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Leronlimab - CytoDyn

Drug Profile

Leronlimab - CytoDyn

Alternative Names: PA-14; PRO-140; Vyrologix - CytoDyn

Latest Information Update: 03 Jun 2020

At a glance

  • Originator Progenics Pharmaceuticals
  • Developer CytoDyn; Progenics Pharmaceuticals
  • Class Antineoplastics; Antiretrovirals; Hepatoprotectants; Immunotherapies; Monoclonal antibodies
  • Mechanism of Action CCR5 receptor antagonists; Virus internalisation inhibitors
  • Orphan Drug Status

    Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.

    Yes - Graft-versus-host disease
  • New Molecular Entity Yes
  • Available For Licensing Yes

Highest Development Phases

  • Preregistration HIV infections
  • Phase III HIV-1 infections
  • Phase II/III COVID 2019 infections
  • Phase II Breast cancer; Graft-versus-host disease; Non-alcoholic steatohepatitis; Solid tumours

Most Recent Events

  • 01 Jun 2020 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)
  • 19 May 2020 CytoDyn in collaboration with Mexican National Institutes of Health plans a clinical trial for COVID-19 infections in Mexico
  • 15 May 2020 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

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) and cancer. 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. 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. The drug is under review in the US for HIV infections. Clinical development for breast cancer, solid tumours, HIV infections, HIV-1 infections, non-alcoholic steatohepatitis (NASH), COVID-2019 infections and graft versus host disease is underway in the US.

CytoDyn discontinued the development of intravenous formulation of lernolimab in HIV-1 infections in the US. No recent reports of development have been identified for preclinical development in prevention of HIV-1 infections in the US.

Leronlimab was originally discovered and developed by Progenics Pharmaceuticals 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] .

CytoDyn is actively seeking partnership for the development of leronlimab in China, France, Japan and the US [2] [3] .

Company Agreements

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. [4]

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. [5]

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. [6]

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. [7]

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. [8]

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 [9] .

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 [10] . In January 2006, Protein Design Labs changed its name to PDL BioPharma [11] .

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 [12] . In September 2005, ViroLogic changed its name to Monogram Biosciences [13] .

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

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) [14] .

COVID-2019 infections

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 COVID-19 patients in Mexico [15] .

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 [15] [16] .

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 [17] .

In May 2020, CytoDyn released the efficacy data from compassionate care treatment in critically ill patients with COVID-19 infections [18] .

In April 2020, CytoDyn initiated and first patient was enrolled in a phase IIb/III trial under the same granted emergency IND for the treatment of critically ill patients with COVID-2019 infections(NCT04347239; CD12_COVID-19) [19] . Patients enrolled in this trial are expected to be administered leronlimab for two weeks with the primary endpoint being the mortality rate at 14 days. The study intends to enrol approximately 390 patients in the US.The company had filed a second clinical trial protocol for leronlimab with the US FDA for COVID-19, earlier in April 2020, CytoDyn intends to enrol 75 patients rapidly and report results to the FDA [20] [21] [22] [23] [24] [25] .

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 [21] [26] [27] [23] [24] [28] [29] [30] [31] [32] [33] [34] [35] .

In March 2020, CytoDyn announced that the company will request a preliminary Breakthrough Therapy designation meeting based on the recommendations by the US FDA [36] .

Cancer

In February 2020, CytoDyn initiated the phase II basket trial of leronlimab for the treatment of approximately 22 different solid tumour cancers, including melanoma, brain-glioblastoma, throat, lung, stomach, colon carcinoma, breast, testicular, ovarian, uterine, pancreas, bladder, among other indications. The trial intends to enrol approximately 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 [37] . 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 intends to file for Breakthrough Therapy designation for all solid tumor cancers [38] [39] [40] [41] .

In January 2020, CytoDyn announced the filing of Breakthrough Therapy designation (BTD) with the US Food and Drug Administration (FDA) for the use of leronlimab as an adjuvant therapy for the treatment of metastatic triple-negative breast cancer (mTNBC). In August 2019, under emergency Investigational New Drug Application of the US FDA, first patient with metastatic triple-negative breast cancer was treated with leronlimab. The CytoDyn is potential to seek Breakthrough Therapy Designation and Accelerated approval with the US FDA for the use of leronlimab, based upon the results of phase II trial [42] [43] [44] .

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 [45] .

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 [46] [47] [48] [49] .

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 [46] [50] .

Earlier in January 2019, CytoDyn initiated a phase Ib/II trial of leronlimab for the treatment of patients with metastatic triple-negative breast cancer (CD07TNBC; NCT03838367). The open label trial intends to enrol 48 patients in the US. 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 [51] [46] [3] [52] [53] [54] . 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 [55] [43] . 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 [56] . In February 2020, updated interim efficacy data from the trial were released by CytoDyn [39] . 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 [36] .

Leronlimab binds to CCR5 in human breast cancer, blocks cytokines induced CCR5 signaling and human breast cancer cell invasion [57] .

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) [58] .

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 [59] .

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 [49] .

In August 2019, CytoDyn announced that leronlimab treatment in mice models suppressed growth of colon carcinoma in both low and high CCR5 expression tumours [60] . In August 2018, CytoDyn released the preclinical data for leronlimab in human colorectal cancer. Leronlimab was in preclinical development for colorectal cancer since 2017 [61] .

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 [62] [63] .

HIV infections

In June 2020, CytoDyn filed a request to the US FDA for a Priority Review designation for the BLA. In May 2020, CytoDyn completed the submission of rolling BLA by submitting updated clinical datasets to 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 from March 12 and March 20, 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] [64] [65] [16] [66] [67] [68] [69] . 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 700mg 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 [70] [68] [71] [72] .

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 [73] [74] . 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 [75] .

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 [76] .

CytoDyn, in October 2016, initiated a phase IIb/III study to evaluate the safety and efficacy of leronlimab SC maintenance therapy in virologically suppressed patients with CCR5-tropic HIV-1 infection (NCT02859961; PRO140CD03). The study is expected to enrol approximately 390 clinically stable subjects in the US, who will be shifted from suppressive combination antiretroviral therapy to leronlimabsingle agent maintenance therapy for 48 weeks. As of August 2017, more than 100 patients have been enrolled in the trial. In July 2018, CytoDyn announced that it had 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 will be 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 [77] [78] [79] [80] . In March 2019, CytoDyn presented the interim efficacy and safety results at the 26th Conference on Retroviruses and Opportunistic Infections (CROI-2019) [81] [82] . In August 2019, CytoDyn released updated efficacy results from the trial. As of October 2019, the phase III portion of the trial was initiated [83] [84] .

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) [85] [86] . The double-blind, randomised trial was initiated in June 2015 and enrolled 52 patients in the US and Puerto Rico [87] [88] [89] [90] [91] [92] [93] . 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 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 [94] [95] [87] [96] [97] [72] [98] [99] [100] .

In February 2015, CytoDyn reported that its first phase IIb trial achieved 98% success with 4 weeks of treatment with leronlimab. This US based 14 week trial evaluated the efficacy of once-weekly leronlimab monotherapy as treatment substitution for the maintenance of viral suppression in HIV patients (n=43) who were stable on combination HAART, but needed or wished to discontinue HAART therapy temporarily (NCT02175680). 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 [101] [102] [103] [104] . The company is 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 treatment with 350mg subcutaneously administered leronlimab weekly, as monotherapy, was generally well tolerated in HIV-1 infected patients with no treatment-related adverse events (AEs) or study discontinuations due to AEs. Out of 39 enrolled patients, 21 of them reached the trial endpoint of 14 weeks without virologic failure (two consecutive HIV-1 RNA levels of ≥400 copies/ml), and rest of the 18 patients had achieved re-suppressed viral load upon resuming their prior antiretroviral regimen. CytoDyn also reported that patients, who had successfully reached the trial endpoint, will continue to the extension study [105] [69] . 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). The trial intends to enrol 30 patients in the US [106] [100] [107] [92] [108] [109] .

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 [110] .

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 [90] [102] [111] .

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 [112] . 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 [113] .

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 [114] . 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) [115] . 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 [116] [117] .

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) [118] . The SC administration study was initiated in April 2008 (NCT00642707) [119] . 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 [120] [121] [122] [123] .

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 [124] .

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 [122] [125] [126] [127] [128] [129] .

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) [130] [131] . 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 [123] .

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 [132] .

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 USFDA granted orphan drug designation to leronlimab for the prevention of GvHD. The application for the orphan drug designation was filed in December 2015 [133] (CytoDyn, Form S-1, February 2016).

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 GVHD prophylaxis treatment, for prevention of acute GVHD in adult patients with AML or MDS undergoing allogeneic stem-cell transplantation (NCT02737306; 140CD03GVHD). The randomised, double-blind trial is 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 [134] [85] [135] . 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 [136] [137] . 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 [138] .

In the near future, CytoDyn expects to file the Breakthrough Therapy designation for the treatment of GvHD in patients requiring bone marrow transplants [134] .

Non-alcoholic Steatohepatitis (NASH)

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 [83] [139] .

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 [83] [140] .

Results from a preclinical study of leronlimab in the treatment of NASH were released by CytoDyn, in November 2019. [141] .

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 [142] .

Financing information

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 [143] .

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 [144] .

Patent Information

CytoDyn, in April 2020, received a notice of allowance from the United States Patent and Trademark Office (USPTO) for the Vyrologix mark [14] .

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, Hepatoprotectants, Immunotherapies, Monoclonal antibodies
  • 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)

    L01X-C (Monoclonal antibodies)

    L03 (Immunostimulants)

    R07 (Other Respiratory System Products)

  • EPhMRA code

    A5B (Hepatic Protectors, Lipotropics)

    J5C (HIV antivirals)

    L1G (Monoclonal Antibody Antineoplastics)

    L3 (Immunostimulating Agents)

    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

HIV infections

Exclusion

CD4

CCR5

1

1

HIV infections

Inclusion

CCR5

1

HIV infections

Outcome Measure

CD4

CCR5

1

1

HIV infections

Safety

CD4

CCR5

1

1

HIV-1 infections

Inclusion

CD4

2

HIV-1 infections

Outcome Measure

CD4

4

HIV-1 infections

Safety

CD4

4

Biomarker

Drug Name Biomarker Name Biomarker Function
Leronlimab - CytoDyn CCR5 Exclusion, Inclusion, Outcome Measure, Safety
CD4 Exclusion, Inclusion, Outcome Measure, Safety
For more detail, check out BiomarkerBase: the leading source of information about biomarkers used in drug development and diagnostic tests, tracking a comprehensive list of biomarker uses worldwide by over 800 companies

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Breast cancer triple-negative Combination therapy, Late-stage disease, Metastatic disease, Recurrent Phase II USA (fast track) SC / Injection CytoDyn 09 Sep 2019
COVID 2019 infections - - Phase II/III USA Parenteral / unspecified CytoDyn 13 Apr 2020
Graft-versus-host disease In adult patients with AML or MDS undergoing allogeneic stem-cell transplantation Prevention Phase II USA IV / unspecified CytoDyn 01 Nov 2016
HIV infections rolling BLA Combination therapy, Treatment-experienced Preregistration USA (fast track) IV / Infusion CytoDyn 18 Mar 2019
HIV infections - Prevention Preclinical USA IV / Infusion CytoDyn 27 Jan 2020
HIV-1 infections maintenance therapy Monotherapy, Treatment-experienced Phase III USA SC / Injection CytoDyn 01 Oct 2019
HIV-1 infections - Combination therapy, Treatment-experienced Phase II/III USA SC / Injection CytoDyn 12 Apr 2019
HIV-1 infections - - Discontinued (II) USA IV / Infusion Progenics Pharmaceuticals 11 Feb 2009
Non-alcoholic steatohepatitis - - Phase II USA Parenteral / unspecified CytoDyn 01 Oct 2019
Solid tumours - Late-stage disease, Metastatic disease Phase II USA SC / Injection CytoDyn 17 Feb 2020

Priority Development Status

Type Region Indication
Fast Track US Breast cancer; HIV infections

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
Vyera Pharmaceuticals 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
Cleveland Clinic Collaborator USA
Drexel University College of Medicine Collaborator USA
Thai Red Cross AIDS Research Centre Collaborator Thailand

Licensing Availability

Licensing Organisation Available Indication Available Phase Region Date
CytoDyn - Clinical Phase Unknown - 07 Jan 2019

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 [152] .

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 [130] [162] .

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 [103] . According to data from the related extension study, leronlimab monotherapy was well tolerated in all treated patients [106] .

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 [81] [80] .

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 [95] [87] [86] .

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 [121] .

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) [151] [106] [108] .

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 [114] [154] . These results were consistent with previously reported interim results [121] .

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 [125] .

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 [130] .

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 [126] .

Pharmacodynamics

Summary

Preclinical study in macaques demonstrated that the leronlimab prevented the intrarectal transmission of Simian-Human Immunodeficiency Virus (SHIV) [58] .

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 [61] .

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 [146] .

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 [141] .

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 [153] .

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 [151] [106] [108] .

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 [130] .

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 [162] . 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 [161] .

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 [156] .

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 [155] .

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 [174] .

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 [167] .

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 [165] .

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 [164] .

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 [163] .

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 [160] .

Leronlimab also exhibits potent and reproducible synergy in vitro with another HIV entry inhibitor, maraviroc [159] .

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 [169] .

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 [168] [172] .

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 [170] .

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 [166] .

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 [158] .

Therapeutic Trials

Phase Ib/II: 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 [39] [56] [43] [54]

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 [95] [87] [97] [86] .

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 [84] [81] [77] [80] [82] .

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 [92] . 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 [150] [100] [107] [93] [103] . Updated results indicated that some patients treated with leronlimab remained virally suppressed for more than four years [149] .

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 [120] [121] .

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 [151] [106] [108] .

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 [114] [154] . 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 [121] .

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 [26] [22] [35] .

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 [125] [157] [126] .

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 [156] .

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 [16] [21] [145] [35] .

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 [18] .

Future Events

Expected Date Event Type Description Updated
31 Dec 2020 Trial Update CytoDyn plans a pivotal phase III clinical trial for HIV-1 infections (Monotherapy) in 2020 (9266290) [148] 09 May 2019
31 Dec 2020 Regulatory Status CytoDyn expects to launch leronlimab in HIV infections by the fourth quarter of 2020 [143] 07 Apr 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 [16] 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 [24] 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 [40] 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 [43] 16 Jan 2020
31 Dec 2019 Trial Update CytoDyn plans a PrEP clinical trial for HIV infection in Thailand in 2020(700308578) [147] 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) [66] 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 [61] 21 Aug 2018

Development History

Event Date Update Type Comment
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) [64] Updated 03 Jun 2020
19 May 2020 Trial Update CytoDyn in collaboration with Mexican National Institutes of Health plans a clinical trial for COVID-19 infections in Mexico [15] 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 [17] 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) [65] Updated 17 May 2020
06 May 2020 Scientific Update Efficacy data from a compassionate trial in COVID-19 infections released by CytoDyn [18] 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) [16] 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) [16] Updated 06 May 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 [16] Updated 14 May 2020
27 Apr 2020 Patent Information CytoDyn receives patent allowance for vyrologix mark in USA [14] Updated 05 May 2020
13 Apr 2020 Phase Change - II/III Phase-II/III clinical trials in COVID-2019 infections in USA (Parenteral) [21] [22] Updated 07 Apr 2020
09 Apr 2020 Scientific Update Efficacy data from clinical trial in COVID-2019 infections released by CytoDyn [145] Updated 15 Apr 2020
02 Apr 2020 Scientific Update Efficacy data from phase II trial in COVID-2019 infections released by CytoDyn [22] [26] Updated 07 Apr 2020
01 Apr 2020 Regulatory Status CytoDyn files a second clinical trial protocol with the US FDA in USA for COVID-2019 infections [23] Updated 07 Apr 2020
01 Apr 2020 Trial Update CytoDyn plans a second clinical trial for COVID-2019 infections [23] Updated 07 Apr 2020
31 Mar 2020 Regulatory Status CytoDyn expects to launch leronlimab in HIV infections by the fourth quarter of 2020 [143] 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 [24] 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 [24] 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 [24] Updated 31 Mar 2020
19 Mar 2020 Phase Change - II Phase-II trials in COVID-2019 infections in USA (Parenteral) [29] 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 [29] 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 [30] Updated 19 Mar 2020
08 Mar 2020 Regulatory Status CytoDyn files an IND application with the US FDA for COVID 2019 infections [31] Updated 12 Mar 2020
08 Mar 2020 Trial Update CytoDyn plans a phase II trial for Respiratory distress syndrome due to COVID 2019 infections [31] 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 [38] 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) [39] [38] Updated 27 Feb 2020
14 Feb 2020 Regulatory Status CytoDyn intends to file the breakthrough therapy designation for Solid tumor with the US FDA [39] 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 [39] 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 [4] 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 [40] 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 [40] 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 [34] Updated 30 Jan 2020
27 Jan 2020 Phase Change - Preclinical Preclinical trials in HIV infections (Prevention) in USA (IV) [58] Updated 05 Feb 2020
27 Jan 2020 Scientific Update Pharmacodynamics data from a preclinical studies in Simian-Human Immunodeficiency Virus (SHIV)released by CytoDyn [58] Updated 29 Jan 2020
22 Jan 2020 Scientific Update Interim efficacy data from a phase Ib/II trial in Breast cancer released by CytoDyn [56] 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 [42] Updated 16 Jan 2020
17 Dec 2019 Licensing Status Leronlimab licensed to Vyera Pharmaceuticals for HIV infections for commercialisation and supply in USA [5] 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 [43] Updated 16 Jan 2020
03 Dec 2019 Scientific Update Early efficacy data from a phase Ib/II trial in Breast cancer released by CytoDyn [43] Updated 09 Dec 2019
21 Nov 2019 Scientific Update Pharmacodynamics data from a preclinical study in Non-alcoholic steatohepatitis released by CytoDyn [141] Updated 03 Dec 2019
19 Nov 2019 Scientific Update Pharmacodynamics data from a preclinical trial in Lung and Liver Cancer released by CytoDyn [146] 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 [45] Updated 14 Nov 2019
01 Oct 2019 Phase Change - II Phase-II clinical trials in Non-alcoholic steatohepatitis in USA (Parenteral) [83] Updated 09 Oct 2019
01 Oct 2019 Phase Change - III Phase-III clinical trials in HIV-1 infections (Monotherapy, Treatment-experienced) in USA (SC) [83] Updated 04 Oct 2019
01 Oct 2019 Regulatory Status The US FDA approves IND application for leronlimab in Non alcoholic steatohepatitis [83] Updated 04 Oct 2019
01 Oct 2019 Trial Update CytoDyn plans a phase II trial for Non-alcoholic steatohepatitis in USA [83] Updated 04 Oct 2019
09 Sep 2019 Phase Change - II Phase-II clinical trials in Breast cancer (Combination therapy, Metastatic disease, Late-stage disease, Recurrent) in USA (SC) [46] Updated 10 Sep 2019
09 Sep 2019 Regulatory Status The US FDA approves a phase II trial for Colorectal cancer (Metastatic disease, Combination therapy) [46] 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 [139] Updated 06 Sep 2019
14 Aug 2019 Scientific Update Efficacy data from a phase IIb/III trial in HIV-1 infections released by CytoDyn [84] 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 [50] Updated 13 Aug 2019
08 Aug 2019 Trial Update CytoDyn plans a phase II trial for Colorectal cancer (Metastatic disease, Combination therapy) [50] 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 [147] Updated 05 Feb 2020
30 Jul 2019 Licensing Status CytoDyn and IncellDX signs worldwide licensing agreement to sell non-commercial grade quantities of leronlimab [6] 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 [7] 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) [7] Updated 19 Jun 2019
07 Jun 2019 Trial Update CytoDyn plans a clinical trial for HIV-1 infections (Prevention) in Southeast Asia [73] 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 [74] Updated 21 May 2019
13 May 2019 Phase Change - Preclinical Preclinical trials in Non-alcoholic steatohepatitis in USA (Parenteral) [142] Updated 16 May 2019
13 May 2019 Trial Update CytoDyn plans a phase II trial for Non alcoholic steatohepatitis [142] Updated 16 May 2019
08 May 2019 Trial Update CytoDyn plans an expanded-access programme for Breast cancer [47] Updated 15 May 2019
07 May 2019 Regulatory Status Leronlimab receives Fast Track designation for Breast cancer (Parenteral) (Metastatic disease) in USA [48] 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 [82] (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 [66] Updated 28 Mar 2019
18 Mar 2019 Phase Change - Preregistration Preregistration for HIV infections (Combination therapy, Treatment-experienced) in USA (IV) [66] 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 [53] [66] 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 [59] 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) [81] Updated 03 May 2019
04 Mar 2019 Regulatory Status The US FDA grants rolling review for planned BLA for HIV infections [67] Updated 15 Mar 2019
22 Feb 2019 Regulatory Status Cytodyn applies for Orphan Drug status in triple-negative Breast cancer [49] 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 [3] Updated 11 Jan 2019
07 Jan 2019 Phase Change - I/II Phase-I/II clinical trials in Breast cancer (Combination therapy, Metastatic disease, Late-stage disease) in USA (SC) [3] (NCT03838367) Updated 11 Jan 2019
07 Jan 2019 Trial Update CytoDyn plans registration-directed trial for HIV-infections (Monotherapy) [3] Updated 11 Jan 2019
26 Nov 2018 Regulatory Status CytoDyn plans to file for breakthrough therapy designation and orphan drug designation for Breast cancer [52] Updated 28 Nov 2018
23 Nov 2018 Regulatory Status US FDA approves IND application for leronlimab in Breast cancer [52] Updated 28 Nov 2018
20 Nov 2018 Trial Update CytoDyn plans a pivotal phase III clinical trial for HIV-1 infections (Monotherapy) in 2020 [148] Updated 09 May 2019
19 Nov 2018 Scientific Update Updated efficacy data from a phase IIb trial in HIV infections (Monotherapy) released by CytoDyn [149] 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 [77] Updated 20 Nov 2018
05 Nov 2018 Regulatory Status CytoDyn expects to file for breakthrough therapy designation for Breast cancer [53] Updated 12 Nov 2018
05 Nov 2018 Regulatory Status CytoDyn files an IND application with the US FDA for Breast Cancer [53] 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 [61] Updated 21 Aug 2018
15 Aug 2018 Scientific Update Pharmacodynamics data from preclinical studies in Colorectal cancer released by CytoDyn [61] Updated 21 Aug 2018
14 Aug 2018 Trial Update CytoDyn plans a phase II clinical trial in Breast and Prostate cancer [150] [61] 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 [78] 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 [87] Updated 18 Jul 2018
16 Jul 2018 Trial Update CytoDyn plans to conduct phase II trials in Cancer [87] Updated 18 Jul 2018
16 Jul 2018 Trial Update CytoDyn completes the phase II/III CD02 trial in HIV infections in USA (SC) [87] (NCT02483078) Updated 18 Jul 2018
12 Jul 2018 Phase Change - Preclinical Preclinical trials in Prostate cancer in USA (Parenteral) before July 2018 [61] [62] Updated 21 Aug 2018
26 Jun 2018 Phase Change - Preclinical Preclinical trials in Breast cancer in USA (Parenteral) [63] Updated 03 Jul 2018
24 Jun 2018 Biomarker Update Biomarkers information updated Updated 31 Aug 2018
22 Jun 2018 Regulatory Status CytoDyn successfully conducts pre-BLA meeting with US FDA for HIV infections [71] 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 [138] 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) [95] Updated 19 Jul 2018
20 Feb 2018 Scientific Update Efficacy data from a phase IIb/III trial in HIV infections released by CytoDyn [97] Updated 23 Feb 2018
06 Oct 2017 Regulatory Status CytoDyn announces intention to submit BLA to US FDA for HIV infections (Combination therapy) [98] [99] [96] Updated 10 Oct 2017
05 Oct 2017 Regulatory Status PRO 140 receives Orphan Drug status for Graft-versus-host disease (Prevention) in USA [133] 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
15 Aug 2017 Phase Change - Preclinical Preclinical trials in Colorectal cancer in USA (Parenteral) [61] 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) [151] 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 (IV) (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 [106] 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 [134] 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 [100] Updated 23 Sep 2015
15 Jul 2015 Scientific Update Interim efficacy data from a phase IIb extension trial in HIV infections released by CytoDyn [107] Updated 17 Jul 2015
24 Jun 2015 Phase Change - Preclinical Preclinical trials in Graft-versus-host disease in USA (IV) [85] Updated 29 Jun 2015
09 Jun 2015 Regulatory Status The US FDA approves clinical trial protocol of phase III trial in HIV infections [90] 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 [91] Updated 09 May 2015
04 Feb 2015 Scientific Update Efficacy data from a phase IIb trial in HIV-1 infections released by CytoDyn [92] 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 [92] 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 [93] Updated 17 Oct 2014
14 Oct 2014 Scientific Update Efficacy data from a phase IIb trial in HIV-1 infections released by CytoDyn [93] 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 [103] 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 [111] 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 [112] 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 [9] 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) [152] , [153] 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) [114] , [154] 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) [121] 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 [125] and Viral Infections pharmacodynamics [155] and therapeutic trials [125] 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 [156] 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 [157] , [158] 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 [126] 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 [159] 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 [160] 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 [130] 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 [161] 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 [162] 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 [163] Updated 19 Feb 2004
11 Dec 2002 Scientific Update A preclinical study has been added to the Viral Infections pharmacodynamics section [164] Updated 11 Dec 2002
17 Jul 2002 Scientific Update An animal study has been added to the Viral Infections pharmacodynamics section [165] 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 [166] Updated 05 Feb 2002
24 Apr 2001 Scientific Update A preclinical study has been added to the Viral Infections pharmacodynamics section [167] 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 [168] Updated 16 Oct 2000
12 Oct 2000 Scientific Update A study has been added to the Viral Infections antimicrobial activity section [168] Updated 12 Oct 2000
09 Jul 1999 Scientific Update A study has been added to the Viral Infections antimicrobial activity section [169] 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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    Media Release
  2. CytoDyn to Deliver Presentation at Biotech Showcase Conference.

    Media Release
  3. CytoDyn Names Richard G. Pestell, M.D., Ph.D. as Vice Chairman of its Board of Directors.

    Media Release
  4. CytoDyn Signs Letter of Intent for the Joint Development and Licensing of Leronlimab in China with Longen China Group.

    Media Release
  5. CytoDyn Signs Definitive Agreements with Vyera Pharmaceuticals to Commercialize Leronlimab in the U.S. for the Treatment of HIV.

    Media Release
  6. CytoDyn Executes Exclusive Worldwide Licensing Agreement with IncellDX for PA-14 and PRO 140 for Diagnostic Testing Purposes.

    Media Release
  7. 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
  8. Samsung Biologics Signs CMO Deal with CytoDyn of the U.S.

    Media Release
  9. CytoDyn Announces Entry into Agreement with Progenics Pharmaceuticals, Inc. to Acquire PRO 140.

    Media Release
  10. 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
  11. Protein Design Labs Becomes PDL BioPharma.

    Media Release
  12. Progenics' HIV Entry Inhibitor, Pro 542, Continues to Provide Encouraging Phase II Results

    Media Release
  13. ViroLogic Changes Its Name to Monogram Biosciences.

    Media Release
  14. CytoDyn Announces Vyrologix as Proprietary Name for Leronlimab as a Combination Therapy for Highly Treatment Experienced HIV Patients in the United States.

    Media Release
  15. CytoDyn and the Mexican National Institutes of Health Participate in a Collaborative Study of Leronlimab for the Treatment of Severe/Critical COVID-19 Population.

    Media Release
  16. 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.

    Media Release
  17. CytoDyn to Prepare a Phase 3 Protocol to Submit to the FDA for a Three-Arm Comparative and Combination Trial of Leronlimab and Remdesivir.

    Media Release
  18. 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.

    Media Release
  19. First Patient Treated with Leronlimab in Phase 2b/3 Trial for COVID-19.

    Media Release
  20. Novant Health Initiates Phase 2b/3 Trial with CytoDyn's Leronlimab for Severely and Critically Ill COVID-19 Patients.

    Media Release
  21. 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.

    Media Release
  22. Treatment with CytoDyn's Leronlimab Indicates Significant Trend Toward Immunological Restoration in Severely Ill COVID-19 Patients.

    Media Release
  23. 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.

    Media Release
  24. 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.

    Media Release
  25. 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)

    ctiprofile
  26. 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.

    Media Release
  27. 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.

    Media Release
  28. Two Additional Coronavirus Patients Treated at Leading New York Hospital with CytoDyn's Leronlimab, Bringing the Total to Four Patients.

    Media Release
  29. U.S. Food and Drug Administration (FDA) Grants Emergency IND for Two Coronavirus Patients Treated in New York with CytoDyn's Leronlimab.

    Media Release
  30. CytoDyn Appoints Jacob Lalezari, M.D. as Interim Chief Medical Officer.

    Media Release
  31. CytoDyn Files IND and Protocol for Phase 2 Clinical Trial for Treatment of Patients with Coronavirus with Leronlimab (PRO 140).

    Media Release
  32. Three Additional Patients with Severe COVID-19 Treated with Leronlimab in New York Medical Center Bringing the Total to 10 Patients.

    Media Release
  33. 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.

    Media Release
  34. Leronlimab Under Evaluation for Potential Treatment of Coronavirus.

    Media Release
  35. 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)

    ctiprofile
  36. 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
  37. 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
  38. CytoDyn Receives Institutional Review Board Approval to Initiate Phase 2 Basket Trial for 22 Solid Tumor Cancers.

    Media Release
  39. 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
  40. CytoDyn Files a Phase 2 Basket Trial with Leronlimab (PRO 140) for Treatment of All Solid Tumor Cancers.

    Media Release
  41. 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
  42. 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
  43. CytoDyn Reports Early Results from First Patient in its Phase 1b/2 CCR5+ Metastatic Triple-Negative Breast Cancer Trial.

    Media Release
  44. Patient Treated with Leronlimab (PRO 140) for Metastatic Triple-Negative Breast Cancer under Emergency IND, Launching CytoDyn into Oncology.

    Media Release
  45. CytoDyn Receives IRB Approval To Proceed With Compassionate Use Of Leronlimab For Patients With Triple-Negative Breast Cancer.

    Media Release
  46. 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
  47. CytoDyn Provides Updated Pre-Clinical Data Showing Leronlimab (PRO 140) Continues to Suppress Breast Cancer Metastatic Burden >98% Compared with Untreated Animals.

    Media Release
  48. FDA Grants CytoDyn Fast Track Designation for Leronlimab (PRO 140) in metastatic Triple-Negative Breast Cancer, an Unmet Medical Need.

    Media Release
  49. Leronlimab (PRO 140) reduces by more than 98% human breast cancer metastasis in mouse xenografts for over 6 weeks.

    Media Release
  50. 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
  51. 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
  52. CytoDyn Announces Initiation of Metastatic Triple Negative Breast Cancer Trial and Reiterates Phase 3 Goal in Cancer.

    Media Release
  53. CytoDyn Files IND and Protocol for Phase 1b/2 Clinical Trial in Metastatic Triple-Negative Breast Cancer with PRO 140 (Leronlimab).

    Media Release
  54. A Phase Ib/II Study of Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC)

    ctiprofile
  55. 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
  56. Impressive Results Continue from CytoDyn's Clinical Trials Evaluating Two Patients with Leronlimab, One in mTNBC and One in MBC.

    Media Release
  57. CytoDyn Interim Chief Medical Officer Dr. Richard Pestell to Keynote 11th Annual Conference on Stem Cell and Regenerative Medicine.

    Media Release
  58. CytoDyn Announces CROI's Acceptance of Late-Breaking Abstract by Dr. Jonah Sacha for use of Leronlimab as PrEP.

    Media Release
  59. 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
  60. CytoDyn Sponsored Research Reaffirms the Role of CCR5 in Cancer Biology and Provides a New Potential Cancer Treatment Modality.

    Media Release
  61. CytoDyn Announces Strong Preclinical Results Using PRO 140 in Human Colon Carcinoma.

    Media Release
  62. CytoDyn to Expand Strategic Focus with PRO 140 to Cancer and Immunologic Disorders.

    Media Release
  63. New Research Supports Potential for CytoDyn's PRO 140 to Inhibit Breast Cancer Metastasis.

    Media Release
  64. CytoDyn Files Request With FDA for Priority Review of BLA for First Approval.

    Media Release
  65. CytoDyn Completed Submission of All Remaining Parts of Biologics License Application (##8220##BLA##8221##) on May 11, 2020.

    Media Release
  66. CytoDyn Reaches Historical Milestone, Submits First of Three Sections of BLA to FDA for Leronlimab (PRO 140) as a Combination Therapy for HIV.

    Media Release
  67. FDA Grants Rolling Review for CytoDyn's Planned BLA for Investigational HIV Therapy Leronlimab (PRO 140).

    Media Release
  68. CytoDyn Announces Productive Conference Call with FDA Regarding First BLA Submission for Leronlimab (PRO 140) Combination Therapy at 700 mg Dose.

    Media Release
  69. CytoDyn Injects First Patient in Its Current Phase 3 Study.

    Media Release
  70. 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.

    Media Release
  71. CytoDyn Announces Productive Pre-BLA Meeting with FDA for PRO 140 Combination Therapy.

    Media Release
  72. CytoDyn Provides Update on PRO 140 Combination Therapy Pivotal Trial in HIV Patients Following Constructive Meeting With FDA.

    Media Release
  73. CytoDyn and FDA Will Meet to Potentially Finalize Protocol for Pivotal Monotherapy Trial for Leronlimab.

    Media Release
  74. CytoDyn Files Pivotal Trial Protocol for HIV Monotherapy with FDA.

    Media Release
  75. CytoDyn Announces Strategy to Complete Development of Novel ProstaGene Gene-based Prostate Cancer Prognostic Test.

    Media Release
  76. A Multi-center, Two-Part, Single-Arm, Open Label, 25-Week Trial With PRO 140 in Treatment-Experienced HIV-1 Subjects

    ctiprofile
  77. CytoDyn's PRO 140 (leronlimab) HIV Monotherapy Trial Results Show 92% Responder's Rate at 700 mg Dose.

    Media Release
  78. CytoDyn Announces Significantly Improved Response Rate at Higher Dose of PRO 140 in HIV Phase 3 Monotherapy Trial.

    Media Release
  79. CytoDyn Provides Update on Enrollment in its Pivotal Phase 2b/3 HIV Combination Trial.

    Media Release
  80. 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

    ctiprofile
  81. 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
  82. CytoDyn's Monotherapy Trial with Leronlimab (PRO 140) Exceeds Expectations.

    Media Release
  83. CytoDyn Announces FDA Clearance to Proceed with Phase 2 Clinical Trial of Leronlimab (PRO 140) for Treatment of NASH.

    Media Release
  84. CytoDyn Provides Update on Dose Escalating Trial with Leronlimab for HIV Monotherapy for a Potential Pivotal Trial.

    Media Release
  85. CytoDyn to Expand Clinical Applications for PRO 140 Beyond Therapy for HIV.

    Media Release
  86. 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

    ctiprofile
  87. CytoDyn Announces Positive Results from Completed Pivotal PRO 140 HIV Combination Trial.

    Media Release
  88. Cytodyn Initiates First Clinical Site for Phase 3 Trial of PRO 140.

    Media Release
  89. CytoDyn Completes Qualification of PRO 140 Material for Phase 3.

    Media Release
  90. CytoDyn Cleared by FDA to Start Phase 3 of First Injectable Antibody for HIV.

    Media Release
  91. CytoDyn Submits Phase 3 Protocol to FDA After Agreement on Protocol Synopsis.

    Media Release
  92. CytoDyn Concludes Phase 2b Study With 98% Success With 4 Weeks of Monotherapy - Many HIV Patients in Extension Study With Some Approaching 6 Months.

    Media Release
  93. CytoDyn Announces 100% Success With PRO 140 in Four-Week Monotherapy Clinical Trial.

    Media Release
  94. Data from PRO 140 (leronlimab) HIV Monotherapy Trial Selected for Presentation at CROI 2019.

    Media Release
  95. 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
  96. CytoDyn Announces Presentation of Positive Efficacy Results from Pivotal PRO140 Combination Therapy Trial in HIV at ASM Microbe 2018.

    Media Release
  97. CytoDyn Reports Primary Endpoint Achieved in PRO 140 Pivotal Combination Therapy Trial in HIV Infection.

    Media Release
  98. CytoDyn Provides Update on PRO 140 Pivotal Combination Therapy Trial in Patients with HIV.

    Media Release
  99. CytoDyn Provides Further Update on PRO 140 Pivotal Combination Therapy Trial in Patients with HIV.

    Media Release
  100. HIV Patients Successfully Reach One Year of Virologic Suppression in PRO 140 Monotherapy Study.

    Media Release
  101. CytoDyn Inc. Announces First HIV Patient Dosing With PRO 140 in Phase 2b Clinical Trial for Treatment Substitution Protocol.

    Media Release
  102. CytoDyn Submits Protocol to FDA for Phase 2b Clinical Study of PRO 140 for Treatment Substitution in Patients with HIV.

    Media Release
  103. CytoDyn Announces Positive Interim Results From Its Treatment Substitution Study in Patients With HIV.

    Media Release
  104. 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

    ctiprofile
  105. Results of CytoDyn's PRO 140 CD01 Trial and Extension Study Published in HIV Clinical Trials.

    Media Release
  106. Eleven HIV Patients Successfully Reach One Year of Full Virologic Suppression in PRO 140 Monotherapy Phase 2b Extension Study.

    Media Release
  107. Evidence of HIV Suppression With PRO 140 Monotherapy Reaching Nearly 11 Months.

    Media Release
  108. 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 24 Weeks in Adult Subjects w/ HIV-1

    ctiprofile
  109. An Expanded Compassionate Access Protocol for a Single Subject Who Has Completed 24-Weeks of Treatment in PRO140_CD02 Study

    ctiprofile
  110. PRO 140 2103: A Phase 2a, Randomized Study of PRO 140 by Subcutaneous Injection in Adult Subjects With Human Immunodeficiency Virus Type 1 Infection

    ctiprofile
  111. 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.

    Media Release
  112. CytoDyn Announces Phase IIB Clinical Trial Agreement with Dr. Jeffrey Jacobson, Drexel University College of Medicine.

    Media Release
  113. 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.

    Media Release
  114. Progenics Selects Subcutaneous Form of PRO 140, a Novel HIV Antibody Therapy, for Further Development.

    Media Release
  115. 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

    ctiprofile
  116. CytoDyn Announces FDA Approval of Patient Screening for Phase 2b Study with Lead Product Candidate PRO 140 for the Treatment of HIV Type 1.

    Media Release
  117. CytoDyn Submits Phase IIb Protocol for PRO 140 Clinical Trial to FDA.

    Media Release
  118. 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

    ctiprofile
  119. 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

    ctiprofile
  120. 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
  121. Progenics Reports Positive Interim Phase 2 Results for Two Dosage Forms of Novel HIV Therapy PRO 140.

    Media Release
  122. Progenics Announces Progress and Presentations in HIV Therapy Program.

    Media Release
  123. Progenics Initiates Phase 2 Clinical Trials for PRO 140, a Novel HIV Antibody Therapy.

    Media Release
  124. 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

    ctiprofile
  125. 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.

  126. Progenics Announces Positive Results in Clinical Trial of Novel HIV Therapy.

    Media Release
  127. Progenics Pharmaceuticals Reports Fourth Quarter and Year End Results.

    Media Release
  128. Progenics Achieves Enrollment Target in Clinical Trial of HIV Entry Inhibitor PRO 140.

    Media Release
  129. 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

    ctiprofile
  130. 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
  131. 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

    ctiprofile
  132. Progenics Pharmaceuticals' HIV Drug, PRO 140, Receives FDA Fast-Track Designation.

    Media Release
  133. CytoDyn Receives Orphan Drug Designation for PRO 140 for Prevention of Graft Versus Host Disease.

    Media Release
  134. CytoDyn Files an IND and Full Protocol for Phase 2 Study in GvHD.

    Media Release
  135. 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

    ctiprofile
  136. CytoDyn Treats First Patient with Leronlimab in Phase 2 Trial for GvHD under Modified Trial Protocol.

    Media Release
  137. CytoDyn to Amend Protocol for PRO 140 Phase 2 Trial in GvHD.

    Media Release
  138. CytoDyn Provides Update on Phase 2 Clinical Trial with PRO 140 in GvHD.

    Media Release
  139. CytoDyn Files an IND and a Phase 2 Protocol with the FDA for the Treatment of NASH with Leronlimab.

    Media Release
  140. A phase II trial assessing leronlimab for the prevention of devastating liver fibrosis associated with non-alcoholic steatohepatitis(NASH)

    ctiprofile
  141. CytoDyn Reports Strong Positive Preclinical Data to Demonstrate Potential of Leronlimab in Treating Nonalcoholic Fatty Liver Disease (NAFLD) in Humanized Mouse Model.

    Media Release
  142. 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.

    Media Release
  143. CytoDyn Completes Non-dilutive $15 Million Convertible Note Financing with Conversion Rate at $4.50 Per Share without Warrants.

    Media Release
  144. CytoDyn Inc. Completes $14.5 Million Private Equity Offering.

    Media Release
  145. 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.

    Media Release
  146. CytoDyn's Lead Product Candidate Leronlimab (PRO 140) Inhibits Colon Carcinoma Metastases to Liver and Lung in Preclinical Studies.

    Media Release
  147. CytoDyn Granted Small Business Waiver of Application Fees by FDA for Leronlimab (PRO 140) BLA Filing.

    Media Release
  148. USAN Council Assigns Leronlimab as the Official Name for CytoDyn's PRO 140.

    Media Release
  149. CytoDyn Completes Acquisition of ProstaGene and Names Dr. Richard G. Pestell to Board of Directors.

    Media Release
  150. CytoDyn Appoints Michael A. Klump to Board of Directors.

    Media Release
  151. 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
  152. 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
  153. 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
  154. 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
  155. 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.

  156. Progenics Presents Additional Positive Clinical Results for HIV-Entry Inhibitor PRO 140 at International AIDS Meeting.

    Media Release
  157. 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.

  158. 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.

  159. 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.

    PubMed | CrossRef Fulltext
  160. 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.

  161. 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.

    Media Release
  162. 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.

  163. 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.

    Available from: URL: http://www.retroconference.org/2004
  164. 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.

  165. 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.

  166. 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.

  167. 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.

  168. 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).

  169. 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.

  170. 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).

  171. CytoDyn and Samsung BioLogics Formalize Manufacturing Partnership.

    Media Release
  172. 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.

    PubMed | CrossRef Fulltext
  173. 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.

    Media Release
  174. Progenics identifies novel HIV product and presents Pro 542 clinical results.

  175. CytoDyn Announces Plan to Develop PRO 140 for Metastatic Triple-Negative Breast Cancer as Initial Oncology Indication.

    Media Release
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