Acrivon Therapeutics (ACRV) Study Update summary

Study design, platform, and patient selection

• Registrational intent phase II trial of ACR-368 in high-grade endometrial cancer uses a Simon 2-stage design and prospective selection with the OncoSignature assay, enrolling patients who progressed on prior anti-PD-1 therapy.

• The AP3 platform enables high-resolution, functional proteomics and machine learning to identify drug-responsive biomarkers, optimize compounds, and support rational drug design and patient selection.

• OncoSignature predicts individual patient sensitivity to ACR-368, independent of molecular or histological subtype.

• The trial explores ultra-low dose gemcitabine to sensitize OncoSignature-negative patients.

• AP3 platform is broadly applicable across oncology and non-oncology, supporting rapid drug optimization and companion diagnostic development.

Key interim results and clinical impact

• Confirmed ORR in OncoSignature-positive endometrial cancer patients is 63% or 62.5% (95% CI: 30.4–86.5%), with all responders still on therapy and median duration of response not yet reached (~6 months at data cutoff).

• Statistically significant segregation between OncoSignature-positive and negative patients (p=0.009), validating the biomarker approach.

• Responses are rapid and durable, including in patients with prior progressive disease on anti-PD-1 therapy.

• Ultra-low dose gemcitabine shows initial disease control in OncoSignature-negative patients, with some achieving confirmed responses.

• Confirmed responses observed across molecular and histological subtypes.

Safety and tolerability

• Safety profile is favorable, with mainly transient, reversible hematological adverse events typical of DDR inhibition and no long-lasting myelosuppression.

• Notable absence of neuropathies, liver toxicities, and pneumonitis seen with other therapies.

• Prophylactic G-CSF is used to manage generally mild and transient neutropenia.

• No significant non-hematological adverse events observed; GI toxicity is minimal.