23andMe To Present Data On Two Clinical Stage Immuno-Oncology Programs At The AACR Annual Meeting 2024

Author: Benzinga Newsdesk | April 05, 2024 04:06pm

• 23ME-01473, antibody targeting ULBP6: Data will be presented on the discovery and biology of ULBP6, and the potential to restore natural killer and T cell-mediated anti-tumor immunity by targeting ULBP6
• 23ME-00610, antibody targeting CD200R1: Preclinical data will be presented on targeting the CD200R1 pathway in T cells and natural killer cells using 23ME-00610 as a single agent, or in combination with other anti-tumor therapies
  
   

SAN DIEGO, April 05, 2024 (GLOBE NEWSWIRE) -- 23andMe Holding Co. (NASDAQ:ME) ("23andMe"), a leading human genetics and biopharmaceutical company, will present data on its two clinical stage programs, 23ME-01473 targeting ULBP6, and 23ME-00610 targeting CD200R1, at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place in San Diego, CA, April 5-10, 2024.

23ME-001473 (‘1473) - Clinical-Stage Dual Mechanism Monoclonal Antibody Targeting ULBP6

Key takeaways:

• 23andMe used its proprietary database of human genetic and health information to discover germline variants of ULBP6 associated with higher risks of immune disease and lower risks of cancer, suggesting the potential of ULBP6 as a novel immuno-oncology (I/O) drug target.
• 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.
  
   

Key details:

• ULBP6 is a stress-induced ligand that is upregulated on the surface of cancer cells and binds to the activating immunoreceptor NKG2D found on NK and T cells.
• ULBP6 can be shed from the cell surface of tumor cells into a soluble form that acts as an immunosuppressive decoy to evade immune surveillance. Soluble ULBP6 is elevated in cancer patient plasma.
• Of all human NKG2D ligands, ULBP6 exhibits the highest binding affinity to NKG2D, which correlates with the high potency of soluble ULBP6 in suppressing PBMC-mediated interferon-gamma secretion and promoting tumor cell growth in vitro.
• Expression profiling of ULBP6 in various tumors using The Cancer Genome Atlas and immunohistochemistry reveals its elevated expression in squamous cell carcinomas and a subset of adenocarcinomas.
• ‘1473's dual synergistic activation of NKG2D and FcγRIIIa leads to optimal activation of NK cells, which may reverse immune suppression and circumvent resistance to immune-checkpoint inhibitors due to the loss of neoantigen presentation in tumors.
• ‘1473 is currently being evaluated in a Phase I clinical trial for patients with advanced solid tumors (NCT06290388).

23ME-00610 - Clinical-Stage Monoclonal Antibody Targeting CD200R1

Key Takeaways:

• CD200R1 is a dominant immune checkpoint and differentiated from PD-1, based on both the pattern of expression on tumor infiltrating immune cells from patient tumors and the pattern of activation on patient peripheral mononuclear blood cells.
• 23andMe preclinical results support the potential for 23ME-00610 to combine with anti-PD-1 and antiangiogenics.

Key Details:

• Prevalence of CD200R1 and its ligand CD200 was characterized on tumor samples from patients with clear cell renal cell and serous ovarian carcinomas.
• CD200R1 is broadly expressed on tumor-infiltrating immune cells, including T cells and NK cells, whereas expression of PD-1 is predominantly restricted to T cells.
• 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/R1 is an independent immunosuppressive pathway from PD/L-1, with potential for synergism in patients with cancer based on preclinical combination data with primary human T cells.
• 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.
• 23ME-00610 is currently in the Phase 2a portion of a Phase 1/2a clinical trial (NCT05199272).

The presentations will be available on the 23andMe Investor Relations and Therapeutics websites on April 8, 2024.

Presentation details - 23ME-01473:

Oral presentation

• Title: Discovery of ULBP6 as a novel immuno-oncology target using pleiotropic signals from 23andMeʼs genetic and health survey database
• Session Type: Minisymposium
• Session Category: Experimental and Molecular Therapeutics
• Session Title: Drug Discovery 1: New Targets and Approaches
• Session Date and Time: Monday, April 8, 2024, 3:20-3:35 PM PT
• Location: Room 30, Upper Level of the San Diego Convention Center
• Published Abstract Number: 3903
  
   

Poster presentation

• Title: 23ME-01473, a novel anti-ULBP6/2/5 monoclonal antibody, reinvigorates anti-tumor NK cell function through NKG2D and FcγRIIIa activation
• Session Category: Clinical Research
• Session Title: Antibodies 1
• Session Date and Time: Monday, April 8, 2024, 9:00 AM - 12:30 PM PT
• Location: Poster Section 38
• Poster Board Number: 21
• Published Abstract Number: 2375
  
   

Presentation Details: 23ME-00610:

Poster presentation

• Title: New insights into targeting the CD200R1 pathway in T and NK cells using 23ME-00610 as a single agent or in combination
• Session Category: Clinical Research
• Session Title: Antibodies 1
• Session Date and Time: Monday, April 8, 2024, 9:00 AM - 12:30 PM PT
• Location: Poster Section 38
• Poster Board Number: 5
  • Published Abstract Number: 2359

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