Acrivon Therapeutics has announced positive data from its ongoing Phase 2 trial of ACR-368 in endometrial cancer, alongside the FDA clearance of the Investigational New Drug (IND) application for ACR-2316. The data, presented at ESMO, highlight the potential of ACR-368 in treating advanced endometrial cancer, particularly in patients who have progressed on prior anti-PD-1 therapy. The company's AP3 Interactome platform is also playing a crucial role in identifying responders and driving the development of new drug candidates.
ACR-368 Demonstrates Significant Efficacy in Endometrial Cancer
The Phase 2 trial of ACR-368 in patients with locally advanced or metastatic, recurrent endometrial cancer who had progressed on prior anti-PD-1 therapy showed a confirmed overall response rate (ORR) of 62.5% (95% CI, 30.4-86.5) in OncoSignature-positive patients. This is particularly significant given the historical ORR of 14.7% for second-line chemotherapy in this patient population (Makker et al; N Engl J Medicine, 2022).
The study also demonstrated a statistically significant segregation of responders based on the OncoSignature biomarker (p = 0.009), validating Acrivon's biomarker-driven approach. The median duration of response (mDOR) has not yet been reached, with all responding patients still on therapy at the time of data cut-off, approximately 6 months. This suggests durable responses with ACR-368 treatment.
Peter Blume-Jensen, M.D., Ph.D., chief executive officer, president, and founder of Acrivon, stated, "Given the strength of the data we believe endometrial cancer might provide the first potential approval opportunity for ACR-368."
ACR-2316 Advances to Phase 1 Clinical Trial
Acrivon also announced that the FDA has cleared the IND for ACR-2316, a novel, dual WEE1/PKMYT1 inhibitor. First-in-human dosing is anticipated in the fourth quarter of 2024. Multiple clinical sites have been activated for the Phase 1 dose optimization study.
AP3 Interactome Platform Drives Precision Medicine Approach
Acrivon's AP3 Interactome platform is a key component of its precision medicine strategy. The platform enables the identification of patients most likely to respond to Acrivon's drug candidates and is used for rational drug design, predictive biomarkers, and indication finding.
The AP3 Interactome platform's ability to prospectively identify responders to ACR-368 is a significant achievement, potentially reducing the risk and cost of clinical development. The integration of machine learning into the AP3 Interactome for comprehensive analyses of phosphoproteomic data is cutting-edge and could accelerate drug discovery and development processes.
Market Opportunity and Financial Implications
The potential for ACR-368 in endometrial cancer represents a substantial market opportunity, estimated at approximately 30,000 new cases per year in the second-line setting. The company is actively evaluating potential confirmatory trial designs, including front line, for a potential future label expansion.
However, investors should note that while promising, these are still early-stage results. The company will need substantial capital to fund pivotal trials and potential commercialization efforts.
