23ME-01473 / 23andMe - LARVOL DELTA

23ME-01473, an Fc Effector-Enhanced Anti-ULBP6/2/5 Antibody, Restores NK Cell-Mediated Antitumor Immunity through NKG2D and FcγRIIIa Activation. (PubMed, Cancer Res Commun) - "We identify ULBP6 as a potential keystone member of the NKG2D pathway, which is important for antitumor immunity. Targeting ULBP6 may hold therapeutic promise for patients with cancer."

Journal • Immunology • Oncology • NKG2D • RAET1L

23ME-01473-CLIN-001: Study of 23ME-01473 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: 23andMe, Inc. | N=82 ➔ 5 | Trial completion date: Jun 2026 ➔ Nov 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2026 ➔ Nov 2024; Sponsor cancelled study

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor

23andMe Announces Business Restructuring to Streamline Operations, Reduce Costs and Position Company for the Future (GlobeNewswire) - "In addition, 23andMe is discontinuing further development of all its therapeutics programs, while evaluating strategic alternatives for its clinical and preclinical assets....In parallel with the discontinuation of its therapeutics division, the Company is actively exploring all strategic options for a limited time to maximize the value of its therapeutics programs, including licensing agreements, asset sales or other transactions....The Company’s therapeutic programs include 23ME-00610 (a Phase 1/2a therapeutic antibody that is designed to restore the immune system’s ability to kill cancer cells by blocking the immune checkpoint CD200R1), 23ME-01473 (a Phase 1 therapeutic antibody that targets ULBP6, which can be expressed and secreted by tumor cells to suppress immune activity), and other preclinical immunology and inflammation programs."

Discontinued • Solid Tumor

23ME-01473, an Fc-enhanced anti-ULBP6/2/5 antibody, restores anti-tumor NK cell function through NKG2D and FcgRIIIa activation (ESMO 2024) - P1/2 | "23ME-01473 is a novel anti-ULBP6/2/5 that reverses sULBP6-mediated immunosuppression and activates NKG2D and FcγRIIIa to synergistically enhance NK-mediated anti-tumor immunity, and may have potential anti-tumor activity in diverse tumors."

IO biomarker • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • IFNG • NKG2D • RAET1L

A phase I/IIa dose escalation and expansion study of 23ME-01473, an anti-ULBP6/2/5 antibody, for patients with advanced solid malignancies (ESMO 2024) - P1/2 | "The target engagement and immunomodulatory profile of 23ME-01473, baseline tumor characteristics, and germline genotype are being evaluated and used to correlate with safety and efficacy outcomes. 23ME-01473 will be evaluated in multiple cohorts of immunologically active cancers with high ULBP6/2/5 expression in the expansion phase, with a primary objective of objective response rate based on RECIST 1.1."

Clinical • IO biomarker • Metastases • P1/2 data • Oncology • Solid Tumor • NKG2D • RAET1L

23andMe Therapeutics Announces Positive In Vivo Results for 23ME-01473, a Dual-Mechanism ULBP6-Targeting Antibody Currently in a Phase 1 Trial (GlobeNewswire) - "23andMe Holding Co...announced nonclinical data supporting the anti-tumor activity of its first-in-class 23ME-01473 (’1473) antibody targeting the NKG2D ligand ULBP6 at the European Society of Medical Oncology (ESMO) Congress 2024 in Barcelona, September 13-17. In a poster presentation at the 2024 ESMO Congress, 23andMe Therapeutics presented new data showing that 23ME-01473 inhibits growth of non-small cell lung cancer in a patient-derived xenograft mouse model. The presentation also included data showing elevated plasma soluble and tumor expression levels of ULBP6 in squamous cell carcinomas and a subset of adenocarcinomas."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

23andMe to Present Updates on Clinical Immuno-oncology Programs 23ME-00610 and 23ME-01473 at ESMO Congress 2024 (GlobeNewswire) - "23andMe Holding Co...announced that it will display three poster presentations on 23ME-00610, a first-in-class anti-CD200R1 antibody, and two on 23ME-01473, an anti-ULBP6 monoclonal antibody, at the European Society for Medical Oncology (ESMO) Congress 2024, taking place September 13 – September 17 in Barcelona, Spain. 23andMe will present additional preliminary clinical data, including efficacy data, for the clear-cell renal-cell carcinoma and high tumor microsatellite instability and/or high tumor mutational burden patient cohorts in the Phase 2a portion of its ongoing Phase 1/2a clinical trial evaluating 23ME-00610, as well as share further analyses on an exploratory tissue-based biomarker, CD200. The Company will present preclinical data on the 23ME-01473 program, as well as a trials in progress presentation on the Phase 1 clinical trial that began in March 2024."

P2a data • Preclinical • Trial status • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Microsatellite Instability • Oncology • Renal Cell Carcinoma • Solid Tumor

23ME-01473, a novel anti-ULBP6/2/5 monoclonal antibody, reinvigorates anti-tumor NK cell function through NKG2D and FcγRIIIa activation (AACR 2024) - "The combination of NKG2D and FcγRIIIa activation resulted in synergistic PBMC-mediated IFNγ secretion and enhanced tumor cell killing, compared to activation of either NKG2D or FcγRIIIa. Taken together, these results reveal ULBP6 as a novel cancer therapeutic target, and given the dual activation of NKG2D and FcγRIIIa, suggest the potential of 23ME-01473 to activate NK cells and elicit anti-tumor immunity."

IO biomarker • Oncology • CD8 • GZMB • IFNG • NKG2D • RAET1G • RAET1L • ULBP2

23andMe to Present Data on Two Clinical Stage Immuno-Oncology Programs at the American Association for Cancer Research (AACR) Annual Meeting 2024 (GlobeNewswire) - "Data also show soluble ULBP6 is a dominant immunosuppressor compared to other soluble NKG2D ligands due to its highest binding affinity to NKG2D among all NKG2D ligands. ‘1473 is a high affinity, Fc effector-enhanced, anti-ULBP6 antibody that restores the activation and tumor cell killing capacity of natural killer (NK) and T cells through the dual mechanisms of NKG2D and FcγRIIIa activation."

Preclinical • Oncology

Study of 23ME-01473 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2 | N=82 | Recruiting | Sponsor: 23andMe, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

23andMe Initiates Phase 1 Clinical Trial for its Dual Mechanism Antibody, 23ME-01473, Targeting ULBP6 (GlobeNewswire) - "23andMe Holding Co...announced the first participant has been dosed in a Phase 1 clinical trial evaluating 23ME-01473 (‘1473) in advanced solid tumors. The target for the new investigational antibody, ULBP6, was discovered through 23andMe’s proprietary research platform, the world's largest recontactable database of de-identified human genetic and phenotypic information."

Trial status • Oncology • Solid Tumor

Study of 23ME-01473 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2 | N=82 | Not yet recruiting | Sponsor: 23andMe, Inc.

Metastases • New P1/2 trial • Oncology • Solid Tumor

23andMe Announces Three Presentations from Clinical-Stage Immuno-Oncology Programs at the American Association for Cancer Research (AACR) Annual Meeting 2024 (GlobeNewswire) - "The oral presentation will detail the use of the 23andMe genetic and health survey database to discover ULBP6, the highest affinity ligand of the NK and T-cell activation receptor, NKG2D. ULBP6 is the primary target for 23ME-01473 (‘1473), a dual mechanism monoclonal antibody. The Company will also present a poster on the biology of ULBP6, and how ‘1473 reinvigorates anti-tumor NK cell function through NKG2D and FcγRIIIa activation. These presentations will be the first scientific communications the Company has prepared on ‘1473 since announcing its pursuit of this novel, genetically-validated target....23andMe will also present a non-clinical poster on 23ME-00610, an inhibitor of the CD200R1 receptor, which will include new insights into targeting the CD200R1 pathway in T and NK cells using 23ME-00610 as a single agent or in combination with other anti-tumor therapies."

Preclinical • Solid Tumor

23andMe Announces FDA Clearance of IND Application for its Dual Mechanism Antibody, 23ME-01473, Targeting ULBP6 (GlobeNewswire) - "23andMe Holding...announced the U.S. Food and Drug Administration (FDA) has cleared the investigational new drug application for 23ME-01473 (‘1473), a natural killer (NK) cell activator intended to treat cancer. 23andMe plans to evaluate ‘1473 in participants with advanced solid tumors in a Phase 1 clinical study beginning in the first half of 2024."

IND • New P1 trial • Solid Tumor