8-K: Acrivon Unveils Strong Clinical Data for ACR-368 & ACR-2316

Acrivon Therapeutics presented positive clinical data for its lead oncology candidates, ACR-368 and ACR-2316, alongside updates on its AP3 platform and a new development candidate, ACR-6840.

Summary

• ACR-368, a CHK1/2 inhibitor, demonstrated an Overall Response Rate (ORR) of 39% as a single agent and 26% with ULDG sensitization in OncoSignature-positive (BM+) endometrial cancer subjects with at least two prior lines of therapy.
• In BM+ endometrial cancer subjects with at least two prior lines, ACR-368 monotherapy achieved an ORR of 44%, with a 67% ORR in serous subtype patients.
• For all-comer serous endometrial cancer subjects (biomarker-unselected) with at least two prior lines, ACR-368 with ULDG sensitization showed an ORR of 52%, with a Disease Control Rate (DCR) of 92% and Clinical Benefit Rate (CBR) of 83% in BM+ serous subjects.
• ACR-2316, a WEE1/PKMYT1 inhibitor, showed initial clinical activity in AP3-predicted solid tumor types, including confirmed partial responses (PR) in endometrial cancer, squamous non-small cell lung cancer (Sq NSCLC), and small cell lung cancer (SCLC), which are tumor types not typically sensitive to previous WEE1/PKMYT1 inhibitors.
• Weekly oral dosing regimens for ACR-2316 (160 mg QD 3d on/4d off and 240 mg QD 2d on/5d off) have been established with a favorable tolerability profile, primarily transient neutropenia.
• Acrivon nominated ACR-6840 as a new preclinical cell cycle development candidate, a potential first-in-class, potent, selective, orally available CDK11 inhibitor.
• The company reported approximate cash and investments of $119 million as of December 31, 2025, providing a projected runway into Q2 2027, assuming no additional financing.
• Fully diluted shares outstanding were approximately 45.1 million as of December 31, 2025.

Sentiment

Score: 9

Explanation: The filing presents highly positive clinical data for both lead candidates, ACR-368 and ACR-2316, in challenging oncology indications. The high response rates, favorable safety profiles, validation of the AP3 platform, and the introduction of a promising new development candidate (ACR-6840) indicate strong progress and future potential. The projected cash runway also provides stability.

Positives

• ACR-368 monotherapy achieved a 67% ORR in OncoSignature-positive serous endometrial cancer subjects with at least two prior lines of therapy, indicating high sensitivity.
• ACR-368 with ULDG sensitization demonstrated a 52% ORR in biomarker-unselected serous endometrial cancer subjects with at least two prior lines, addressing a significant unmet medical need.
• ACR-368 has Breakthrough Device & Fast Track Designations, potentially accelerating regulatory pathways.
• Preclinical data shows strong synergy of ACR-368 with anti-PD-(L)1 therapy, resulting in complete tumor regression and immune memory in 100% of mice, supporting a planned Phase 3 trial.
• ACR-368 exhibits a favorable tolerability profile with only transient, mechanism-based hematological adverse events (AEs) and notable absence of non-hematological AEs.
• ACR-2316 demonstrated initial clinical activity, including partial responses, in AP3-predicted tumor types like SCLC and Sq NSCLC, which have historically been challenging for WEE1/PKMYT1 inhibitors.
• ACR-2316 has a favorable tolerability profile with transient, mechanism-based hematological AEs, primarily neutropenia, and a notable absence of GI toxicities or long-lasting myelosuppression.
• The AP3 Generative Phosphoproteomics platform is validated by the clinical activity of ACR-2316 in AP3-predicted tumor types, fueling streamlined drug development.
• ACR-6840, a potential first-in-class CDK11 inhibitor, shows promising preclinical antitumor activity, high selectivity, and synergy with BCL2 inhibitors.
• The company has a projected cash runway into Q2 2027, providing financial stability for ongoing development.

Risks

• Forward-looking statements are subject to risks and uncertainties, including factors described in SEC filings, and actual results may differ materially from projections.
• New risks and uncertainties may emerge over time, which are not currently predictable and could impact forward-looking statements.

Future Outlook

Acrivon plans to initiate a Phase 3 confirmatory trial for ACR-368 plus anti-PD-1 in frontline treatment for MMRp, primary advanced or recurrent endometrial cancer, based on strong preclinical synergy. Enrollment for the ACR-368-201 Arm 3 (all-comer serous EC) is anticipated to be completed in Q4 2026, with initial data expected mid-2026. For ACR-2316, a bi-weekly oral dosing regimen is being explored for maximal dosing flexibility, and potential development paths include single agent in later lines or combination therapy with chemotherapy, anti-PD(L)1, and TOPO1 payload ADCs. An IND submission for the new CDK11 inhibitor, ACR-6840, is targeted for Q4 2026.

Management Comments

• Peter Blume-Jensen, CEO, President, and Co-Founder, highlighted Acrivon's Generative AI-driven AP3 platform as enabling an exact match between disease-driving pathways and drug mechanisms of action.
• The team emphasized the importance of balanced inhibition of CHK1 and CHK2 for RECIST monotherapy activity of ACR-368.
• Management believes the potent synergy of ACR-368 with anti-PD-L1, demonstrating immune memory in 100% of mice, provides a strong rationale for a confirmatory Phase 3 trial.
• The team noted that ACR-2316's superior single agent activity, high selectivity, and potency were designed using Acrivon's AP3 platform.
• Management highlighted that ACR-2316's established weekly oral dosing regimens with a favorable tolerability profile provide strong rationale for exploring a bi-weekly regimen for potent tumor cell killing and maximal dosing flexibility.
• The team underscored that the AP3 Generative Phosphoproteomics platform is fueling streamlined drug development and clinical deliverables.

Industry Context

The announcement positions Acrivon as a key player in precision oncology, leveraging its AP3 platform to address significant unmet needs in aggressive cancers like serous endometrial cancer, SCLC, and Sq NSCLC. Serous endometrial cancer, accounting for ~40% of endometrial cancer deaths, currently has limited effective targeted therapies and poor durability of responses with existing treatments. The observed clinical activity of ACR-368 and ACR-2316 in these challenging tumor types, particularly where other WEE1/PKMYT1 inhibitors have not shown sensitivity, suggests a potential for Acrivon's candidates to offer new therapeutic options and improve patient outcomes beyond current standards of care, which often yield low ORRs and short PFS in later lines.

Comparison to Industry Standards

• For serous endometrial cancer in the 3rd line, the standard of care (SOC) with single agent chemotherapy typically yields an ORR of ~10-14% and ~3 months PFS. ACR-368 monotherapy in BM+ serous endometrial cancer subjects (with at least two prior lines) achieved an ORR of 67%, significantly outperforming the SOC.
• ACR-2316 demonstrated initial clinical activity, including partial responses, in SCLC and squamous NSCLC, tumor types that have not shown sensitivity to previous clinical WEE1 or PKMYT1 inhibitors, suggesting a potential advantage over competitors in these indications.
• Preclinical studies showed ACR-2316 to be 5-20-fold more potent than clinical benchmarks, with complete tumor regression, indicating a potentially superior efficacy profile.

Stakeholder Impact

• Shareholders: Positive clinical data and pipeline expansion could lead to increased investor confidence and potential share price appreciation.
• Patients: The promising efficacy and favorable tolerability of ACR-368 and ACR-2316 offer potential new treatment options for patients with aggressive and difficult-to-treat cancers, particularly serous endometrial cancer, SCLC, and Sq NSCLC.
• Healthcare Providers: New therapeutic options could provide clinicians with more effective tools for managing advanced cancers, especially in areas of high unmet need.

Next Steps

• Start of ACR-368 clinical data and dose expansion in 1H 2026.
• ACR-368 clinical update and Phase 3 confirmatory trial readiness by Mid-2026.
• Initial clinical data for ACR-368 + ULDG sensitization by Mid-2026.
• Enrollment completion for ACR-368-201 Arm 3 (all-comer serous EC) in Q4 2026.
• Submission of Phase 3 trial design and protocol for ACR-368 plus anti-PD-1 to the FDA.
• Exploration of a bi-weekly oral dosing regimen for ACR-2316 (2d on/12d off).
• IND Submission for ACR-6840 (CDK11 inhibitor) in Q4 2026.

Key Dates

Recommendation

The clinical data presented for ACR-368 in serous endometrial cancer is exceptionally strong, with an ORR of 67% in a biomarker-selected population and 52% in an all-comer serous population, significantly exceeding current standards of care. The initial clinical activity of ACR-2316 in previously insensitive tumor types like SCLC and Sq NSCLC, coupled with a favorable safety profile, further validates Acrivon's AP3 platform and pipeline. The introduction of a promising new preclinical candidate, ACR-6840, adds to the long-term growth potential. With a solid cash runway into Q2 2027 and clear next steps towards registrational trials, Acrivon demonstrates robust progress and significant upside potential, making it a strong buy for investors.

Keywords

Acrivon Therapeutics, ACR-368, ACR-2316, ACR-6840, Endometrial Cancer, Serous Endometrial Cancer, CHK1/2 Inhibitor, WEE1/PKMYT1 Inhibitor, CDK11 Inhibitor, OncoSignature, AP3 Platform, Precision Medicine, Oncology, Clinical Data, Phase 2b, Phase 1, Small Cell Lung Cancer, Squamous Non-Small Cell Lung Cancer, Drug Development, Biotechnology