Humanigen Announces Cooperative Research and Development Agreement with the U.S. government to Develop Lenzilumab for COVID-19 - BiopharmaDirect

Humanigen Announces Cooperative Research and Development Agreement with the U.S. government to Develop Lenzilumab for COVID-19

November 6, 2020

• The Cooperative Research and Development Agreement (CRADA) with the Department of Defense (DoD) supports the development of lenzilumab as a potential treatment for patients with Covid-19
• Humanigen's development efforts complemented by full-scale, integrated team of federal leading experts dedicated to advancing lenzilumab ahead of a potential Emergency Use Authorization (EUA) submission

Burlingame, CA – Humanigen, Inc., (HGEN) ("Humanigen"), a clinical stage biopharmaceutical company focused on preventing and treating an immune hyper-response called a cytokine storm with its lead drug candidate lenzilumab^TM, today announced that the company and the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) have entered into a Cooperative Research and Development Agreement (CRADA) in collaboration with the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services, to help meet the federal government's Operation Warp Speed goals. The agreement supports development of lenzilumab in advance of a potential Emergency Use Authorization (EUA) for COVID-19.

"We are pleased to have dosed our first patient in an additional arm of our Phase 1b trial of Cami in solid tumors, which is intended to identify an appropriate dosing regimen for Cami in combination with pembrolizumab and detect signals of clinical activity in expansion cohorts using the identified dosing regimen," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "The preliminary pharmacokinetic and biomarker data from the Phase 1b trial that we presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, as well as a preclinical study recently published in the Journal for ImmunoTherapy of Cancer, support the evaluation of Cami in combination with other immune-modulating therapies. We look forward to the continued evaluation of our CD25-targeted ADC, as monotherapy and in combination with a checkpoint inhibitor, as a novel immuno-oncology approach for the treatment of solid tumor cancers."

Cami targets CD25, which is expressed on regulatory T cells (Tregs) that infiltrate the local tumor microenvironment. In preclinical models, a single dose of the CD25-targeted ADC induced strong and durable anti-tumor activity against established CD25-negative solid tumors with infiltrating Tregs both as monotherapy and in combination with a checkpoint inhibitor.

The ongoing, multicenter, open-label, dose-escalation and dose-expansion Phase 1b trial is evaluating the safety, tolerability, pharmacokinetics and antitumor activity of Cami as monotherapy or in combination with pembrolizumab in patients with selected advanced solid tumors. Approximately 95 patients will be enrolled in the trial. For more information about the Company's Phase 1b clinical trial of Cami in solid tumors, please visit www.clinicaltrials.gov (identifier NCT03621982).

Camidanlumab tesirine (Cami, formerly ADCT-301) is an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds to CD25 (HuMax^®-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once bound to a CD25-expressing cell, ADCT-301 is internalized into the cell where enzymes release the PBD-based warhead killing the cell. This applies to CD25-expressing tumor cells, and also to CD25-expressing Tregs. The intra-tumoral release of its PBD warhead may also cause bystander killing of neighboring tumor cells. PBDs have also been shown to induce immunogenic cell death. All of these properties of Cami may enhance immune-mediated anti-tumor activity. Cami is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (HL) and a Phase 1b clinical trial as monotherapy and in combination with pembrolizumab in solid tumors.

The CRADA complements Humanigen's development efforts, 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. The CRADA also provides that federal experts will work hand-in-hand with the company on U.S. Food and Drug Administration (FDA) communications, meetings and regulatory filings. The CRADA aims to support the ongoing lenzilumab Phase 3 clinical trials, focusing on efficiently generating EUA and BLA submissions. In addition to providing access under EUA, the CRADA allows for lenzliumab to possibly receive the benefits provided by Public Law 115-92.

Humanigen's investigational treatment lenzilumab, a proprietary Humaneered^® anti-human granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody, is designed to prevent and treat an immune hyper-response called a cytokine storm, a complication considered to be a leading cause of COVID-19 death. Data showed that up to 89 percent of hospitalized patients with COVID-19 are at risk of this immune hyper-response, which is believed to trigger the acute respiratory distress syndrome in severe cases of COVID-19.

Cameron Durrant, MD, MBA, chief executive officer of Humanigen said, "We are honored to be part of Operation Warp Speed, receive this CRADA, and collaborate with JPEO-CBRND to advance lenzilumab as a potential response treatment and seek a potential EUA. We have been working tirelessly to advance lenzilumab for COVID-19 and are excited to have the integrated expert team at OWS prioritize lenzilumab research and development during this critical time."

Lenzilumab was also selected by the National Institutes of Health (NIH) to be evaluated among the promising COVID-19 agents for its ACTIV-5 "Big Effect Trial" (ACTIV-5/BET) which will enroll patients at up to 40 sites in the U.S.

Humanigen, Inc. is developing its portfolio of clinical and pre-clinical therapies for the treatment of cancers and infectious diseases via its novel, cutting-edge GM-CSF neutralization and gene-knockout platforms. We believe that our GM-CSF neutralization and gene-editing platform technologies have the potential to reduce the inflammatory cascade associated with coronavirus infection. The company’s immediate focus is to prevent or minimize the cytokine release syndrome that precedes severe lung dysfunction and ARDS in serious cases of SARS-CoV-2 infection. The company is also focused on creating next-generation combinatory gene-edited CAR-T therapies using strategies to improve efficacy while employing GM-CSF gene knockout technologies to control toxicity. In addition, the company is developing its own portfolio of proprietary first-in-class EphA3-CAR-T for various solid cancers and EMR1-CAR-T for various eosinophilic disorders. The company is also exploring the effectiveness of its GM-CSF neutralization technologies (either through the use of lenzilumab as a neutralizing antibody or through GM-CSF gene knockout) in combination with other CAR-T, bispecific or natural killer (NK) T cell engaging immunotherapy treatments to break the efficacy/toxicity linkage, including to prevent and/or treat graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Additionally, Humanigen and Kite, a Gilead Company, are evaluating lenzilumab in combination with Yescarta^® (axicabtagene ciloleucel) in patients with relapsed or refractory large B-cell lymphoma in a clinical collaboration.

Source:www.humanigen.com