Humanigen - Lenzilumab Being Studied as a Potential First Treatment in Thirty Years with a Novel Mechanism of Action for Chronic Myelomonocytic Leukemia (CMML), an Orphan Form of Leukemia

• CMML is an aggressive, poorly understood cancer; approximately 20% of patients survive three years from diagnosis

• Eleven subjects dosed with lenzilumab and with current standard of care, azacitidine

• Six evaluable subjects, including those with high risk CMML, demonstrated clinical benefit at three months follow-up

• Lenzilumab appears to be well-tolerated

Short Hills, New Jersey and Adelaide, South Australia--(Newsfile Corp. - April 14, 2023) - Humanigen, Inc. (Nasdaq: HGEN), Humanigen Australia Pty Ltd, (Humanigen) and the South Australian Health and Medical Research Institute (SAHMRI) today presented (poster CT085/13); the design and baseline results of the Precision Approach to Chronic Myelomonocytic Leukemia (PREACH-M) study of lenzilumab in chronic myelomonocytic leukemia (CMML), at the 2023 annual meeting of the American Association of Cancer Research being held in Orlando, FL April 14-19. PREACH-M is currently treating 11 intermediate and high risk CMML subjects (five male, six female; mean age 68 years) with lenzilumab, a granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibody, and azacitidine, the current standard of care for CMML. As of December 31, 2022, six subjects were evaluable based on at least three months of follow-up and all demonstrated clinical benefit. Ten grade 3/4 Serious Adverse Events were observed, of which two were assessed by the investigator as possibly related to lenzilumab.

CMML remains a disease with high unmet medical need and there have been no new therapeutic agents with a novel mechanism of action for patients with high-risk CMML in the last 30 years.1 Treatment options for these patients are limited to blood transfusions, hydroxyurea and supportive care alongside the current standard of care, which includes hypomethylating agents such as azacytidine and decitabine with limited response rates of 7-18%2,3,4 and no proven increase in overall survival.

“GM-CSF is a cytokine that helps make white blood cells in the body and promotes myeloid cell development and maturation, playing a major role in the development of CMML.5 The clinical benefits of GM-CSF neutralization in life-threatening conditions such as CMML may be highlighted by these early results,” said Cameron Durrant, MD, MBA, Chairman and CEO, Humanigen. “PREACH-M has brought together experts from around the world and enabled Humanigen and its clinical partners to quickly obtain important data that may help us address a critical unmet need in oncology. We believe that the results observed to date have the potential to qualify lenzilumab for expedited regulatory pathways.”

“PREACH-M is enrolling intermediate and high risk CMML patients with TET2 and RAS pathway mutations who would ordinarily be treated only with azacitidine or another hypomethylating agent, the standard of care for the past thirty years. These patients have significant hematologic indices and constitutional symptoms of CMML,” said Associate Professor Daniel Thomas, principal investigator of the PREACH-M study and Program Leader for Blood Cancers at SAHMRI and Associate Professor of Medicine at the University of Adelaide. “The current early data from PREACH-M suggests promise in improving treatment response rates in CMML through GM-CSF neutralization with lenzilumab. Patients undergoing treatment in PREACH-M also appear to tolerate lenzilumab well.”

Treatment with lenzilumab and azacitidine led to rapid clinical response in all evaluable patients. Three high-risk patients, as defined by CMML-specific prognostic scoring system-Molecular (CPSS-Mol)6 achieved clinical benefits, as defined by the Savona criteria7 for myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Quality of life is also being measured.

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About CMML

CMML is an orphan disease with an approximate annual incidence of 1-4 cases per million9 in western countries and has limited therapeutic options. CMML is an aggressive and poorly understood cancer with only about 20% of patients surviving up to the three-year mark.10 The median overall survival for patients with CMML after diagnosis ranges from 12-29 months.9

The incidence of CMML in the US, UK, and Australia is about 1,700 patients annually.11 As an orphan disease, lenzilumab may qualify for certain regulatory and commercial advantages that could expedite development and potential approval. Humanigen and the Principal Investigator are assessing regulatory pathways that may enable early results to support a regulatory submission and potential approval by the Therapeutic Goods Administration in Australia, which could be expanded through Project Orbis12 to the United States and the United Kingdom (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis).

About the PREACH-M Trial

PREACH-M (PREcision Approach to CHronic Myelomonocytic Leukemia) is a Phase 2/3, non-randomized, open-label clinical trial investigating precision medicine for adults with CMML.13 This trial investigates treatment response rates determined by the Savona Criteria for patients with CMML after administration of lenzilumab alongside azacitidine in patients with RAS pathway mutations. The study also measures the patients’ quality of life, using the MPN Symptoms Assessment Form: Total Symptom Score.

Eleven of twenty-nine subjects were enrolled in the study as of December 31, 2022, of which eight were treated (five females, mean age of 67 years; three males, mean age of 69 years), and six were evaluable based on at least three months of follow-up.

During the active treatment phase of the study, participants are required to attend clinic visits on Days 1 & 15 of the first cycle, and then on Day 1 of each subsequent 28-day cycle to assess how the participant is tolerating the therapy and ensure ongoing safety.14 In addition to regular safety blood tests throughout each cycle, participants’ disease response assessments are scheduled after 3, 6, 12 and 24 cycles of therapy to measure their disease response.14 Such assessments include blood tests, bone marrow aspirate and trephine, ultrasound of the spleen, physical exam and assessment of transfusion requirements and clinical symptoms.14

Participants who complete 24 cycles of active treatment enter the follow-up phase of the study where they are followed up every 6 months for 24 months for survival, disease status and further CMML-related treatment.13 For patients with confirmed progressive disease or relapse during the active treatment phase of the study, further study treatment will cease. Patients remain on study and are followed up for disease status, survival and further CMML-related treatment every 6 months until 48 months from Cycle 1, Day 1.13 During the follow-up period, participants no longer receive any investigational drugs but are permitted to receive any CMML treatment at the discretion of the treating clinician.

As part of the screening process, participants are required to have a bone marrow aspirate and trephine to test for certain acquired mutations that can be present in CMML.13 The study is seeking participants with TET2 and/or RAS pathway mutations. Participants with RAS pathway mutations or both TET2 and RAS mutations, receive azacitidine (administered subcutaneously at a dose of 75mg/m2 on Days 1-5, 8-9 or Days 1-7 for a total of 7 doses per 28-day cycle) in combination with lenzilumab (administered intravenously at a dose of 552mg on Days 1 & 15 of Cycle 1. Day 1 only for all subsequent cycles).13

The trial is 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 provides lenzilumab for use in the study through its Australian subsidiary, Humanigen Australia Pty Ltd. Enrollment is open to newly diagnosed CMML patients who haven’t received any treatment.

Anyone who is interested in learning more about the study, or additional information can visit the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au).

About Humanigen

Humanigen, Inc. (Nasdaq: HGEN) (“Humanigen”) Source: Humanigen, is a clinical-stage biopharmaceutical company focused on developing lenzilumab, a first-in-class antibody that binds to and neutralizes granulocyte-macrophage colony-stimulating factor. Humanigen is developing lenzilumab as a treatment for chronic myelomonocytic leukemia. Humanigen is also exploring use of lenzilumab to prevent toxicities associated with CAR-T therapy through investigator-initiated trials. Humanigen is also developing an antibody drug conjugate (ADC) utilizing its EphA-3 targeted monoclonal antibody ifabotuzumab (“ifab”) for solid tumors. For more information, visit www.humanigen.com.

About Lenzilumab

Lenzilumab is a proprietary Humaneered® first-in-class monoclonal antibody that has been proven to neutralize GM-CSF with high specificity and affinity to prevent signaling through its receptor. GM-CSF along with RAS pathway mutations play key roles in CMML and other cancers, including juvenile myelomonocytic leukemia (JMML), myelodysplastic syndromes, myeloproliferative neoplasms, and acute myeloid leukemia.15,16,17 GM-CSF is also of critical importance in the hyperinflammatory cascade, sometimes referred to as cytokine release syndrome, or cytokine storm, associated with COVID-19 and common to chimeric antigen receptor T-cell (CAR-T) therapy, acute Graft versus Host Disease (aGvHD) and other indications.

About SAHMRI

SAHMRI is South Australia’s flagship independent not-for-profit health and medical research institute. The Precision Cancer Medicine Theme is committed to understanding the factors that determine patient-specific responses to disease or therapeutic intervention, enabling us to better predict patient outcomes, to stratify patients to the best treatment options and to develop more personalized, targeted interventions.

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.

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; 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 or arbitration; 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 press release to reflect events or circumstances after the date hereof, to reflect new information or the occurrence of unanticipated events, or 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.

Humanigen Investor Relations Contact

Ed Jordan
Chief Commercial Officer
IR@humanigen.com
650-243-3181

Humanigen Media Relations Contact

Charlotte Wray
cwray@rxmedyn.com
646-247-3405

References

1. Aim of first-ever CMML study - to improve survival. Leukaemia Foundation. (2023, January 3). Retrieved January 3, 2023, from https://www.leukaemia.org.au/stories/aim-of-first-ever-cmml-study-to-improve-survival/
2. Costa, R., et. al. (2010). Activity of azacitidine in chronic myelomonocytic leukemia. Cancer, 117(12), 2690-2696. https://doi.org/10.1002/cncr.25759.
3. South Australian Registry data, South Australian Health and Medical Research Institute, April 14, 2021
4. Pleyer, L., et. al. (2014). Azacitidine in CMML: Matched-pair analyses of daily-life patients reveal modest effects on clinical course and survival. Leukemia Research, 38(4), 475-483. https://doi.org/10.1016/j.leukres.2014.01.006
5. Egea, L., Hirata, Y., & Kagnoff, M. F. (2010). GM-CSF: a role in immune and inflammatory reactions in the intestine. Expert review of gastroenterology & hepatology, 4(6), 723-731.
6. Elena C, Galli A, Such E, et al. (2016) Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood.128(10):1408-1417
7. Savona, et al. (2015) An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. BLOOD.125: 1857. https://doi: 10.1182/blood-2014-10-607341.
8. Myeloproliferative Neoplasm symptom assessment form. Retrieved January 3, 2023, from https://www.jakafi.com/pdf/mpn-symptoms-form.pdf
9. Ma, L., Jiang, L., Yang, W., Luo, Y., Mei, C., Zhou, X., Xu, G., Xu, W., Ye, L., Ren, Y., Lu, C., Lin, P., Jin, J., & Tong, H. (2021). Real-world data of chronic myelomonocytic leukemia: A chinese single-center retrospective study. Cancer medicine, 10(5), 1715-1725. https://doi.org/10.1002/cam4.3774
10. Incidence extrapolated by applying NIH SEER incidence rate of five per one million people found at https://seer.cancer.gov/statistics-network/explorer to the population of U.S., UK, and Australia, Prevalence data also from NIH SEER.
11. Incidence extrapolated by applying NIH SEER incidence rate of five per one million people found at https://seer.cancer.gov/statistics-network/explorer to the population of U.S., UK, and Australia, Prevalence data also from NIH SEER.
12. U.S. Food and Drug Administration. A framework for concurrent submission and review of Oncology Products.. Retrieved March 20, 2023, from https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis
13. Australian New Zealand Clinical Trials Registry. Retrieved March 20, 2023, from https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12621000223831
14. Preach-M : Precision medicine for chronic myelomonocytic leukaemia in adults: A phase II trial studying the efficacy of lenzilumab and high dose ascorbate with azacitidine based on molecular profiling. PREACH-M - Victorian Cancer Trials Link. (n.d.). Retrieved January 3, 2023, from https://trials.cancervic.org.au/details.aspx?ID=vctl_actrn12621000223831
15. Gupta, A. et al. (2021). Juvenile myelomonocytic leukemia-A comprehensive review and recent advances in management. American Journal of Blood Research, 11(1), 1-21. Retrieved July 21, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010610/pdf/ajbr0011-0001.pdf
16. Padron, E., 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
17. Emanuel, P. D., et al. (1991). Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors. Blood, 77(5), 925-929. https://doi.org/10.1182/blood.v77.5.925.925

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