First Patient Dosed in Phase 2 Precision Medicine Study of Lenzilumab in Patients with Chronic Myelomonocytic Leukemia (CMML)

• Earlier studies have shown the granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing effect of lenzilumab may benefit CMML patients with RAS pathway mutations
• Study is intended to build on evidence that certain CMML patients have mutations associated with hyper-proliferative features and may be sensitive to GM-CSF neutralization

BURLINGAME, Calif.--(BUSINESS WIRE)--Humanigen, Inc. (Nasdaq: HGEN) (“Humanigen”), today announced the first patient was dosed with lenzilumab in the Precision Approach to Chronic Myelomonocytic Leukemia (‘PREACH-M’) clinical trial being sponsored by the South Australian Health and Medical Research Institute (SAHMRI) and funded by a Medical Research Future Fund grant from the National Health and Medical Research Council of the Australian government to the University of Adelaide. Humanigen is providing lenzilumab for use in the study through its Australian subsidiary, Humanigen Australia Pty Ltd.

“The prognosis for CMML is poor, with median survival of 30 months, and it has remained essentially unchanged over the past 30 years,” said Associate Professor Daniel Thomas, the coordinating investigator for the trial and Associate Professor of Hematology at the University of Adelaide. “The overarching goal of the clinical trial is to improve response rates and survival. If we can improve response rates to 30%-50%, from the current 18% response rate normally seen in CMML patients treated with azacitidine, we think median survival may be increased to more than three years.”

The PREACH-M trial is designed to focus on Chronic Myelomonocytic Leukemia (CMML) patients who carry mutations believed to drive the leukemia. One arm of the study (n≈29) will focus on patients with RAS pathway mutations (KRAS, NRAS, or CBL) that appear to be associated with hyper-proliferative features and sensitivity to GM-CSF neutralization. These patients will be treated with high-dose azacitidine and lenzilumab, Humanigen’s proprietary GM-CSF neutralizing antibody. Results will be compared to historical trials of azacitidine alone and with the South Australian MDS Registry data.

“We have been encouraged by our prior Phase 1 results in CMML and are privileged to partner with SAHMRI and the University of Adelaide to further assess the potential of lenzilumab in this rare form of cancer for which there has been so little progress in treatment over the past 30 years,” said Dr. Cameron Durrant, CEO of Humanigen, Inc. “Following results from our Phase 3 LIVE-AIR study of lenzilumab in hospitalized patients with COVID-19 and the positive outcome of the Phase 1b portion of the ZUMA-19 study of lenzilumab in CAR-T, we are excited about the opportunity the PREACH-M study affords to validate our expectation that lenzilumab may offer potential benefits across multiple therapeutic indications.”

About PREACH-M

The study is a precision medicine approach to treating CMML. Investigators at 5 sites in Australia plan to enroll a total of 72 CMML patients with specific mutations. Patients with RAS pathway mutations such as KRAS, NRAS, or CBL, will be enrolled in the lenzilumab and azacitidine arm. Those who have the TET2 mutation will be enrolled in an arm of the study (n≈40) testing high-dose sodium ascorbate (vitamin C) and azacitidine. Those who have both TET2, and RAS pathway mutations will be allocated to the lenzilumab arm, unless they meet an exclusion criterion for the lenzilumab cohort. Those who do not have mutations in either category will be considered screening failures. However, these patients will still benefit from study because it includes free gene sequencing for all trial participants and gene sequencing is otherwise not a pathology test funded by Medicare, the Australian government funded universal health insurance system. With an incidence rate for CMML of just 0.3 per 100,000 Australians, SAHMRI, expects enrollment may take three years. The primary outcome will be the frequency of complete response (CR) and partial response (PR) at any point during the first 12 months of active therapy. Overall and progression-free survival will each be key secondary endpoints measured during the two-year period following initiation of treatment.

Those who would like to learn more about PREACH-M should refer to the ANZCTR website: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380941

“SAHMRI and South Australia enjoy several natural advantages when it comes to running clinical trials such as PREACH-M,” said SAHMRI Executive Director, Professor Steve Wesselingh. “Our size, geography, outstanding centralized public health system and cooperative population mean we have been remarkably resistant to COVID-19 outbreaks. South Australia also has a track record of success specific to phase III kinase inhibitor studies in patients with blood cancers, such as chronic myeloid leukaemia. It is exciting to be able to apply this expertise to CMML.”

Evidence of potential for lenzilumab in CMML

The PREACH-M trial was conceived, in part, based on evidence from earlier in-vitro, in-vivo and Phase 1 studies showing the GM-CSF neutralizing ability of lenzilumab and clinical benefits in CMML. An in-vitro study of bone marrow-mononuclear cells (BM-MNC) from 20 patients with CMML showed that patients with signaling mutations (KRAS, NRAS, or CBL) have greater sensitivity to GM-CSF and the level of hypersensitivity was an indicator of disease severity. The in-vitro results also correlated with reduced colony formation by BM-MNC, in a dose-dependent manner, and viability of CMML cells from patients with GM-CSF hypersensitivity.¹ A subsequent Phase 1 study of lenzilumab showed a clinical benefit in 33% of the 15 CMML patients dosed and those with an NRAS mutation showed a proportionally higher response (3 of 4). Those responses demonstrated greater clinical benefit and reduction in bone marrow blasts.²

About Humanigen, Inc.

Humanigen, Inc. (Nasdaq: HGEN) (“Humanigen”), is a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’. Lenzilumab is a first-in class antibody that binds to and neutralizes granulocyte-macrophage colony-stimulating factor (GM-CSF). Results of preclinical models indicate GM-CSF is an upstream regulator of many inflammatory cytokines and chemokines involved in the cytokine storm. Early in the COVID-19 pandemic, investigation showed high levels of GM-CSF secreting T cells were associated with disease severity and intensive care unit admission. Humanigen’s Phase 3 LIVE-AIR study suggests early intervention with lenzilumab may prevent consequences of a full-blown cytokine storm in hospitalized patients with COVID-19. Humanigen is developing lenzilumab as a treatment for cytokine storm associated with CD19-targeted CAR-T cell therapies and exploring the effectiveness of lenzilumab in other inflammatory conditions such as acute Graft versus Host Disease in patients undergoing allogeneic hematopoietic stem cell transplantation, eosinophilic asthma, and rheumatoid arthritis. Humanigen is also developing a portfolio of clinical and pre-clinical therapies for the treatment of inflammation and immuno-oncology. For more information, visit www.humanigen.com and follow Humanigen on LinkedIn, Twitter, and Facebook.

About SAHMRI

SAHMRI is South Australia’s flagship not-for-profit health and medical research institute. Located in Adelaide, South Australia, SAHMRI is home to around 700 researchers and collaborates broadly with local universities and the public health system to perform translational research to improve health outcomes.

Humanigen Forward-Looking Statements

All statements other than statements of historical facts contained in this press release are 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 investigators’ expectations for improvement in response rates and survival of CMML patients participating in the PREACH-M trial; our partner SAHMRI’s ability to enroll patients and complete the study on the timeline indicated; our beliefs regarding potential benefits of lenzilumab as a therapy for certain hospitalized patients with COVID-19; and our other plans to explore the effectiveness of lenzilumab and other candidates in our development portfolio as therapies for other indications.

Forward-looking statements are subject to a number of risks and uncertainties including, but not limited to, the risks inherent in our lack of profitability and need for additional capital to grow our business; our dependence on partners to further the development of our product candidates; the uncertainties inherent in the development, attainment of the requisite regulatory authorizations and approvals 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 of our latest annual and quarterly reports and other filings with the SEC.

All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You should not rely upon any forward-looking statements as predictions of future events. We undertake no obligation to revise or update any forward-looking statements made in this presentation to reflect events or circumstances after the date hereof, to reflect new information or the occurrence of unanticipated events, to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, in each case, except as required by law.

References

1. Padron, E., Painter, J. S., Kunigal, S., et al. (2013). GM-CSF–dependent PSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia. Blood, 121(25), 5068–5077. https://doi.org/10.1182/blood-2012-10-460170
2. Patnaik, M. M., Sallman, D. A., Mangaonkar, A. A., et al. (2019). 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). Blood, 134(Supplement_1), 4234–4234. https://doi.org/10.1182/blood-2019-131181

Ken Trbovich
Humanigen
trbo@humanigen.com
650-410-3206