23ME-00610 / 23andMe - LARVOL DELTA

First-in-human study of 23ME-00610, an antagonistic antibody for genetically validated CD200R1 immune checkpoint, in participants with advanced solid malignancies. (PubMed, Cancer Res Commun) - P1/2 | "23ME-00610 has mild-to-moderate on-target adverse events and PK/PD consistent with tumor target saturation and dosing Q3W. The trend for clinical benefit in participants with tumor CD200 expression suggests 23ME-00610 inhibits CD200R1 signaling and may reverse CD200-mediated immune evasion. Based on PK/PD, safety, and preliminary anti-tumor activity, 1400 mg Q3W was selected as the dose for further study."

Journal • Metastases • P1 data • Dermatology • Endocrine Cancer • Endocrine Disorders • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Pruritus • Solid Tumor • CD200 • CD200R1

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

CD200R1 immune checkpoint blockade by the first-in-human anti-CD200R1 antibody 23ME-00610: molecular mechanism and engineering of a surrogate antibody. (PubMed, MAbs) - "This engineering approach does not require a priori knowledge of structural and functional mapping of antibody-antigen interaction and thus is generally applicable for therapeutic antibody development when desired ortholog binding is lacking. These findings provide foundational insights as 23ME-00610 advances in clinical studies to gain understanding of the hCD200R1 immune checkpoint as a target in immuno-oncology."

Checkpoint block • Checkpoint inhibition • IO biomarker • Journal • P1 data • Oncology • CD200 • CD200R1

23andMe Therapeutics Announces Phase 2 Results for Two Additional Cancer Cohorts and Correlative Biomarker Data from 23ME-00610 Study (GlobeNewswire) - P1/2a | N=141 | NCT05199272 | Sponsor: 23andMe, Inc | "23andMe Holding Co...announced positive preliminary Phase 2 safety and efficacy data from its Phase 1/2a clinical trial covering two new patient cohorts from 23ME-00610...Confirmed partial response (38% decrease in measured tumor burden) in a patient with refractory ccRCC (>11 cycles at data cut-off); 23ME-00610 monotherapy continues to demonstrate acceptable safety and tolerability, and achieves the prespecified targets for maximal pharmacology at 1400 mg dosed every three weeks; The safety and tolerability profile remains acceptable and promising for potential anti-cancer combinations in ccRCC patients; Higher tumor cell expression of CD200 associates with 23ME-00610 in some patients, and is further augmented if combined with genetic based host immune set point readouts; Neuroendocrine tumors that had tumor shrinkage or prolonged stable disease tended to be less inflamed at baseline..."

Biomarker • P2 data • Clear Cell Renal Cell Carcinoma • Microsatellite Instability • Neuroendocrine Tumor

Phase I/IIa trial of CD200R1 inhibitor 23ME-00610: Exploratory analyses of tissue-based and genetic biomarkers (ESMO 2024) - P1/2 | "Higher tumor expression of CD200 correlated with CB in some patients treated with 23ME-00610, warranting further exploration of this biomarker for potential future patient selection. Early data suggests that 23ME-00610 may reverse the immunosuppressive state of CD200+ tumor microenvironment. Ongoing genetic analyses will evaluate if immune-mediated phenotypes may be associated with increased risk to develop irAEs as has been demonstrated in other studies (Khan et al., 2019 and 2021)."

Biomarker • P1/2 data • Tumor mutational burden • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD163 • CD200 • CD200R1 • CD68 • IFNG • TMB

Efficacy, safety and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced or metastatic clear-cell renal cell carcinoma (ccRCC): Results from a multi-center multi-country phase I/IIa expansion cohort (ESMO 2024) - P1/2 | "23ME-00610 shows anti-tumor activity in immunotherapy-refractory ccRCC and continues to show an acceptable safety and tolerability profile, full peripheral target engagement, and PK that supports Q3W dosing."

Clinical • IO biomarker • Metastases • P1/2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CD200 • CD200R1 • PD-1

Efficacy, safety and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with tumor mutational burden-high (TMB-H) and/or microsatellite instability-high (MSI-H) cancers: Results from an expansion cohort (ESMO 2024) - P1/2 | "23ME-00610 continues to show acceptable safety and tolerability, full peripheral target engagement, and PK that supports Q3W dosing, though limited anti-tumor activity as monotherapy in a small cohort of participants with TMB-H/MSI-H tumors. 1. Rasco, et al."

Clinical • IO biomarker • Tumor mutational burden • Microsatellite Instability • Oncology • CD200 • CD200R1 • MSI • TMB

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

Safety, efficacy, and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced neuroendocrine cancers: Results from a multi-center multi-country phase 1/2a expansion cohort. (ASCO 2024) - P1/2 | "23ME-00610 continues to show encouraging PKPD, safety, and disease control in a subset of unselected patients with advanced neuroendocrine cancers. Exploratory biomarker data warrant additional analyses to examine the potential for biomarker stratification on disease outcomes. Phase 2a expansion trials of 23ME-00610 utilizing retrospective biomarker analysis are ongoing in multiple indications."

Clinical • IO biomarker • Metastases • P1/2 data • Dermatology • Endocrine Cancer • Fatigue • Immunology • Neuroendocrine Tumor • Oncology • Pruritus • Solid Tumor • CD200 • CD200R1

Safety, efficacy, and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced or metastatic ovarian cancer: Results from a multi-center multi-country phase 1/2a expansion cohort. (ASCO 2024) - P1/2 | "23ME-00610 continues to show encouraging PKPD and acceptable safety, but only modest disease control in unselected advanced ovarian cancer patients. Phase 2a expansion trials of 23ME-00610 utilizing retrospective biomarker analyses are ongoing in multiple indications."

Clinical • IO biomarker • Metastases • P1/2 data • Cardiovascular • Dermatology • Endocrine Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Ovarian Cancer • Peritoneal Cancer • Pneumonia • Pruritus • Respiratory Diseases • Solid Tumor • Thrombosis • Venous Thromboembolism • CD200 • CD200R1

23andMe Therapeutics Announces Positive Preliminary Phase 2 Safety and Efficacy Results for 23ME-00610, targeting CD200R1, at the 2024 ASCO Annual Meeting (GlobeNewswire) - P1/2a | N=141 | NCT05199272 | Sponsor: 23andMe, Inc. | "Confirmed partial response (PR) in patient with well-differentiated pancreatic neuroendocrine cancer (pNET) (> 24 cycles at data cut-off) and qualitative clinical benefit with durable treatment duration (> 12 cycles at data cut-off) and tumor shrinkage in patient with mesonephric adenocarcinoma (a form of ovarian cancer)....A patient with well-differentiated mesonephric adenocarcinoma progressing prior to study enrollment has shown qualitative clinical benefit and durable treatment duration (> 12 cycles), including decreasing CA-125, substantial decreases in malignant ascites, and tumor reduction while on 23ME-00610 treatment."

P1/2 data • Gynecologic Cancers • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Solid Tumor

A Phase 1/2a Study of 23ME-00610 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2 | N=141 | Active, not recruiting | Sponsor: 23andMe, Inc. | Trial completion date: Jun 2024 ➔ Mar 2025 | Trial primary completion date: Jun 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Endocrine Cancer • Fallopian Tube Cancer • Genito-urinary Cancer • Lung Cancer • Microsatellite Instability • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor

23andMe to Present Preliminary Efficacy and Biomarker Data for 23ME-00610 at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "23andMe Holding...announced that two abstracts on 23ME-00610, a first-in-class anti-CD200R1 antibody, have been accepted for poster presentations at the 2024 ASCO Annual Meeting, taking place May 31 - June 4 in Chicago. 23andMe will present clinical data, including preliminary efficacy and exploratory biomarker analyses, for the neuroendocrine and ovarian cancer patient cohorts in the Phase 2a portion of its ongoing Phase 1/2a clinical trial."

Biomarker • P2a data • Neuroendocrine Tumor • Ovarian Cancer

New insights into targeting the CD200R1 pathway in T and NK cells using 23ME-00610 as a single agent or in combination (AACR 2024) - P1/2 | "Taken together, these data demonstrate that 23ME-00610 can enhance both NK and T cell antitumor effector functions, and 23ME-00610 could synergize with anti-PD-1 to further increase the activity of T cells against cancer cells. The results of this study provide evidence that 23ME-00610 could expand IO treatment options for patients with advanced solid malignancies as a single agent or in combination with other anti-tumor therapeutics."

IO biomarker • Oncology • Solid Tumor • CD200 • CD200R1 • IFNG • PD-L1

23andMe to Present Data on Two Clinical Stage Immuno-Oncology Programs at the American Association for Cancer Research (AACR) Annual Meeting 2024 (GlobeNewswire) - "Prevalence of CD200R1 and its ligand CD200 was characterized on tumor samples from patients with clear cell renal cell and serous ovarian carcinomas....23ME-00610 differentially enhanced interferon-gamma secretion from cancer patient peripheral blood mononuclear cells relative to anti-PD-1, and 23ME-00610 enhanced both T and NK cell anti-tumor activity....CD200, the ligand of CD200R1, is expressed on both tumor cells and endothelial cells, and combination anti-CD200 with anti-VEGF led to tumor growth inhibition relative to single agents in a preclinical mouse model."

Preclinical • Clear Cell Renal Cell Carcinoma • Ovarian Cancer

A Phase 1/2a Study of 23ME-00610 in Patients With Advanced Solid Malignancies (clinicaltrials.gov) - P1/2 | N=141 | Active, not recruiting | Sponsor: 23andMe, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Clear Cell Renal Cell Carcinoma • Endocrine Cancer • Fallopian Tube Cancer • Genito-urinary Cancer • Lung Cancer • Microsatellite Instability • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Peritoneal Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • 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 Reports Third Quarter Fiscal 2024 Financial Results (GlobeNewswire) - "Phase 2a enrollment is ongoing with initial efficacy and cohort data expected in 2024."

Enrollment status • P2a data • Solid Tumor

23andMe announces further expansion of 23ME-00610 Phase 1/2a clinical trial in advanced neuroendocrine and ovarian cancer patient cohorts (GlobeNewswire) - "23andMe Holding Co...announced the further expansion of the ongoing 23ME-00610 Phase 1/2a study to include an additional 30 patients with advanced neuroendocrine and ovarian cancers, above the original enrollment goals. The ongoing study has been enrolling the Phase 2a portion of the Phase 1/2a clinical trial evaluating the anti-CD200R1 monoclonal antibody since February 2023....23andMe and the investigators for this clinical trial plan to share Phase 2a data from the ongoing Phase 1/2a study at scientific conferences in 2024."

P2a data • Trial status • Gynecologic Cancers • Neuroendocrine Tumor • Oncology • Ovarian Cancer • Solid Tumor

23andMe Reports Second Quarter Fiscal 2024 Financial Results (GlobeNewswire) - "Presented updated data for 23ME-00610 at the Society for Immunotherapy of Cancer (SITC) conference on November 3....Phase 2a enrollment is ongoing with initial efficacy and cohort data expected in 2024."

P2a data • Trial status • Oncology • Solid Tumor

23andMe Announces Updated Safety and Preliminary Efficacy Data From the Phase 1/2a Study of 23ME-00610, an Investigational Antibody Targeting CD200R1 (GlobeNewswire) - P1/2 | N=141 | NCT05199272 | Sponsor: 23andMe, Inc | "Updated data from the now completed dose escalation phase continue to showcase the manageable safety profile of 23ME-00610 at the dose levels tested, and highlight preliminary efficacy results...Of the phase 1 patients enrolled across all doses of the dose escalation, there was a 52% stable disease rate. One patient with pancreatic neuroendocrine cancer had a maximum reduction in sum of longest target lesion diameters of 19% and remained on treatment with stable disease at 40 weeks on study at the time of data cut off...Preliminary PK data support dosing 23ME-00610 every three weeks...The Phase 2a portion of the Phase 1/2a study is currently enrolling...The expansion cohorts will enroll patients with clear cell renal cell carcinoma; epithelial ovarian, fallopian tube or primary peritoneal carcinoma; neuroendocrine cancers; small cell lung cancer; and microsatellite instability-high..."

P1/2 data • Trial status • Clear Cell Renal Cell Carcinoma • Fallopian Tube Cancer • Microsatellite Instability • Neuroendocrine Tumor • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Small Cell Lung Cancer

First-in-class anti-CD200R1 antibody 23ME-00610 in patients with advanced solid malignancies: updated phase 1 results (SITC 2023) - "The irAEs are consistent with 23ME-00610-mediated immune modulation. The data continue to support evaluation of 1400 mg 23ME-00610 Q3W (RP2D) in the ongoing Phase 2a."

Clinical • Metastases • P1 data • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • CD200 • CD200R1

Phase 1/2a dose selection of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced solid malignancies (SITC 2023) - P1/2 | "Doses in the linear PK range demonstrated sustained peripheral target engagement and 23ME-00610 had a manageable safety profile. The clinical PK, PD, safety, and translational data support evaluation of 23ME-00610 1400 mg Q3W in the ongoing Phase 2a."

Clinical • Metastases • P1/2 data • Oncology • Solid Tumor • CD200 • CD200R1

23andMe Announces Poster Presentations on 23ME-00610, an Investigational Antibody Targeting CD200R1, at The Society for Immunotherapy of Cancer’s (SITC) 2023 Annual Meeting (GlobeNewswire) - "The presentations will include updated safety and efficacy data from the Phase 1 portion of the ongoing Phase 1/2a study of 23ME-00610 in patients with advanced solid malignancies. The Company will also present data on the pharmacokinetics, pharmacodynamics and safety data supporting the Phase 1 and Phase 2 dose selection for the 23ME-00610 study."

P1 data • PK/PD data • Oncology • Solid Tumor

23ME-00610, a genetically informed, first-in-class antibody targeting CD200R1 to enhance antitumor T cell function. (PubMed, Oncoimmunology) - "23ME-00610 induced T-cell cytokine production and enhanced T cell-mediated tumor cell killing in vitro. Blockade of the CD200:CD200R1 immune checkpoint inhibited tumor growth and engaged immune activation pathways in an S91 tumor cell model of melanoma in mice."

Journal • Immune Modulation • Immunology • Melanoma • Oncology • Solid Tumor • CD200 • CD200R1