- Improved survival demonstrated with GM-CSF knockout CAR-T
- GM-CSF knockout CAR-T results in altered gene transcriptome with decreased death receptors including Fas
- Presentation received an ASH Abstract Achievement Award
BURLINGAME, CA / ACCESSWIRE / December 11, 2019 / Humanigen, Inc., (OTCQB:HGEN) ("Humanigen"), a clinical stage biopharmaceutical company focused on the development of next generation chimeric antigen receptor T cell (CAR-T) and other cell therapies, presented results from the study of granulocyte-macrophage colony-stimulating factor (GM-CSF) gene knockout (k/o) CAR-T cells and GM-CSF neutralization with lenzilumab, the company's proprietary Humaneered® anti-human-GM-CSF monoclonal antibody, at the 2019 annual meeting of the American Society of Hematology (ASH).
The presentation, entitled "Improved Anti-Tumor Response of Chimeric Antigen Receptor T Cell (CART) Therapy after GM-CSF Inhibition Is Mechanistically Supported By a Novel Direct Interaction of GM-CSF with Activated CARTs" by Michelle Cox and colleagues was delivered on Monday, December 9, 2019.
Using a xenograft model for relapsed acute lymphoblastic leukemia (ALL), treatment with GM-CSF k/o CART19 resulted in improved overall survival compared to wildtype CART19. The lack of myeloid cells in this model pointed to an intrinsic effect of GM-CSF on CAR-T cells.
While resting CAR-T cells do not express GM-CSF receptors, the data demonstrate that activated CAR-T cells significantly upregulate GM-CSF receptors and signal through these receptors. GM-CSF k/o CAR-T cells show a distinct transcriptome signature that more closely resembles untransduced T cells than wildtype CAR-T cells based on principle component analysis. There also appeared to be significant inhibition of death receptor expression including the Fas death pathway receptor, a known critical pathway in inducing CAR-T cell death, with GM-CSF knockout CAR-T. This may also mean that CAR-T cells with GM-CSF k/o could be viewed as fitter T cells, which have been associated with improved durable efficacy. Collectively, these results illuminate a novel mechanism for a direct modulatory effect of GM-CSF on activated CAR-T cells that helps to explain the improved survival with GM-CSF neutralization or knockout.
The presentation received a 2019 ASH Abstract Achievement Award.
The abstract, entitled "Improved Anti-Tumor Response of Chimeric Antigen Receptor T Cell (CART) Therapy after GM-CSF Inhibition Is Mechanistically Supported By a Novel Direct Interaction of GM-CSF with Activated CARTs" can be accessed at: https://ash.confex.com/ash/2019/webprogram/Paper129349.html
"It is gratifying to receive recognition for the second year in succession that we have presented GM-CSF -related data for the pioneering work that we are conducting to make CAR-T therapy potentially more efficacious and safer through GM-CSF neutralization" stated Dr. Cameron Durrant, CEO of Humanigen. "We are looking forward to bringing lenzilumab into the clinic as we begin dosing patients in ZUMA-19 in 2020 with our partner, Kite Pharma".
About Humanigen, Inc.
Humanigen, Inc. is developing its portfolio of next-generation cell and gene therapies for the treatment of cancers via its novel, cutting-edge GM-CSF neutralization and gene-knockout platforms. There is a direct correlation between the efficacy of CAR-T therapy and the incidence of life-threatening toxicities (referred to as the efficacy/toxicity linkage). We believe that our GM-CSF neutralization and gene-editing platform technologies have the potential to reduce the inflammatory cascade associated with 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 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
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 future development of lenzilumab 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 operate our business as a going concern; 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.
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SOURCE: Humanigen, Inc.