23andMe Therapeutics Reports Positive In Vivo Results for 23ME-01473 in Phase 1 Trial

23andMe Holding Co. has unveiled promising nonclinical data at the European Society of Medical Oncology (ESMO) Congress 2024, underpinning the anti-tumor efficacy of its novel antibody, 23ME-01473 (‘1473’), which targets the NKG2D ligand ULBP6. The Congress, held in Barcelona from September 13-17, served as a platform for 23andMe Therapeutics to present these findings.

During the poster presentation at ESMO, 23andMe showcased data illustrating that 23ME-01473 inhibits the growth of non-small cell lung cancer (NSCLC) in a patient-derived xenograft mouse model. Additionally, the research highlighted that both soluble and tumor-bound ULBP6 levels are elevated in squamous cell carcinomas and certain adenocarcinomas. These observations have led to the prioritization of four specific cancer types for further investigation in the Phase 2a dose expansion of the ongoing Phase 1/2a trial. These cancer types include head and neck squamous cell carcinoma, squamous non-small cell lung cancer, colorectal cancer, and triple-negative breast cancer. The trial, which commenced in March 2024, aims to explore these indications further based on the promising preclinical results.

Dr. Jennifer Low, Head of Therapeutics Development at 23andMe, emphasized the significance of this data in the context of the ongoing clinical trials. She pointed out that the findings not only support the current studies but also underscore the potential of leveraging human genetics to identify new therapeutic targets and develop innovative drugs in immuno-oncology.

23ME-01473 targets ULBP6 to reestablish anti-tumor immunity via NK and T cells. ULBPs are stress-induced ligands present on cancer cells that interact with the NKG2D receptor on NK and T cells. Cancer cells evade immune detection by shedding ULBP ligands, which act as immunosuppressive decoys. By blocking the binding of soluble ULBP6 to NKG2D, 23ME-01473 can potentially restore the immune system’s ability to recognize and destroy cancer cells. The antibody is also enhanced for Fc-effector function, providing an additional pathway for NK cells to induce the death of ULBP6-expressing cancer cells.

The identification of ULBP6 as a target emerged from 23andMe’s immuno-oncology genetic signature approach. This method uses genetic data to pinpoint immune-related genes that influence cancer biology. Specifically, germline genetics can reveal which immune-related genes harbor genetic variants that might alter an individual's cancer risk, thereby providing potential targets for new cancer therapies.

The Phase 1 trial of 23ME-01473 is a first-in-human, multi-center, open-label study designed to assess the safety and tolerability of the antibody in patients with locally advanced or metastatic solid tumors that have not responded to standard treatments. The study aims to determine the optimal dose and dosing schedule by evaluating the pharmacokinetic and pharmacodynamic profiles of 23ME-01473.

23andMe, known for its consumer-focused genetic testing services, has expanded its mission to include healthcare and therapeutics, aiming to foster a healthier future by leveraging genetic insights. The ongoing clinical trials and the development of 23ME-01473 reflect the company’s commitment to translating genetic research into practical, potentially life-saving therapies.