23ME-00610

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.

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.

P1/2, N=141, Active, not recruiting, 23andMe, Inc. | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Mar 2025

P1/2 | "Clinical Trial Registration Number: NCT05199272"

P1/2, N=141, Active, not recruiting, 23andMe, Inc. | Recruiting --> Active, not recruiting

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.

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.

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.

23ME-00610 demonstrated an acceptable safety and tolerability profile, with favorable PK and peripheral CD200R1 saturation. Increased immune-related AEs were observed at higher, pharmacologically relevant dose levels. Based on Phase 1 data, 1400 mg 23ME-00610 Q3W will be evaluated in Phase 2a.

The statistical analyses will primarily be descriptive. Participants reflecting the characteristics for the indication-specific cohorts with regards to age, sex, race, and ethnicity, including those from the Black, Latinx/Hispanic and Indigenous communities, will be prioritized for enrollment.