Acrivon Therapeutics (NASDAQ:ACRV) highlighted new interim clinical results for its lead program ACR368 in endometrial cancer and provided early clinical and preclinical updates across its pipeline during a conference call hosted by CFO and Head of Investor Relations Adam Levy.
AP3 platform positioned as core of pipeline strategy
Chief Executive Officer, President, and Co-founder Peter Blume-Jensen said the company is centered on its predictive precision proteomics platform, AP3, which uses mass spectrometry and computational “generative phosphoproteomics” to identify compound effects on signaling pathways in intact cells. Blume-Jensen said the approach aims to enable predictive biomarkers for drug efficacy, support indication selection ahead of clinical testing, and guide drug discovery and resistance mechanism work.
ACR368 phase 2 endometrial cancer results: response signal in serous subtype
Chief Medical Officer Mansour Mirza reviewed an ongoing open-label phase 2, multi-center trial enrolling at 48 U.S. sites in relapsed endometrial cancer across histopathologies (including serous, clear cell, carcinosarcoma, and high-grade endometrioid). Eligible patients must have received prior platinum-based chemotherapy and an immune checkpoint inhibitor, with up to three prior systemic therapy lines allowed.
- Arm 1: biomarker-positive patients receive ACR368 monotherapy (described as registrational intent).
- Arm 2: biomarker-negative patients receive ACR368 plus ultra-low-dose gemcitabine (ULDG) as a sensitizer (exploratory).
At interim analysis, the company said 36 subjects were enrolled in Arm 1 and 16 in Arm 2. In Arm 1 (biomarker-positive ACR368 monotherapy), Acrivon reported an overall response rate (ORR) of 39% and a disease control rate (DCR) of over 80%, noting that final blinded independent central review (BICR) adjudication would be completed at the end of enrollment and that the interim figures reflected the best of BICR or investigator assessment.
Mirza also cited an ORR of 44% for biomarker-positive patients who had received up to two prior lines of therapy. In Arm 2 (biomarker-negative ACR368 + ULDG), the company reported an ORR of 26%. Mirza said ULDG’s role as a sensitizer was supported by AP3 platform work and by preclinical and prior clinical evidence, and he emphasized that 10 mg/m² gemcitabine was described as about 1% of a standard dose and, per the company, not expected to have activity on its own.
Looking by subtype, Acrivon said the serous subtype contributed most strongly to responses among biomarker-positive patients, with a confirmed ORR of 67% in biomarker-positive serous tumors. The company then highlighted what Mirza called a key message: among serous “all-comer” patients with up to two prior lines of therapy, Acrivon reported a confirmed ORR of 52%, compared with 22% in the non-serous population with up to two prior lines.
For disease control and clinical benefit at 16 weeks, Acrivon reported:
- Biomarker-positive: DCR 92%, clinical benefit rate 83%
- Biomarker-negative: DCR 55%, clinical benefit rate 45%
Management also discussed the serous endometrial cancer opportunity, stating that serous disease accounts for around 40% of endometrial cancer deaths. Blume-Jensen cited estimates of approximately 20,000 serous endometrial cancer deaths per year in the U.S. and EU combined and a prevalence pool estimate of 55,000–60,000 patients, while describing limited options in later lines of therapy.
New Arm 3 and phase 3 protocol submission described
In response to the observed activity in serous disease, Mirza said the company initiated an Arm 3 evaluating ACR368 with ULDG in biomarker-unselected serous endometrial cancer patients with up to two prior lines of therapy. He said the trial is ongoing at 48 U.S. sites and is being expanded to more than 20 EU sites in France, Germany, Italy, and Spain, and he characterized Arm 3 as a potential “fastest path” to approval. Blume-Jensen added that Arm 3 is designed as an all-comer approach without biopsy or biomarker requirements upfront, with retrospective OncoSignature assessment.
Separately, Blume-Jensen said the company submitted a phase 3 confirmatory trial protocol to the FDA on November 12, 2025. The planned study was described as a double-blind, placebo-controlled switch maintenance trial in advanced and/or recurrent pMMR endometrial cancer, with the goal of improving progression-free and overall survival by adding ACR368 to anti-PD-1 therapy in maintenance. The rationale cited included preclinical synergy with immunotherapy in mouse models.
ACR2316 early phase 1 update and ACR6840 preclinical candidate disclosure
Acrivon also provided initial clinical observations for ACR2316, its internally developed oral dual WEE1/PKMYT1 inhibitor. Mirza said 33 patients have been dosed in two weekly dosing regimens in an ongoing phase 1 monotherapy dose escalation study: 160 mg daily (three days on, four days off) and 240 mg daily (two days on, five days off). The company also initiated a biweekly schedule (two days on, 12 days off) based on a rationale that Cmax drives tumor cell killing and observed transient neutropenia.
On safety, Mirza said tolerability was encouraging and primarily limited to transient, mechanism-based adverse events, mainly neutropenia. He added that the company did not observe grade 3 or higher non-hematological adverse events. In the 160 mg schedule, no grade 4 toxicity was observed; in the 240 mg schedule, one subject had grade 4 neutropenia.
On activity, Acrivon reported tumor shrinkage in 9 out of 20 evaluable patients treated at dose levels of 120 mg and above, and highlighted activity in tumor types the company said had not shown sensitivity to prior clinical WEE1/PKMYT1 inhibitors, including small cell lung cancer and squamous non-small cell lung cancer.
Finally, Levy introduced a new preclinical development candidate, ACR6840, targeting CDK11, which management described as a master regulator of the cell cycle with roles including mRNA processing/splicing and mitotic control. Levy said the company observed selectivity, potency, and preclinical anti-tumor activity, including downregulation of MCL1 and apoptosis induction in an AML cell line. Acrivon guided to an IND submission in Q4 of the current year.
In closing financial comments, Levy said the company ended the quarter on December 31, 2025 with approximate cash and investments of $119 million and reiterated projected runway into Q2 2027, noting the figures were preliminary and unaudited.
About Acrivon Therapeutics (NASDAQ:ACRV)
Acrivon Therapeutics (NASDAQ:ACRV) is a clinical-stage biotechnology company focused on the discovery and development of stapled peptide therapeutics for the treatment of RAS-driven cancers. Its proprietary platform is designed to enhance the stability, cell permeability and target specificity of peptide molecules, enabling the disruption of protein–protein interactions that are traditionally challenging to inhibit with small-molecule drugs or biologics.
The company’s lead development candidate is a hydrocarbon-stapled peptide selectively targeting the KRAS G12C mutation, currently in early clinical trials.
