IND Cleared for Solid Tumor Trial of ULBP6-Targeting Natural Killer (NK) Cell Activator
The ULBP6 target was discovered through 23andMe’s proprietary research platform of de-identified human genetic and phenotypic information.
The FDA has cleared 23andMe’s investigational new drug (IND) application for 23ME-01473, a ULBP6-targeting natural killer (NK) cell activator, to be evaluated in solid tumors.1
“This program further validates the 23andMe database as a proven resource for identifying novel therapeutic targets,” Jennifer Low, Head, Therapeutics Development, 23andMe, said in a statement.1 “The team is excited to initiate our next immuno-oncology program, ‘1473, which is particularly interesting given its two mechanisms of action, which may synergize to enhance NK and T cell immunity against certain tumors.”
23ME-01473 is a dual mechanism antibody designed to block the immunosuppressive effects of soluble ULBP6and induce Fc receptor-mediated killing of ULBP6-expressing cancer cells through enhanced Fc effector function. These mechanisms may restore immune cell recognition and killing of cancers. 23andMe plans to evaluate the therapy in participants with advanced solid tumors in a Phase 1 clinical trial beginning in the first half of 2024 in NK cells. The company also believes that 23ME-01473 may delay tumor resistance seen in treatment with traditional checkpoint inhibitors.
The ULBP6 target was discovered through 23andMe’s proprietary research platform, recontactable database of de-identified human genetic and phenotypic information.
The treatment landscape for solid tumors recently had a breakthrough with the early approval of Iovance Biotherapeutics’ tumor-derived autologous T cell immunotherapy lifileucel (branded now as Amtagvi). Lifileucel, approved for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, or treated with a BRAF inhibitor with or without a MEK inhibitor in the instance that the patient is if BRAF V600 positive, became the first approved therapy for treating a solid tumor indication.
“The accelerated approval of Amtagvi is the first step in realizing Iovance’s ambition to usher in the next generation of cell therapy by bringing this breakthrough to patients with advanced solid tumors,” Frederick Vogt, PhD, JD, the interim CEP and president of Iovance, said in a statement.3 “Given the significant unmet needs in the advanced melanoma community, we are proud to offer a personalized, one-time therapeutic option for these patients. We are continuing our development efforts to address additional unmet medical needs in patients with solid tumor cancers, making our novel cell therapies available to more patients with melanoma and other types of cancers.”
Iovance said on an investor call that the cost for Amtagvi would be $515,000 yearly. According to the FDA, the prescribing information for the therapy contains a Boxed Warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Lifileucel is a tumor-infiltrating lymphocyte (TIL) therapy, and the biologics license application (BLA) for it was supported by the phase 2 C-144-01 (NCT02360579) clinical trial, data from which demonstrated an independent review committee-assessed objective response rate (ORR) of 31.4%, with 9 complete responses and 39 partial responses; a median overall survival (OS) of 13.9 months; and a 12-month OS rate of 54% (95% CI, 45.6-61.6).4
REFERENCES
1. 23andMe Announces FDA Clearance of IND Application for its Dual Mechanism Antibody, 23ME-01473, Targeting ULBP6. News release. January 31, 2024. https://investors.23andme.com/news-releases/news-release-details/23andme-announces-fda-clearance-ind-application-its-dual
2. FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed February 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma
3. Iovance’s AMTAGVI™ (lifileucel) Receives U.S. FDA Accelerated Approval for Advanced Melanoma. News release. Iovance. February 16, 2024. Accessed February 16, 2024. https://ir.iovance.com/news-releases/news-release-details/iovances-amtagvitm-lifileucel-receives-us-fda-accelerated
4. Sarnaik A. Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors (ICI) and targeted therapy: Pooled analysis of consecutive cohorts (C-144-01 study). Presented at: Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting November 8-12, 2022; Boston, Massachusetts. #789
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