Acrivon Therapeutics (NASDAQ:ACRV) used its presentation at the 46th annual TD Cowen healthcare conference to highlight progress on its lead clinical program, ACR-368, and provide an update on earlier-stage pipeline efforts built from its AP3 precision medicine platform.
AP3 platform positioned as a precision proteomics engine
Chief Executive Officer and President Peter Blume-Jensen described Acrivon’s AP3 platform as a proteomics-based precision medicine approach that is “driven by generative AI.” He said the company uses the platform to assess, in an unbiased way, how a drug affects signaling pathways inside cells. That pathway-level readout is then used to help design molecules with specific pathway effects and to identify factors that may drive tumor survival or resistance.
ACR-368 data in endometrial cancer, with focus on serous subtype
Blume-Jensen discussed recent engagement with clinicians at ESGO, including an expert panel of gynecologic cancer specialists. He said panelists expressed strong enthusiasm for ACR-368, which he described as a dual CHK1/2 inhibitor, particularly in serous endometrial cancer—an aggressive subtype he characterized as having limited treatment options and contributing disproportionately to mortality.
He framed serous endometrial cancer as a high unmet need setting, stating that it accounts for about half of endometrial cancer mortality despite a smaller incidence, and that most cases are p53-mutated and pMMR, with only modest benefit from immunotherapy. He referenced second-line and later outcomes from KEYNOTE-775, citing a 15% response rate and median progression-free survival (PFS) of about 3.4 months.
Trial structure: Arm 1 biomarker strategy and new serous expansion arm
The company’s ongoing Phase 2 study includes multiple arms. Blume-Jensen described Arm 1 as “registrational intent” and based on a prospective protein-based biomarker, the company’s “OncoSignature,” intended to predict benefit from ACR-368 across endometrial cancer subtypes. He reported that, at the time of the analysis discussed, Arm 1 showed a 44% confirmed response rate, with two additional responses not yet confirmed.
He said the company also explored an “ultra-low dose” gemcitabine (ULDG) approach, based on AP3 findings that ULDG could sensitize tumors to ACR-368 in resistant settings. Arm 2 was described as exploratory and designed to assess that contribution, and Blume-Jensen said Arm 2 has been completed.
Based on additional analysis from the ongoing study, the company identified what it characterized as a high response rate in serous endometrial cancer. Blume-Jensen said serous patients represented roughly 35% to 40% of second- and third-line patients in the study and reported an approximately 50% confirmed response rate in the serous subgroup, “regardless biomarker status,” along with deep responses in a waterfall plot.
He also emphasized tolerability, saying ACR-368’s adverse events have been primarily hematologic and transient, with febrile neutropenia occurring in a small percentage. He contrasted this with adverse events he associated with other treatment classes, stating the company has not observed issues such as interstitial lung disease, gastrointestinal toxicities, stomatitis, ocular toxicity, or peripheral neuropathy in its ACR-368 dataset as presented. He cited a disease control/clinical benefit rate of 65% beyond 16 weeks and described durability as “approaching 6 months.”
Enrollment expectations and regulatory framing
Acrivon has added a new Arm 3 focused on serous endometrial cancer and expanded the study in a way that does not require a pre-treatment tumor biopsy. Blume-Jensen said removing the biopsy requirement materially improves feasibility, particularly in Europe, and described the serous histology as a “lineage biomarker” that can be determined through routine pathology subtyping.
He said Arm 3 has opened and is being initiated across four major European countries, with anticipated enrollment completion of up to 90 patients by the beginning of the fourth quarter of the year. He also said the company believes an interim readout “much, much earlier” could be informative and noted ongoing dialogue with the FDA.
On the efficacy bar for accelerated approval, Blume-Jensen suggested that even a lower response rate than the company has observed to date could remain meaningfully above standard of care in serous endometrial cancer, referencing a lower bound confidence interval of 33% and stating the company believes a response rate in the “35%+” range, combined with observed durability and safety, could be sufficient. He said Arm 1 and Arm 3 are both registrational-intent.
Discussing potential adoption, he cited comments from the ESGO expert panel indicating physicians would use the drug in a significant portion of patients if the data hold up, describing estimates of at least 75% in second line and 100% in third line, with second-line use influenced by HER2-targeted therapy practices in HER2-positive patients.
Confirmatory trial concept and pipeline updates: ACR-2316 and CDK11
For a potential confirmatory Phase 3 strategy, Blume-Jensen said the company has submitted a Phase 3 protocol design and statistical analysis plan based on combining ACR-368 with immunotherapy. He described preclinical rationale including complete regression and immune memory in a syngeneic mouse model when ACR-368 was combined with immunotherapy. He also discussed the potential for synergy with topoisomerase I inhibitors, which he said are common payloads for many antibody-drug conjugates (ADCs), outlining a resistance rationale in which CHK1/2-mediated DNA repair becomes a vulnerability after topo I exposure. He added that the submitted protocol was developed before the company’s insight into serous sensitivity and could potentially be modified to include hierarchical testing starting with serous disease.
Blume-Jensen noted Acrivon has publicly stated it expects “trial readiness” for the combination program by mid-year and said the company is in discussions with large pharmaceutical companies that have immunotherapy agents.
Turning to the pipeline, Blume-Jensen provided an update on ACR-2316, which he described as an internally developed dual WEE1/PKMYT1 inhibitor designed using AP3 to address resistance mechanisms to WEE1 inhibition. He said the molecule is intended to provide superior single-agent activity and reported that, in preclinical comparisons, the company observed strong pro-apoptotic tumor cell death and complete regressions across tested models. He said early clinical activity has been seen during dose escalation, including in small cell lung cancer and squamous non-small cell lung cancer—tumor types he said have not previously been sensitive to other WEE1 or PKMYT1 inhibitors. He cited an 80% disease control rate in active doses (120 mg and above) during dose escalation and said 9 out of 20 patients had tumor shrinkage. He also said the observed adverse events have been primarily transient neutropenia.
Blume-Jensen said the company has developed two weekly oral dosing regimens and is evaluating a bi-weekly schedule intended to allow bone marrow recovery. He indicated expansion tumor types could include lung cancer, based on observed activity and unmet need.
Finally, he discussed a newly declared development candidate targeting CDK11, calling it a potentially first-in-class program. He described CDK11 as a master regulator of the cell cycle with broad roles in global transcription and cell cycle progression. He said the program is in IND-enabling studies, early rodent toxicology has been encouraging, and the company plans to have an IND ready by the end of the year.
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.
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