On July 26, 2022 Humanigen, Inc. (Nasdaq: HGEN) ("Humanigen"), a clinical-stage biopharmaceutical company focused on developing lenzilumab, a first-in class antibody that neutralizes granulocyte-macrophage colony-stimulating factor (GM-CSF), reported a strategic realignment of its pipeline and resources to achieve key clinical milestones (Press release, Humanigen, JUL 26, 2022, View Source [SID1234616941]). The Company plans to accelerate the development of lenzilumab in chronic myelomonocytic leukemia ("CMML"), a rare blood cancer, for which the PREACH-M study is already underway. Humanigen will also advance its plan to study lenzilumab in acute graft versus host disease ("aGvHD") that occurs in patients undergoing bone marrow transplant, which will be the focus of the RATinG study that is expected to enroll its first patient in 3Q22. These studies are majority funded by our clinical partners.
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As part of this realignment, Humanigen expects to significantly reduce its go-forward, cash-based operating expenses including elimination of ongoing lenzilumab manufacturing, significant reduction in other R&D costs, and some reduction in general and administrative expenses through headcount reduction as well as other initiatives.
Key elements of the strategic realignment plan include:
·Advancing and expanding the ongoing PREACH-M study of lenzilumab for the treatment of high-risk chronic myelomonocytic leukemia ("CMML") in patients with NRAS, KRAS, and CBL genetic mutations to more rapidly reach the initial clinical assessment of this open-label study once sufficient patients have received three cycles of treatment with lenzilumab in addition to azacitidine. Three patients have been enrolled in the study and followed for multiple cycles, all with encouraging results.
oThe current standard of care for CMML are hypomethylating agents such azacitidine and decitabine, which historically have a complete response rate of 11%-22% according to the International Working Group Criteria.1,2,3
oAustralian clinical partners plan to open additional sites in Australia and may also expand the study to centers in New Zealand.
oHumanigen plans to support expansion of the study to U.S. sites and has received approval from the Principal Investigator to share the protocol and provide monitoring to those additional sites.
The incidence of CMML in the US, UK, and Australia is about 1,700 patients annually.4 As a rare disease, lenzilumab may qualify for certain regulatory and commercial advantages that may accelerate development and 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 Orbis to the United States and the United Kingdom.
There have been no new therapeutic agents for patients with high-risk CMML in 30 years5 and independent publications have demonstrated the key role of GM-CSF and RAS pathway mutations in this and other cancers, including juvenile myelomonocytic leukemia ("JMML"), myelodysplastic syndromes, myeloproliferative neoplasms, and acute myeloid leukemia.6,7,8
oA clinical protocol is also being developed for JMML with NRAS, KRAS, PTPN11 and/or NF1 genetic mutations
·Continuing to execute the RATinG study for lenzilumab for the early treatment of aGvHD with the goal of reporting a planned interim assessment of the first 20 patients in 2Q23
oThe study is being run and funded primarily by the IMPACT partnership; a group of transplant centers located in the UK.
oLenzilumab will be administered to patients that are identified as having markers for high-risk steroid refractory aGvHD, a population known to have four-fold higher mortality than those identified as low-risk using the same biomarkers.9
·Identifying and supporting further clinical assessment of lenzilumab for prevention of CAR-T therapy related toxicities through an investigator-initiated trial
oPhase 1 ZUMA-19 study completed and target dose defined for further study.
oHumanigen to provide lenzilumab to investigators free of charge to support investigator-initiated trials.
·Seeking potential inclusion of lenzilumab in international, large-scale COVID-19 platform studies through partnerships
·Planning to continue the development of ifabotuzumab, an EphA-3 targeted monoclonal antibody currently in phase 1 development, as part of an antibody drug conjugate, for certain solid tumors.
·Eliminating long-term debt on the balance sheet by fully retiring the Company’s senior secured term loan, reducing interest expense, and enhancing our ability to generate additional liquidity from our intellectual property by freeing it from the loan’s collateral requirements
"We remain committed to advancing the scientific effort to prove the clinical benefits of neutralizing GM-CSF in life-threatening conditions for patients and have had to take difficult though necessary measures to do so," said Cameron Durrant, Chairman and CEO, Humanigen. "Sharpening our in-house pipeline focus and partnering other resource-intensive programs may enable Humanigen and its clinical partners to rapidly derive important data in these indications. Our CMML, aGvHD programs are already primarily funded by partners and we hope to utilize a similar approach with our other programs, reducing our cash-based R&D expenses. We believe this strategic plan offers an opportunity to return value to our stockholders while providing hope to patients with serious and life-threatening conditions for improved outcomes."