Acrivon Therapeutics (ACRV) Status Update summary

Platform and R&D strategy

• AP3 Predictive Precision Proteomics platform uses mass spectrometry and AI-driven phosphoproteomics for direct measurement of disease-driving pathway activity, optimizing drug design and selectivity.

• Generative phosphoproteomics and machine learning models are applied for drug mechanism analysis, biomarker identification, and in silico screening, with proprietary data covering nearly the entire kinome.

• AP3 Interactome data portal provides rapid access to multimodal, machine learning-enabled pathway and biomarker analyses across 148,900 phosphosites and 9,685 proteins.

• Single-cell phosphoproteomics, pioneered by Olsen Lab, is being developed to address tumor heterogeneity and autoimmune disorders, supporting deep proteomic profiling.

Clinical program update: Endometrial cancer

• ACR-368, predicted by AP3 to be effective in endometrial cancer, shows a 35% confirmed response rate and 80% disease control rate in biomarker-positive, heavily pretreated patients, more than doubling the response rate of prior therapies.

• Durable responses observed, with some patients on treatment for over a year and median duration not yet reached (>7.9 months).

• Safety profile is favorable, with mostly transient, reversible hematologic adverse events and minimal GI or severe non-hematologic toxicity; no fatal treatment-related events.

• Combination with low-dose gemcitabine in biomarker-negative patients shows evidence of sensitization and comparable response rates to prior lines, supporting a potential all-comer strategy.

• Patients enrolled are mostly stage 4, with aggressive histologies and high prior treatment burden, including universal prior anti-PD-1 and platinum-based chemo.

Competitive positioning and strategic focus

• Endometrial cancer is prioritized as the lead registration opportunity due to high unmet need and strong clinical data; ovarian and bladder cancer programs are deprioritized.

• Confirmatory trial strategies include switch maintenance and label expansion in frontline settings, leveraging non-overlapping toxicities with anti-PD-1 and ADCs.

• Preclinical and early clinical data support combination strategies and potential expansion into autoimmune and inflammatory indications.