Humanigen Planning Phase III Study of Coronavirus Treatment

March 20, 2020

Study to tackle leading cause of death in COVID-19 patients


  • Lenzilumab is a monoclonal antibody that neutralizes GM-CSF, a cytokine up-regulated in COVID-19 patients that can cause a harmful immune response
  • Clinical evidence suggests that this response contributes to cytokine storm caused by SARS-CoV-2 in COVID-19 patients with, or at risk of, developing acute respiratory distress syndrome
  • Lenzilumab has published evidence in the prevention of cytokine storm and is in a clinical study to prevent cytokine storm in the context of CAR-T cancer therapy with Kite Pharma (“Kite”), a Gilead company


Burlingame, CA, March 20, 2020 – Humanigen, Inc., (HGEN) (“Humanigen”), a clinical stage biopharmaceutical company focused on preventing and treating cytokine storm with lenzilumab, the company’s proprietary Humaneered® anti-human- granulocyte-macrophage colony stimulating factor(GM-CSF) monoclonal antibody, announced that the company is seeking to conduct a Phase III, randomized, controlled, clinical trial to rapidly advance the clinical development of lenzilumab for the prevention and treatment of cytokine storm which can lead to acute respiratory distress syndrome (ARDS) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in COVID-19.


Lenzilumab is a late clinical-stage, monoclonal antibody targeting GM-CSF, a pro-inflammatory cytokine up-regulated in the serum of COVID-19 patients1. The percentages of GM-CSF-expressing CD4+ T cells and CD8+ T cells are significantly higher in the blood of ICU-admitted COVID-19 patients compared with healthy controls and more pronounced in ICU-admitted COVID-19 patients versus non-ICU patients2.

In severe patients infected with COVID-19, published research suggests GM-CSF could be the key link between the ‘pulmonary syndrome-initiating capacity’ of pathogenic Th1 cells and the feedback loop of inflammatory monocytes – which in turn secrete additional GM-CSF and IL-62.


“Humanigen has pioneered the field of GM-CSF neutralization and, unlike others, has already conducted two Phase I and two Phase II studies, including in patients with severe respiratory conditions, with excellent safety results,” said Dr. Cameron Durrant, chief executive officer of Humanigen. “While other anti-GM-CSF antibodies have been primarily focused on arthritic and other inflammatory conditions, we have been working on prevention of cytokine storm for nearly three years and consider lenzilumab, which has been developed over more than a decade, with its published data in prevention of cytokine storm in animal models and the ongoing ZUMA-19 clinical study in collaboration with Kite, to be the leading anti-GM-CSF monoclonal antibody. Lenzilumab has an excellent safety and tolerability profile and has not been associated with serious adverse events, including in patients who are immunosuppressed or with severe asthma.

Further, we have filed extensive IP in GM-CSF neutralization across a wide range of areas, including COVID-19, over the course of many years,” he stated further.


Durrant continued, “We have been conducting work on targeting GM-CSF to prevent or treat cytokine storm in a number of conditions. It now appears that this is a key trigger in ARDS associated with COVID-19 and we look forward to continuing to lead in the area of GM-CSF neutralization in this setting.


While there has been use of, and investigational studies planned, which are focused on IL-6 neutralization, unfortunately these compounds are associated with increased rates of infection in pulmonary conditions, which in some cases is reflected in a Black Box Warning for these products.”


“We look forward to studying whether, with its excellent and proven safety and tolerability profile, lenzilumab may offer an alternative potential therapeutic solution in COVID-19 for already fragile, high-risk patients,” Durrant concluded.

Clinical trials of lenzilumab in patients with COVID-19 will commence upon approval by relevant regulatory authorities. In addition, the company is planning on making lenzilumab available on a compassionate use basis. Enquiries related to compassionate use in COVID-19 to help prevent and treat cytokine storm should be directed by email to Adrian Lo, alo@humanigen.com


1.  Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in

Wuhan, China. Lancet. 2020;395(10223):497-506. doi:10.1016/s0140-6736(20)30183-5.


2. Zhou Y, Fu B, Zheng X, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. Pre-Print. 2020. https://doi.org/10.1101/2020.02.12.945576.


About COVID-19-Induced ARDS


COVID-19 is an infectious disease caused by SARS-CoV-2. COVID-19 has become a global pandemic, with over 200,000 confirmed cases and over 8,000 deaths reported to date. Patients with severe cases of COVID-19 experience severe viral pneumonia that can progress to acute respiratory distress syndrome (ARDS) and death.

ARDS is an acute, life-threatening inflammatory lung injury characterized by hypoxia – a lack of oxygen to the tissue – and stiff lungs due to increased pulmonary vascular permeability. ARDS necessitates hospitalization and mechanical ventilation. A rapid increase in patients with ARDS presents a major challenge for the global public health system given limited hospital beds and ventilators. When implementing standard of care, including mechanical ventilation, ARDS has an overall mortality rate of greater than 40%.

About Humanigen, Inc.


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 as well as the serious and potentially life-threatening CAR-T therapy-related side effects while preserving and potentially improving the efficacy of the CAR-T therapy itself, thereby breaking the efficacy/toxicity linkage. The company’s immediate focus is to prevent or minimize the cytokine storm that precedes severe lung dysfunction and ARDS in serious cases of SARS-CoV-2 infection and also in combining FDA-approved and development stage CAR-T therapies with lenzilumab, the company’s proprietary Humaneered® anti-human-GM-CSF immunotherapy, which is its lead product candidate.  A clinical collaboration with Kite, a Gilead Company, was recently announced to evaluate the sequential use of lenzilumab with Yescarta®, axicabtagene ciloleucel, in a multicenter clinical trial in adults with relapsed or refractory large B-cell lymphoma.  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).  The company has established several partnerships with leading institutions to advance its innovative cell and gene therapy pipeline.  For more information, visit www.humanigen.com


Forward-Looking Statements


This release contains forward-looking statements. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct and you should be aware that actual events or results may differ materially from those contained in the forward-looking statements. Words such as "will," "expect," "intend," "plan," "potential," "possible," "goals," "accelerate," "continue," and similar expressions identify forward-looking statements, including, without limitation, statements regarding our expectations for a Phase III study and the future development of lenzilumab to minimize or reduce the severity of lung dysfunction associated with severe coronavirus infections or to help CAR-T reach its full potential or to deliver benefit in preventing GvHD. Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the risks inherent in Black Horse Capital and its affiliates owning more than 50% of our outstanding common stock, including their ability to control the company; our lack of profitability and need for additional capital to conduct the Phase III study and operate our business as a going concern; our dependence on partners to further the development of our product candidates; the uncertainties inherent in the development and launch of any new pharmaceutical product; the outcome of pending or future litigation; and the various risks and uncertainties described in the "Risk Factors" sections and elsewhere in the Company's periodic and other filings with the Securities and Exchange Commission.

All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You should not place undue reliance on any forward-looking statements, which speak only as of the date of this release. We undertake no obligation to revise or update any forward-looking statements made in this press release to reflect events or circumstances after the date hereof or to reflect new information or the occurrence of unanticipated events, except as required by law.


CONTACT:

Investors and media:

Al Palombo – 650-243-3181

ir@humanigen.com

Source: Humanigen, Inc.

Released March 20, 2020

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