoprotein A1s and HDL were noted for 350 mg but not for PLBO-S (n = 5) or placebo. Inflammatory reductions were observed in IL-1 RA, IL-6, sTNFR-2 for the 350 mg group but not in PLBO-S or placebo. CCL5, CCL11, CCL18, VCAM, CCL2, CCL3, and VEGF were reduced in 350 mg and increased or less pronounced in PLBO-S. Significant reductions in PDFF and cT1 were also seen in the 350 mg subgroups with baseline cT1 ≥ 875 ms (n = 14) and cT1 ≥ 950 ms (n = 8) vs placebo. Baseline elevated ALT patients (n = 8) had reductions in ALT for 350 mg compared to placebo (mean 83.7 to 54.3;-29.3 U/L vs 87.4 to 83.2;-4.2 U/L) with corresponding reductions in PDFF (-18% vs 6%) and cT1 (-69 ms vs 5 ms). Other reductions in AST, GGT and Alkaline Phosphatase were likewise observed in the 350 mg group and cT1 subgroups vs placebo [222] . Earlier in a phase II trial in patients with non-alcoholic steatohepatitis showed that leronlimab 350 mg dose versus placebo comparison for the primary endpoint proton density fat fraction (PDFF) was statistically significant. Leronlimab compared to placebo also reached near significance for the secondary endpoint, iron-corrected T1 mapping representative (cT1) [220] . Mean percent change from baseline proton density fat fraction (PDFF) was significantly reduced in the 350 mg group vs placebo (-5.94% vs +9.85%, p = 0.008) but not in the 700 mg group (+3.75% vs +9.85%, p = 0.135). Mean change cT1 was signifi- cantly reduced in the 350 mg group vs placebo ( −24.38 ms vs +27.64 ms, p = 0.021) but not in the 700 mg group ( −2.73 ms vs +27.64 ms, p = 0.059). Significant reductions were seen in the 350 mg subgroup with baseline cT1 ³ 875 ms in both PDFF and cT1 vs placebo (−4.37% vs +9.85%, p = 0.020 and −42.00 ms vs +27.64 ms, p = 0.011) respectively. In subjects with cT1 ³ 950 ms at baseline, PDFF and cT1 were significantly reduced with 350 mg vs placebo (-9.39% vs +9.85%, p = 0.027 and −68.85 ms vs +27.64, p = 0.009) respectively. Mean change in baseline to week 14 for M65 ELISA (cK18 and K18) decreased in the 350 mg group (340.55 to 332.4 U/L; −8.18) while increased in placebo (301.96 to 411.64 U/L; +109.78) [221] .In preliminary data of phase II trial, average cT1 Reduction of 31.2 msec over 14 weeks for all 20 patients were observed. More than 80% of patients (5 out of 6) with severe NASH (cT1>1000 msec) had an average cT1 drop of 108 msec (-48 to -238 msec) and an average of about 20% fatty deposit reduction. 11 of 20 patients (55%) had a decrease in cT1 and PDFF of about 75 msec and 16%, respectively [219] . Results from phase II trial in patients with non-alcoholic steatohepatitis showed that, leronlimab (350 mg) weekly use for 14 weeks in open Label arm produced fibrosis reduction as high as 93 msec amongst first 15 patients with average reduction of 24 msec. The reductions in fat and fibrosis suggestive of a potential therapy not only for NAFLD (Non-Alcoholic Fatty Liver Deposit) but also in NASH. Fat reductions by proton density fat fraction PDFF up to 45% along with reductions in fibrosis up to 8% by CT1 were noted from baseline after just 14 weeks of treatment. The reductions in fibrosis were seen in both severe and mild-moderate NASH cases.Efficacy data obtained from five patients from a phase II trial indicated 45% of lowered fatty deposits in all five patients and 10% lowered fibrosis in four out of five patients compared to the baseline measurements [215] [218] [23] .
Phase II/III:
Results from a randomised, double-blind phase IIb/III trial for leronlimab conducted in patients (n = 52) who failed in their current HIV therapy showed significant reduction in HIV-1 RNA viral load of greater than 0.5log from baseline versus patients in the placebo arm (p < 0.01, ITT population). The study met its primary endpoint. Updated results showed that approximately 81% of patients who completed the trial displayed a suppression of viral load with plasma HIV-1 RNA viral load of less than 50 copies/mL. Treatment of 17 patients is ongoing (as of June 2018) and three discontinued the study early. Data indicated that patients treated with 700mg leronlimab, who achieved suppressed viral load at the six-week mark were highly likely to continue to maintain suppressed viral load. Moreover, responder’s rate with 350mg and 525mg doses were approximately 44% and 71%, respectively [169] [161] [171] [160] .
In a phase IIb/III trial administration of leronlimab 525mg and 700mg weekly indicated a response rate of approximately 90% in HIV infected patients who passed the first 10 weeks of monotherapy without virologic failure. The patients receiving 525 mg dose, 30% of patients failed and 17% patients failed in 700mg dosage group within the first 10 weeks. Those patients who pass the first 10 weeks of monotherapy on a 525 mg dose reached an average total of 32 weeks with sustained viral load suppression. Earlier showed that out of 26 newly enrolled virologically suppressed patients with CCR5-tropic HIV-1 infection, subcutaneously administered with 700mg leronlimab investigative monotherapy trial treated for up to 12 weeks, 24 of them (approximately 92%) achieved viral load suppression, indicating responder’s rate with 700mg dose was approximately 92%. Interim data from 147 patients (4-48 weeks on single-agent maintenance therapy) indicated an odds ratio of 4.43 for the virologic response rates with 525 mg, compared with 350 mg subcutaneous leronlimab. Approximately 150 patients demonstrated sustained viral suppression at approximately one year of monotherapy with dosages of 350 mg, 525 mg, or 700 mg of leronlimab once a week (229, 201, and 134 patients, respectively). Post-10 weeks of monotherapy, the rate of viral load suppuration was 68%, 94%, and 85% with 350 mg, 525 mg, and 700 mg, respectively [153] [154] [141] [158] [155] .
Phase II
Leronlimab suppressed viral load in 98% of HIV infected patients (n=40) for four weeks of monotherapy in a 14 week phase IIb trial. Also, 91%, 82% and 70% of the patients maintained suppressed viral loads after 6 weeks, 8 weeks and 11 weeks of leronlimab monotherapy, respectively [166] . In an interim analysis, substitution of HAART with leronlimab monotherapy for 4 weeks was successful in suppressing viral load in 100% of patients with HIV-1 infections, with no virological failures reported. The trial enrolled 40 patients. The patients were treated with normal drug regimen plus leronlimab for one week followed by up to 12 weeks of therapy with leronlimab alone. Updated results from the trial demonstrated that leronlimab prevented viral escape in patients through several months of interruption from conventional drug therapy [240] [174] [181] [167] [177] . Updated results indicated that some patients treated with leronlimab monotherapy remained virally suppressed for more than six years [239] [88] .
A phase II trial showed that an intravenous (IV) formulation of leronlimab reduced plasma viral loads with prolonged activity in HIV-infected patients with early stage disease, who had not received antiretroviral therapy for at least three months and who had viral loads of > 5000 copies/mL. In the PRO 140-IV study, a total of 31 patients were randomised to receive a single dose of placebo or leronlimab 5 mg/kg or leronlimab 10 mg/kg on day one. In patients treated with 5 mg/kg and 10 mg/kg leronlimab, the maximum mean decrease in viral load was 1.9 log10 and 2.17 log10 (p≤0.0001), respectively. All patients treated with 5 mg/kg experienced a > 1.0 log10 maximum reduction in viral load and those treated with 10 mg/kg experienced a > 2.0 log10 maximum decrease in viral load (p = 0.0079). A greater than 1.0 log10 mean decrease in viral load was maintained for three weeks, with a mean reduction of 1.55 log10 at three weeks, in patients treated with a single dose of leronlimab 10 mg/kg [195] [196] .
Interim results of the phase IIb extension study in patients (n = 5) with HIV infections showed that all five long-term participants successfully maintained HIV suppression via leronlimab monotherapy for over seven years, with no evidence of viral escape. These five participants on leronlimab monotherapy exhibited a higher frequency (7.1%) of transient episodes of plasma viremia, termed viral blips, than those on combinational oral antiretroviral regimens (2.0%) [184] [182] .
According to data from the phase IIb extension trial, 16 of the 17 evaluable patients experienced maximal virologic suppression, for nearly 2 years. Until documentation, 10 patients continued on leronlimab SC monotherapy of which nine patients had completed nearly 2 years of treatment (93–106 weeks). A single-copy HIV-1 RNA values of <1 c/mL were reported in 7 patients; values of 4, 10, and 19 c/mL were reported in 3 patients [241] [180] [182] .
Final data from a phase II trial of subcutaneous (SC) leronlimab have shown that all active doses of SC leronlimab demonstrated potent and highly significant antiviral effects, compared with placebo. A mean maximum reduction in plasma HIV RNA levels of 1.65 log10 (98%) was observed following three weekly doses of 324mg (highest dose tested). A total of 44 patients with HIV infections who were treatment naive or had discontinued therapy for ≥3 months were randomised to receive three weekly doses of leronlimab 162mg , two bi-weekly (every-other-week) doses of leronlimab 324mg , three weekly doses of leronlimab 324mg , or placebo. Patients were followed for a total of 58 days for safety and antiviral effects. For the 324mg weekly group, a mean maximum reduction of 1.65 log10 (p<0.0001) was observed, with a 1.51 log10 mean reduction in viral load (p<0.0001) observed at day 22. For the 324mg dose tested on a bi-weekly basis, a mean maximum reduction of 1.37 log10 (p=0.0001) was observed, with a 1.20 log10 mean reduction in viral load (p=0.0001) observed at day 22. For the 162mg weekly dose group, a mean maximum reduction of 0.99 log10 (p=0.0093) was observed, with a 0.75 log10 mean reduction in viral load (p=0.0072) observed at day 22. The mean viral load decreased with each successive treatment, indicating sustained viral suppression by leronlimab [189] [244] . These results were supported by interim results previously reported. In the PRO 140-SC study, 44 patients were randomised to receive three weekly doses of leronlimab 162mg or 324mg (days 1, 8 and 15), two bi-weekly doses of leronlimab 324mg (days 1 and 15) or placebo. In patients receiving three weekly doses of 324mg leronlimab, the mean maximum viral load reduction was 1.77 log10 and 100% of the patients in this group achieved a maximum reduction in viral load of > 1.0 log10. In both the 324mg weekly and bi-weekly dose groups, >1.0 log10 mean reduction in viral load was maintained for two weeks following the last dose [196] .
Phase I
In a phase Ib trial (n = 39), leronlimab (0.5, 2 or 5 mg/kg, IV-infusion) displayed proof-of-concept as a long-acting antiretroviral agent in patients with HIV infection who had not taken any antiretroviral therapy within the previous three months and who had HIV plasma concentrations ≥ 5000 copies/mL. Response rate increased with leronlimab dose, with 100% of patients in the 5mg cohort responding to treatment. Significant changes in mean maximum log10 in HIV RNA of -0.39, -0.58, -1.20, and -1.83 were observed for placebo, leronlimab 0.5, 2 and 5 mg/kg, respectively. Individual HIV RNA reductions ranged to 2.5 log10 at both 2 and 5 mg/kg. Viral loads fell to their lowest levels at 9 days post-treatment, when mean leronlimab serum levels were 1.4 and 4.1 µg/mL in the two highest dose groups, respectively. Greater than 10 fold decrease in HIV RNA was observed in 1 patient receiving 0.5 mg/kg, 6 patients receiving 2 mg/kg, and 10 patients receiving 5 mg/kg. Patients in the 5 mg/kg cohort had an average maximum decrease in viral concentration of 98.5% (1.83 log10) with some patients achieving reductions up to 99.7% (2.5 log10). Reductions persisted at or below 1.0 log10 for 2-3weeks after dosing [200] [247] [201] .
Updated results from the phase Ib trial showed that a single 5 mg/kg dose of leronlimab reduced HIV-1 RNA levels by, on average, 1.7 log10 at day 10 [246] .
COVID-2019 infections
Phase III:
The updated results from phase III CD12 trial demonstrated that the severe-to-critically ill patients of the USA showed an 82% survival benefit at day 14 after two doses of leronlimab on day 0 and day 7 (Odd Ratio 0.09 (CI 0.01, 0.72), p-value 0.0233) vs. standard of care plus placebo. The survival benefit fell from 82% to 30% after four weeks. Top line results from a phase III study showed that following treatment with leronlimab, mortality is better than placebo. Day zero to day seven, critically ill patients receiving leronlimab (on day zero) experienced a mortality rate 78% lower than patients receiving placebo. Further, patients receiving the second dose of leronlimab achieved maximum benefit of 82% less mortality. However, the effects diminished from day 14 to day 21 and from day 21 to day 28, as the mortality rate decreased to 50% and 31%, respectively. The trial met all its secondary endpoints with statistically significant p-values for the critically ill subpopulation (62 patients). Previous result from a phase III study showed that following treatment with leronlimab five out of six patients on ECMO recovered. Earlier data showed that leronlimab demonstrated substantial improvement in the survival rate, and faster hospital discharge in critically ill patients with COVID-2019 infections. Leronlimaba was reported with a 24% reduction in all-cause mortality (primary endpoint of the study) versus the placebo. The average length of hospital stay was reduced by 6 days for patients who received leronlimab with Standard of Care (SoC) compared to placebo patients who received SoC only (p-value 0.005), using the Rank-ANCOVA model. In addition, patients received leronlimab demonstrated an improved probability of "discharged alive" at day 28 (28% versus 11%), a 166% better rate than in the placebo group. As a consequence of an imbalance among enrolled patients over 65 years of age and under 65, an age adjustment analysis was performed, which gave statistically significant results (p-value = 0.0319) for the primary endpoint (all-cause mortality at Day 28) in participants receiving leronlimab plus SoC compared to participants who received SoC alone in the placebo group in the overall modified intent-to-treat (mITT) population. Statistically significant results (p-value = 0.0552) reported for the primary endpoint among participants who received dexamethasone as the prior or concomitant SoC for COVID-2019 infections, compared to patients who received dexamethasone (without leronlimab) as SoC therapy in the overall mITT population. Amongst all patients in mITT, the primary endpoint was not statistically significant. When age adjustment was conducted, the primary endpoint was much closer to statistically significant value. The population of 65 years and younger leronlimab arm had more than 30% less mortality than placebo and 9% less mortality in participants over 65. With the age adjustment analysis in all other major secondary endpoints, there was consistent numerical superiority over the placebo group, and statistical significance towards secondary endpoints were also reported [90] [91] [93] [92] [89] [65]
Phase II
In data from eight patients with severe COVID-2019 infections in phase II trial, treatment with leronlimab for three days demonstrated improvement in cytokines, IL-6, increase in CD8 T-lymphocytes percentages and normalisation of CD4/CD8 ratios [108] [76] [104] .
A severly ill patient with COVID-2019 infection, treated with leronlimab under Emergency IND (EIND) in a phase II trial, showed improvement in clinical symptoms within 24 hour post therapy and was removed from external ventilation three days later. The patient was treated earlier with IL-6 inhibitors and antiretroviral therapy which did not improve the condition of the patient. Two more patients with moderate COVID-2019 infections, who received leronlimab under an EIND also displayed clinical improvement. These patients were removed from external oxygen support one day following leronlimab treatment, and subsequently discharged from the hospital. Subsequently, a total of five patients were relieved from oxygen support. Updated data showed that a total of 38 infected patients were extubated, improved, or were discharged. Four of 11 critically ill patients survived post-treatment [117] [85] [236] [104] .
Results from compassionate trial in 10 COVID-19 patients administered with leronlimab demonstrated complete CCR5 receptor occupancy on macrophage and T cells, rapid reduction of plasma IL-6, restoration of the CD4/CD8 ratio, and a significant decrease in SARS-CoV-2 plasma viremia. Consistent with reduction of plasma IL-6, single-cell RNA-sequencing revealed declines in transcriptomic myeloid cell clusters expressing IL-6 and interferon-related genes was observed [118] .
Primary endpoint shows early clinical improvement in symptom score at day 3 in patients receiving leronlimab as demonstrated by top-line results from phase II trial in mild-to-moderate COVID-2019 infected patients. Clinical improvement assessed by change in total clinical symptom score. At Day 3, more subjects treated with leronlimab reported improvement in total clinical symptom score compared to the placebo group (90% on leronlimab arm vs. 71% on placebo). The subgroup analysis indicated that among patients with more symptoms at baseline, those who received leronlimab had a greater treatment effect than patients who received the placebo. Leronlimab also demonstrated statistically significant improvement versus placebo in key secondary efficacy endpoint, National Early Warning Score 2 scale (which is an objective scale to identify patients at risk and being used as an endpoint). In all treated patients, at the end of treatment (or day 14), patients in the leronlimab group were more than twice as likely to experience a beneficial improvement in the National Early Warning Score 2 compared to patients in the placebo group (50% vs 20%; p=0.0223). Similar, statistically significant, results were observed at day 3 and day 14 in the analysis of per protocol population (p<0.03 and p<0.02, respectively) [107] [104] .
Post-acute-COVID-19-syndrome
In a phase II trial in patients with post-acute-COVID-19-syndrome, clinically meaningful improvements in leronlimab over placebo were observed for cough, stuffy/runny nose, shortness of breath, tightness of chest, feeling of fast heartbeat, fatigue, muscle aches/cramps, muscle weakness, joint pain/swelling, chills/shivering, feeling hot or feverish, difficulty in concentration, sleep disturbance/insomnia, headache, dizziness, tingling/numbness, sense of taste, and sense of smell. Of the remaining 6 symptoms, sore throat, exertional malaise, anxiety, nausea, and vomiting had no clinically meaningful change [226] [228] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Dec 2024 | Trial Update | Cytodyn in partnership with Albert Einstein College of Medicine and Montefiore Medical Center plans a preclinical trial for Glioblastoma in USA in 2024 (9409182) | 06 Feb 2024 |
| 30 Nov 2021 | Regulatory Status | CytoDyn announces intention to resubmit BLA for HIV infections (Combination therapy, Treatment-experienced) to the US FDA in November 2021 (9339591) [54] | 19 Nov 2021 |
| 31 Dec 2020 | Regulatory Status | CytoDyn expects to launch leronlimab in HIV infections by the fourth quarter of 2020 [231] | 07 Apr 2020 |
| 31 Dec 2020 | Trial Update | CytoDyn plans a phase II trial for Stroke (Parenteral) in multiple countries, in 2020 [229] | 19 Nov 2020 |
| 31 Dec 2020 | Regulatory Status | CytoDyn announces intention to submit IND to the US FDA for COVID-2019 infections and Stroke in 2020 (9306351) | 28 Oct 2020 |
| 31 Dec 2020 | Regulatory Status | CytoDyn announces intention to submit a BLA to the Medicines and Healthcare products Regulatory Agency (MHRA) for leronlimab in HIV infections in United Kingdom in 2020 [80] | 27 Nov 2020 |
| 31 Dec 2020 | Trial Update | CytoDyn announces intention to submit a BLA to the Health Canada for leronlimab in HIV infections in Canada in 2020 [80] | 27 Nov 2020 |
| 31 Dec 2020 | Trial Update | CytoDyn plans a pivotal phase III clinical trial for HIV-1 infections (Monotherapy) in 2020 (9266290) (700300580) [139] | 27 Aug 2020 |
| 04 Sep 2020 | Regulatory Status | The US FDA will respond to CytoDyn's questions regarding BLA resubmission for HIV infections (Combination therapy, Treatment-experienced) by September 4, 2020 [128] | 16 Oct 2020 |
| 11 May 2020 | Regulatory Status | CytoDyn plans to complete the filing of a Biologics License Application for leronlimab for HIV infections (Treatment-experienced, Combination therapy) in May 2020 [117] | 14 May 2020 |
| 03 Apr 2020 | Regulatory Status | CytoDyn plans to file second trial protocol as per the FDA suggestion for severely ill COVID-19 patients [87] | 07 Apr 2020 |
| 31 Mar 2020 | Trial Update | CytoDyn plans a phase II basket trial in Solid tumours (Late-stage disease, Metastatic disease) in USA (SC) in March 2020 [27] | 27 Feb 2020 |
| 31 Jan 2020 | Regulatory Status | CytoDyn announces intention to file for Breakthrough Therapy designation in metastatic Triple-negative breast cancer before the end of January 2020 [31] | 16 Jan 2020 |
| 31 Dec 2019 | Trial Update | CytoDyn plans a PrEP clinical trial for HIV infection in Thailand in 2020(700308578) [238] | 05 Feb 2020 |
| 31 Mar 2019 | Regulatory Status | CytoDyn expects to complete the filing of a Biological License Application (BLA) and Chemistry, Manufacturing and Controls submission in the first half of 2019 for HIV infections (Combination therapy) to the US FDA (9253486) [132] | 25 Mar 2019 |
| 28 Feb 2019 | Trial Update | CytoDyn plans a phase Ib/II trial for Breast cancer (Combination therapy, Metastatic disease, Late-stage disease) in US in February 2019 (SC) (NCT03838367) (700300582) | 27 May 2019 |
| 30 Sep 2018 | Regulatory Status | CytoDyn plans to file an IND application with the US FDA in USA for Colorectal cancer [59] | 21 Aug 2018 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 29 Feb 2024 | Regulatory Status | U.S. FDA has lifted the clinical hold on the a pre-exposure prophylaxis (PrEP) clinical trial of Leronlimab in HIV infections [119] Updated 07 Mar 2024 |
| 06 Feb 2024 | Trial Update | Cytodyn in partnership with Albert Einstein College of Medicine and Montefiore Medical Center plans a preclinical trial for Glioblastoma in USA in 2024 [3] Updated 15 Feb 2024 |
| 01 Feb 2024 | Regulatory Status | Cytodyn in collaboration with Albert Einstein College of Medicine has submitted its revised HIV clinical trial protocol to the FDA [3] Updated 15 Feb 2024 |
| 31 Dec 2023 | Licensing Status | Cytodyn, Albert Einstein College of Medicine and Montefiore Medical Center enter into a partnership to evaluate leronlimab in USA for Glioblastoma [3] Updated 15 Feb 2024 |
| 27 Feb 2023 | Trial Update | CytoDyn withdraws a phase II trial prior to enrollment for Colorectal cancer (Metastatic disease, Inoperable/Unresectable, Second line therapy or greater, Combination therapy) (SC) (NCT05730673) Updated 27 Feb 2023 |
| 31 Jan 2023 | Trial Update | CytoDyn completes a phase II trials in Non-alcoholic steatohepatitis in USA (Parenteral) (NCT04521114) Updated 17 Mar 2023 |
| 09 Nov 2022 | Scientific Update | Efficacy data from a phase Ib/II, phase II BASKET trial and compassionate use trial in Cancer released by CytoDyn [51] Updated 09 Nov 2022 |
| 04 Nov 2022 | Scientific Update | Updated efficacy data from phase II trial in Non-alcoholic steatohepatitis presented at the 73rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD-2022) [222] Updated 03 Jan 2023 |
| 31 Oct 2022 | Regulatory Status | CytoDyn withdraws BLA for HIV infections [51] Updated 01 Nov 2022 |
| 12 Oct 2022 | Phase Change - Preclinical | Preclinical trials in Multiple sclerosis in USA (CytoDyn pipeline, October 2022) Updated 12 Oct 2022 |
| 22 Jun 2022 | Scientific Update | Updated safety and efficacy data from phase II trial in non-alcoholic steatohepatitis presented at The International Liver Congress 2022 (ILC-2022) [221] Updated 30 Aug 2022 |
| 03 Jun 2022 | Scientific Update | Pooled data from a phase Ib/II, phase II BASKET trial and compassionate use trial presented at 58th Annual Meeting of the American Society of Clinical Oncology (ASCO-2022) [234] Updated 11 Jul 2022 |
| 25 Apr 2022 | Trial Update | CytoDyn suspends phase III trial in COVID-19 pneumonia in Brazil (NCT04901689) Updated 25 Apr 2022 |
| 15 Apr 2022 | Trial Update | CytoDyn suspends phase III trial in COVID-19 pneumonia in Brazil (NCT04901676) Updated 25 Apr 2022 |
| 12 Apr 2022 | Scientific Update | Interim efficacy data from a phase II extension trial in HIV infections released by CytoDyn [184] Updated 18 Apr 2022 |
| 12 Apr 2022 | Scientific Update | Pharmacodynamics data from a preclinical trial in HIV infections released by CytoDyn [184] Updated 18 Apr 2022 |
| 08 Apr 2022 | Scientific Update | Pooled data from a phase Ib/II, phase II BASKET trial and compassionate use trial presented at 113th annual meeting of the American Association for Cancer Research (AACR-2022) [52] Updated 30 May 2022 |
| 07 Apr 2022 | Regulatory Status | The US FDA places a full clinical hold on a phase III trial of leronlimab in COVID-2019 infections (Combination therapy) and suspends the trial Updated 15 Apr 2022 |
| 07 Apr 2022 | Regulatory Status | The US FDA places a partial clinical hold on a phase II/III trial of leronlimab in HIV-1 infections and suspends the trial (NCT03902522) Updated 15 Apr 2022 |
| 07 Apr 2022 | Regulatory Status | The US FDA places a partial clinical hold on a phase III trial of leronlimab in HIV infections (Monotherapy) and suspends the trial Updated 15 Apr 2022 |
| 07 Apr 2022 | Regulatory Status | The US FDA places a partial clinical hold on a pre-exposure prophylaxis (PrEP) clinical trial of leronlimab in HIV infections in Thailand and suspends the trial Updated 15 Apr 2022 |
| 30 Mar 2022 | Phase Change - Suspended(III) | Suspended - Phase-III for COVID-2019 infections in USA (SC), Brazil (IV) [62] Updated 14 Apr 2022 |
| 30 Mar 2022 | Regulatory Status | The US FDA places a partial clinical hold and suspended the HIV program in US [62] Updated 01 Apr 2022 |
| 30 Mar 2022 | Regulatory Status | The US FDA places full clinical hold and suspended the COVID-19 program in US and Brazil [62] Updated 01 Apr 2022 |
| 10 Jan 2022 | Scientific Update | Pharmacodynamics data from a preclinical study in HIV-infection released by CytoDyn [208] Updated 16 Jan 2022 |
| 10 Jan 2022 | Trial Update | CytoDyn plans a clinical trial in Chronic fatigue syndrome [208] Updated 16 Jan 2022 |
| 10 Jan 2022 | Licensing Status | Regnum, CytoDyn and SevenScore Pharmaceuticals enters into a assignment of the commercialization and license agreement and a related supply agreement to commercialize leronlimab in the US [4] Updated 14 Jan 2022 |
| 05 Jan 2022 | Scientific Update | Updated safety and efficacy data from phase II trial in non-alcoholic steatohepatitis released by the company [220] Updated 10 Jan 2022 |
| 21 Dec 2021 | Regulatory Status | CytoDyn receives positive response from the US FDA to conduct a phase III trial for COVID-19 pneumonia with need for Invasive Mechanical Ventilation (IMV) or Extracorporeal Membrane Oxygenation (ECMO) [64] Updated 23 Dec 2021 |
| 14 Dec 2021 | Regulatory Status | CytoDyn intends to submit Breakthrough Therapy designation in Non-alcoholic steatohepatitis [219] Updated 19 Dec 2021 |
| 14 Dec 2021 | Scientific Update | Efficacy data from a phase II trial in Non-alcoholic steatohepatitis released by CytoDyn [219] Updated 19 Dec 2021 |
| 09 Dec 2021 | Regulatory Status | CytoDyn files for an approval of Expanded Access Use of leronlimab in HIV-infections with the US FDA [143] Updated 16 Dec 2021 |
| 09 Dec 2021 | Regulatory Status | CytoDyn files an IND application with the US FDA in USA for a phase III trial in COVID-19 pneumonia [65] Updated 15 Dec 2021 |
| 09 Dec 2021 | Scientific Update | Efficacy data from a phase II/III CD12 trial in COVID-2019 infections released by CytoDyn [65] Updated 15 Dec 2021 |
| 09 Dec 2021 | Trial Update | CytoDyn plans a phase III trial in COVID-19 pneumonia in USA (IV, Infusion) [65] Updated 15 Dec 2021 |
| 08 Dec 2021 | Regulatory Status | CytoDyn plans to submit revised protocol for the phase III CD16 trial in COVID-2019 infections [70] Updated 16 Dec 2021 |
| 08 Dec 2021 | Regulatory Status | The Brazilian Health Regulatory Agency (ANVISA) approves for modification in the phase III CD16 trial in COVID-2019 infections [70] Updated 16 Dec 2021 |
| 07 Dec 2021 | Scientific Update | Safety and efficacy data from phase Ib/II study in Brest cancer presented at the 44th Annual San Antonio Breast Cancer Symposium (SABCS-2022) [50] Updated 10 Feb 2022 |
| 03 Dec 2021 | Phase Change - Preregistration | Preregistration for HIV infections (Combination therapy, Treatment-experienced) in USA (SC) [121] Updated 03 Dec 2021 |
| 01 Dec 2021 | Regulatory Status | CytoDyn submits non-clinical and CMC section of BLA to the US FDA for the treatment of patients with HIV infections (Combination therapy, Treatment-experienced) [121] Updated 03 Dec 2021 |
| 24 Nov 2021 | Regulatory Status | CytoDyn plans to request accelerated approval with the USFDA for leronlimab Non-alcoholic steatohepatitis and Non-alcoholic-fatty-liver-disease in the US and abroad [23] [219] Updated 26 Nov 2021 |
| 24 Nov 2021 | Scientific Update | Efficacy data from a phase II trial in Non-alcoholic steatohepatitis released by CytoDyn [23] Updated 26 Nov 2021 |
| 24 Nov 2021 | Trial Update | CytoDyn completes phase II trials in Triple-negative-breast cancer (Combination therapy, Metastatic disease, Late-stage disease, Recurrent) in USA (SC) [23] (NCT03838367) Updated 26 Nov 2021 |
| 24 Nov 2021 | Trial Update | CytoDyn completes the phase II BASKET trial in Solid tumours (Late-stage disease, Metastatic disease) in USA (SC) [23] Updated 26 Nov 2021 |
| 24 Nov 2021 | Trial Update | CytoDyn plans to initiate phase III trials in Non alcoholic steatohepatitis (SC) [23] [219] Updated 26 Nov 2021 |
| 10 Nov 2021 | Phase Change - Registered | Registered for Triple-negative-breast cancer (Metastatic disease) in Canada (SC) [21] Updated 20 Nov 2021 |
| 10 Nov 2021 | Regulatory Status | CytoDyn receives Emergency use authorization from Health Canada for Leronlimab in metastatic triple-negative breast cancer (mTNBC) [21] Updated 20 Nov 2021 |
| 10 Nov 2021 | Trial Update | CytoDyn plans a registration-directed trial for HIV infections (Monotherapy) [122] Updated 19 Nov 2021 |
| 10 Nov 2021 | Trial Update | CytoDyn plans an expanded-access programme for HIV infections in USA [122] Updated 19 Nov 2021 |
| 08 Nov 2021 | Regulatory Status | CytoDyn submits an application for Breakthrough Therapy designation to the US FDA for leronlimab for Metastatic triple-negative breast cancer [29] Updated 12 Nov 2021 |
| 08 Nov 2021 | Scientific Update | Updated efficacy data from compassionate use study, phase Ib/II trial, and basket trial in Breast cancer released by CytoDyn [29] Updated 12 Nov 2021 |
| 03 Nov 2021 | Scientific Update | Efficacy data from a phase II trial in Non-alcoholic steatohepatitis released by CytoDyn [215] Updated 11 Nov 2021 |
| 03 Nov 2021 | Scientific Update | Pooled efficacy data from compassionate use study, phase Ib/II trial, and basket trial in Breast cancer released by CytoDyn [235] Updated 10 Nov 2021 |
| 25 Oct 2021 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections in Brazil (IV) Updated 27 Oct 2021 |
| 23 Oct 2021 | Trial Update | CytoDyn initiates a phase III trial in COVID-19 pneumonia in Brazil (NCT04901689) Updated 10 Nov 2021 |
| 07 Oct 2021 | Regulatory Status | CytoDyn announces intention to resubmit BLA for HIV infections (Combination therapy, Treatment-experienced) to the US FDA in November 2021 [123] [54] Updated 19 Nov 2021 |
| 28 Sep 2021 | Trial Update | CytoDyn completed enrolment in the phase II/III extension trial for HIV infections in USA (NCT02990858) Updated 12 Jul 2022 |
| 24 Sep 2021 | Regulatory Status | Brazil’s regulatory authority ANVISA (Agência Nacional de Vigilância Sanitária) approved the phase III CD16 trial for COVID-19 pneumonia [71] Updated 24 Sep 2021 |
| 09 Sep 2021 | Phase Change - III | Phase-III clinical trials in COVID-19 pneumonia in Brazil (SC) [72] (NCT04901676) Updated 16 Sep 2021 |
| 09 Sep 2021 | Regulatory Status | Brazil’s regulatory authority ANVISA (Agência Nacional de Vigilância Sanitária) clears a second phase III trial for COVID-19 pneumonia with a condition of more information about CMC from CytoDyn [72] Updated 16 Sep 2021 |
| 31 Aug 2021 | Biomarker Update | Biomarkers information updated Updated 17 Sep 2021 |
| 25 Aug 2021 | Regulatory Status | CytoDyn plans to update its Breakthrough Therapy designation application and file for Breast cancer (Metastatic disease) Updated 27 Aug 2021 |
| 11 Aug 2021 | Regulatory Status | CytoDyn receives guidance from the US FDA on a dose justification report to advance its planned resubmission of BLA for leronlimab for HIV infections [124] Updated 18 Aug 2021 |
| 04 Aug 2021 | Regulatory Status | CytoDyn submits clinical trial protocol to Brazil’s regulatory authority ANVISA (Agência Nacional de Vigilância Sanitária) to commence phase III CD17 trial in COVID-19 infections, prior to August 2021 [73] Updated 05 Aug 2021 |
| 04 Aug 2021 | Regulatory Status | The Brazil’s regulatory authority ANVISA (Agência Nacional de Vigilância Sanitária) approves clinical trial protocol to commence phase III CD17 trial in COVID-19 infections [73] Updated 05 Aug 2021 |
| 02 Aug 2021 | Trial Update | CytoDyn completes a phase II trial for Post-acute-COVID-19-syndrome in USA (SC) in July 2021 (NCT04678830) Updated 09 Aug 2021 |
| 19 Jul 2021 | Scientific Update | Preliminary interim efficacy data from a phase Ib/II trial in Breast cancer released by CytoDyn [49] Updated 21 Jul 2021 |
| 12 Jul 2021 | Phase Change - II | Phase-II clinical trials in Triple-negative-breast cancer (Combination therapy, Metastatic disease, Late-stage disease, Recurrent) in USA (SC) [48] Updated 10 Sep 2019 |
| 06 Jul 2021 | Patent Information | CytoDyn has patent protection for leronlimab for treatment of hyperinflammation associated with COVID-2019 infections in USA [233] Updated 09 Jul 2021 |
| 06 Jul 2021 | Regulatory Status | CytoDyn announced intention to request Breakthrough Therapy designation with the US FDA in COVID-2019 infections [233] Updated 09 Jul 2021 |
| 01 Jul 2021 | Regulatory Status | CytoDyn submits dose justification report to US FDA to advance its planned resubmission of BLA for leronlimab for HIV infections [125] Updated 06 Jul 2021 |
| 21 Jun 2021 | Scientific Update | Preliminary efficacy and adverse events data from a phase II trial in Post-acute-COVID-19-syndrome released by CytoDyn [228] Updated 25 Jun 2021 |
| 27 May 2021 | Regulatory Status | Biomm announces intention to submit an authorization to Brazilian National Health Surveillance Agency (“ANVISA”) for phase III studies for COVID-2019 infections in next few days Updated 31 May 2021 |
| 25 May 2021 | Trial Update | Albert Einstein Israelite Hospital in collaboration with CytoDyn plans a phase III trial for COVID-19 pneumonia in Brazil in June 2021 (SC) (NCT04901676) Updated 09 Jul 2021 |
| 25 May 2021 | Trial Update | Albert Einstein Israelite Hospital in collaboration with CytoDyn plans a phase III trial for COVID-19 pneumonia in Brazil in June 2021 (IV) (NCT04901689) Updated 09 Jul 2021 |
| 18 May 2021 | Regulatory Status | CytoDyn intends to submit regulatory filings to various regulatory agencies including India and the Philippines for COVID-2019 infections [90] Updated 20 May 2021 |
| 18 May 2021 | Scientific Update | Top line efficacy data from a phase II/III trial in COVID-2019 infections released by CytoDyn [90] Updated 20 May 2021 |
| 13 May 2021 | Regulatory Status | CytoDyn intends to pursue emergency use authorization and compassionate use access to leronlimab for COVID-2019 infections in India [5] Updated 21 May 2021 |
| 13 May 2021 | Regulatory Status | CytoDyn plans to commercialise leronlimab for COVID-2019 infections in India [5] Updated 21 May 2021 |
| 05 May 2021 | Licensing Status | CytoDyn and Albert Einstein Israelite Hospital agree to co-develop leronlimab in Brazil for COVID-2019 infections [6] Updated 13 May 2021 |
| 05 May 2021 | Regulatory Status | CytoDyn announces intention to seek Emergency use authorization to the Brazilian regulatory authority (ANVISA) for COVID-2019 infections [6] Updated 13 May 2021 |
| 05 May 2021 | Regulatory Status | CytoDyn plans to launch leronlimab for COVID-2019 infections in Brazil [6] Updated 13 May 2021 |
| 05 May 2021 | Trial Update | CytoDyn plans two phase III trials for COVID-2019 infections in Brazil [6] Updated 13 May 2021 |
| 19 Apr 2021 | Regulatory Status | CytoDyn plans to submit clinical trial protocol to Brazilian regulatory authority (ANVISA) for COVID-2019 infection [94] Updated 21 Apr 2021 |
| 19 Apr 2021 | Trial Update | CytoDyn plans clinical trials for COVID-2019 infections in USA (IV, SC) [94] Updated 21 Apr 2021 |
| 09 Apr 2021 | Licensing Status | Leronlimab licensed to Biomm for distribution and supply in Brazil for COVID-2019 infections [7] Updated 12 Apr 2021 |
| 05 Apr 2021 | Phase Change - Clinical | Clinical trials in COVID-2019 infections in Philippines (SC) before April 2021 [95] Updated 07 Apr 2021 |
| 05 Apr 2021 | Regulatory Status | CytoDyn receives Compassionate Special Permit in Philippines for COVID-2019 infections [95] Updated 07 Apr 2021 |
| 29 Mar 2021 | Scientific Update | Updated efficacy data from a phase III trial in COVID-2019 infections released by CytoDyn [91] Updated 05 Apr 2021 |
| 23 Mar 2021 | Phase Change - Preregistration | Preregistration for COVID-2019 infections in Canada (SC) [94] Updated 21 Apr 2021 |
| 08 Mar 2021 | Regulatory Status | CytoDyn announces intention to submit Accelerated rolling review to Medicines and Healthcare products Regulatory Agency for COVID-2019 infections Updated 09 Mar 2021 |
| 08 Mar 2021 | Scientific Update | Efficacy and safety data from a phase III trial in COVID-2019 infections released by CytoDyn [92] [93] Updated 09 Mar 2021 |
| 01 Mar 2021 | Phase Change - II | Phase-II clinical trials in Post-acute-COVID-19-syndrome in USA (SC) (NCT04678830) Updated 17 Aug 2022 |
| 28 Dec 2020 | Regulatory Status | the US FDA approves Leronlimab for severe-to-critical COVID-19 infection, under emergency IND (eIND) in the US [99] Updated 28 Dec 2020 |
| 24 Dec 2020 | Regulatory Status | CytoDyn receives guidance from the US FDA to incorporate open-label extension to phase III trial protocol for COVID-2019 infections [98] Updated 29 Dec 2020 |
| 22 Dec 2020 | Trial Update | CytoDyn terminates a phase-II clinical trial in Graft-versus-host disease (Prevention) in USA, due to lack of patient enrollments in the trial due to COVID-19 pandemic (SC) (NCT02737306) [99] Updated 28 Dec 2020 |
| 15 Dec 2020 | Regulatory Status | CytoDyn announces intention to file for Emergency Use Authorisation (EUA) to Food and Drug Administration in Philippines for COVID-2019 infection in 2021 [79] Updated 18 Dec 2020 |
| 15 Dec 2020 | Trial Update | CytoDyn completes enrolment in the phase III portion of phase II/III trial for COVID-2019 infections in USA, UK [79] Updated 18 Dec 2020 |
| 24 Nov 2020 | Licensing Status | CytoDyn entered an agreement with amfAR to test leronlimab for the treatment of HIV [8] Updated 27 Nov 2020 |
| 23 Nov 2020 | Regulatory Status | CytoDyn announces intention to submit a BLA to the Medicines and Healthcare products Regulatory Agency (MHRA) for leronlimab in HIV infections in United Kingdom in 2020 [80] Updated 27 Nov 2020 |
| 23 Nov 2020 | Trial Update | CytoDyn announces intention to submit a BLA to the Health Canada for leronlimab in HIV infections in Canada in 2020 [80] Updated 27 Nov 2020 |
| 17 Nov 2020 | Regulatory Status | CytoDyn files a protocol with the US FDA for a phase II trial for leronlimab in Post-acute-COVID-19-syndrome [151] Updated 19 Nov 2020 |
| 17 Nov 2020 | Trial Update | CytoDyn completes a phase IIb/III trial in HIV-1 infections (Monotherapy, Treatment-experienced) in USA (SC), prior to November 2020 [151] (NCT02859961) Updated 19 Nov 2020 |
| 17 Nov 2020 | Trial Update | CytoDyn plans a phase II trial for Post-acute-COVID-19-syndrome in up to 10 sites in multiple countries (Parenteral) [151] Updated 19 Nov 2020 |
| 28 Oct 2020 | Regulatory Status | CytoDyn announces intention to submit IND to the US FDA for COVID-2019 infections and Stroke in 2020 [229] Updated 28 Oct 2020 |
| 26 Oct 2020 | Trial Update | CytoDyn plans a phase II trial for Stroke (Parenteral) in multiple countries, in 2020 [229] Updated 19 Nov 2020 |
| 26 Oct 2020 | Phase Change - Preclinical | Preclinical trials in Stroke in USA (Parenteral) in October 2020 [229] Updated 28 Oct 2020 |
| 26 Oct 2020 | Phase Change - Preclinical | Preclinical trials in Traumatic brain injuries in USA (Parenteral) in October 2020 [229] Updated 28 Oct 2020 |
| 26 Oct 2020 | Regulatory Status | Medicines & Healthcare product Regulatory Agency (MHRA) clears CytoDyn to file its BLA for leronlimab [136] Updated 28 Oct 2020 |
| 12 Oct 2020 | Regulatory Status | CytoDyn announces intention to submit NDA to FDA (Phillipines) for COVID-2019 infections [96] Updated 16 Oct 2020 |
| 02 Sep 2020 | Regulatory Status | Medicines & Healthcare product Regulatory Agency (MHRA) has requested a meeting with CytoDyn on 9 September 2020 for the discussion of fast track approval request for leronlimab to treat COVID-2019 infections. [127] Updated 08 Sep 2020 |
| 02 Sep 2020 | Regulatory Status | US FDA has scheduled a type A meeting with CytoDyn on 8 September 2020 for BLA of leronlimab in the treatment of HIV patients. [127] Updated 08 Sep 2020 |
| 25 Aug 2020 | Scientific Update | Updated efficacy data from a phase IIb trial in HIV infections (Monotherapy) released by CytoDyn [88] Updated 27 Aug 2020 |
| 20 Aug 2020 | Regulatory Status | The US FDA will respond to CytoDyn's questions regarding BLA resubmission for HIV infections (Combination therapy, Treatment-experienced) by September 4, 2020 [128] Updated 16 Oct 2020 |
| 20 Aug 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections in United Kingdom (SC) [77] (NCT04347239) Updated 26 Aug 2020 |
| 20 Aug 2020 | Regulatory Status | The Medicines and Healthcare Products Regulatory Agency (MHRA) authorises CytoDyn to enrol for its ongoing clinical trial for COVID-2019 infections in United Kingdom [77] Updated 26 Aug 2020 |
| 20 Aug 2020 | Regulatory Status | CytoDyn intends to conduct a Type A meeting with the US FDA regarding potential resubmission of BLA in HIV infections (Combination therapy, Treatment-experienced) in writing, instead of a teleconference (per FDA's recommendation) [128] Updated 24 Aug 2020 |
| 20 Aug 2020 | Regulatory Status | CytoDyn intends to resubmit BLA for HIV infections (Combination therapy, Treatment-experienced) to the US FDA [128] Updated 24 Aug 2020 |
| 18 Aug 2020 | Regulatory Status | CytoDyn requests a regulatory pathway for Fast Track approval to Medicines and Healthcare Products Regulatory Agency (MHRA), UK for COVID-2019 infections [102] Updated 20 Aug 2020 |
| 18 Aug 2020 | Regulatory Status | CytoDyn requests a Type A meeting with the US FDA for additional information to resubmit BLA for HIV infections (Combination therapy) [102] Updated 20 Aug 2020 |
| 11 Aug 2020 | Regulatory Status | CytoDyn plans regulatory filings for approval of leronlimab for COVID-2019 infections in USA, UK and other countries around the world [107] Updated 14 Aug 2020 |
| 11 Aug 2020 | Scientific Update | Adverse events and efficacy data from a phase II trial in COVID-2019 infections released by CytoDyn [107] Updated 14 Aug 2020 |
| 06 Aug 2020 | Regulatory Status | CytoDyn announces inention to submit request for pre-submission meeting with Medicines and Healthcare Products Regulatory Agency for leronlimab in HIV infections in United Kingdom [81] Updated 10 Aug 2020 |
| 06 Aug 2020 | Regulatory Status | CytoDyn announces inention to submit request for pre-submission meeting with European Medicines Agency (EMA) for leronlimab in HIV infections in European Union countries [81] Updated 10 Aug 2020 |
| 06 Aug 2020 | Regulatory Status | CytoDyn announces intention to submit phase II data for emergency approval to Medicines and Healthcare Products Regulatory Agency (MHRA) for COVID-19 infections in United Kingdom [81] Updated 10 Aug 2020 |
| 06 Aug 2020 | Regulatory Status | CytoDyn receives positive recommendation from Data Safety Monitoring Committee for phase III trial in COVID-19 infections [82] Updated 06 Aug 2020 |
| 04 Aug 2020 | Trial Update | CytoDyn completes the phase II trial in COVID-19 infections in USA (SC) (NCT04343651) [82] Updated 06 Aug 2020 |
| 21 Jul 2020 | Scientific Update | Adverse events data from a phase II trial for COVID-2019 infections released by CytoDyn [106] [105] Updated 23 Jul 2020 |
| 13 Jul 2020 | Phase Change - III | Phase-III clinical trials in COVID-2019 infections in USA (SC) [83] Updated 15 Jul 2020 |
| 13 Jul 2020 | Regulatory Status | CytoDyn announces intention to request a Type A meeting with the US FDA to discuss additional data requirements [83] Updated 15 Jul 2020 |
| 13 Jul 2020 | Regulatory Status | CytoDyn receives Refusal to File letter from the US FDA for leronlimab in HIV infections (Combination therapy, Treatment-experienced) [83] Updated 15 Jul 2020 |
| 03 Jul 2020 | Licensing Status | Leronlimab licensed to American Regent for COVID-2019 infections for distribution and supply in USA [9] Updated 07 Jul 2020 |
| 03 Jul 2020 | Trial Update | CytoDyn completes enrolment in its phase II trial for COVID-2019 infections in the US [9] Updated 07 Jul 2020 |
| 29 Jun 2020 | Licensing Status | CytoDyn and Mexican National Institutes of Health enters into a Memorandum of Understanding (MOU) to conduct a phase III trial of leronlimab for COVID-2019 infections in Mexico [10] Updated 02 Jul 2020 |
| 16 Jun 2020 | Company Involvement | Progenics Pharmaceuticals has been acquired by Lantheus Holdings Updated 19 Jun 2020 |
| 11 Jun 2020 | Trial Update | CytoDyn completes enrolment in its phase II trial for COVID-2019 infections in USA [103] (NCT04343651) Updated 16 Jun 2020 |
| 11 Jun 2020 | Trial Update | CytoDyn initiates enrolment in a phase II trial for Non-alcoholic steatohepatitis in USA [103] Updated 16 Jun 2020 |
| 08 Jun 2020 | Regulatory Status | CytoDyn receives Biologics License Application (BLA)Acknowledgment Letter for HIV infections from the US FDA, stating the company could receive PDUFA date on July 10, 2020 [129] Updated 10 Jun 2020 |
| 01 Jun 2020 | Regulatory Status | CytoDyn files a request with the US FDA to seek priority review of a Biologics License Application for leronlimab in combination therapy for HIV infections (Combination therapy, Treatment experienced) [130] Updated 03 Jun 2020 |
| 19 May 2020 | Trial Update | CytoDyn in collaboration with Mexican National Institutes of Health plans a phase III trial for COVID-19 infections in Mexico [100] [10] Updated 26 May 2020 |
| 15 May 2020 | Regulatory Status | CytoDyn plans to submit a protocol to the US FDA for a factorial design of phase III trial to compare effectiveness of leronlimab versus remdesivir and in combination with remdesivir for the treatment of COVID-19 infections [101] Updated 20 May 2020 |
| 11 May 2020 | Regulatory Status | CytoDyn completes filing of rolling BLA with the US FDA in USA for HIV infection (Combination therapy, Treatment experienced) [131] Updated 17 May 2020 |
| 06 May 2020 | Scientific Update | Efficacy data from a compassionate trial in COVID-19 infections released by CytoDyn [118] Updated 13 May 2020 |
| 04 May 2020 | Regulatory Status | CytoDyn intends to apply for Priority Review for its BLA for HIV infections (Combination therapy, Treatment-experienced) [117] Updated 06 May 2020 |
| 04 May 2020 | Regulatory Status | CytoDyn submits request to the US FDA seeking 'compassionate access' for use of leronlimab for COVID-2019 infections (for patients not participating in two ongoing clinical trials) [117] Updated 06 May 2020 |
| 01 May 2020 | Trial Update | CytoDyn initiates a phase II trial for Solid tumours (Late-stage disease, Metastatic disease) in USA (SC) (NCT04504942) Updated 11 Aug 2020 |
| 30 Apr 2020 | Regulatory Status | CytoDyn plans to complete the filing of a Biologics License Application for leronlimab for HIV infections (Treatment-experienced, Combination therapy) in May 2020 [117] Updated 14 May 2020 |
| 27 Apr 2020 | Patent Information | CytoDyn receives patent allowance for vyrologix mark in USA [147] Updated 05 May 2020 |
| 13 Apr 2020 | Phase Change - II/III | Phase-II/III clinical trials in COVID-2019 infections in USA (SC) [85] [76] (NCT04347239) Updated 07 Apr 2020 |
| 09 Apr 2020 | Scientific Update | Efficacy data from clinical trial in COVID-2019 infections released by CytoDyn [236] Updated 15 Apr 2020 |
| 02 Apr 2020 | Scientific Update | Efficacy data from phase II trial in COVID-2019 infections released by CytoDyn [76] [108] Updated 07 Apr 2020 |
| 01 Apr 2020 | Trial Update | CytoDyn initiates enrolment in a phase II trial for COVID-2019 infections in USA (NCT04343651) Updated 16 Jun 2020 |
| 01 Apr 2020 | Regulatory Status | CytoDyn files a second clinical trial protocol with the US FDA in USA for COVID-2019 infections [86] Updated 07 Apr 2020 |
| 01 Apr 2020 | Trial Update | CytoDyn plans a second clinical trial for COVID-2019 infections [86] Updated 07 Apr 2020 |
| 31 Mar 2020 | Regulatory Status | CytoDyn expects to launch leronlimab in HIV infections by the fourth quarter of 2020 [231] Updated 07 Apr 2020 |
| 27 Mar 2020 | Regulatory Status | CytoDyn plans to file second trial protocol as per the FDA suggestion for severely ill COVID-19 patients [87] Updated 07 Apr 2020 |
| 27 Mar 2020 | Regulatory Status | CytoDyn files modifications to its IND and protocol for a phase II trial in Respiratory distress syndrome due to COVID-19 infections [87] Updated 31 Mar 2020 |
| 27 Mar 2020 | Regulatory Status | FDA suggests to file a second randomized protocol for all COVID-19 patients in severe condition to preclude from filing an emergency IND [87] Updated 31 Mar 2020 |
| 19 Mar 2020 | Phase Change - II | Phase-II trials in COVID-2019 infections in USA (Parenteral) [111] Updated 23 Mar 2020 |
| 19 Mar 2020 | Regulatory Status | The US FDA approves IND application for leronlimab in Respiratory distress syndrome due to COVID-19 infections [111] Updated 23 Mar 2020 |
| 13 Mar 2020 | Regulatory Status | CytoDyn plans to file modified trial protocol for planned phase II trial in COVID-2019 infections [112] Updated 19 Mar 2020 |
| 08 Mar 2020 | Regulatory Status | CytoDyn files an IND application with the US FDA for COVID 2019 infections [113] Updated 12 Mar 2020 |
| 08 Mar 2020 | Trial Update | CytoDyn plans a phase II trial for Respiratory distress syndrome due to COVID 2019 infections [113] Updated 12 Mar 2020 |
| 28 Feb 2020 | Regulatory Status | CytoDyn intends to file an IND submission and phase II trial protocol with the US FDA for Coronavirus infections Updated 03 Mar 2020 |
| 21 Feb 2020 | Regulatory Status | CytoDyn receives Institutional Review Board approval to initiate a phase II basket trial for Solid tumours in USA [25] Updated 26 Feb 2020 |
| 17 Feb 2020 | Phase Change - II | Phase-II clinical trials in Solid tumours (Late-stage disease, Metastatic disease) in USA (SC) [26] [25] Updated 27 Feb 2020 |
| 14 Feb 2020 | Regulatory Status | CytoDyn intends to file the breakthrough therapy designation for Solid tumor with the US FDA [26] Updated 19 Feb 2020 |
| 14 Feb 2020 | Scientific Update | Updated interim efficacy data from a phase Ib/II trial in Breast cancer released by CytoDyn [26] Updated 19 Feb 2020 |
| 12 Feb 2020 | Licensing Status | CytoDyn and Longen China Group sign a nonbinding letter of intent to develop and license leronlimab for the treatment of 2019 novel coronavirus (2019-nCoV) and cancer [11] Updated 19 Feb 2020 |
| 06 Feb 2020 | Trial Update | CytoDyn plans a phase II basket trial in Solid tumours (Late-stage disease, Metastatic disease) in USA (SC) in March 2020 [27] Updated 27 Feb 2020 |
| 06 Feb 2020 | Regulatory Status | CytoDyn files an IND application with the US FDA for a phase II basket trial in Cancer [27] Updated 13 Feb 2020 |
| 28 Jan 2020 | Other | CytoDyn announces intention to assess potential of leronlimab for treatment of 2019 novel coronavirus (2019-nCoV) infections [116] Updated 30 Jan 2020 |
| 27 Jan 2020 | Phase Change - Preclinical | Preclinical trials in HIV infections (Prevention) in USA (IV) [56] Updated 05 Feb 2020 |
| 27 Jan 2020 | Scientific Update | Pharmacodynamics data from a preclinical studies in Simian-Human Immunodeficiency Virus (SHIV)released by CytoDyn [56] Updated 29 Jan 2020 |
| 22 Jan 2020 | Scientific Update | Interim efficacy data from a phase Ib/II trial in Breast cancer released by CytoDyn [46] Updated 24 Jan 2020 |
| 14 Jan 2020 | Regulatory Status | CytoDyn files for Breakthrough Therapy Designation with the US FDA for leronlimab in Metastatic triple-negative breast cancer [30] Updated 16 Jan 2020 |
| 17 Dec 2019 | Licensing Status | Leronlimab licensed to Vyera Pharmaceuticals for HIV infections for commercialisation and supply in USA [12] Updated 20 Dec 2019 |
| 03 Dec 2019 | Regulatory Status | CytoDyn announces intention to file for Breakthrough Therapy designation in metastatic Triple-negative breast cancer before the end of January 2020 [31] Updated 16 Jan 2020 |
| 03 Dec 2019 | Scientific Update | Early efficacy data from a phase Ib/II trial in Breast cancer released by CytoDyn [31] Updated 09 Dec 2019 |
| 21 Nov 2019 | Scientific Update | Pharmacodynamics data from a preclinical study in Non-alcoholic steatohepatitis released by CytoDyn [224] Updated 03 Dec 2019 |
| 19 Nov 2019 | Scientific Update | Pharmacodynamics data from a preclinical trial in Lung and Liver Cancer released by CytoDyn [237] Updated 09 Dec 2019 |
| 12 Nov 2019 | Regulatory Status | Leronlimab is available in a compassionate use programme for the treatment Triple negative breast cancer in USA [33] Updated 14 Nov 2019 |
| 01 Oct 2019 | Phase Change - II | Phase-II clinical trials in Non-alcoholic steatohepatitis in USA (Parenteral) (NCT04521114) [152] Updated 09 Oct 2019 |
| 01 Oct 2019 | Phase Change - III | Phase-III clinical trials in HIV-1 infections (Monotherapy, Treatment-experienced) in USA (SC) [152] Updated 04 Oct 2019 |
| 01 Oct 2019 | Regulatory Status | The US FDA approves IND application for leronlimab in Non alcoholic steatohepatitis [152] Updated 04 Oct 2019 |
| 01 Oct 2019 | Trial Update | CytoDyn plans a phase II trial for Non-alcoholic steatohepatitis in USA [152] Updated 04 Oct 2019 |
| 09 Sep 2019 | Regulatory Status | The US FDA approves a phase II trial for Colorectal cancer (Metastatic disease, Combination therapy) [34] Updated 10 Sep 2019 |
| 04 Sep 2019 | Regulatory Status | CytoDyn files an IND application with the US FDA in for a phase II trial in Non-alcoholic steatohepatitis [223] Updated 06 Sep 2019 |
| 14 Aug 2019 | Scientific Update | Efficacy data from a phase IIb/III trial in HIV-1 infections released by CytoDyn [153] Updated 19 Aug 2019 |
| 08 Aug 2019 | Regulatory Status | CytoDyn files a phase II protocol with the US FDA for a combination therapy of leronlimab and regorafenib for Colorectal cancer [38] Updated 13 Aug 2019 |
| 08 Aug 2019 | Trial Update | CytoDyn plans a phase II trial for Colorectal cancer (Metastatic disease, Combination therapy) [38] Updated 13 Aug 2019 |
| 08 Aug 2019 | Phase Change | Investigation in Malignant melanoma in USA (Parenteral) before August 2019 (CytoDyn pipeline, August 2019) Updated 08 Aug 2019 |
| 08 Aug 2019 | Phase Change - Preclinical | Preclinical trials in Gastric cancer in USA (Parenteral) before August 2019 (CytoDyn pipeline, August 2019) Updated 08 Aug 2019 |
| 08 Aug 2019 | Phase Change - Preclinical | Preclinical trials in Liver cancer in USA (Parenteral) before August 2019 (CytoDyn pipeline, August 2019) Updated 08 Aug 2019 |
| 08 Aug 2019 | Phase Change - Preclinical | Preclinical trials in Lung cancer in USA (Parenteral) before August 2019 (CytoDyn pipeline, August 2019) Updated 08 Aug 2019 |
| 08 Aug 2019 | Phase Change - Preclinical | Preclinical trials in Pancreatic cancer in USA (Parenteral) before August 2019 (CytoDyn pipeline, August 2019) Updated 08 Aug 2019 |
| 05 Aug 2019 | Trial Update | CytoDyn plans a PrEP clinical trial for HIV infection in Thailand in 2020 [238] Updated 05 Feb 2020 |
| 30 Jul 2019 | Licensing Status | CytoDyn and IncellDX signs worldwide licensing agreement to sell non-commercial grade quantities of leronlimab [13] Updated 07 Aug 2019 |
| 17 Jun 2019 | Licensing Status | CytoDyn signs a Memorandum of Understanding with Thai Red Cross AIDS Research Centre to conduct clinical trial of leronlimab for a pre-exposure prophylaxis of HIV infections [14] Updated 19 Jun 2019 |
| 17 Jun 2019 | Trial Update | CytoDyn and Thai Red Cross AIDS Research Centre plan a clinical trial for HIV infections (Prevention) [14] Updated 19 Jun 2019 |
| 07 Jun 2019 | Trial Update | CytoDyn plans a clinical trial for HIV-1 infections (Prevention) in Southeast Asia [148] Updated 13 Jun 2019 |
| 15 May 2019 | Regulatory Status | CytoDyn files with the US FDA the pivotal trial protocol for leronlimab as a monotherapy for HIV patients [149] Updated 21 May 2019 |
| 13 May 2019 | Phase Change - Preclinical | Preclinical trials in Non-alcoholic steatohepatitis in USA (Parenteral) [225] Updated 16 May 2019 |
| 13 May 2019 | Trial Update | CytoDyn plans a phase II trial for Non alcoholic steatohepatitis [225] Updated 16 May 2019 |
| 08 May 2019 | Trial Update | CytoDyn plans an expanded-access programme for Breast cancer [35] Updated 15 May 2019 |
| 07 May 2019 | Regulatory Status | Leronlimab receives Fast Track designation for Breast cancer (Parenteral) (Metastatic disease) in USA [36] Updated 09 May 2019 |
| 08 Apr 2019 | Phase Change - II/III | Phase-II/III clinical trials in HIV-1 infections (Combination therapy, Treatment-experienced) in USA (SC) Updated 12 Apr 2019 |
| 01 Apr 2019 | Trial Update | CytoDyn plans a clinical trial for Breast cancer Updated 05 Apr 2019 |
| 01 Apr 2019 | Trial Update | CytoDyn plans to initiate additional phase II trials in Cancer Updated 05 Apr 2019 |
| 27 Mar 2019 | Scientific Update | Efficacy data from a phase IIb/III trial in HIV-1 infections released by CytoDyn [155] (NCT02859961) Updated 29 Mar 2019 |
| 18 Mar 2019 | Regulatory Status | CytoDyn plans to file BLA for a label expansion for leronlimab as a monotherapy for HIV [132] Updated 28 Mar 2019 |
| 18 Mar 2019 | Phase Change - Preregistration | Preregistration for HIV infections (Combination therapy, Treatment-experienced) in USA (IV) [132] Updated 25 Mar 2019 |
| 18 Mar 2019 | Regulatory Status | CytoDyn expects to complete the filing of a Biological License Application (BLA) and Chemistry, Manufacturing and Controls submission in the first half of 2019 for HIV infections (Combination therapy) to the US FDA [43] [132] Updated 25 Mar 2019 |
| 11 Mar 2019 | Regulatory Status | CytoDyn files an application with the USFDA for Fast Track Designation for leronlimab in Metastatic-Triple Negative Breast Cancer [57] Updated 13 Mar 2019 |
| 04 Mar 2019 | Scientific Update | Interim efficacy and adverse events data from a phase IIb/III trial in HIV-1 infections (Monotherapy) presented at the 26th Conference on Retroviruses and Opportunistic Infections (CROI-2019) [154] Updated 03 May 2019 |
| 04 Mar 2019 | Regulatory Status | The US FDA grants rolling review for planned BLA for HIV infections [133] Updated 15 Mar 2019 |
| 22 Feb 2019 | Regulatory Status | Cytodyn applies for Orphan Drug status in triple-negative Breast cancer [37] Updated 08 Mar 2019 |
| 19 Feb 2019 | Regulatory Status | CytoDyn announces intention to submit IND to regulatory body for Melanoma, Pancreatic, Breast cancer, Prostate cancer, Colon cancer, Lung cancer, Liver cancer, and Gastric Cancer Updated 21 Feb 2019 |
| 19 Feb 2019 | Trial Update | CytoDyn plans eight phase II trials for Melanoma, Pancreatic, Breast cancer, Prostate cancer, Colon cancer, Lung cancer, Liver cancer, and Gastric Cancer Updated 21 Feb 2019 |
| 14 Feb 2019 | Trial Update | CytoDyn plans a phase Ib/II trial for Breast cancer (Combination therapy, Metastatic disease, Late-stage disease) in US in February 2019 (SC) (NCT03838367) Updated 27 May 2019 |
| 07 Jan 2019 | Licensing Status | Leronlimab is available for licensing as of 07 Jan 2019 [41] Updated 11 Jan 2019 |
| 07 Jan 2019 | Phase Change - I/II | Phase-I/II clinical trials in Triple-negative-breast cancer (Combination therapy, Metastatic disease, Late-stage disease) in USA (SC) [41] (NCT03838367) Updated 11 Jan 2019 |
| 07 Jan 2019 | Trial Update | CytoDyn plans registration-directed trial for HIV-infections (Monotherapy) [41] Updated 11 Jan 2019 |
| 26 Nov 2018 | Regulatory Status | CytoDyn plans to file for breakthrough therapy designation and orphan drug designation for Breast cancer [42] Updated 28 Nov 2018 |
| 23 Nov 2018 | Regulatory Status | US FDA approves IND application for leronlimab in Breast cancer [42] Updated 28 Nov 2018 |
| 20 Nov 2018 | Trial Update | CytoDyn plans a pivotal phase III clinical trial for HIV-1 infections (Monotherapy) in 2020 [138] [139] Updated 27 Aug 2020 |
| 19 Nov 2018 | Scientific Update | Updated efficacy data from a phase IIb trial in HIV infections (Monotherapy) released by CytoDyn [239] Updated 26 Nov 2018 |
| 13 Nov 2018 | Scientific Update | Efficacy data from a phase IIb/III trial in HIV-1 infections (Monotherapy) released by CytoDyn [141] Updated 20 Nov 2018 |
| 05 Nov 2018 | Regulatory Status | CytoDyn expects to file for breakthrough therapy designation for Breast cancer [43] Updated 12 Nov 2018 |
| 05 Nov 2018 | Regulatory Status | CytoDyn files an IND application with the US FDA for Breast Cancer [43] Updated 12 Nov 2018 |
| 15 Aug 2018 | Regulatory Status | CytoDyn plans to file an IND application with the US FDA in USA for Colorectal cancer [59] Updated 21 Aug 2018 |
| 15 Aug 2018 | Scientific Update | Pharmacodynamics data from preclinical studies in Colorectal cancer released by CytoDyn [59] Updated 21 Aug 2018 |
| 14 Aug 2018 | Trial Update | CytoDyn plans a phase II clinical trial in Breast and Prostate cancer [240] [59] Updated 20 Aug 2018 |
| 30 Jul 2018 | Regulatory Status | The independent Institutional Review Board (IRB) announces clearance of a phase III trial for HIV infections in USA [156] Updated 01 Aug 2018 |
| 16 Jul 2018 | Scientific Update | Updated efficacy and safety data from the phase II/III CD02 trial in HIV infections released by CytoDyn [161] Updated 18 Jul 2018 |
| 16 Jul 2018 | Trial Update | CytoDyn plans to conduct phase II trials in Cancer [161] Updated 18 Jul 2018 |
| 16 Jul 2018 | Trial Update | CytoDyn completes the phase II/III CD02 trial in HIV infections in USA (SC) [161] (NCT02483078) Updated 18 Jul 2018 |
| 12 Jul 2018 | Phase Change - Preclinical | Preclinical trials in Prostate cancer in USA (Parenteral) before July 2018 [59] [60] Updated 21 Aug 2018 |
| 26 Jun 2018 | Phase Change - Preclinical | Preclinical trials in Triple-negative-breast cancer in USA (Parenteral) [61] Updated 03 Jul 2018 |
| 22 Jun 2018 | Regulatory Status | CytoDyn successfully conducts pre-BLA meeting with US FDA for HIV infections [145] Updated 27 Jun 2018 |
| 20 Jun 2018 | Regulatory Status | The central Institutional Review Board (IRB) approves an amended protocol of phase II trial for Graft-versus-host disease [214] Updated 25 Jun 2018 |
| 07 Jun 2018 | Scientific Update | Updated efficacy and safety data from a II/III CD02 trial in HIV infections presented at the at the American Society for Microbiology's Microbe 2018 (ASMM-2018) [169] Updated 19 Jul 2018 |
| 20 Feb 2018 | Scientific Update | Efficacy data from a phase IIb/III trial in HIV infections released by CytoDyn [171] Updated 23 Feb 2018 |
| 06 Oct 2017 | Regulatory Status | CytoDyn announces intention to submit BLA to US FDA for HIV infections (Combination therapy) [172] [173] [170] Updated 10 Oct 2017 |
| 05 Oct 2017 | Regulatory Status | PRO 140 receives Orphan Drug status for Graft-versus-host disease (Prevention) in USA [209] Updated 10 Oct 2017 |
| 30 Aug 2017 | Trial Update | CytoDyn completes an expanded access trial for HIV-1 infections (Monotherapy) in USA (NCT02759042) Updated 14 Sep 2017 |
| 29 Aug 2017 | Trial Update | CytoDyn initiates a phase IIb/III extension protocol trial in HIV-1 infections (Monotherapy, Treatment-experienced) in USA (SC), (NCT05271370) Updated 11 Mar 2022 |
| 15 Aug 2017 | Phase Change - Preclinical | Preclinical trials in Colorectal cancer in USA (Parenteral) [59] Updated 21 Aug 2018 |
| 01 Mar 2017 | Trial Update | Drexel University and National Institute on Drug Abuse withdraw a phase II trial prior to enrolment in HIV-1-infections (Adjunctive treatment) in USA before March 2017 (NCT02438345) Updated 07 Mar 2017 |
| 13 Feb 2017 | Scientific Update | Interim efficacy, adverse events and pharmacokinetics data from a phase IIb extension trial in HIV-1-infections presented at the 24th Conference on Retroviruses and Opportunistic Infections (CROI-2017) [241] Updated 24 Mar 2017 |
| 01 Feb 2017 | Trial Update | CytoDyn withdraws a phase II trial prior to enrollment due to lack of enrollment in HIV-1-infections (Adjunctive treatment) in USA (SC, Injection) (NCT01272258) Updated 16 Feb 2017 |
| 01 Nov 2016 | Phase Change - II | Phase-II clinical trials in Graft-versus-host disease (Prevention) in USA (SC) (NCT02737306) Updated 05 Jul 2016 |
| 01 Oct 2016 | Trial Update | CytoDyn initiates enrolment in an expanded access trial for HIV-1 infections (Monotherapy) in USA (NCT02759042) Updated 14 Sep 2017 |
| 01 Oct 2016 | Trial Update | CytoDyn initiates enrolment in a phase II/III extension trial for HIV infections in USA (NCT02990858) Updated 20 Dec 2016 |
| 01 Oct 2016 | Phase Change - II/III | Phase-II/III clinical trials in HIV-1 infections (Monotherapy, Treatment-experienced) in USA (SC) (NCT02859961) Updated 19 Oct 2016 |
| 01 Sep 2016 | Trial Update | CytoDyn completes a phase IIb trial in HIV infections (Monotherapy) in USA (NCT02175680) Updated 28 Dec 2016 |
| 16 Jul 2016 | Phase Change - No development reported | No recent reports of development identified for preclinical development in HIV-1-infections (Prevention) in USA (SC, Injection) Updated 16 Jul 2016 |
| 03 Feb 2016 | Patent Information | CytoDyn has patent protection for PRO 140 in USA (CytoDyn, Form S-1, February 2016) Updated 05 Jul 2016 |
| 31 Dec 2015 | Regulatory Status | CytoDyn applies for Orphan Drug status in Graft-versus-host disease in USA (CytoDyn, Form S-1, February 2016) Updated 05 Jul 2016 |
| 01 Dec 2015 | Scientific Update | Updated efficacy and adverse events data from a phase IIb extension trial in HIV infections released by CytoDyn [180] Updated 05 Dec 2015 |
| 20 Oct 2015 | Regulatory Status | CytoDyn files an IND application with the US FDA in USA for Graft versus Host Disease [210] Updated 23 Oct 2015 |
| 20 Oct 2015 | Trial Update | CytoDyn plans a phase II trial for Graft versus Host Disease in USA (SC) (NCT02737306) Updated 23 Oct 2015 |
| 21 Sep 2015 | Scientific Update | Updated efficacy data from a phase IIb extension trial in HIV infections released by CytoDyn [174] Updated 23 Sep 2015 |
| 15 Jul 2015 | Scientific Update | Interim efficacy data from a phase IIb extension trial in HIV infections released by CytoDyn [181] Updated 17 Jul 2015 |
| 24 Jun 2015 | Phase Change - Preclinical | Preclinical trials in Graft-versus-host disease in USA (IV) [159] Updated 29 Jun 2015 |
| 09 Jun 2015 | Regulatory Status | The US FDA approves clinical trial protocol of phase III trial in HIV infections [164] Updated 11 Jun 2015 |
| 01 Jun 2015 | Phase Change - III | Phase-III clinical trials in HIV infections (Combination therapy, Treatment-experienced) in USA (IV) (NCT02483078) Updated 12 Aug 2015 |
| 04 May 2015 | Trial Update | CytoDyn plans a phase III trial for HIV-1 infections in [165] Updated 09 May 2015 |
| 04 Feb 2015 | Scientific Update | Efficacy data from a phase IIb trial in HIV-1 infections released by CytoDyn [166] Updated 07 Feb 2015 |
| 04 Feb 2015 | Regulatory Status | CytoDyn completes an End-of-Phase IIb meeting with the US FDA for PRO 140 in HIV infections [166] Updated 06 Feb 2015 |
| 01 Nov 2014 | Trial Update | CytoDyn initiates enrolment in a phase IIb extension trial for HIV-1 infections (Monotherapy) in USA (NCT02355184) Updated 10 Feb 2015 |
| 14 Oct 2014 | Regulatory Status | CytoDyn requests an end of phase IIb meeting with the US FDA in [167] Updated 17 Oct 2014 |
| 14 Oct 2014 | Scientific Update | Efficacy data from a phase IIb trial in HIV-1 infections released by CytoDyn [167] Updated 17 Oct 2014 |
| 01 Sep 2014 | Trial Update | Drexel University initiates enrolment in a phase IIa trial for HIV-1 infections (Monotherapy) in USA (NCT02257788) Updated 07 Nov 2014 |
| 31 Jul 2014 | Scientific Update | Interim efficacy and adverse events data from a phase IIb trial in HIV-1 infections released by CytoDyn [177] Updated 29 Aug 2014 |
| 14 May 2014 | Phase Change - II | Phase-II clinical trials in HIV infections (Monotherapy) in USA (SC) Updated 16 May 2014 |
| 28 Jan 2014 | Trial Update | CytoDyn plans two phase IIb trials for undisclosed indications in USA [186] Updated 30 Jan 2014 |
| 26 Feb 2013 | Phase Change - Preclinical | Preclinical trials in HIV infections in USA (SC) Updated 01 Mar 2013 |
| 16 Nov 2012 | Trial Update | CytoDyn enters into a phase IIb clinical trial agreement with Drexel University College of Medicine [187] Updated 20 Nov 2012 |
| 17 Oct 2012 | Licensing Status | CytoDyn completes the acquisition of PRO 140 from Progenics Pharmaceuticals [1] Updated 19 Oct 2012 |
| 30 Jul 2012 | Licensing Status | CytoDyn enters into an asset purchase agreement with Progenics to acquire PRO 140; the transaction is expected to close within 90 days [16] Updated 31 Jul 2012 |
| 23 Nov 2011 | Licensing Status | PRO 140 is available for licensing as of 09 Nov 2011. http://www.progenics.com Updated 23 Nov 2011 |
| 16 Feb 2010 | Scientific Update | Interim pharmacokinetics and pharmacodynamics data from clinical trials in HIV infections presented at the 17th Conference on Retroviruses and Opportunistic Infections (CROI-2010) [242] , [243] Updated 08 Mar 2010 |
| 05 Aug 2009 | Company Involvement | Monogram Biosciences has been acquired by Laboratory Corporation of America Holdings Updated 06 Aug 2009 |
| 11 Feb 2009 | Phase Change - Discontinued(II) | Discontinued - Phase-II for HIV-1 infections in USA (IV) Updated 20 Nov 2012 |
| 11 Feb 2009 | Scientific Update | Final efficacy & adverse events data from a phase II trial of SC PRO 140 in HIV infections presented at the 16th Conference on Retroviruses and Opportunisitic Infections (CROI-2009) [189] , [244] Updated 16 Feb 2009 |
| 11 Feb 2009 | Trial Update | Progenics selects the SC formulation of PRO 140 for further development Updated 16 Feb 2009 |
| 27 Oct 2008 | Scientific Update | Interim efficacy and safety data from two phase II trials in HIV-1 infections presented at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy and 46th Annual Meeting of the Infectious Diseases Society of America (ICAAC/IDSA-2008) [196] Updated 30 Oct 2008 |
| 02 Oct 2008 | Trial Update | Progenics Pharmaceuticals completes enrolment in two phase-II trials for HIV-1 infections in the US Updated 06 Oct 2008 |
| 31 Mar 2008 | Phase Change - II | Phase-II clinical trials in HIV-1 infections treatment in USA (SC) Updated 17 Jan 2008 |
| 31 Dec 2007 | Phase Change - II | Phase-II clinical trials in HIV-1 infections treatment in USA (IV) Updated 17 Jan 2008 |
| 05 Oct 2007 | Scientific Update | Data presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2007) added to the adverse events [200] and Viral Infections pharmacodynamics [245] and therapeutic trials [200] sections Updated 05 Oct 2007 |
| 30 Jul 2007 | Phase Change - Preclinical | Preclinical trials in HIV infections treatment in USA (SC) Updated 30 Jul 2007 |
| 30 Jul 2007 | Scientific Update | Results from a phase Ib clinical trial in HIV infections added to the Viral Infections pharmacodynamics and therapeutic trials sections [246] Updated 30 Jul 2007 |
| 25 Jul 2007 | Scientific Update | Data presented at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS-2007) added to the Viral Infections antimicrobial activity and therapeutic trials sections [247] , [248] Updated 20 Aug 2007 |
| 03 May 2007 | Scientific Update | Results from a phase Ib clinical trial in patients with HIV infection added to the adverse events and Viral Infections therapeutic trials sections [201] Updated 03 May 2007 |
| 14 Dec 2006 | Trial Update | Progenics completed enrolment and dosing in its phase Ib trial for HIV in the US Updated 19 Dec 2006 |
| 31 Oct 2006 | Scientific Update | A preclinical study has been added to the Viral Infections antimicrobial activity section [249] Updated 29 Aug 2008 |
| 18 Oct 2006 | Scientific Update | Data presented at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2006) have been added to the Viral Infections antimicrobial activity section [250] Updated 18 Oct 2006 |
| 23 Feb 2006 | Scientific Update | Data presented at the 13th Conference on Retroviruses and Opportunistic Infections (CROI-2006) have been added to the pharmacokinetics and Viral Infections pharmacodynamics sections [205] Updated 23 Feb 2006 |
| 22 Feb 2006 | Regulatory Status | PRO 140 receives Fast Track designation for HIV-1 infections [SC,Injection] (Monotherapy) in USA Updated 01 Sep 2014 |
| 22 Feb 2006 | Regulatory Status | PRO 140 has received fast track status for HIV infections treatment in USA Updated 24 Feb 2006 |
| 09 Jan 2006 | Company Involvement | Protein Design Labs is now called PDL BioPharma Updated 20 Jan 2006 |
| 01 Dec 2005 | Trial Update | Progenics has initiated a phase Ib trial for HIV infections treatment Updated 14 Dec 2005 |
| 16 Sep 2005 | Scientific Update | Clinical data from a media release have been added to the adverse events and Viral infections pharmacodynamics sections [251] Updated 16 Sep 2005 |
| 06 Sep 2005 | Company Involvement | ViroLogic is now called Monogram Biosciences Updated 29 Aug 2008 |
| 29 Jul 2005 | Trial Update | Progenics has completed enrolment in a phase I trial for HIV infections treatment in USA Updated 29 Jul 2005 |
| 27 Jul 2005 | Scientific Update | A clinical study has been added to the adverse events, pharmacokinetics and Viral Infections pharmacodynamics sections [252] Updated 23 Aug 2005 |
| 30 Apr 2004 | Phase Change - I | Phase-I clinical trials in healthy volunteers (for HIV infections treatment) in USA (IV) Updated 07 May 2004 |
| 19 Feb 2004 | Scientific Update | Data presented at the 11th Conference on Retroviruses and Opportunistic Infections (CROI-2004) have been added to the Viral Infections pharmacodynamics section [253] Updated 19 Feb 2004 |
| 11 Dec 2002 | Scientific Update | A preclinical study has been added to the Viral Infections pharmacodynamics section [254] Updated 11 Dec 2002 |
| 17 Jul 2002 | Scientific Update | An animal study has been added to the Viral Infections pharmacodynamics section [255] Updated 17 Jul 2002 |
| 11 Jul 2002 | Company Involvement | Progenics has an agreement to use ViroLogic's proprietary HIV resistance testing technology in the development of PRO 140 Updated 11 Jul 2002 |
| 03 May 2002 | Other | A humanised form of PRO 140 has been selected for clinical testing Updated 03 May 2002 |
| 05 Feb 2002 | Scientific Update | A preclinical study has been added to the Viral Infections antimicrobial activity section [256] Updated 05 Feb 2002 |
| 24 Apr 2001 | Scientific Update | A preclinical study has been added to the Viral Infections pharmacodynamics section [257] Updated 24 Apr 2001 |
| 16 Oct 2000 | Scientific Update | A study of synergy with other fusion inhibitors has been added to the Viral Infections antimicrobial activity section [258] Updated 16 Oct 2000 |
| 12 Oct 2000 | Scientific Update | A study has been added to the Viral Infections antimicrobial activity section [258] Updated 12 Oct 2000 |
| 09 Jul 1999 | Scientific Update | A study has been added to the Viral Infections antimicrobial activity section [259] Updated 09 Jul 1999 |
| 03 Jun 1999 | Other | PRO 140 will be humanised by Protein Design Labs Updated 03 Jun 1999 |
| 18 Feb 1999 | Phase Change - Preclinical | Preclinical development for HIV infections treatment in USA (IV) Updated 18 Feb 1999 |
References
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CytoDyn Announces Acquisition of Pro 140.
Media Release -
Progenics Stockholders Approve Merger with Lantheus.
Media Release -
CytoDyn Announces Submission of Clinical Protocol to FDA and Initiation of Pre-Clinical Study in Glioblastoma.
Media Release -
Regnum Signs Assignment and Assumption Agreement with CytoDyn and SevenScore Pharmaceuticals to Commercialize Leronlimab in the U.S. for the Treatment of HIV.
Media Release -
CytoDyn Signs Distribution Agreement with Macleods Pharmaceuticals Ltd. to Pursue EUA and Compassionate Use Access to Leronlimab in India.
Media Release -
CytoDyn Reaches Agreement with Albert Einstein Israelite Hospital in Brazil to Conduct Two COVID-19 Trials - a Small Trial in Critically Ill and a Large Trial in Severe Populations.
Media Release -
CytoDyn Signs Exclusive Supply and Distribution Agreement with Biomm S.A. in Brazil for COVID-19 and All Other Leronlimab Indications.
Media Release -
CytoDyn Announces Partnership with amfAR to Accelerate HIV Cure Research.
Media Release -
CytoDyn Announces Execution of Exclusive Agreement with American Regent for Distribution and Supply of Leronlimab for Treatment of COVID-19 in United States.
Media Release -
CytoDyn and NIH of Mexico Complete Memorandum of Understanding to Conduct Small Covid-19 Phase 3 Trial for Severe and Critically Ill Patients.
Media Release -
CytoDyn Signs Letter of Intent for the Joint Development and Licensing of Leronlimab in China with Longen China Group.
Media Release -
CytoDyn Signs Definitive Agreements with Vyera Pharmaceuticals to Commercialize Leronlimab in the U.S. for the Treatment of HIV.
Media Release -
CytoDyn Executes Exclusive Worldwide Licensing Agreement with IncellDX for PA-14 and PRO 140 for Diagnostic Testing Purposes.
Media Release -
CytoDyn Signs Groundbreaking Memorandum of Understanding with Thai Red Cross AIDS Research Centre to Study Pre-Exposure Prophylaxis Use of Leronlimab (PRO 140) in People at High Risk of Acquiring HIV.
Media Release -
Samsung Biologics Signs CMO Deal with CytoDyn of the U.S.
Media Release -
CytoDyn Announces Entry into Agreement with Progenics Pharmaceuticals, Inc. to Acquire PRO 140.
Media Release -
Progenics selects clinical candidate for HIV therapy: humanized PRO 140 antibody blocks viral entry - novel small-molecule inhibitors of CCR5-mediated HIV entry are also identified.
Media Release -
Protein Design Labs Becomes PDL BioPharma.
Media Release -
Progenics' HIV Entry Inhibitor, Pro 542, Continues to Provide Encouraging Phase II Results
Media Release -
ViroLogic Changes Its Name to Monogram Biosciences.
Media Release -
Health Canada Authorizes Emergency Use of Leronlimab for Treatment of First Triple-Negative Breast Cancer Patient in Canada.
Media Release -
CytoDyn's Phase 2 Basket Trial for 22 Solid Cancer Tumors Treats First Patient with Leronlimab; Patient Enrollment Delayed Due to COVID-19.
Media Release -
Leronlimab (350 mg) Weekly Use for 14 Weeks in Open Label Arm of NASH Trial Produces Fibrosis Reduction as High as 93 msec Amongst First 15 Patients with Average Reduction of 24 msec.
Media Release -
Basket Study of Leronlimab (PRO 140) in Patients With CCR5+ Locally Advanced or Metastatic Solid Tumors
ctiprofile -
CytoDyn Receives Institutional Review Board Approval to Initiate Phase 2 Basket Trial for 22 Solid Tumor Cancers.
Media Release -
CytoDyn Reports Continued Positive Clinical Data on its Phase 1b/2 mTNBC and Expanded Access Studies for MBC Ahead of Breakthrough Therapy Designation Decision From the FDA.
Media Release -
CytoDyn Files a Phase 2 Basket Trial with Leronlimab (PRO 140) for Treatment of All Solid Tumor Cancers.
Media Release -
A phase 2 basket trial of Leronlimab for the treatment of approximately 22 different solid tumor cancers, including melanoma, brain-glioblastoma, throat, lung, stomach, colon carcinoma, breast, testicular, ovarian, uterine, pancreas, bladder, among other indications
ctiprofile -
CytoDyn Submits Breakthrough Therapy Designation Application to FDA for Leronlimab as a Treatment for Metastatic Triple-Negative Breast Cancer (mTNBC); Fast Track Designation for mTNBC was received previously.
Media Release -
CytoDyn Files for Breakthrough Therapy Designation with the FDA for the Use of Leronlimab for the Treatment of Metastatic Triple-Negative Breast Cancer.
Media Release -
CytoDyn Reports Early Results from First Patient in its Phase 1b/2 CCR5+ Metastatic Triple-Negative Breast Cancer Trial.
Media Release -
Patient Treated with Leronlimab (PRO 140) for Metastatic Triple-Negative Breast Cancer under Emergency IND, Launching CytoDyn into Oncology.
Media Release -
CytoDyn Receives IRB Approval To Proceed With Compassionate Use Of Leronlimab For Patients With Triple-Negative Breast Cancer.
Media Release -
CytoDyn Announces FDA Clearance to Proceed with Phase 2 Study of Leronlimab (PRO 140) and Regorafenib as a Combination Therapy for Metastatic Colorectal Cancer.
Media Release -
CytoDyn Provides Updated Pre-Clinical Data Showing Leronlimab (PRO 140) Continues to Suppress Breast Cancer Metastatic Burden >98% Compared with Untreated Animals.
Media Release -
FDA Grants CytoDyn Fast Track Designation for Leronlimab (PRO 140) in metastatic Triple-Negative Breast Cancer, an Unmet Medical Need.
Media Release -
Leronlimab (PRO 140) reduces by more than 98% human breast cancer metastasis in mouse xenografts for over 6 weeks.
Media Release -
CytoDyn Files a Phase 2 Protocol with the FDA for Leronlimab (PRO 140) and Regorafenib as a Combination Therapy for Metastatic Colorectal Cancer.
Media Release -
A Phase II Study of Leronlimab (PRO 140) in Combination With Regorafenib in Patients With CCR5+, Microsatellite Stable (MSS), Metastatic Colorectal Cancer (mCRC)
ctiprofile -
CytoDyn Treats First Patient in Phase 1b/2 Clinical Trial with Leronlimab (PRO 140) for Patients with Treatment-Naive, Metastatic Triple-Negative Breast Cancer.
Media Release -
CytoDyn Names Richard G. Pestell, M.D., Ph.D. as Vice Chairman of its Board of Directors.
Media Release -
CytoDyn Announces Initiation of Metastatic Triple Negative Breast Cancer Trial and Reiterates Phase 3 Goal in Cancer.
Media Release -
CytoDyn Files IND and Protocol for Phase 1b/2 Clinical Trial in Metastatic Triple-Negative Breast Cancer with PRO 140 (Leronlimab).
Media Release -
A Phase Ib/II Study of Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC)
ctiprofile -
CytoDyn Reports Early, But Strong Positive Clinical Responses for Two Patients, One in Metastatic Breast Cancer and One in Metastatic Triple-Negative Breast Cancer Trials.
Media Release -
Impressive Results Continue from CytoDyn's Clinical Trials Evaluating Two Patients with Leronlimab, One in mTNBC and One in MBC.
Media Release -
CytoDyn's First mTNBC Patient in Phase 1b/2 is in Remission and Oncologist Ordered Termination of Treatment with Carboplatin (chemotherapy drug) and Remains on Leronlimab Only as Monotherapy; Patient's Testimony about Her Condition After Nearly 6 Months of Leronlimab Treatment is Very Strong.
Media Release -
CytoDyns Trial for Metastatic Triple-Negative Breast Cancer Demonstrates Safety with 350 mg, 525 mg and 700 mg Dosages; Officially Advances to Phase 2 from Phase 1b.
Media Release -
CytoDyn Announces Preliminary Results from 30 mTNBC Patients Treated with Leronlimab. Decreases in CAMLs after 4 Doses of Leronlimab were Identified in Over 70% of Patients and were Associated with a 450% Significant Increase in Overall Survival at 12-Month Analysis.
Media Release -
Cristofanilli M, Chittoria N, Ehsani S, Rui H, Dolezal M, Stork-Sloots L, et al. A phase Ib/II study of leronlimab combined with carboplatin in patients with CCR5+ metastatic triple-negative breast cancer (mTNBC). SABCS-2021 2021; abstr. P5-17-08.
Available from: URL: https://www.abstractsonline.com/pp8/#!/10462/presentation/1700 -
CytoDyn Announces Voluntary Withdrawal of BLA for HIV-MDR Due to CRO Data Management Issues.
Media Release -
Adams DL, Raghavakaimal A, Tang C-M, Gardner KP, Ray NG, Pourhassan N. Changes in circulating tumor associated cells predicts progression free and overall survival in metastatic TNBC patients after induction of the anti-CCR5 drug leronlimab. AACR-2022 2022; abstr. CT156 / 24.
Available from: URL: https://www.abstractsonline.com/pp8/10517/presentation/20627 -
A Compassionate Use Study of Leronlimab (PRO 140) in Combination With Treatment of Physician's Choice in Patients With CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC)
ctiprofile -
CytoDyn Announces Study to Evaluate Potential Synergistic Effects of Leronlimab with Immune Checkpoint Blockade (ICB).
Media Release -
CytoDyn Interim Chief Medical Officer Dr. Richard Pestell to Keynote 11th Annual Conference on Stem Cell and Regenerative Medicine.
Media Release -
CytoDyn Announces CROI's Acceptance of Late-Breaking Abstract by Dr. Jonah Sacha for use of Leronlimab as PrEP.
Media Release -
CytoDyn Reports Significant Reduction in Breast Cancer Tumor Metastasis in Preclinical Study and Requests FDA Fast Track Designation for Leronlimab (PRO 140) in Metastatic-Triple Negative Breast Cancer (mTNBC).
Media Release -
CytoDyn Sponsored Research Reaffirms the Role of CCR5 in Cancer Biology and Provides a New Potential Cancer Treatment Modality.
Media Release -
CytoDyn Announces Strong Preclinical Results Using PRO 140 in Human Colon Carcinoma.
Media Release -
CytoDyn to Expand Strategic Focus with PRO 140 to Cancer and Immunologic Disorders.
Media Release -
New Research Supports Potential for CytoDyn's PRO 140 to Inhibit Breast Cancer Metastasis.
Media Release -
CytoDyn Announces Partial Clinical Hold of HIV Program and Full Clinical Hold of COVID-19 Program.
Media Release -
A phase 3, randomized, double blind, placebo controlled trial to evaluate the efficacy and safety of leronlimab in combination with standard of care for critically ill patients with COVID-19 pneumonia with need for invasive mechanical ventilation ("IMV") or Extracorporeal Membrane Oxygenation ("ECMO")
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CytoDyn Receives Positive Response From FDA in Regard to its Phase 3, Registrational Trial in COVID-19 Critically Ill Population.
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CytoDyn Submits Protocol with the FDA for Phase 3 Registrational Trial of Leronlimab for Critically Ill COVID-19 Population.
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A Phase 3, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Leronlimab in Combination With Standard of Care for Patients With Coronavirus Disease 2019 (COVID-19) With Need for Mechanical Ventilation or Extracorporeal Membrane Oxygenation
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A Phase 3, Randomized, Double Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Leronlimab in Combination With Standard of Care for Moderately Ill Patients With Coronavirus Disease 2019 (COVID-19) Pneumonia
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CytoDyn Announces Treatment of First Patient in Pivotal Phase 3 Trial for Critically Ill COVID-19 Patients in Brazil.
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A small phase 3 trial of Leronlimab in critically ill Covid 19 patients
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CytoDyns CRO in Brazil Met with ANVISA to Modify CD16 Trial for Critically Ill COVID-19 Patients to Expedite Interim Analysis After 51 Patients, Potentially in 1Q2022.
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CytoDyn Receives Clearance from Brazils FDA (ANVISA) to Commence a Pivotal Phase 3 Trial in Critically Ill COVID-19 Patients with IV Administration of Four Doses (700mg/week).
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CytoDyn Announces Treatment of the First Patient in its Pivotal Phase 3 COVID-19 Trial in Brazil for Patients with Severe Symptoms.
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CytoDyn Receives Clearance from Brazils ANVISA to Commence Phase 3 Trial for Severe COVID-19 Patients.
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CytoDyn to Hold Webcast on May 18 to Discuss FDA's Statement on Leronlimab.
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First Patient Treated with Leronlimab in Phase 2b/3 Trial for COVID-19.
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Treatment with CytoDyn's Leronlimab Indicates Significant Trend Toward Immunological Restoration in Severely Ill COVID-19 Patients.
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After Several Months of Providing Requested Information About Manufacturing and Safety of Leronlimab, U.K.'s MHRA Accepts CytoDyn's Request to Enroll in its Current Phase 3 Trial for COVID-19 Patients with Severe-to-Critical Symptoms.
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CytoDyn in Discussions with U.S. FDA, MHRA and Health Canada After Unblinding its CD12 Trial Data for Severe-to-Critically Ill COVID-19 Patients.
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CytoDyn Completes Enrollment for Phase 3 Registrational Trial for 390 Patients with Severe-to-Critical COVID-19 .
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CytoDyn Reaches Enrollment Target of 293 Patients for 2nd DSMC Interim Analysis of Phase 3 COVID-19 Trial and Expects to Enroll the Remaining 97 Patients in the Next Few Weeks to Complete the Trial This Year.
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CytoDyn Seeks UK Approval of Leronlimab for HIV and COVID-19.
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CytoDyn Receives Positive DSMC Recommendation for Leronlimab Phase 3 COVID-19 Trial with No Safety Concerns.
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Update on HIV-BLA-PDUFA: FDA requested more information to complete a substantive review. No additional trials required. CytoDyn plans to submit the requested information and will ask for a Type A meeting with the FDA per the agency's suggestion.
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Novant Health Initiates Phase 2b/3 Trial with CytoDyn's Leronlimab for Severely and Critically Ill COVID-19 Patients.
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Southern California Patients Treated with Leronlimab for COVID-19 under Emergency IND: 4 Patients with Moderate Indications Removed from Oxygen; 3 Patients Discharged from Hospital; 1 Patient Scheduled for Discharge Today; 1 Patient with Severe Indications Discharged, for Total of 5 Patients Discharged.
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CytoDyn Files a Clinical Trial Protocol with the FDA to Treat Severely Ill COVID-19 Patients with Leronlimab where the Primary Endpoint is Mortality Rate at Two Weeks.
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CytoDyn Files FDA-Suggested Modifications to IND and Protocol for Phase 2 Clinical Trial for COVID-19 Patients with Mild to Moderate Indications and a Second Randomized Protocol for All COVID-19 Patients in Severe Condition Will be Filed Next Week per FDA Recommendation.
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CytoDyn Reaches Enrollment of 195 Patients in its Phase 3 Trial for COVID-19 Patients with Severe-to-Critical Symptoms.
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A Phase 2b/3, Randomized, Double Blind, Placebo Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of Leronlimab for Patients With Severe or Critical Coronavirus Disease 2019 (COVID-19)
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CytoDyn to Submit Newly Completed Topline Report of CD12 Trial Results to Regulatory Agencies in Multiple Countries including India and Philippines.
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Remarkable Turnaround Following Leronlimab Treatment in Critically Ill COVID-19 Patient After 84 days on ECMO; Case Study Published in Journal of Translational Autoimmunity.
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CytoDyn's Phase 3 Trial Demonstrates Safety, a 24% Reduction in Mortality and Faster Hospital Discharge for Mechanically Ventilated Critically Ill COVID-19 Patients Treated with Leronlimab.
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CytoDyn to Release CD12 Trial Detailed Results via Form 8-K After Investment Community Webcast, Monday, March 8.
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CytoDyn Submits First and Most Crucial Section (CMC) of Interim Order Application to Health Canada for COVID-19 Under Rolling Review.
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First Compassionate Special Permit (CSP) Patient in Philippines Improved Significantly 35 hours After First Injection of Leronlimab and Released 3 Days Later.
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CytoDyn Appoints Chiral Pharma to Secure Leronlimab for Local FDA Approval in Philippines.
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CytoDyn to File Accelerated Rolling Review with MHRA and Interim Order (IO) with Health Canada for COVID-19.
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FDA Provides Guidance for Adding an Open-Label Extension to CytoDyn's Phase 3 Trial for Severe-to-Critical COVID-19 Patients Until Trial Data is Unblinded.
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FDA Resumes eIND Approval for Severe-to-Critical COVID-19 Patients Use of Vyrologix(TM) (leronlimab) Following Full Enrollment in CytoDyn's Phase 3 Trial.
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CytoDyn and the Mexican National Institutes of Health Participate in a Collaborative Study of Leronlimab for the Treatment of Severe/Critical COVID-19 Population.
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CytoDyn to Prepare a Phase 3 Protocol to Submit to the FDA for a Three-Arm Comparative and Combination Trial of Leronlimab and Remdesivir.
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CytoDyn Requests ##8220##Fast Track Approval##8221## for COVID-19 Patients from U.K.'s Regulatory Agency MHRA based on its Top-line Report Showing Statistically Significant Endpoint, NEWS2 (p < 0.023) and Notable Safety Results.
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CytoDyn Initiates Phase 2 Clinical Trial With Leronlimab for Treatment of NASH.
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A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab for Mild to Moderate Coronavirus Disease 2019 (COVID-19)
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Impressive Results From CytoDyn's Phase 2 Covid-19 Trial.
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UPDATE - Impressive Results From CytoDyn's Phase 2 COVID-19 Trial.
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CytoDyn Announces Clinically Significant Top-line Results from its Phase 2 Trial in Mild-to-Moderate COVID-19 Patients.
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Blood Samples at Day 0, 3 and 7 for Severely Ill COVID-19 Patients Clearly Indicate Leronlimab Has Significantly Reduced the Cytokine Storm in All (7) Patients and All Patients Demonstrated Immunological Benefit at Both Day 3 and Day 7.
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First Two Patients Enrolled in Randomized Phase 2, COVID-19 Trial with Leronlimab; Five More Severely Ill COVID-19 Patients Treated Under Emergency IND and Two Patients Have Already Extubated.
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Two Additional Coronavirus Patients Treated at Leading New York Hospital with CytoDyn's Leronlimab, Bringing the Total to Four Patients.
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U.S. Food and Drug Administration (FDA) Grants Emergency IND for Two Coronavirus Patients Treated in New York with CytoDyn's Leronlimab.
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CytoDyn Appoints Jacob Lalezari, M.D. as Interim Chief Medical Officer.
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CytoDyn Files IND and Protocol for Phase 2 Clinical Trial for Treatment of Patients with Coronavirus with Leronlimab (PRO 140).
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Three Additional Patients with Severe COVID-19 Treated with Leronlimab in New York Medical Center Bringing the Total to 10 Patients.
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Leronlimab Used in Seven Patients with Severe COVID-19 Demonstrated Promise with Two Intubated Patients in ICU, Removed from ICU and Extubated with Reduced Pulmonary Inflammation.
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Leronlimab Under Evaluation for Potential Treatment of Coronavirus.
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FDA Approves 54 Emergency INDs for Leronlimab Treatment of Coronavirus - CytoDyn Requests Compassionate Use from FDA for COVID-19 Patients Not Eligible for Participation in Two Ongoing Clinical Trials in U.S. - CytoDyn Targets Enrollment Completion for its 75 Patient, Phase 2 Trial by End of May.
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Manuscript Describes How CytoDyn's Leronlimab Disrupts CCL5/RANTES-CCR5 Pathway, Thereby Restoring Immune Homeostasis, Reducing Plasma Viral Load, Reversing Hyper Immune Activation and Inflammation in Critical COVID-19 Patients.
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CytoDyn Announces FDA Has Lifted Clinical Hold.
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A pre-exposure prophylaxis (PrEP) clinical trial of leronlimab (PRO 140) in subjects at high risk of HIV infection
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CytoDyn Submits CMC (Manufacturing) Section of HIV BLA to FDA Under Previously Authorized Rolling Review; Last (Clinical) Section Will Complete Full BLA Submission.
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CytoDyn Submits the First of Three Main Sections of HIV BLA to FDA Under Previously Authorized Rolling Review.
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CytoDyn Announces FDA Accepts Revised Rolling Review Timeline for Resubmission of its BLA.
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CytoDyn Receives FDA Guidance for its HIV BLA Dose Justification Report.
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CytoDyn Submits Dose Justification Report to FDA to Begin Overcoming Deficiencies in its BLA for HIV.
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CYTODYN INC FORM 10-Q. Internet-Doc 2021;.
Available from: URL: https://www.cytodyn.com/investors/sec-filings/all-sec-filings/content/0001193125-21-004744/0001193125-21-004744.pdf -
U.K. MHRA Grants Meeting to CytoDyn to Discuss Fast Track Approval of Leronlimab for COVID-19 Patients.
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To Avoid Delay, the FDA Recommends CytoDyn Conduct Its Type A Meeting in Writing with FDA Response Goal Date of September 4.
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CytoDyn Receives BLA Acknowledgment Letter From the FDA.
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CytoDyn Files Request With FDA for Priority Review of BLA for First Approval.
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CytoDyn Completed Submission of All Remaining Parts of Biologics License Application (##8220##BLA##8221##) on May 11, 2020.
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CytoDyn Reaches Historical Milestone, Submits First of Three Sections of BLA to FDA for Leronlimab (PRO 140) as a Combination Therapy for HIV.
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FDA Grants Rolling Review for CytoDyn's Planned BLA for Investigational HIV Therapy Leronlimab (PRO 140).
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CytoDyn Announces Productive Conference Call with FDA Regarding First BLA Submission for Leronlimab (PRO 140) Combination Therapy at 700 mg Dose.
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CytoDyn Injects First Patient in Its Current Phase 3 Study.
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U.K. MHRA Clears CytoDyn to File its BLA for Leronlimab as One Injection per Week for Combination HIV Therapy.
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A phase 3 study of leronlimab (PRO 140) in combination with remdesivir for the treatment of COVID-19
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CytoDyn's Monotherapy Trial with Leronlimab (PRO 140) Reaches its Ultimate Goals.
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USAN Council Assigns Leronlimab as the Official Name for CytoDyn's PRO 140.
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CytoDyn Announces Strategy to Complete Development of Novel ProstaGene Gene-based Prostate Cancer Prognostic Test.
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CytoDyn's PRO 140 (leronlimab) HIV Monotherapy Trial Results Show 92% Responder's Rate at 700 mg Dose.
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A Registration-Directed Study to Investigate Leronlimab Single-Agent Maintenance Therapy for HIV-Infected Patients
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CytoDyn Files for Expanded Access Use of Leronlimab for Multi-Drug Resistance HIV Patients.
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CytoDyn to Present Pivotal Data at ASM Microbe 2019 Demonstrating Efficacy and Safety of Leronlimab (PRO 140) in HIV Patients with Multiple ARV Class Resistance.
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CytoDyn Announces Productive Pre-BLA Meeting with FDA for PRO 140 Combination Therapy.
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CytoDyn Provides Update on PRO 140 Combination Therapy Pivotal Trial in HIV Patients Following Constructive Meeting With FDA.
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CytoDyn Announces Vyrologix as Proprietary Name for Leronlimab as a Combination Therapy for Highly Treatment Experienced HIV Patients in the United States.
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CytoDyn and FDA Will Meet to Potentially Finalize Protocol for Pivotal Monotherapy Trial for Leronlimab.
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CytoDyn Files Pivotal Trial Protocol for HIV Monotherapy with FDA.
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A Multi-center, Two-Part, Single-Arm, Open Label, 25-Week Trial With PRO 140 in Treatment-Experienced HIV-1 Subjects
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CytoDyn Files Protocol with U.S. FDA for Phase 2 Clinical Trial for COVID-19 Patients with Long-Hauler Symptoms.
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CytoDyn Announces FDA Clearance to Proceed with Phase 2 Clinical Trial of Leronlimab (PRO 140) for Treatment of NASH.
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CytoDyn Provides Update on Dose Escalating Trial with Leronlimab for HIV Monotherapy for a Potential Pivotal Trial.
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Dhody K, Kazempour K, Pourhassan N, Maddon PJ. Pro 140 Sc: Long-Acting, Single-Agent Maintenance Therapy for Hiv-1 Infection. CROI-2019 2019; abstr. 486.
Available from: URL: http://www.croiconference.org/sessions/pro-140-sc-long-acting-single-agent-maintenance-therapy-hiv-1-infection -
CytoDyn's Monotherapy Trial with Leronlimab (PRO 140) Exceeds Expectations.
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CytoDyn Announces Significantly Improved Response Rate at Higher Dose of PRO 140 in HIV Phase 3 Monotherapy Trial.
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CytoDyn Provides Update on Enrollment in its Pivotal Phase 2b/3 HIV Combination Trial.
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A Phase 2b/3, Multicenter Study to Assess the Treatment Strategy of Using PRO 140 SC as Long-Acting Single-Agent Maintenance Therapy for 48 Weeks in Virologically Suppressed Subjects With CCR5-tropic HIV-1 Infection
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CytoDyn to Expand Clinical Applications for PRO 140 Beyond Therapy for HIV.
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A Multi-center, Randomized, Double-blind, Placebo-controlled Trial, Followed by Single-arm Treatment of PRO 140 in Combination With Optimized Background Therapy in Treatment-Experienced HIV-1 Subjects
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CytoDyn Announces Positive Results from Completed Pivotal PRO 140 HIV Combination Trial.
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Cytodyn Initiates First Clinical Site for Phase 3 Trial of PRO 140.
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CytoDyn Completes Qualification of PRO 140 Material for Phase 3.
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CytoDyn Cleared by FDA to Start Phase 3 of First Injectable Antibody for HIV.
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CytoDyn Submits Phase 3 Protocol to FDA After Agreement on Protocol Synopsis.
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CytoDyn Concludes Phase 2b Study With 98% Success With 4 Weeks of Monotherapy - Many HIV Patients in Extension Study With Some Approaching 6 Months.
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CytoDyn Announces 100% Success With PRO 140 in Four-Week Monotherapy Clinical Trial.
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Data from PRO 140 (leronlimab) HIV Monotherapy Trial Selected for Presentation at CROI 2019.
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Dhody K, Kazempour K, Pourhassan N, Maddon PJ. Primary Efficacy Results of PRO 140 SC in a Pivotal Phase 2b/3 Study in Heavily Treatment-Experienced HIV-1 Patients. ASMM-2018 2018; abstr. 7818.
Available from: URL: https://www.asm.org/index.php/abstracts-microbe-2018 -
CytoDyn Announces Presentation of Positive Efficacy Results from Pivotal PRO140 Combination Therapy Trial in HIV at ASM Microbe 2018.
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CytoDyn Reports Primary Endpoint Achieved in PRO 140 Pivotal Combination Therapy Trial in HIV Infection.
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CytoDyn Provides Update on PRO 140 Pivotal Combination Therapy Trial in Patients with HIV.
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CytoDyn Provides Further Update on PRO 140 Pivotal Combination Therapy Trial in Patients with HIV.
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HIV Patients Successfully Reach One Year of Virologic Suppression in PRO 140 Monotherapy Study.
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CytoDyn Inc. Announces First HIV Patient Dosing With PRO 140 in Phase 2b Clinical Trial for Treatment Substitution Protocol.
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CytoDyn Submits Protocol to FDA for Phase 2b Clinical Study of PRO 140 for Treatment Substitution in Patients with HIV.
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CytoDyn Announces Positive Interim Results From Its Treatment Substitution Study in Patients With HIV.
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A Phase 2b Study to Assess Suppression of HIV-1 Replication Following Substitution of Stable Combination Antiretroviral Therapy With a PRO 140 (Monoclonal CCR5 Antibody) Monotherapy in Adult Subjects With HIV-1 Infection
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Results of CytoDyn's PRO 140 CD01 Trial and Extension Study Published in HIV Clinical Trials.
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Eleven HIV Patients Successfully Reach One Year of Full Virologic Suppression in PRO 140 Monotherapy Phase 2b Extension Study.
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Evidence of HIV Suppression With PRO 140 Monotherapy Reaching Nearly 11 Months.
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Extension of Protocol PRO140_CD01 to Evaluate Long-term Suppression of HIV-1 Replication Following Substitution of Stable Combination ART With PRO 140 (Monoclonal CCR5 Antibody) Monotherapy for Additional 160 Weeks in Adult Subjects w/ HIV-1
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An Expanded Compassionate Access Protocol for a Single Subject Who Has Completed 24-Weeks of Treatment in PRO140_CD02 Study
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CytoDyn Announces Publication of Peer-Reviewed Paper, Suppression of Human and Simian Immunodeficiency Virus Replication with the CCR5-Specific Antibody Leronlimab in Two Species.
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PRO 140 2103: A Phase 2a, Randomized Study of PRO 140 by Subcutaneous Injection in Adult Subjects With Human Immunodeficiency Virus Type 1 Infection
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CytoDyn Signs Agreement with Amarex Clinical Research LLC to Prepare Two Phase 2b Clinical Trial Protocols to Explore Two Additional Therapeutic Indications for PRO 140.
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CytoDyn Announces Phase IIB Clinical Trial Agreement with Dr. Jeffrey Jacobson, Drexel University College of Medicine.
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CytoDyn Announces Collaboration with Dr. Bruce Torbett, The Scripps Research Institute, to study PRO 140 in a Pre-exposure Prophylaxis (PrEP) Model of HIV Infection.
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Progenics Selects Subcutaneous Form of PRO 140, a Novel HIV Antibody Therapy, for Further Development.
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A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Observed Systemic, Long-Acting, Anti-HIV Treatment With a Monoclonal Anti CCR5 Antibody (PRO 140) as an Adjunct to a New, Optimized, Oral Antiretroviral Regimen in HIV-Infected Injection Drug Users With Viral Rebound and Documented Poor Adherence to the Previous Antiretroviral Regimen
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CytoDyn Announces FDA Approval of Patient Screening for Phase 2b Study with Lead Product Candidate PRO 140 for the Treatment of HIV Type 1.
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CytoDyn Submits Phase IIb Protocol for PRO 140 Clinical Trial to FDA.
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A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study of PRO 140 by Intravenous Administration in Adult Subjects With Human Immunodeficiency Virus Type 1 Infection
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A Phase 2a, randomized, double blind, placebo controlled study of PRO 140 by subcutaneous administration in adult subjects with human immunodeficiency virus type 1 infection
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Jacobson J, Thompson M, Fischl M, Saag M, Zingman B, Liporace R, et al. Phase 2a Study of PRO 140 in HIV-Infected Adults. 49th-ICAAC 2009; abstr. H-1229.
Available from: URL: http://www.icaac.org -
Progenics Reports Positive Interim Phase 2 Results for Two Dosage Forms of Novel HIV Therapy PRO 140.
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Progenics Announces Progress and Presentations in HIV Therapy Program.
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Progenics Initiates Phase 2 Clinical Trials for PRO 140, a Novel HIV Antibody Therapy.
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A Phase 2b, Randomized, Double-blind, Placebo-controlled Clinical Trial of Observed Systemic, Long-acting, Anti-HIV Treatment With a Monoclonal CCR5 Antibody (PRO 140) as an Adjunct to a New, Optimized, Oral Antiretroviral Regimen in HIV-infected Recreational Drug Users With Viral Rebound and Poor Adherence to the Previous Antiretroviral Regimen
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Jacobson JM, hompson M, Saag MS, Fischl M, Liporace R, Reichman RC, et al. Antiretroviral activity and pharmacodynamics of PRO 140, a CCR5 monoclonal antibody, in HIV-infected individuals. 47th-ICAAC-2007 2007;296 (plus oral presentation) abstr. H-716.
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Progenics Announces Positive Results in Clinical Trial of Novel HIV Therapy.
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Progenics Pharmaceuticals Reports Fourth Quarter and Year End Results.
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Progenics Achieves Enrollment Target in Clinical Trial of HIV Entry Inhibitor PRO 140.
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A phase Ib, double-blind, randomized, dose-cohort escalation study of intravenous PRO 140 [PRO-140] or placebo in adult patients with HIV-1 infection
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Olson WC, Doshan H, ZHAN C, Mezzatesta J, Assumma A, Czarnecky R, et al. Prolonged coating of CCR5 lymphocytes bt PRO 140, a humanized CCR5 monoclonal antibody for HIV-1 therapy. 13th-Conf-Retrovirus-Opport-Infect 2006;abstr. 515.
Available from: URL: http://www.retroconference.org -
A phase I, randomized, double blind, placebo controlled, single-dose, rising dose cohort study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PRO 140 in healthy volunteers
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Progenics Pharmaceuticals' HIV Drug, PRO 140, Receives FDA Fast-Track Designation.
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Published Paper Indicates Leronlimab Shows Activity Against 4-Class Drug Resistant HIV-1 From Heavily Treatment Experienced (HTE) Subjects.
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CytoDyn Receives Orphan Drug Designation for PRO 140 for Prevention of Graft Versus Host Disease.
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CytoDyn Files an IND and Full Protocol for Phase 2 Study in GvHD.
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An Open-Label, Single-Arm, Phase II Multicenter Study of the Safety and Efficacy of PRO 140 for Prophylaxis of Acute Graft-Versus-Host Disease (GVHD) in Patients Undergoing Reduced Intensity Conditioning (RIC) Allogeneic Stem-Cell Transplantation
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CytoDyn Treats First Patient with Leronlimab in Phase 2 Trial for GvHD under Modified Trial Protocol.
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CytoDyn to Amend Protocol for PRO 140 Phase 2 Trial in GvHD.
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CytoDyn Provides Update on Phase 2 Clinical Trial with PRO 140 in GvHD.
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CytoDyn Reports Preliminary Results from First Five Patients in Phase 2 NASH Open Label Leronlimab Trial. Lower Fatty Deposits in All 5 Patients by as Much as 45% and Lower Fibrosis in 4 Patients by as Much as 10% Compared to Baseline.
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CytoDyn's Long-Haulers COVID-19 Trial Enrolled 20 Patients Within 10 Days; Enrollment to be Completed This Month.
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CytoDyn Announces First Patient Enrolled in Phase 2 Trial for NASH.
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A Phase II, Multi-center, Two-Part, Three-Arm, Dose-Ranging Study of the Safety and Efficacy of Leronlimab (PRO 140) in Adult Patients With Nonalcoholic Steatohepatitis (NASH)
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NASH Phase 2 Trial Open-Label Portion Demonstrates Average 80 msec cT1 Reduction in 50% of Patients and Reduction of Nearly 50 msec in 80% of Patients.
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Leronlimab 14-Week, NASH Clinical Trial Met Primary Endpoint (PDFF) and Secondary Endpoint (cT1) for Per Protocol Population in 350 mg Weekly Dose.
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Noureddin M, Lawitz E, Ritter A, Hassanein T, Bowman K, Kelly S, et al. Efficacy and safety of leronlimab in patients with non-alcoholic steatohepatitis: topline results of NASH01 clinical trial. ILC-2022 2022; abstr. SAT101.
Available from: URL: https://easl.eu/event/international-liver-congress-2022/ -
Noureddin M, Lawitz EJ, Ritter A, Hassanein TI, Kelly S, Meidling J, et al. Leronlimab in Patients with Nonalcoholic Steatohepatitis: Results from Nash01 Metabolic and Immunomodulatory Mechanisms of Action. AASLD-2022 2022; abstr. 2446.
Available from: URL: https://www.aasld.org/the-liver-meeting -
CytoDyn Files an IND and a Phase 2 Protocol with the FDA for the Treatment of NASH with Leronlimab.
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CytoDyn Reports Strong Positive Preclinical Data to Demonstrate Potential of Leronlimab in Treating Nonalcoholic Fatty Liver Disease (NAFLD) in Humanized Mouse Model.
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CytoDyn Initiates Pre-Clinical Study of Leronlimab (PRO 140) to Prevent NASH with The Cleveland Clinic's Dr. Daniel J. Lindner, M.D., Ph.D.
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A Phase 2, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Leronlimab in Patients Experiencing Prolonged Coronavirus Disease 2019 (COVID-19) Symptoms [Long-Haulers]
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CytoDyn's COVID-19 Long-Hauler's Trial Closed as Enrollment Exceeds Goals.
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CytoDyn Inc. Announces Positive Preliminary Results of Unblinded Data from Long-Haulers Trial Showing Greater Improvement in Leronlimab Group over Placebo in 18 of 24 Symptoms.
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Leronlimab Shows Early, but Promising Clinical Responses in First Two Patients Recovering from Stroke.
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CytoDyn Completes Second Non-dilutive $28.5 Million Convertible Note Financing with Conversion Rate at $10.00 Per Share Without Warrants to Help Expedite License Applications Here and Abroad and Successful COVID-19 Trials.
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CytoDyn Completes Non-dilutive $15 Million Convertible Note Financing with Conversion Rate at $4.50 Per Share without Warrants.
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CytoDyn Inc. Completes $14.5 Million Private Equity Offering.
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CytoDyn Granted a Significant Patent by USPTO for Methods of Treating Coronavirus Infection with Leronlimab.
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Adams DL, Raghavakaimal A, Tang C-M, Gardner KP, Kelly S, Pourhassan N, et al. Safety, efficacy, and clinical outcomes of the anti-CCR5 inhibitor (Leronlimab):A pooled analysis of three clinical trials in patients with mTNBC. ASCO-2022 2022; abstr. e13062.
Available from: URL: https://link.adisinsight.com/Jp6d3 -
CytoDyn Announces Cancer Update: 12-month Analysis of 28 mTNBC Patients Receiving Leronlimab Suggests an Increase of 3600% in 12-month OS in 75% of Patients with a Lower Level of Circulating Cells After Leronlimab Induction or at Baseline; 12-month PFS Continues at Near 600% Increase.
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Severely Ill COVID-19 Patient at Leading Southern California Medical Center Extubated Three Days After Treatment with CytoDyn's Leronlimab; Two Moderate COVID-19 Patients Removed from External Oxygen Following One Day of Treatment with Leronlimab and Discharged from Hospital.
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CytoDyn's Lead Product Candidate Leronlimab (PRO 140) Inhibits Colon Carcinoma Metastases to Liver and Lung in Preclinical Studies.
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CytoDyn Granted Small Business Waiver of Application Fees by FDA for Leronlimab (PRO 140) BLA Filing.
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CytoDyn Completes Acquisition of ProstaGene and Names Dr. Richard G. Pestell to Board of Directors.
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CytoDyn Appoints Michael A. Klump to Board of Directors.
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Lalezari J, Dhody K, Kowalczyk U, Kazempour K, Pourhassan N, Maddon PJ. Pro140 Single-Agent Maintenance Therapy for Hiv-1 Infection: a 2-Year Update. CROI-2017 2017; abstr. 437.
Available from: URL: http://www.croiconference.org/sessions/pro140-single-agent-maintenance-therapy-hiv-1-infection-2-year-update -
Thompson M, Jacobson J, Hole M, D'Ambrosio P, Morris S. Achieving a target exposure to PRO 140 results in maximal viral load reduction by subcutaneous or intravenous administration. 17-CROI-2010 2010; abstr. 597.
Available from: URL: http://retroconference.org/2010 -
Jacobson J, Morris S, Carpenito J, D'Ambrosio P, Huang W, Petropoulos C, et al. Co-receptor tropism and viral resistance following short-term monotherapy with the anti-CCR5 monoclonal antibody PRO 140. 17-CROI-2010 2010; abstr. 531.
Available from: URL: http://retroconference.org/2010 -
Thompson M, Lalezari J, Saag M, Jacobson J, Zingman B, Stambler N, et al. Weekly and biweekly subcutaneous PRO 140 demonstrates potent, sustained antiviral activity. 16th-CROI-2009 2009; abstr. 571a.
Available from: URL: http://www.retroconference.org -
Ketas TJ, Maddon PJ, Olson WC. Comparative susceptibility of HIV-1 and HIV-2 to the humanized CCR5 monoclonal antibody PRO 140. 47th-ICAAC-2007 2007;302.
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Progenics Presents Additional Positive Clinical Results for HIV-Entry Inhibitor PRO 140 at International AIDS Meeting.
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Saag MS, Jacobson JM, Thompson M, Fischl M, Liporace R, Reichman RC, et al. Antiviral effects and tolerability of the CCR5 monoclonal antibody PRO 140: a proof of concept study in HIV-infected individuals. 4th-IAS-2007-Late 2007;30-31 (plus oral presentation) abstr. WESS201.
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Ketas TJ, DiPippo VA, Lam E, Maddon PJ, Olson WC. PRO 140, a humanized CCR5 monoclonal antibody, is active against genotypically diverse and enfuvirtide-resistant strains of HIV-1. 4th-IAS-2007 2007;207.
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Murga JD, Franti M, Pevear DC, Maddon PJ, Olson WC. Potent antiviral synergy between monoclonal antibody and small-molecule CCR5 inhibitors of human immunodeficiency virus type 1. Antimicrob-Agents-Chemother 2006;50(10):3289-3296.
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Olson WC, Ketas TJ, Franti M, Kuhmann SE, Moore JP, Maddon PJ. The CCR5 mAb PRO 140 and small-molecule CCR5 antagonists possess complementary HIV-1 resistance profiles. 46th-Intersci-Conf-Antimicrobial-Agents-Chemother 2006;273.
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Progenics Reports Positive Results from Phase 1 Clinical Trial of PRO 140, a Novel Monoclonal Antibody That Blocks HIV Entry; Single Dose Coats Immune Cells for Two Months, Potential Long-Acting HIV Therapy.
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Olson W, Doshan H, ZHAN C, Mezzatesta J, Assumma A, Czarnecky R, et al. First-in-humans trial of PRO 140, a humanized CCR5 monoclonal antibody for HIV-1 therapy. 3rd-IAS-2005 2005;290.
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Franti M, Ramos L, Maloveste S, Geerdes D, Nagashima KA, et al. Control of HIV-1 replication in the hu-PBL-SCID mouse model by an anti-CCR5 monoclonal antibody. 11th-Conf-Retroviruses-Opportun-Infect 2004;[1 page] abstr. 537.
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Olson WC, Gardner JP, Ketas TJ, Sullivan BM, Rosenfield SI, et al. Inhibition of HIV-1 entry without receptor antagonism by the humanized anti-CCR5 antibody PRO 140. 42nd-ICAAC 2002;264.
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Franti M, Nagashima K, Maddon P, Burton DR, Olson W, et al. The CCR5 co-receptor inhibitor PRO 140 effectively controls established HIV-1 infection in vivo. 9th-Conf-Retroviruses-Opportun-infect 2002;abstr. 403-T.
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Olson WC, Franti M, Ketas TJ, Nagashima KA, Maddon PJ, et al. The HIV-1 entry inhibitor PRO 140 potently and durably suppresses viral replication in vitro and in vivo. 41st-ICAAC 2001;240.
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O'Hara BM, Franti M, Olson WC, Nagashima KA, Burton DR, et al. Potent in vivo suppression of HIV-1 replication with single-dose PRO 140, a novel inhibitor of CCR5-mediated viral entry. 14th-Int-Conf-Antiviral-Res-Late 2001;10.
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Olson WC, Ketas TJ, Nagashima KA, Zhao L, Maddon PJ, et al. Potent, broad-spectrum inhibition of HIV-1 by the CCR4 antibody PRO 140. 40th-ICAAC 2000;283 (plus poster).
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Progenics report on novel HIV inhibitor is published in the Journal of Virology - anti-CCR5 monoclonal antibody shown to potently and selectively inhibit HIV entry.
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Olson WC, Nagashima KA, Rosenfield S, Maddon PJ, et al. Potent, synergistic inhibition of HIV-1 by combinations of the viral entry inhibitors PRO 542 and T-20. 40th-ICAAC 2000;283 (plus poster).
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CytoDyn and Samsung BioLogics Formalize Manufacturing Partnership.
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Trkola A, Ketas TJ, Nagashima KA, Zhao L, Cilliers T, et al. Potent, broad-spectrum inhibition of human immunodeficiency virus type 1 by the CCR5 monoclonal antibody PRO 140. J-Virol 2001;75579-588.
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Uptick Newswire Hosts The President and CEO of CytoDyn Inc. to Discuss The Incredible Potential Breakthroughs The Company is Working Towards in HIV and Cancer Treatment.
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Progenics identifies novel HIV product and presents Pro 542 clinical results.
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CytoDyn Announces Plan to Develop PRO 140 for Metastatic Triple-Negative Breast Cancer as Initial Oncology Indication.
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