8-K: Acrivon Therapeutics Announces Positive Phase 2 Data for ACR-368 in Endometrial Cancer and Advances ACR-2316 to Phase 1

Acrivon Therapeutics reported a 62.5% objective response rate in OncoSignature-positive endometrial cancer patients treated with ACR-368 and announced the advancement of ACR-2316 into Phase 1 trials.

Summary

• Acrivon Therapeutics presented positive Phase 2 clinical data for ACR-368 in endometrial cancer at the ESMO Congress 2024, showing a 62.5% objective response rate in OncoSignature-positive patients.
• The company's OncoSignature assay successfully predicted responders, with a statistically significant segregation of responders in the OncoSignature-positive group compared to the negative group (p-value = 0.009).
• The median duration of response for ACR-368 in endometrial cancer has not yet been reached, with all responders still on therapy at approximately 6 months at the time of the data cut-off.
• The Investigational New Drug application for ACR-2316, a dual WEE1/PKMYT1 inhibitor, has been cleared by the FDA, and the first-in-human dosing for the Phase 1 study is expected in the fourth quarter of 2024.
• Acrivon's AP3 Interactome platform is generating proprietary insights using machine learning to analyze phosphoproteomic data.
• The company reiterated that its existing cash, cash equivalents, and investments of $220.4 million as of June 30, 2024, are expected to fund operations into the second half of 2026.

Sentiment

Score: 8

Explanation: The document presents very positive clinical data for ACR-368, a promising pipeline update with ACR-2316, and a strong cash position. The sentiment is very positive due to the potential for a new treatment option in an area of high unmet need.

Positives

• The 62.5% objective response rate for ACR-368 in OncoSignature-positive endometrial cancer patients is very promising.
• The statistically significant segregation of responders based on the OncoSignature assay validates the company's precision medicine approach.
• The fact that the median duration of response has not yet been reached and all responders are still on therapy suggests a durable treatment effect.
• The FDA clearance of the IND for ACR-2316 ahead of schedule is a positive development for the company's pipeline.
• The AP3 Interactome platform is providing valuable insights for drug development and patient selection.
• The company's strong cash position provides financial stability and runway into the second half of 2026.

Negatives

• The data is based on a relatively small sample size of 23 efficacy-evaluable patients.
• The 95% confidence interval for the ORR in OncoSignature-positive patients is wide (30.4-86.5%), indicating some uncertainty in the estimate.
• While treatment-related adverse events were limited, hematological adverse events were observed.

Risks

• The clinical trial data is still preliminary and further studies are needed to confirm the efficacy and safety of ACR-368.
• The development of ACR-2316 is still in early stages, and there is no guarantee of success in clinical trials.
• The company's reliance on its AP3 platform for drug discovery and patient selection carries the risk that the platform may not perform as expected.
• The company's financial runway is dependent on its current cash position and may require additional funding in the future.

Future Outlook

The company expects its current cash to fund operations into the second half of 2026 and is actively evaluating potential confirmatory trial designs for ACR-368, including front line settings, and is planning for the first-in-human dosing of ACR-2316 in Q4 2024.

Management Comments

• Peter Blume-Jensen, M.D., Ph.D., chief executive officer, president, and founder of Acrivon, stated that the company is very excited to provide several significant, positive updates across its rapidly advancing clinical pipeline.
• He also noted that the endometrial cancer data confirms their AP3 indication finding screening approach and that the lower bound of the 95% confidence interval is now 30%, above their targeted goal for this metric.
• He further stated that the company believes endometrial cancer might provide the first potential approval opportunity for ACR-368.

Industry Context

This announcement is significant in the context of the evolving treatment landscape for endometrial cancer, where there is a high unmet need for effective second-line therapies after progression on anti-PD-1 treatments. The positive data for ACR-368 and the advancement of ACR-2316 position Acrivon as a potential player in this space.

Comparison to Industry Standards

• The reported 62.5% ORR for ACR-368 in OncoSignature-positive patients is significantly higher than the 14.7% ORR reported for chemotherapy in second-line endometrial cancer (Makker et al; N Engl J Medicine, 2022).
• The median PFS of 3.8 months for second-line chemotherapy also highlights the potential for ACR-368 to provide a more effective treatment option.
• The company is also comparing their results to the recent approval of pembrolizumab plus chemotherapy as a first-line treatment, which leaves a significant unmet need in the second-line setting.
• The company is also comparing their results to the recent approval of pembrolizumab plus chemotherapy as a first-line treatment, which leaves a significant unmet need in the second-line setting.
• The company is also comparing their results to the recent approval of pembrolizumab plus chemotherapy as a first-line treatment, which leaves a significant unmet need in the second-line setting.

Stakeholder Impact

• Shareholders will likely react positively to the strong clinical data and pipeline progress.
• Patients with endometrial cancer may benefit from a new treatment option with a higher response rate.
• Employees may be motivated by the company's progress and potential for success.
• The company's financial stability provides confidence to creditors and suppliers.

Next Steps

• The company will continue enrollment in ongoing multicenter phase 2 trials in ovarian and bladder cancer.
• The company will initiate a Phase 1 study for ACR-2316 in the fourth quarter of 2024.
• The company is actively evaluating potential confirmatory trial designs for ACR-368, including front line settings.
• The company will continue to advance its AP3 Interactome platform for drug discovery and patient selection.

Key Dates

Keywords

Acrivon Therapeutics, ACR-368, ACR-2316, Endometrial Cancer, OncoSignature, AP3 Interactome, Precision Medicine, Phase 2 Trial, Phase 1 Trial, WEE1/PKMYT1 Inhibitor, Objective Response Rate, Biomarker, FDA Clearance