Acrivon’s ACR-368 Shows Potent Synergy with Topo1 ADCs; ACR-2316 Yields Durable Tumor Regression
ACRV’s CHK1/2 inhibitor ACR-368 showed potent preclinical synergy with Topo 1 inhibitor payloads in ADC models, overcoming resistance via CHK1/2 pathway inhibition. ACR-2316 combined with anti-PD-L1 achieved complete, durable tumor regressions in syngeneic mouse models.
1. Preclinical Synergy of ACR-368 with Topo 1 ADC Payloads
ACR-368, a CHK1/2 inhibitor in registrational-intent Phase 2b, demonstrated potent synergy when combined with Topo 1 inhibitor ADC payloads in multiple preclinical tumor models. In vitro and in vivo studies showed that ACR-368 blocked the CHK1/2-mediated DNA damage repair response triggered by Topo 1 agents, resulting in enhanced tumor cell killing compared with monotherapy arms.
2. ACR-2316 Combined with Anti-PD-L1 Induces Durable Tumor Regression
ACR-2316, a WEE1/PKMYT1 inhibitor in Phase 1, achieved complete and lasting tumor regressions in immunocompetent syngeneic mouse models when dosed with anti-PD-L1. The combination activated both innate and adaptive immune pathways, leading to immunological memory and sustained protection upon tumor rechallenge.
3. AACR Presentations and AP3 Platform Insights
Acrivon will present three posters at the AACR Annual Meeting April 17–22, including a late-breaking immunology session. The data leverage the Generative Phosphoproteomics AP3 platform to identify and validate drug combinations with high translational potential, guiding ACR-368’s and ACR-2316’s clinical development strategies.