Acrivon Therapeutics presents data on AP platform, ACR-368 OncoSignature Assay

Acrivon Therapeutics announced data highlighting its AP3 approach to identify and evaluate biomarkers for its OncoSignature assay designed specifically to predict sensitivity to ACR-368, the company’s selective small molecule inhibitor targeting CHK1 and CHK2, currently in registrational-intent Phase 2 clinical trials. The data were presented in two posters at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston this past week. The poster titled “Identification of Biomarkers Predictive of Sensitivity to the CHK1/2 Inhibitor ACR-368 Using High-Resolution Phosphoproteomics and Development of an ACR-368-Tailored Patient Responder Identification 3-Marker Test, ACR-368 OncoSignature” showed data leveraging the company’s AP3 approach, including ultra-high resolution, quantitative mass spectrometry-based phosphoproteomics profiling combined with proprietary approaches to identify three classes of functionally orthogonal candidate biomarkers specifically predictive of sensitivity to ACR-368. Biomarker candidates were initially evaluated through pathway reconstitution and in cellular functional assays, after which they were assembled into the ACR-368 OncoSignature assay for further functional validation. The quantitative multiplex in situ ACR-368 OncoSignature assay was used to provide a direct readout of the activity state of the drug target signaling axis regulated by ACR-368 and that the tumor depends on for dysregulated CHK1/2-driven DNA repair and replication stress. These data support the use of the company’s ACR-368 OncoSignature assay in its ongoing registrational-intent Phase 2 clinical trials, and demonstrate the distinctive, practical application of the company’s AP3 platform. The poster titled “Validation of the OncoSignature Assay, an ACR-368-Tailored Response-Predictive Quantitative Multiplexed Immunofluorescent Assay for Prediction of Sensitivity to the CHK1/2 Inhibitor ACR-368 in Individual Patients with Cancer” provided data validating the ability of the AP3-derived ACR-368-specific OncoSignature assay to predict tumor response to ACR-368 in multiple blinded, prospectively-designed preclinical studies, including two separate studies on pretreatment tumor biopsies from past Phase 2 clinical trials in patients with ovarian cancer and in tumor types predicted sensitive to ACR-368, including endometrial cancer. In the two pretreatment tumor biopsy studies, the ACR-368 OncoSignature test was overall able to segregate responders from non-responders with high accuracy and enrich for responders, achieving an overall response rate of 47% and 58% with strong statistical significance. Endometrial and bladder cancers were identified as new tumor types predicted sensitive to ACR-368 in 30-40% of cases. Data in the poster confirmed the predicted efficacy in genetically non-modified, PDX models of endometrial cancer, and further demonstrated that the ACR-368 OncoSignature assay could predict sensitive from insensitive models with an AUC of 0.88 in blinded studies.