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Lenzilumab - Humanigen

Drug Profile

Lenzilumab - Humanigen

Alternative Names: Humaneered® anti-human GM-CSF monoclonal Antibody; KB-003

Latest Information Update: 30 Apr 2021

At a glance

  • Originator KaloBios Pharmaceuticals
  • Developer Humanigen; KaloBios Pharmaceuticals; Kite Pharma; National Institute of Allergy and Infectious Diseases; Peter MacCallum Cancer Centre
  • Class Anti-inflammatories; Antiallergics; Antiasthmatics; Antineoplastics; Antirheumatics; Immunotherapies; Monoclonal antibodies
  • Mechanism of Action Granulocyte macrophage colony stimulating factor antagonists
  • Orphan Drug Status

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

    No
  • New Molecular Entity Yes
  • Available For Licensing Yes - Asthma; COVID 2019 infections

Highest Development Phases

  • Phase III COVID 2019 infections; Cytokine release syndrome
  • Phase I/II B-cell lymphoma; Drug hypersensitivity
  • Preclinical Graft-versus-host disease; Precursor cell lymphoblastic leukaemia-lymphoma
  • No development reported Chronic myelomonocytic leukaemia; Solid tumours
  • Discontinued Asthma; Rheumatoid arthritis

Most Recent Events

  • 19 Apr 2021 Humanigen terminates its clinical collaboration with Kite Pharma related to phase I/II ZUMA-19 trial
  • 19 Apr 2021 Humanigen plans a protocol submission to US FDA for the approval of a phase II trial in patients with B-cell lymphoma (Combination therapy)
  • 19 Apr 2021 Efficacy and safety data from a phase I/II ZUMA-19 trial in B-cell lymphoma released by Humanigen

Development Overview

Introduction

Lenzilumab is a humaneered® antibody being developed by Humanigen (formerly KaloBios Pharmaceuticals) for the treatment of various types of cancers, COVID-2019 infections, COVID-19 pneumonia and drug hypersensitivity. Humaneered® technology uses bacterial expression systems to convert non-human antibodies (typically mouse) into high affinity humanised antibodies that are close to human germline in sequence. Lenzilumab is a selective antibody targeting circulating granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is the driver causing CCR2+ myeloid cells to traffic to the site of inflammation and initiating a self perpetuating inflammatory cascade within tissues, including in the central nervous system. By neutralising circulating GM-CSF, and upon demonstrating effects on neurotoxicity without affecting the efficacy of CAR-T, lenzilumab has the potential to make CAR-T therapy safer and more effective by allowing higher CAR-T doses, greater CAR-T expansion, and potentially reducing myeloid-derived suppressor cells (MDSC) that inhibit T cell function. Lenzilumab is designed for the prevention and treatment of an immune hyper-response called cytokine storm in COVID-2019 patients. Clinical development for drug hypersensitivity, B-cell lymphoma, COVID-19 pneumonia and COVID-2019 infections is underway in the US, Australia and Brazil. Preclinical development for acute graft-versus-host disease and acute lymphoblastic leukemia (precursor cell lymphoblastic leukaemia lymphoma) is underway in the UK and the US, respectively.

Phase I development in chronic myelomonocytic leukaemia was conducted in the US. Early research development in solid tumours was conducted in the US. As at October 2020, no recent reports of development were identified. Phase II development for the treatment of asthma and rheumatoid arthritis was discontinued previously because of programme refocus.

Lenzilumab shares the same epitope and pharmacokinetic properties as KB 002 [see AdisInsight drug profile 800021215], a chimeric mouse precursor and prototype drug candidate that was discontinued in favour of lenzilumab. KaloBios was leveraging data from the phase I/II clinical studies of KB 002 in patients with asthma for the development of lenzilumab.

In August 2017, KaloBios Pharmaceuticals changed its name to Humanigen [1] .

Humanigen is seeking for partnerships for lenzilumab in the US, Australia, and the EU, for eosinophilic asthma and coronavirus infections (Humanigen pipeline, June 2020) [2] .

Humanigen is seeking partnerships to distribute lenzilumab in other regions outside the United States [3] .

Company Agreements

In July 2004, KaloBios Pharmaceuticals in-licensed an antibody drug candidates for the treatment of autoimmune diseases from the Ludwig Institute for Cancer Research (LICR). The initial clinical trials of this antibody will be in patients with rheumatoid arthritis. KaloBios is responsible for using commercially reasonable efforts to research, develop, and sell lenzilumab. Company paid LICR a quarterly license fee and are obligated to pay to LICR a royalty from 1.5% to 3% of net sales of licensed products, subject to certain potential offsets and deductions. Royalty obligation applies on a country-by-country and licensed product-by-licensed product basis, and will begin on the first commercial sale of a licensed product in a given country and end on the later of the expiration of the last to expire patent covering a licensed product in a given country (which in the US is currently expected in 2029 for the composition of matter and 2038 for methods of use in CAR-T) or 10 years from first commercial sale of such licensed product in the country. In year 2006, KaloBios licensed the intellectual property rights of the ifabotuzumab prototype from the Ludwig Institute for Cancer Research (LICR). Under the terms of the agreement, KaloBios paid LICR an upfront fee of $US50 000 and a further fee of $US50 000, after obtaining the exclusive license to ifabotuzumab. LICR is entitled to receive milestone payments of approximately $US2.5 million and 3% royalties on net sales. LICR is obligated to obtain a percentage of the payments received by KaloBios, if the company exercises the option to sub-license ifabotuzumab. As per the license agreement with LICR pursuant to which LICR granted to us certain exclusive rights to the ifabotuzumab prototype (IIIA4) which targets EphA3 and EphA3-related intellectual property. Under the agreement, KaloBios obtained rights to develop and commercialise products made through use of licensed patents and any improvements thereto, including human antibodies that bind to or modulate EphA3. KaloBios royalty obligation exists on a country-by-country and licensed product-by-licensed product basis, which will begin on the first commercial sale and end on the later of the expiration of the last to expire patent covering such licensed product in such country, which in the US is currently expected in 2031, or 10 years from first commercial sale of such licensed product in such country [4] [5]

In April 2021, Humanigen terminated the clinical collaboration and announced that both parties will collaborate to wind down current study activities. Earlier in June 2019, Kite and Humanigen entered into a clinical collaboration to conduct a phase I/II study, to determine the effect of lenzilumab on the safety of axicabtagene ciloleucel in patients suffering with relapsed or refactory diffuse large B-cell lymphoma (DLBCL). Kite will both, conduct and sponsor the study. No other information was disclosed. [6] [7]

In February 2021, Humanigen Inc entered into a manufacturing services agreement with Avid Bioservices Inc to expand production capacity for lenzilumab, designed for the prevention and treatment of immune hyper-response called cytokine storm associated with COVID-2019 infections. Under the terms of the agreement, Avid will initiate technical transfer and analytical validation activities for Humanigen's lenzilumab under the current Good Manufacturing Practice (cGMP) drug substance batches to support the regulatory and potential commercial activities, and for potential filings for emergency use authorisation (EUA) and subsequent biologics license application (BLA) for the drug.
[8]

In January 2021, Ajinomoto Bio-Pharma Services and Humanigen expanded manufacturing agreement to support fill finish for investigational COVID-19 therapeutic, Lenzilumab. In May 2020, Ajinomoto Bio-Pharma Services and Humanigen entered into a manufacturing agreement for the fill finish supply of lenzilumab. [9] [10]

In January 2021, Humanigen announced an expansion to the Cooperative Research and Development Agreement (CRADA) that the company had previously entered into with the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), to gain access to manufacturing capacity reserved by the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the US Department of Health and Human Services. The agreement supports development of lenzilumab in advance of a potential Emergency Use Authorization (EUA) for COVID-19. The amended CRADA, now co-signed by BARDA, provides Humanigen with access to manufacturing capacity reserved by BARDA for fill-finish product to accelerate the drug product manufacturing of lenzilumab. The initial agreement, originally signed in November 2020, complements Humanigen’s development efforts for lenzilumab by providing access to a full-scale, integrated team of manufacturing and regulatory subject matter experts and statistical support in anticipation of applying for EUA and subsequently a Biologics License Application (BLA) for lenzilumab as a potential treatment for COVID-19. Earlier, in November 2020, Humanigen and the Department of Defense (DoD) JPEO-CBRND or JPEO entered into a CRADA in collaboration with BARDA, in support of Operation Warp Speed (OWS). The CRADA will provide access to OWS manufacturing and regulatory subject matter experts, leading decision makers and statistical support for Emergency Use Authorization (EUA) and subsequently a Biologics License Application for lenzilumab as a treatment for COVID-19. The CRADA also provides that OWS regulatory experts will work with the Humanigen on US FDA communications, meetings and regulatory filings. The CRADA aims to support the ongoing lenzilumab phase III clinical trials. Also, CRADA will ensure lenzilumab receives the benefits provided by Public Law 115-92 [11] [12]

In January 2021, Humanigen and EVERSANA-Life Science entered in an agreement for commercialisation of lenzilumab. According to the terms of the agreement, Humanigen will be granted access to the services of EVERSANA-Life Science, that are not limited to marketing, market access, medical education, health economics and outcomes research, medical information, compliance and medical science liaison teams and predictive analytics. [13]

In November 2020, Humanigen entered into a licensing agreement with Telcon RF Pharmaceutical (affiliate of KPM Tech) for development and commercialisation rights to lenzilumab for COVID-19 in South Korea and the Philippines. The licensing agreement includes payments of up to $US20 million with $US6 million as an upfront payment upon execution of the licensing agreement and the balance of $US14 million in two payments based on achievement of specified milestones in the US by Humanigen. Telcon and KPM Tech will be responsible for gaining regulatory approval and subsequent commercialisation of lenzilumab in its territories. Humanigen will earn double-digit royalties following receipt of those approvals on net sales subsequent to commercialisation. Further details were not disclosed. [14]

In September 2020, Humanigen entered into collaboration with Thermo Fisher Scientific for lenzilumab, currently in a phase III registration study in patients with COVID-19, to support a potential Emergency Use Authorization (EUA). Thermo Fisher will begin the technical transfer of the lenzilumab bulk drug substance process and commercial scale production could begin before the end of this year
[15]

In September 2020, Humanigen entered into a manufacturing agreement with Lonza to expand manufacturing of lenzilumab in advance of potential Emergency Use Authorization in 2020 and subsequent commercialisation. Under the agreement, Humanigen will leverage Lonza's monoclonal antibody manufacturing and regulatory expertise. The collaboration also provides Humanigen with additional capacity for cGMP production of the candidate with operations intended to start in 2021. Production of will begin at Lonza's 2,000L manufacturing facilities at Hayward (CA), USA and technology transfer is expected to begin in Q3 2020. Other financial details of the agreement were not disclosed. [16]

In July 2020, Humanigen entered into a research and development agreement with National Institute of Allergy and Infectious Diseases (NIAID) to evaluate lenzilumab in an NIAID-sponsored Big Effect Trial (BET) in hospitalised patients with COVID 2019 infections. As per agreement terms, BET will help advance NIAID’s strategic plan for COVID 2019 research, including studies to advance high-priority therapeutic candidates. Identification of agents with mechanisms of action for therapy is a strategic priority. [17]

In July 2020, Humanigen expanded previously signed supply agreement. Under the terms of expanded partnership, Catalent will provide development, manufacturing and commercialisation services for lenzilumab. Earlier, in May 2020, Humanigen entered into an agreement with Catalent for clinical supply support. Under the terms of agreement, Catalent will provide clinical supply support to Humanigen and its partners to accelerate the investigation of phase III study for lenzilumab in COVID patients from its Philadelphia facility. [18] [19]

In July 2019, Humanigen signed an exclusive worldwide licensing agreement with the University of Zurich (UZH), licensing from the latter, technology used to prevent graft versus host disease (GvHD), through GM-CSF neutralisation. The license provides coverage for multiple patent applications filed by UZH. [20]

In April 2018, Humanigen entered into a research agreement with the University of Texas M. D. Anderson Cancer Center to begin investigator-led research on lenzilumab and its potential to support chimeric antigen receptor T cell (CAR-T) therapy [21]

KaloBios was granted a non-exclusive licence to the Potelligent® technology of BioWa, which is used to enhance antibody-dependent cellular cytotoxicity (ADCC). The agreement was announced in October 2008. The technology is being used to improve the ADCC of select therapeutic antibodies of KaloBios. KaloBios will be able to research, develop and commercialise therapeutic antibodies by use of Potelligent® for an undisclosed number of targets. The application of Potelligent® reduces the quantity of fucose in the carbohydrate structure of an antibody, thereby improving ADCC. The mechanism behind the enhanced ADCC of a low/no-fucose antibody is its increased affinity to FcγRIIIa (CD16), the major Fc receptor for ADCC in humans. An upfront payment to BioWa by KaloBios was included in the agreement, along with development milestone payments and royalty payments to BioWa [22] .

Key Development Milestones

COVID-19 Infections and COVID-19 pneumonia

In March 2021, Humanigen announced intension to file Emergency Use Authorization (EUA) to the US FDA for lenzilumab in the treatment for hospitalized and hypoxic patients with COVID-2019 infections. Company have plans to begin the distribution of lenzilumab if the drug is approved under EUA [3] .

In March 2021, Humanigen announced that, plans to submit conditional approval Marketing Authorization Application (MAA) for lenzilumab in COVID-2019 infections to the European Medicines Agency for use in Europe and to the Medicines and Healthcare Products Regulatory Agency for use in the United Kingdom [3] .

In March 2021, Humanigen reported that, plans to submit Biologics License Application (BLA) for lenzilumab in COVID-2019 infections to the US FDA [3] .

As of November 2020, lenzilumab was part of Operation Warp Speed [11] .

In November 2020, Humanigen announced intention to apply for Emergency Use Authorization (EUA) for COVID-2019 pneumonia in the first quarter of 2021 [23] .

As of October 2020, Humanigen received written guidance from the US FDA following type B meeting to obtain feedback on Emergency Use Authorization of lenzilumab for the treatment ofCOVID-2019 pneumonia [24] .

Prior to October 2020, Humanigen received Emergency Use Authorization as single use IND (often referred to as compassionate use) for lenzilumab in the treatment of COVID-2019 pneumonia and associated acute respiratory distress syndrome in the US [25] .

A case control study was conducted to evaluate effects of lenzilumab in patients with COVID-2019 infections. A total of 39 patients were included, including 12 who received lenzilumab, and 27 who received standard of care treatment. Data from the study were released in September 2020 [26] .

In March 2021, Humanigen completed pivotal phase III trial in hospitalised patients with pneumonia associated with SARS-CoV-2 infection in COVID-19 patients (HGEN003-06; NCT04351152) [7] . The trial is designed to evaluate whether the use of lenzilumab in addition to current standard of care can alleviate the immune-mediated cytokine release syndrome and prevent progression to respiratory failure and/or death in high risk patients. The randomised, double blind, placebo-controlled trial initiated in May 2020 enrolled 520 patients in the US and Brazil. The trial enrolment was completed in January 2021 [27] [18] [28] . As of October 2020, Humanigen has received permission from US FDA, Brazilian regulatory agency and Mexican regulatory agency to initiate the trial [24] [29] [30] . Earlier in March 2020,Humanigen submitted an initial protocol synopsis to the US FDA for the same [31] [2] . In June 2020, Humanigen released clinical and safety data in 12 patients. In September 2020, the company reported that following a planned interim analysis that was conducted after 50% of the expected recovery threshold was reached, an independent Data and Safety Monitoring Board recommended continuation of the phase III study without any modifications [32] [33] [34] . In November 2020, interim analysis for sizing and powering suggests that lenzilumab had a clinically meaningful impact on patient recovery, the HR was calculated to be 1.37, with an approximately 37% more recoveries were observed in the lenzilumab arm. As per the recommendation of the DSMB, the company plans to increase enrollment to achieve 402 events (approximately 515 patients) to maintain the power of the trial at 90%. The next interim analysis for efficacy planned when the trial reaches 75% events (302 events) which will require approximately 390 patients to be enrolled in the trial [35] . As of January 2021, Humanigen is preparing for a potential COVID-19 Emergency Use Authorization (EUA) for lenzilumab [10] . In March 2021, updated efficacy and safety data from the trial were released by the Company [36] . In May 2021, Humanigen announced online publication of the results from the phase III study [37] .

In December 2020, Peter MacCallum Cancer Centre initiated the phase III C-SMART trial to evaluate prophylactic effect of interferon-alpha in cancer patients with no COVID-2019 infection or positive contact (arm 1), as post exposure prophylactic in cancer patients with confirmed exposure (arm 2), effect of selinexor [see ADIS Insight Drug profile800036503] for treatment of patients with moderate COVID-2019 infections (arm 3) and effect of lenzilumab for the treatment of cancer patients with severe COVID-2019 infections (arm 4) (NCT04534725; Peter Mac ID 20/135; ACTRN12620000844943). The sequential multiple assignment randomized, placebo-controlled trial intends to enrol approximately 2 282 participants in Australia [38] .

In March 2021, National Institute of Allergy and Infectious Diseases (NIAID),re-initiated enrolment in the phase II ACTIV-5 / Big Effect Trial (BET-B) trial of putative therapeutics for the treatment of COVID-19 infections. Earlier in February 2021, enrolment in the trial was suspended in the trial due to decision of Institutional Review Boars (IRB). The primary endpoint of the trial is to evaluate clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalised with COVID-19 according to clinical status (8-point ordinal scale) at day 8 (NCT04583969; 20-0013B). The double-blind, parallel, prospective, randomized trial was initiated in October 2020 and intends to recruit approximately 200 participants in the US [39] [40] .

B-cell lymphoma

As of April 2021, Humanigen intends to initiate a randomized, multicenter, potentially registrational, phase II clinical trial to evaluate the efficacy and safety of lenzilumab in combination with all commercially available CD19 CAR-T therapies in DLBCL. The study is estimated to enroll approximately 150 patients in the US. Humanigen also announced that the protocol is being submitted to the US FDA [7] .

In April 2020, Kite Pharmaceuticals and Humanigen initiated the phase I/II ZUMA-19 trial of lenzilumab and axicabtagene ciloleucel [see Adis Insight Drug profile 800039436], in patients with relapsed or refractory large B-cell Lymphoma (KT-US-471-0119; EudraCT 2019-004568-23; NCT04314843). The open label trial intends to enrol 36 patients in US. In July 2020, Humanigen announced that the first patient was infused in the trial [41] [29] [42] . In April 2021, Humanigen announced positive efficacy and safety data from the Ib part of the trial, and also announced the recommended phase II dose [7] .

Asthma

KaloBios Pharmaceuticals completed a 24-week proof-of-concept phase II efficacy and safety trial of lenzilumab in January 2014, in patients with moderate-to-severe asthma that is inadequately controlled with corticosteroids (KB003-04; NCT01603277). This randomised, double-blind, placebo-controlled study assessed the change in percent predicted FEV1 after 400mg single doses, which were intravenously administered every four weeks with one additional dose at week 2. Patient enrolment was completed ahead of schedule in June 2013. The trial enrolled 160 patients in the US, Australia, France, Poland, and the United Kingdom. Top-line data were announced in January 2014. The trial did not meet its primary clinical endpoint of improvement in FEV1 compared with placebo in the overall study participants. Based on these data, KaloBios decided to discontinue development of lenzilumab in severe asthma [43] [44] [45] [46] [47]

Chimeric antigen receptor T-cell

(CAR-T) neurotoxicity: Humanigen is conducting a phase Ib/II trial of lenzilumab for the prevention of CAR-T induced neurotoxicity (Humanigen pipeline, May 2018). The company believes that lenzilumab has the potential to make CAR-T therapy more effective by reducing neurotoxicity, allowing higher CAR-T doses, greater CAR-T expansion, and potentially reducing myeloid-derived suppressor cells (MDSC) that inhibit T-cell function [48] [49] .

Acute graft-versus-host disease

As of December 2020, Humanigen is in planning stage for initiation of phase II/III trial of lenzilumab in treat patients who have undergone allogeneic hematopoietic stem cell therapy who are at high and intermediate risk for acute GvHD. The trial is expected to be conducted by the IMPACT Partnership in the UK [5] .

Preclinical development is ongoing in the UK for acute GvHD.

Haematological malignancies

In February 2020, Humanigen completed a phase I trial that evaluated the safety, pharmacokinetics and efficacy of lenzilumab in previously-treated patients with chronic myelomonocytic leukaemia (CMML) (NCT02546284; HGEN003-05; KB003-05). The open label trial was initiated in July 2016, and enrolled 15 patients in the US. The trial was previously suspended in early November 2015 by the company further to its decision to wind down operations. The US FDA cleared the IND application for this trial in July 2015. In December 2019, Humanigen presented safety and efficacy data from the study at the 61st Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2019) [50] [21] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] .

In July 2017, KaloBios announced that it plans to submit an application for rare paediatric designation and orphan drug designation for lenzilumab in myeloid leukaemia (juvenile myelomonocytic leukaemia) [62] .

Humanigen intends to initiate a phase I trial of lenzilumab in juvenile myelomonocytic leukaemia (JMML). Data from the phase I/II trial in CMML will determine the feasibility of the trial in JMML [63] .

In November 2015, KaloBios reported preclinical results demonstrating the potential of lenzilumab to cause apoptosis in CMML cells by antagonising granulocyte macrophage colony stimulating factor [52] .

In preclinical studies, lenzilumab, along with CD19 targeted chimeric antigen receptor T-cell therapy (CART19), was shown to reduce neurotoxicity (NT) and cytokine release syndrome (CRS) and enhance CART19 proliferation and effector functions [64] ..

Rheumatoid arthritis

In September 2011, due to a programme refocus, KaloBios Pharmaceuticals terminated the phase II trial of intravenous lenzilumab in patients with rheumatoid arthritis who had an inadequate response to biologics (NCT00995449). Lenzilumab was dosed five times over 14 weeks, and the primary endpoint was ACR20 response. The randomised, double-blind, placebo-controlled, dose-ranging trial was to enrol 208 patients, but only recruited total of eight patients [65] .

Patient dosing in a phase I dose-escalation trial of lenzilumab was completed by KaloBios in April 2008. The placebo-controlled, single-dose study aimed to evaluate safety and immunogenicity of the agent among healthy volunteers [66] .

Solid tumours

Lenzilumab has the potential to reduce tumour viability and allow immune cell killing for the treatment of solid tumours, including prostate, renal, and breast cancer that express the functional receptor for granulocyte macrophage-colony stimulating factor (GM-CSF) (KaloBios website, November 2015).

Preclinical

In November 2018, Humanigen released final results from the xenograft study of lenzilumab which demonstrated that lenzilumab in combination with CAR-T cell therapy prevents cytokine release syndrome and neuro-inflammation and improved durable control of acute lymphoblastic leukemia [67] [68] .

Financing information

In April 2021, Humanigen completed its underwritten public offering of common stock, resulting in gross proceeds to Humanigen of approximately $US92.5 million. Humanigen intends to use the net proceeds from the offering for manufacturing and commercial preparation in the event of receipt of an Emergency Use Authorization from the Food and Drug Administration for lenzilumab™ in hospitalised COVID-19 patients, as well as for working capital and other general corporate purposes [69] [70] [71] .

In March 2021, Humanigen obtained a term loan facility from Hercules Capital of up to $US80 million of secured debt financing. The funds will be utilised to support the production of lenzilumab [72] .

In September 2020, Humanigen announced that it has completed its previously announced underwritten public offering of common stock. Humanigen raised net proceeds of approximately $US72.8 million from the sale of 9 200 000 shares in the offering. Humanigen intends to use the net proceeds from the offering to support its manufacturing, production and commercial preparation activities relating to lenzilumab as a potential therapy for COVID-19 patients and for general corporate purposes [73] .

In September 2020, Humanigen announced that it has commenced an underwritten public offering of 8,000,000 shares of common stock, that are expected to generate gross proceeds of approximately $US68 million. Humanigen also announced its intention to grant the underwriters a 30-day option to purchase up to an additional 1,200,000 shares. The company intends to use the net proceeds from the offering to support its manufacturing, production and commercial preparation activities of lenzilumab as a potential therapy for COVID-2019 infections and for general corporate purposes [74] [75] .

In December 2017, Humanigen reported that it will receive a $US3 million investment from an affiliate of Black Horse Capital to fund the further development of lenzilumab [48] .

In March 2017, KaloBios Pharmaceuticals received additional funding of approximately $US5.5 million from its existing investors, through an amendment to its term loan facility. The proceeds will used to support the ongoing development of lenzilumab for treatment of chronic myelomonocytic leukemia [76] .

In November 2015, KaloBios reported that the development of lenzilumab has been resumed after acquisition of 70% of its outstanding shares by an investor group. KaloBios will receive an equity investment of at least $US3 million plus a $US10 million equity financing facility from the group of investors, subject to applicable shareholder approval. The company has approximately $US5 million in cash as at November 2015 [52] [77] .

KaloBios completed a long-term debt financing deal worth up to $US15 million in September 2012. This deal followed the closing of Series E Preferred Stock financing, which raised $US20.25 million. The funds were to be used to support clinical development of the company's lead candidates, including phase II trials for lenzilumab [78] .

In September 2008, KaloBios raised $US20 million in the first closing of its Series D venture financing. In December 2008, the company raised an additional $US12 million in the second closing of its Series D financing. The funds, amongst other things, enabled the company to complete the current trials for lenzilumab and to prepare for phase IIb trials [79] [80] .

Patent Information

In February 2021, United States Patent and Trademark Office (USPTO) issued a patent titled "Method of reducing tumour relapse rate in immunotherapy by administration of lenzilumab" (Patent No US 10 927 168 B2). The patent covers the use of lenzilumab for reducing relapse rate or preventing occurrence of tumour relapse during immunotherapy, as well as treating or preventing immunotherapy-related toxicity associated with adoptive cell transfer, including chimeric antigen receptor-expressing T-cells (CAR-T cells), T-cell receptor (TCR) modified T-cells, tumour-infiltrating lymphocytes (TILs), chimeric antigen receptor (CAR)-modified natural killer cells, or combination thereof; administration of monoclonal antibodies; administration of cytokines; administration of a cancer vaccine; T-cell-engaging therapies; or any combination thereof [81] .

The United States Patent and Trademark Office (USPTO) in January 2021 issued a patent titled "Method of reducing the level of non-GM-CSF cytokines/chemokines in immunotherapy related toxicity" (Patent No. US 10 899 831 B2). The patent covers the use of lenzilumab for reducing relapse rate or preventing occurrence of tumour relapse during immunotherapy in the presence or absence of immunotherapy-related toxicity; reducing cytokine or chemokine levels other than GM-CSF during immunotherapy-related toxicity and treating or preventing immunotherapy-related toxicity associated with adoptive cell transfer, including chimeric antigen receptor-expressing T-cells (CAR T-cells), T-cell receptor (TCR) modified T-cells, tumour-infiltrating lymphocytes, chimeric antigen receptor (CAR)-modified natural killer cells, or combination thereof; administration of monoclonal antibodies; administration of cytokines; administration of a cancer vaccine; T-cell engaging therapies; or any combination thereof [81] .

In December 2020, Humanigen announced that the United States Patent and Trademark Office issued a patent titled “Methods of Treating Immunotherapy-Related Toxicity using a GM-CSF Antagonist,” (Patent No. 10,870,703). The patent covers the use of lenzilumab in prevention or treatment of cytokine storm and neurotoxicity in patients undergoing chimeric antigen receptor T (CAR-T) cell therapy [82]

According to KaloBios Pharmaceuticals form 10-K filed in March 2015, the company has developed and own a composition of matter patent covering lenzilumab and related Humaneered® anti-GM-CSF antibodies which provides patent protection through April 2029. The company have additional pending patents covering various methods of treatment in the US and a number of other countries.

Drug Properties & Chemical Synopsis

  • Route of administration IV, Parenteral
  • Formulation Infusion, unspecified
  • Class Anti-inflammatories, Antiallergics, Antiasthmatics, Antineoplastics, Antirheumatics, Immunotherapies, Monoclonal antibodies
  • Target Granulocyte macrophage colony stimulating factor
  • Mechanism of Action Granulocyte macrophage colony stimulating factor antagonists
  • WHO ATC code

    J05 (Antivirals for Systemic Use)

    L01X-C (Monoclonal antibodies)

    L04A-X (Other immunosuppressants)

    M01 (Antiinflammatory and Antirheumatic Products)

    R03 (Drugs for Obstructive Airway Diseases)

  • EPhMRA code

    J5 (Antivirals for Systemic Use)

    L1G (Monoclonal Antibody Antineoplastics)

    L4X (Other Immunosuppressants)

    M1 (Anti-Inflammatory and Anti-Rheumatic Products)

    M1A (Anti-Rheumatics, Non-Steroidal)

    R3 (Anti-Asthma and COPD Products)

  • Chemical name immunoglobulin G1-kappa, anti-[Homo sapiens CSF2 (colony stimulating factor 2 (granulocyte-macrophage), granulocyte macrophage colony stimulating factor, GM-CSF)], Homo sapiens monoclonal antibody
  • Molecular formula C6474 H10024 N1748 O2010 S42
  • CAS Registry Number 1229575-09-0

Development Status

Summary Table

Indication Qualifier Patient Segment Phase Countries Route / Formulation Developers Event Date
Asthma - - Discontinued (II) Australia, France, Poland, USA, United Kingdom IV / Infusion KaloBios Pharmaceuticals 29 Jan 2014
B-cell lymphoma - Combination therapy, Second-line therapy or greater Phase I/II USA IV / Infusion Humanigen, Kite Pharma 16 Apr 2020
COVID 2019 infections in patients with cancer - Phase III Australia IV / Infusion Humanigen, Peter MacCallum Cancer Centre 17 Dec 2020
COVID 2019 infections in combination with remdesivir; in hospitalised patients Combination therapy Phase II USA IV / Infusion National Institute of Allergy and Infectious Diseases 19 Oct 2020
Chronic myelomonocytic leukaemia - Second-line therapy or greater No development reported (I) USA IV / Infusion Humanigen 28 Oct 2020
Cytokine release syndrome Associated with COVID-19 infections associated with COVID-19 infection Combination therapy Phase III Brazil, USA IV / Infusion Humanigen 05 Oct 2020
Drug hypersensitivity CAR-T induced neurotoxicity Prevention Phase I/II Unknown IV / unspecified Humanigen 30 May 2018
Graft-versus-host disease - - Preclinical United Kingdom unspecified / unspecified Humanigen 01 Oct 2019
Precursor cell lymphoblastic leukaemia-lymphoma In combination with CART19 cell therapy Combination therapy Preclinical USA Parenteral / unspecified Humanigen 30 Nov 2018
Rheumatoid arthritis - - Discontinued (II) USA IV / unspecified KaloBios Pharmaceuticals 05 Feb 2013
Solid tumours - - No development reported (Research) USA Parenteral / unspecified Humanigen 28 Oct 2020

Commercial Information

Involved Organisations

Organisation Involvement Countries
KaloBios Pharmaceuticals Originator USA
Humanigen Owner USA
Telcon RF Pharmaceutical Licensee Philippines, South Korea
Ludwig Institute for Cancer Research Technology Provider USA
BioWa Technology Provider USA
University of Zurich Technology Provider Switzerland
Mayo Clinic Collaborator USA
H. Lee Moffitt Cancer Center and Research Institute Collaborator USA
EVERSANA Life Science Collaborator USA
National Institute of Allergy and Infectious Diseases Collaborator USA
Peter MacCallum Cancer Centre Collaborator Australia
University of Texas M. D. Anderson Cancer Center Collaborator USA
Biomedical Advanced Research and Development Authority Collaborator USA
Department of defence Collaborator USA

Licensing Availability

Licensing Organisation Available Indication Available Phase Region Date
Humanigen Asthma Phase III Australia, European Union, USA 01 Jun 2020
Humanigen COVID 2019 infections Unspecified - 09 Mar 2020

Scientific Summary

Adverse Events

B-cell lymphoma

Phase I/II:

Initial result from phase Ib part of the phase I/II ZUMA-19 trial showed that lenzilumab (in doses 600 mg and 1800 mg) in combination with CAR-T cell therapy (axicabtagene ciloleucel) was safe and no adverse events were reported throughout the study [7] [42] .

Lenzilumab was generally safe and well tolerated in a phase II trial in 160 patients with severe asthma (NCT01603277) [44] .

In phase I trial, lenzilumab was well-tolerated in patients (n = 15) with chronic myelomonocytic leukaemia. The safety profile was observed to be consistent with previous studies and no dose limiting toxicities as well as treatment emergent grade 3 or 4 toxicities were reported. Majority of patients discontinued the treatment due to lack of disease progression or lack of response (69%) [50] [61] .

COVID-19 infections

Phase III

Updated results from a phase III trial, lenzilumab appeared to be safe and well-tolerated. No new serious adverse events (SAEs) were identified, and none were attributed to lenzilumab. SAEs were balanced in both study arms and the SAE profile was similar to that previously documented in prior lenzilumab studies. Previous results from 12 patients showed no reported mortality. No treatment-emergent adverse events attributable to lenzilumab was observed and it was well-tolerated [36] [33] [27] .

In a case control study in 39 patients with COVID-2019 infections, treatment with lenzilumab was safe, with no treatment-related adverse events [26] .

Pharmacodynamics

Summary

In xenograft study of lenzilumab utilizing human acute lymphoblastic leukemia (ALL), human CD19 targeted CAR-T (CART19), and human peripheral blood mononuclear cells (PBMCs) in mouse, within 4-6 days after treatment with CART19, animals began to develop a syndrome characterized by motor weakness, hunched bodies, and progressive weight loss in a model which recapitulates symptoms consistent with cytokine release syndrome (CRS) and neuro-inflammation (NI). Administration of prophylactic lenzilumab to the CART19 therapy prevented physical symptoms of the syndrome. Prophylactic lenzilumab also resulted in a 75% reduction in NI by quantitative MRI and demonstrated exponential increase in T cell proliferation, enhanced anti-tumor activity, and improved overall survival. Neutralization of GM-CSF with lenzilumab resulted in a statistically significant reduction in ten other cytokines and chemokines supposed to be involved in development of CRS and NI. Lenzilumab in combination with CART19 therapy resulted in a significant improvement in leukemic disease control sustained over time for at least 35 days post CART19 administration as compared to CART19 plus isotype control [67] [68] .

In a case control study in 39 patients with COVID-2019 infections, treatment with lenzilumab significantly reduced c-reactive protein levels (p=0.01), and improved lymphocyte counts (p=0.04), versus the control group [26] .

Therapeutic Trials

B-cell lymphoma

Phase I/II:

Initial result from phase Ib part of the phase I/II ZUMA-19 trial showed that lenzilumab in combination with CAR-T cell therapy (axicabtagene ciloleucel) demonstrated 100% overall response rate (ORR), and dose-dependently reduced myeloid cytokines IL-6, IL-8, MCP-1, and IP-10 (CXCL-10) and systemic inflammatory markers CRP, ferritin, and SAA in patients (n=3), at the recommended phase II dose (1800 mg). The patients (n=3) in the first cohort (600 mg dose) did not showed 100% ORR, and the overall ORR of the study in patients (n=5) was 83%, with four complete responses (CR). In the second cohort (1800 mg), the toxicity-free CR (CRS and NT < grade 2) was 66% (n=2). No severe CRS or severe NT reported at this dose [7] [42] .

In phase I trial in 15 patients with chronic myelomonocytic leukaemia (CMML), durable clinical benefit was achieved by 33% of patients (5/15) three platelet responses, one neutrophil response, and one spleen response. Reduction in bone marrow myeloblast from 6% to 1% was observed in one additional patient which was bridged to allogeneic stem cell transplantation. The mean duration on therapy was 221.8 days (14-787 days). Statistically, the somatic mutations or changes in pSTAT5 between screening and cycle 3 were not associated with clinical response, however, three out of four patients with NRAS mutation achieved clinical benefit or had clinical meaningful bone marrow myeloblast reductions [50] [61] .

COVID-19 infections

Phase III

Updated results from a phase III trial in patients hospitalized with COVID-19 showed that, patients who received lenzilumab and other treatments, including steroids and/or remdesivir, had a 54% greater relative likelihood of survival without the need for invasive mechanical ventilation (IMV) compared with patients receiving placebo and other treatments. Study achieved its primary endpoint of ventilator-free survival measured through day 28 following treatment (HR: 1.54; 95%CI: 1.03-2.33, p = 0.0365). The Kaplan-Meier estimate for IMV and/or death was 15.6% (95%CI: 11.5-21.0) in the lenzilumab arm versus 22.1% (95%CI: 17.4-27.9) in the placebo arm, representing a 54% improvement in the relative likelihood of survival without the need for IMV. Although this study was not powered to demonstrate a difference in mortality, a favorable trend in mortality was observed, 9.6% (95%CI: 6.4-14.2) in the lenzilumab arm compared with 13.9% (95%CI: 10.1-19.0) in the placebo arm (HR: 1.39; 95%CI: 0.82-2.39; p = 0.2287). Approximately 88% of patients received dexamethasone (or other steroids), 62% received remdesivir, and 57% received both, balanced across both arms of the study. Previous results from 12 patients showed rapid clinical improvement with a median time to recovery of five days, median time to discharge of five days with 11 of them discharged from the hospital and 100% survival to the data cut-off date. Patients also demonstrated rapid improvement in oxygenation, temperature, inflammatory cytokines and key hematological parameters consistent with improved clinical outcomes [36] [33] [27] .

In a case control study in 39 patients with COVID-2019 infections, the relative risk of invasive mechanical ventilation and/or death reduced by 80% with lenzilumab, versus the control group who received standard of care treatment (8% versus 41%; p=0.07). Treatment with lenzilumab reduced the median time to resolution of acute respiratory distress syndrome to one day, versus eight days in the control group, with median time to discharge being 5 and 11 days in the lenzilumab and control arms, respectively (p=0.008) [26] .

Lenzilumab administered as an intravenous infusion at 400mg every four weeks did not provide a significant improvement in FEV1 compared with placebo (a primary endpoint) in the overall trial population in a phase II trial in severe asthma. A number of pre-specified subgroup analyses showed that treatment with lenzilumab was associated with a significant improvement in eosinophilic patients (blood eosinophils 0.3 GI/L at baseline) and patients with high reversibility at baseline (>20%) compared with placebo. There was no significant improvement in FEV1 from baseline as compared with placebo in other patient subgroups, including atopic or non-atopic patients. No significant improvement in exacerbations and in asthma control questionnaire (ACQ) scores were observed in patients treated with lenzilumab compared with placebo in the overall patient population (NCT01603277) [85] .

Future Events

Expected Date Event Type Description Updated
31 Dec 2021 Regulatory Status Humanigen plans to commercialise lenzilumab by 2021 [72] 15 Mar 2021
31 Dec 2021 Regulatory Status Humanigen announces intention to submit BLA to the US FDA for COVID-2019 infections in 2021 (9318006) [8] 12 Mar 2021
10 May 2021 Trial Update Humanigen plans the phase II PREACH-M trial for Chronic myelomonocytic leukaemia (Combination therapy, First-line therapy) in Australia, in May 2021 (ACTRN12621000223831p) (700330819) [83] 09 Mar 2021
31 Mar 2021 Regulatory Status Humanigen announces intention to apply for Emergency Use Authorization (EUA) for COVID-2019 pneumonia in the first quarter of 2021 [23] 26 Nov 2020
30 Oct 2020 Trial Update National Institute of Allergy and Infectious Diseases plans a phase II ACTIV-5/BET trial for COVID-2019 infections (Combination therapy) in USA (IV, Infusion) in October 2020 (NCT04583969) (700326271) 02 Nov 2020
01 Sep 2020 Trial Update Karyopharm Therapeutics and Peter MacCallum Cancer Centre plan the phase III C-SMART trial for COVID-2019 infections (Treatment and Prevention) in Australia (IV), in September 2020 (700327099), (ACTRN12620000844943) 29 Dec 2020
31 May 2020 Trial Update Humanigen plans a phase III trial for Cytokine release syndrome (Combination therapy) in USA in May 2020 (IV) (NCT04351152) (700320385) [29] 10 Mar 2021
31 Dec 2019 Trial Update Humanigen in collaboration with Kite plans the phase I/II ZUMA-19 trial for B-cell lymphoma (Second-line therapy or greater, refactory metastatic disease, combination therapy) in the fourth quarter of 2019 in USA [2] 21 Apr 2020
30 Jun 2018 Trial Update Humanigen plans a phase Ib/II trial for Drug hypersensitivity (CAR-T induced neurotoxicity) (Prevention) in the second quarter of 2018 (700291618) [84] 30 May 2018

Development History

Event Date Update Type Comment
19 Apr 2021 Licensing Status Humanigen terminates its clinical collaboration with Kite Pharma related to phase I/II ZUMA-19 trial [7] Updated 30 Apr 2021
19 Apr 2021 Regulatory Status Humanigen plans a protocol submission to US FDA for the approval of a phase II trial in patients with B-cell lymphoma (Combination therapy) [7] Updated 30 Apr 2021
19 Apr 2021 Scientific Update Efficacy and safety data from a phase I/II ZUMA-19 trial in B-cell lymphoma released by Humanigen [7] Updated 30 Apr 2021
31 Mar 2021 Trial Update Humanigen completes pivotal phase III trial in Cytokine release syndrome (associated with COVID-2019 infections) (Combination therapy, Prevention) in USA and Brazil (IV, Infusion) (NCT04351152) [7] Updated 30 Apr 2021
29 Mar 2021 Regulatory Status Humanigen announces intention to apply for Emergency Use Authorization (EUA) to US FDA for Cytokine release syndrome [36] Updated 31 Mar 2021
29 Mar 2021 Scientific Update Updated efficacy and adverse events data from a phase III trial in Cytokine release syndrome released by Humanigen [36] Updated 31 Mar 2021
10 Mar 2021 Regulatory Status Humanigen plans to commercialise lenzilumab by 2021 [72] Updated 15 Mar 2021
10 Mar 2021 Regulatory Status Humanigen announces intention to submit conditional Marketing Authorization Application to the Medicines and Healthcare Products Regulatory Agency, UK for COVID-2019 infections in 2021 [3] Updated 12 Mar 2021
10 Mar 2021 Regulatory Status Humanigen announces intention to submit conditional Marketing Authorization Application to the EMA for COVID-2019 infections in 2021 [3] Updated 12 Mar 2021
10 Mar 2021 Regulatory Status Humanigen announces intention to submit EUA to the US FDA for COVID-2019 infections in 2021 [3] Updated 12 Mar 2021
10 Mar 2021 Trial Update Humanigen plans clinical trials for Graft-versus-host-disease in 2021 [3] Updated 12 Mar 2021
10 Mar 2021 Trial Update Humanigen plans clinical trials for Chronic myelomonocytic leukaemia (IV) in 2021 [3] Updated 12 Mar 2021
03 Mar 2021 Trial Update National Institute of Allergy and Infectious Diseases re-initiates a phase II trial in COVID-2019 infections (Combination therapy) in USA (IV) (NCT04583969) Updated 08 Mar 2021
25 Feb 2021 Trial Update National Institute of Allergy and Infectious Diseases suspends a phase II trial in COVID-2019 infections (Combination therapy) in USA due to Institutional Review Board decision (IV) (NCT04583969) Updated 08 Mar 2021
23 Feb 2021 Patent Information Humanigen has patent protection for use of lenzilumab to improve the efficacy and durability of immunotherapy in USA [81] Updated 05 Mar 2021
03 Feb 2021 Regulatory Status Humanigen announces intention to submit BLA to the US FDA for COVID-2019 infections in 2021 [3] [8] Updated 12 Mar 2021
29 Jan 2021 Trial Update Humanigen completes enrolment in a phase III trial in Cytokine release syndrome (Combination therapy) in USA, Brazil (IV) (NCT04351152) [28] Updated 06 Feb 2021
26 Jan 2021 Patent Information Humanigen has patent protection for use of lenzilumab to reduce non-GM-CSF cytokines/chemokines that contribute to immunotherapy-related toxicity in USA [81] Updated 05 Mar 2021
22 Jan 2021 Company Involvement Humanigen establishes CRADA with Department of Defence and BARDA for the development of lenzilumab in COVID-2019 infections [12] Updated 27 Jan 2021
10 Jan 2021 Licensing Status Humanigen partners with EVERSANA Life-Science to support launch and commercialisation of lenzilumab for COVID-2019 infections [13] Updated 14 Jan 2021
31 Dec 2020 Trial Update Humanigen plans to initiate phase II/III trial in Graft-versus-host disease in United Kingdom [5] Updated 30 Apr 2021
22 Dec 2020 Patent Information Humanigen has patent protection for methods of treating immunotherapy related toxicity using a GM-CSF antagonist in the US [82] Updated 30 Dec 2020
17 Dec 2020 Phase Change - III Phase-III clinical trials in COVID-2019 infections in Australia (IV) (NCT04534725) Updated 29 Dec 2020
23 Nov 2020 Trial Update Humanigen plans the phase II PREACH-M trial for Chronic myelomonocytic leukaemia (Combination therapy, First-line therapy) in Australia, in May 2021 (ACTRN12621000223831p) [83] Updated 09 Mar 2021
11 Nov 2020 Regulatory Status Humanigen announces intention to apply for Emergency Use Authorization (EUA) for COVID-2019 pneumonia in the first quarter of 2021 [23] Updated 26 Nov 2020
06 Nov 2020 Company Involvement Humanigen establishes CRADA with Department of Defence for the development of lenzilumab in COVID-2019 infections [11] Updated 12 Nov 2020
06 Nov 2020 Regulatory Status Lenzilumab is part of Operation Warp Speed for COVID-2019 infections [11] Updated 12 Nov 2020
03 Nov 2020 Licensing Status Telcon RF Pharmaceutical in-licenses lenzilumab in South Korea, Philippines for COVID-2019 from Humanigen [14] Updated 06 Nov 2020
28 Oct 2020 Phase Change - No development reported No recent reports of development identified for phase-I development in Chronic-myelomonocytic-leukaemia(Second-line therapy or greater) in USA (IV, Infusion) Updated 28 Oct 2020
28 Oct 2020 Phase Change - No development reported No recent reports of development identified for research development in Solid-tumours in USA (Parenteral) Updated 28 Oct 2020
19 Oct 2020 Phase Change - II Phase-II clinical trials in COVID-2019 infections (Combination therapy) in USA (IV) (NCT04583969) [40] Updated 02 Nov 2020
12 Oct 2020 Trial Update National Institute of Allergy and Infectious Diseases plans a phase II ACTIV-5/BET trial for COVID-2019 infections (Combination therapy) in USA (IV, Infusion) in October 2020 (NCT04583969) Updated 02 Nov 2020
05 Oct 2020 Phase Change - III Phase-III clinical trials in Cytokine release syndrome (Combination therapy) in Brazil (IV) [24] Updated 06 Oct 2020
05 Oct 2020 Regulatory Status Humanigen intends to submit Biologics License Application to US FDA for the treatment of Pneumonia associated with COVID-19 infections [24] Updated 06 Oct 2020
05 Oct 2020 Regulatory Status Humanigen receives Emergency Use Authorization for single use IND for lenzilumab for COVID-2019 pneumonia (associated with acute respiratory distress syndrome) in USA, prior to October 2020 [25] Updated 06 Oct 2020
16 Sep 2020 Regulatory Status Humanigen announces intention to launch lenzilumab for Pneumonia (associated with COVID-2019 infection) [16] Updated 16 Sep 2020
01 Sep 2020 Scientific Update Efficacy, adverse events and pharmacodynamics data from a case control study in COVID-2019 infections released by Humanigen [26] Updated 03 Sep 2020
01 Sep 2020 Trial Update Humanigen completes a case control study in COVID-2019 infections [26] Updated 03 Sep 2020
31 Aug 2020 Trial Update Karyopharm Therapeutics and Peter MacCallum Cancer Centre plan the phase III C-SMART trial for COVID-2019 infections (Treatment and Prevention) in Australia (IV), in September 2020 , (ACTRN12620000844943) Updated 29 Dec 2020
30 Aug 2020 Trial Update Humanigen initiates a case control study in COVID-2019 infections, prior to August 2020 [26] Updated 03 Sep 2020
24 Aug 2020 Regulatory Status Humanigen announces intention to launch lenzilumab for COVID-19 infections Updated 26 Aug 2020
11 Aug 2020 Regulatory Status The Brazilian regulatory agency, Anvisa grants permission to commence a phase III trial of lenzilumab for COVID-19 infections in Brazil [30] Updated 12 Aug 2020
27 Jul 2020 Licensing Status Humanigen enters into a clinical trial collaboration with National Institute of Allergy and Infectious Diseases (NIAID) to advance COVID 2019 infections [17] Updated 29 Jul 2020
27 Jul 2020 Licensing Status Humanigen plans the clinical Big Effect Trial (BET) for COVID-2019 infections (Combination therapy) [17] Updated 29 Jul 2020
15 Jun 2020 Scientific Update Adverse events and efficacy data from a phase III trial in Pneumonia released by Humanigen [33] Updated 18 Jun 2020
01 Jun 2020 Licensing Status Lenzilumab is available for licensing in USA, Australia, European Union for eosinophilic Asthma as of 01 Jun 2020. https://www.humanigen.com/pipeline Updated 01 Jun 2020
27 May 2020 Licensing Status Ajinomoto Bio-Pharma Services and Humanigen enter into manufacturing agreement for lenzilumab [9] Updated 01 Jun 2020
30 Apr 2020 Phase Change - III Phase-III clinical trials in Cytokine release syndrome (Combination therapy) in USA (IV) (NCT04351152) Updated 13 May 2020
16 Apr 2020 Phase Change - I/II Phase-I/II clinical trials in B-cell lymphoma (Second-line therapy or greater, Combination therapy) in USA (IV) [29] Updated 20 Apr 2020
15 Apr 2020 Trial Update Humanigen plans a phase III trial for Cytokine release syndrome (Combination therapy) in USA in May 2020 (IV) (NCT04351152) [29] Updated 10 Mar 2021
15 Apr 2020 Regulatory Status Humanigen received US FDA approval to initiate phase III trial for Pneumonia associated with COVID-19 infections [29] Updated 28 Apr 2020
27 Mar 2020 Regulatory Status humanigen submits a phase III protocol synopsis to the US FDA for COVID-2019 infections [31] Updated 31 Mar 2020
27 Mar 2020 Trial Update Humanigen plans a phase III trial for COVID-2019 induced Acute respiratory distress syndrome (ARDS) in USA [31] Updated 31 Mar 2020
09 Mar 2020 Trial Update Humanigen in collaboration with Kite plans the phase I/II ZUMA-19 trial for B-cell lymphoma (Second-line therapy or greater, refactory metastatic disease, combination therapy) in the fourth quarter of 2019 in USA [2] Updated 21 Apr 2020
09 Mar 2020 Licensing Status Lenzilumab - Humanigen is available for licensing as of 09 Mar 2020. https://www.humanigen.com/ Updated 17 Mar 2020
29 Feb 2020 Trial Update Humanigen completes a phase I trial in Chronic myelomonocytic leukaemia (Second line therapy or greater) in USA (IV) (NCT02546284) Updated 16 Dec 2019
07 Dec 2019 Scientific Update Efficacy and adverse events data from a phase-I trial in Chronic myelomonocytic leukaemia presented at the 61st Annual Meeting and Exposition of the American Society of Hematology (ASH-Hem-2019) [50] Updated 17 Dec 2019
09 Oct 2019 Trial Update Humanigen plans a phase II trial for Graft versus host disease in United Kingdom Updated 15 Oct 2019
01 Oct 2019 Phase Change - Preclinical Preclinical trials in Graft-versus-host disease in United Kingdom (unspecified route), before October 2019 Updated 15 Oct 2019
22 Jul 2019 Licensing Status Humanigen in-licenses technology used to prevent graft versus host disease from University of Zurich Updated 15 Oct 2019
31 May 2019 Licensing Status Kite Pharma and Humanigen agree to conduct phase I/II clinical trial for lenzilumab and axicabtagene ciloleucel in USA for large B-cell lymphoma [6] Updated 10 Jun 2019
30 Nov 2018 Phase Change - Preclinical Preclinical trials in Precursor cell lymphoblastic leukaemia-lymphoma (Combination therapy) in USA (Parenteral) [67] Updated 26 Mar 2019
30 Nov 2018 Scientific Update Pharmacodynamics data from preclinical xenograft study released by Humanigen [67] [67] Updated 04 Dec 2018
30 Nov 2018 Trial Update Humanigen plans a phase I/II trial for of lenzilumab in combination with CART19 therapies [67] Updated 04 Dec 2018
12 Oct 2018 Active Status Review Lenzilumab is still in phase I trials for Chronic myelomonocytic leukaemia in USA (NCT02546284) Updated 12 Oct 2018
30 May 2018 Phase Change - I/II Phase-I/II clinical trials in Drug hypersensitivity (Prevention) (IV), prior to May 2018 (Humanigen pipeline, May 2018) Updated 30 May 2018
16 Apr 2018 Licensing Status Humanigen and the University of Texas M. D. Anderson Cancer Center agree to co-develop lenzilumab to support chimeric antigen receptor T cell therapy [21] Updated 19 Apr 2018
15 Mar 2018 Trial Update Humanigen completes enrolment in its phase I trial for Chronic myelomonocytic leukaemia [51] Updated 19 Mar 2018
27 Feb 2018 Trial Update Humanigen plans a phase Ib/II trial for Drug hypersensitivity (CAR-T induced neurotoxicity) (Prevention) in the second quarter of 2018 [84] Updated 30 May 2018
21 Dec 2017 Trial Update Humanigen plans a phase I clinical trial for Drug hypersensitivity (CAR-T induced neurotoxicity) (Prevention) [48] Updated 28 Dec 2017
07 Aug 2017 Company Involvement KaloBios Pharmaceuticals is now called Humanigen Updated 08 Aug 2017
27 Jul 2017 Regulatory Status KaloBios intends to apply for Orphan Drug status and Rare paediatric designation for Myeloid leukaemia (juvenile myelomonocytic leukaemia) [62] Updated 31 Jul 2017
29 Nov 2016 Trial Update KaloBios plans a phase I trial in Juvenile myelomonocytic leukaemia [63] Updated 01 Dec 2016
01 Jul 2016 Phase Change - I Phase-I clinical trials in Chronic myelomonocytic leukaemia (Second line therapy or greater) in USA (IV) (NCT02546284) Updated 11 Nov 2015
19 Nov 2015 Phase Change - I/II KaloBios resumes phase-I/II clinical trials in Chronic myelomonocytic leukaemia (Second line therapy or greater) in USA (IV) [52] Updated 26 Nov 2015
13 Nov 2015 Phase Change - Suspended(I) Suspended - Phase-I for Chronic myelomonocytic leukaemia (Second line therapy or greater) in USA (IV) (NCT02546284) Updated 17 Nov 2015
05 Sep 2015 Phase Change Early research in Solid tumours in USA (Parenteral) Updated 26 Nov 2015
29 Jul 2015 Regulatory Status The US FDA clears IND application for lenzilumab in Chronic myelomonocytic leukaemia [54] Updated 31 Jul 2015
22 Apr 2015 Trial Update KaloBios Pharmaceuticals plans a phase I trial for Chronic myelomonocytic leukaemia (NCT02546284) Updated 26 Apr 2015
16 Mar 2015 Patent Information KaloBios Pharmaceuticals has patent protection for lenzilumab and related Humaneered® anti-GM-CSF antibodies in USA Updated 15 Dec 2015
15 Sep 2014 Licensing Status KB 003 is available for licensing (http://www.kalobios.com) Updated 15 Sep 2014
29 Jan 2014 Trial Update KaloBios Pharmaceuticals completes a phase II trial in severe Asthma in the USA, Australia, France, Poland and the United Kingdom (9158859; NCT01603277) Updated 17 Feb 2014
29 Jan 2014 Phase Change - Discontinued(II) Discontinued - Phase-II for Asthma in Australia (IV) Updated 31 Jan 2014
29 Jan 2014 Phase Change - Discontinued(II) Discontinued - Phase-II for Asthma in France (IV) Updated 31 Jan 2014
29 Jan 2014 Phase Change - Discontinued(II) Discontinued - Phase-II for Asthma in Poland (IV) Updated 31 Jan 2014
29 Jan 2014 Phase Change - Discontinued(II) Discontinued - Phase-II for Asthma in United Kingdom (IV) Updated 31 Jan 2014
29 Jan 2014 Phase Change - Discontinued(II) Discontinued - Phase-II for Asthma in USA (IV) Updated 31 Jan 2014
29 Jan 2014 Scientific Update Top-line safety and efficacy data from a phase II trial in Asthma released by KaloBios [44] Updated 31 Jan 2014
27 Jun 2013 Trial Update KaloBios completes enrolment in a phase II trial in severe Asthma in USA, Europe and Australia (NCT01603277) Updated 03 Jul 2013
05 Feb 2013 Phase Change - Discontinued(II) Discontinued - Phase-II for Rheumatoid arthritis in USA (IV) Updated 05 Feb 2013
01 Jan 2013 Phase Change - Preclinical Preclinical trials in Haematological malignancies in USA (Parenteral) Updated 26 Nov 2015
11 Sep 2012 Phase Change - II Phase-II clinical trials in Asthma in Australia (IV) Updated 12 Sep 2012
04 Sep 2012 Phase Change - II Phase-II clinical trials in Asthma in France (IV) Updated 03 Jul 2013
04 Sep 2012 Phase Change - II Phase-II clinical trials in Asthma in Poland (IV) Updated 03 Jul 2013
04 Sep 2012 Phase Change - II Phase-II clinical trials in Asthma in United Kingdom (IV) Updated 12 Sep 2012
31 Jul 2012 Phase Change - II Phase-II clinical trials in Asthma in USA (Parenteral) Updated 27 Aug 2012
16 May 2012 Trial Update KaloBios Pharmaceuticals plans a phase II trial for Asthma in USA (NCT01603277) Updated 19 Jun 2012
30 Sep 2011 Trial Update KaloBios Pharmaceuticals terminates a phase II trial in Rheumatoid arthritis in USA (NCT00995449) Updated 12 Sep 2012
14 Feb 2011 Phase Change - I Phase-I clinical trials in Asthma in USA (IV) Updated 21 Jun 2012
14 Feb 2011 Phase Change - No development reported(I) No development reported - Phase-I for Inflammation in USA (Parenteral) Updated 14 Feb 2011
27 Jan 2011 Trial Update KaloBios Pharmaceuticals completes enrolment in its phase II trial for Rheumatoid arthritis in the US (NCT00995449) Updated 14 Feb 2011
04 Dec 2009 Phase Change - II Phase-II clinical trials in Rheumatoid arthritis in USA (IV) Updated 14 Feb 2011
28 Oct 2008 Company Involvement BioWa licenses its Potelligent® technology to KaloBios for improvement of antibody-dependent cellular cytotoxicity Updated 05 Nov 2008
29 Apr 2008 Phase Change - I Phase-I clinical trials in Inflammation in USA (Parenteral) Updated 30 Apr 2008
11 Mar 2008 Phase Change - Preclinical Preclinical trials in Inflammation in USA (Parenteral) Updated 11 Mar 2008
22 Jul 2004 Licensing Status KaloBios enters into licensing agreement with the Ludwig Institute for Cancer Research for lenzilumab [5] Updated 30 Apr 2021

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  48. Humanigen Signs Definitive Agreements to Exchange Loan Obligations for Equity.

    Media Release
  49. A Phase Ib/II trial of lenzilumab for the prevention of neurotoxicity associated with CAR-T19 therapy

    ctiprofile
  50. Patnaik MM, Sallman DA, Mangaonkar AA, Heuer R, Hirvela J, Zblewski D, et al. A Phase 1 Study of Lenzilumab, a humaneered recombinant Anti-Human Granulocyte-Macrophage Colony- Stimulating Factor (anti-hGM-CSF) Antibody, for Chronic Myelomonocytic Leukemia (CMML). ASH-Hem-2019 2019; abstr. 4234.

    Available from: URL: https://ash.confex.com/ash/2019/webprogram/Paper131181.html
  51. Humanigen Completes Enrollment of Phase 1 Clinical Trial of Lenzilumab for Treatment of Chronic Myelomonocytic Leukemia.

    Media Release
  52. KaloBios Pharmaceuticals, Inc. Appoints Martin Shkreli CEO and Announces New Financing.

    Media Release
  53. KaloBios Reports Second Quarter Financial Results and Provides Clinical Update.

    Media Release
  54. KaloBios Announces FDA Clearance of Investigational New Drug Application for KB003 in Patients with Chronic Myelomonocytic Leukemia.

    Media Release
  55. KaloBios to Present at the 14th Annual Needham Healthcare Conference.

    Media Release
  56. KaloBios Reports Top-Line Data for Phase 2 Study of KB001-A to Treat Pseudomonas Aeruginosa Lung Infections in Cystic Fibrosis Patients.

    Media Release
  57. KaloBios Announces Upcoming Scientific and Investor Conference Participation.

    Media Release
  58. KaloBios Reports Third Quarter Financial Results.

    Media Release
  59. KaloBios Announces Upcoming Participation at ROTH and BioCentury's Future Leaders in the Biotech Industry Conferences.

    Media Release
  60. KaloBios Announces Upcoming Investor Conference Participation.

    Media Release
  61. A Phase 1 Study of Lenzilumab in Subjects With Previously Treated Chronic Myelomonocytic Leukemia (CMML)

    ctiprofile
  62. KaloBios To Change Company Name To Humanigen, Inc.

    Media Release
  63. KaloBios to Present at JMML International Symposium.

    Media Release
  64. Humanigen Announces Positive Topline Study Results.

    Media Release
  65. A Phase 2, Randomized, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety and Efficacy of the Anti-GM-CSF Monoclonal Antibody KB003 in Subjects With Active Rheumatoid Arthritis and Inadequate Prior Treatment Outcome From Biologic Therapy

    ctiprofile
  66. KaloBios Completes Patient Dosing in its U.S. Phase 1 Trial of Its Third Drug Candidate, KB003.

    Media Release
  67. Lenzilumab Study Published in blood, the Official Journal of the American Society of Hematology (ASH), First Edition.

    Media Release
  68. Humanigen Data Presented at the 2019 National Comprehensive Cancer Network (NCCN) Annual Conference Demonstrates Potential to Improve the Efficacy of CAR-T Therapy.

    Media Release
  69. Humanigen Announces Pricing of Public Offering of Five Million Shares of Common Stock.

    Media Release
  70. Humanigen Announces Proposed Public Offering of Five Million Shares of Common Stock.

    Media Release
  71. Humanigen Announces Closing of Public Offering of Common Stock- 6 Apr 2021.

    Media Release
  72. Humanigen Announces $80 Million Loan Facility from Hercules Capital.

    Media Release
  73. Humanigen Announces Closing of Public Offering of Common Stock.

    Media Release
  74. Humanigen Announces Pricing of Public Offering of Common Stock and Commencement of Trading on Nasdaq Under the Symbol HGEN.

    Media Release
  75. Humanigen Announces Proposed Public Offering of Common Stock and Subsequent Listing on Nasdaq.

    Media Release
  76. KaloBios Receives $5.5M in New Financing From Existing Investors.

    Media Release
  77. KaloBios to Wind Down Operations.

    Media Release
  78. KaloBios Completes Debt Financing of Up to $15 Million

    Media Release
  79. KaloBios Raises Additional $12 Million in Series D Venture Financing for a New Total of $32 Million.

    Media Release
  80. KaloBios Raises $20 Million in Series D Venture Financing.

    Media Release
  81. Humanigen Expands its anti-GM-CSF Patent Portfolio.

    Media Release
  82. Humanigen Secures U.S. Patent for Lenzilumab in Preventing Cytokine Storm and Neurotoxicity Related to CAR-T Cell Therapy.

    Media Release
  83. Humanigen Australia Proprietary Limited Established to Facilitate Asia-Pacific Growth Plans.

    Media Release
  84. Humanigen Completes Exchange of Loan Obligations for Equity.

    Media Release
  85. Evotec AG: New Hormone to Treat Diabetes Published in "Cell".

    Media Release
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