Humanigen Expands its anti-GM-CSF Patent Portfolio

• First patent issued for the use of lenzilumab to reduce non-GM-CSF cytokines/chemokines that contribute to immunotherapy-related toxicity
• Second patent issued for the use of lenzilumab to improve the efficacy and durability of immunotherapy

BURLINGAME, Calif.--(BUSINESS WIRE)--Humanigen, Inc. (Nasdaq: HGEN) (“Humanigen”) a clinical stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab™, today announced the company has been awarded two patents by the United States Patent and Trademark Office (USPTO). These two patents expand Humanigen’s patent portfolio and demonstrate the value of the company’s pioneering approach to neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF).

“These two patents underscore the value of GM-CSF as a target in decreasing the levels of cytokines/chemokines that limit the efficacy of immunotherapy and contribute to immune-related toxicity in patients undergoing T-cell engaging therapies including CAR-T cell therapy. This also validates our approach to other disease areas where cytokine storm plays a critical role, including COVID-19 and acute graft-versus-host disease,” said Cameron Durrant, MD, MBA, Chief Executive Officer, Humanigen. “Through Humanigen’s Humaneered® technology, lenzilumab, a recombinant human GM-CSF antagonist, is now recognized as a unique and important tool for improving the efficacy of immunotherapy while reducing immune-related toxicity. Together, these patents continue to solidify Humanigen’s robust intellectual property portfolio which includes over 100 issued patents and over 50 patent applications.”

Lenzilumab binds to and neutralizes GM-CSF, which is a key initiator of the inflammatory cascade triggering immunotherapy-related toxicities, including cytokine storm (cytokine response syndrome, “CRS”) and neurotoxicity. These conditions are associated with prolonged hospitalization and intensive care unit stay.^1,2 The pro-inflammatory activities of GM-CSF are upstream of other pro-inflammatory cytokines and chemokines such as TNF, interleukin (IL)-6, and IL-23, among others, and can perpetuate a positive feedback loop which further elevates these inflammatory mediators.^3,4 We believe that neutralizing the activity of GM-CSF signaling reduces down-stream pro-inflammatory mediators and abrogates CRS, while improving T-cell function by reducing myeloid driven T-lymphocyte suppression.

The first patent, titled METHOD OF REDUCING THE LEVEL OF NON-GM-CSF CYTOKINES/CHEMOKINES IN IMMUNOTHERAPY-RELATED TOXICITY (US 10,899,831 B2), issued January 26, 2021, covers the use of a recombinant human GM-CSF antagonist (lenzilumab) for: a) reducing relapse rate or preventing occurrence of tumor relapse during immunotherapy in the presence or absence of immunotherapy-related toxicity; b) reducing cytokine or chemokine levels other than GM-CSF during immunotherapy-related toxicity; and c) 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, tumor-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.

The second patent, titled METHOD OF REDUCING TUMOR RELAPSE RATE IN IMMUNOTHERAPY BY ADMINISTRATION OF LENZILUMAB (US 10,927,168 B2), issued February 23, 2021, covers the use of lenzilumab for reducing relapse rate or preventing occurrence of tumor 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, tumor-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.

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. Humanigen believes that its GM-CSF neutralization and gene-editing platform technologies have the potential to reduce the inflammatory cascade associated with coronavirus infection. Humanigen’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. Humanigen 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, Humanigen 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. Humanigen 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. For more information, visit www.humanigen.com and follow Humanigen on LinkedIn, Twitter and Facebook.

Humanigen Forward-Looking Statements

This press release contains forward-looking statements. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although Humanigen 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 Humanigen’s beliefs relating to the technologies in Humanigen’s current pipeline. These forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the risks inherent in Humanigen’s lack of profitability and need for additional capital to grow Humanigen’s business; Humanigen’s dependence on partners to further the development of Humanigen’s product candidates; the uncertainties inherent in the development, attainment of the requisite regulatory approvals or authorization for emergency or broader patient use for the product candidate 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 Humanigen'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. Humanigen undertakes 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.

¹ Sterner RM, Sakemura R, Cox MJ, et al. GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts. Blood. 2019;133(7):697-709. doi:10.1182/blood-2018-10-881722

² Fitzgerald JC, Weiss SL, Maude SL, et al. Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell     Therapy for Acute Lymphoblastic Leukemia. Crit Care Med. 2017;45(2):e124-e131. doi:10.1097/CCM.0000000000002053

³ Hamilton JA. GM-CSF in inflammation. J Exp Med. 2020;217(1).

⁴ Zhou Y, Fu B, Zheng X, Wang D, Zhao C, qi Y, et al. Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients. Natl Sci Rev. 2020:nwaa041.

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