31 May 2019 - - US-based biopharmaceutical company Kite, a Gilead Company (NASDAQ: GILD), and Humanigen, Inc. have formed a clinical collaboration to conduct a Phase 1/2 study of lenzilumab, an investigational anti-GM-CSF monoclonal antibody, with Yescarta (axicabtagene ciloleucel) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the company said.
The objective of this study is to determine the effect of lenzilumab on the safety of Yescarta. Kite will act as the sponsor of this study and will be responsible for its conduct.
GM-CSF has been identified, through clinical correlative analysis and preclinical modeling, as a potential key signal in the inflammatory cascade triggering toxicities associated with chimeric antigen receptor T (CAR T) cell therapy.
Toxicities associated with CAR T therapy include neurologic toxicity and cytokine release syndrome. Emerging pre-clinical evidence suggests that lenzilumab inhibition of GM-CSF may have the potential to disrupt CAR T cell mediated inflammation without disrupting CAR T cell anti-tumor efficacy.
Yescarta was the first CAR T cell therapy to be approved by the US Food and Drug Administration for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, and high grade B-cell lymphoma and DLBCL arising from follicular lymphoma.
Lenzilumab, alone or in combination with other therapies such as Yescarta, is investigational and has not been approved by the FDA or any regulatory authority for any uses. Efficacy and safety have not yet been established.
Stifel, Nicolaus and Company, Inc. acted as exclusive financial advisor to Humanigen in this transaction.
Gilead Sciences is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need.
The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.
Humanigen is developing its portfolio of Humaneered monoclonal antibodies to address cutting-edge CAR-T optimization and the need for new oncology drugs that provide safer, better, and more effective cancer therapies.
Derived from the company's Humaneered platform, lenzilumab, ifabotuzumab, and HGEN005 are monoclonal antibodies with first-in-class mechanisms. Lenzilumab, which neutralizes human GM-CSF, is in development as a potential biologic therapy to make CAR-T therapy safer and more effective, as well as a potential treatment for hematologic cancers.
Ifabotuzumab, which targets the Eph type-A receptor 3 (EphA3), is being explored as a potential treatment for a range of solid tumors, as well as a backbone for a novel CAR-T construct, and a bispecific antibody platform.
HGEN005 which selectively targets the eosinophil receptor EMR1 is being explored as a potential treatment for a range of eosinophilic diseases including eosinophilic leukemia both as an optimized naked antibody and as the backbone for a novel CAR-T construct.