ACR-2316 / Acrivon Therap - LARVOL DELTA

Study of ACR-2316 in Specific Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: Acrivon Therapeutics | Phase classification: P1 ➔ P1/2 | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Aug 2026 ➔ Aug 2027

First-in-human • Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Acrivon Predictive Precision Proteomics (AP3)-phosphoproteomics uncovers differential mechanisms driving superior activity of ACR-2316, a novel, clinical-stage WEE1/PKMYT1 inhibitor over clinical-stage WRN helicase inhibitors (EORTC-NCI-AACR 2026) - "Abstract will be available as of 4 November (with consent of the author)"

Clinical • Oncology • PKMYT1 • WRN

Acrivon Therapeutics, Inc…announced that ACR-2316 has advanced into the randomized dose expansion portion of its ongoing Phase 1/2 study. (GlobeNewswire) - "Acrivon has selected 120 mg and 160 mg administered orally once daily (QD) on a 3d on/4d off weekly schedule for further dose optimization and final dose selection...Two weekly (3d on / 4d off QD and 2d on / 5d off QD) oral dosing regimens have been established, while a bi-weekly (3d on / 11d off QD) oral dosing regimen was evaluated, but deprioritized; Amongst the subjects treated with ACR-2316 at ≥120 mg QD in the weekly schedules, tumor shrinkage with long-lasting clinical benefit were observed across multiple tumor types, including PRs in lung cancer and endometrial cancer; In the 7 efficacy-evaluable subjects (median 3 prior lines of systemic therapy) with SCLC, sqNSCLC, and adNSCLC, AP3-predicted tumor types not previously shown to be sensitive to clinical single agent WEE1 or PKMYT1 inhibitors, a disease control rate of 86% (2 PRs, 4 SD, and 1 PD) was observed."

P1 data • Trial status • Endometrial Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Acrivon to Highlight the Power of its AP3 Platform for Streamlined, Pathway-Based Drug Discovery and Development with Oral and Poster Presentations at AACR D3 Conference (GlobeNewswire) - "Data being presented illustrate how AP3 can uncover drug-induced resistance mechanisms, in this case WEE1 inhibition-induced activation of PKMYT1, resulting in phosphorylation of CDK1 on Thr14, a direct PKMYT1 phosphorylation site. Moreover, AP3 enabled the development of ACR-2316 based on optimal intracellular pathway effects, including sustained activation of CDK1, CDK2, but importantly and also of PLK1, to drive potent pro-apoptotic tumor cell death."

Clinical • Oncology

Anticipated Upcoming Milestones (The Manila Times) - “Additional ACR-2316 Phase 1/2 clinical data for weekly and bi-weekly dosing regimens and transition into dose expansion in AP3-identified tumor types in 2026; Submit IND filing to the FDA for ACR-6840, or alternative CDK11 inhibitor candidate, in first half of 2027; Initiate additional internal programs utilizing the AP3 platform in 2026.”

IND • P1/2 data • Pipeline update • Solid Tumor

ACR-2316: A potentially first-in-class, potent, selective WEE1/PKMYT1 inhibitor rationally designed for superior single agent activity through synergistic disruption of cell cycle checkpoints (AACR 2024) - "ACR-2316 is more selective than adavosertib, azenosertib, and lunresertib based on >200 kinases profiled by AP3 and 468 kinases assessed by KINOMEscan...In conclusion, ACR-2316 is a potent, selective dual WEE1/PKMYT1 inhibitor with superior single-agent activity compared to clinical WEE1 or PKMYT1 inhibitors. ACR-2316 is progressing through IND-enabling studies in preparation for clinical monotherapy development."

Oncology • Ovarian Cancer • Solid Tumor • CDK1 • CDK2 • CHEK1 • PKMYT1 • PLK1

Treatment with ACR-2316, a potential first- and best-in-class WEE1/PKMYT1 inhibitor, combined with anti-PD-L1 induces complete tumor regression with durable immune memory (AACR 2026) - "Our findings reveal the dual role of ACR-2316 in inducing tumor intrinsic DNA damage and promoting immune activation through multiple immune sensing mechanisms, resulting in permanent immune memory co-dependent on CD4+ and CD8+ T cell subsets. This provides a strong rationale for combining ACR-2316 with immune checkpoint inhibitors in the clinical setting. ACR-2316 is in a phase 1 monotherapy trial and has already shown initial clinical activity with tumor shrinkage and a confirmed partial response during dose escalation across solid tumors predicted by our AP3 platform to be sensitive to ACR-2316."

Colorectal Cancer • Oncology • Solid Tumor • CD4 • CD8 • IFIH1 • PKMYT1

Acrivon to Highlight Preclinical Data with Three Posters at AACR Demonstrating Strong ACR-368 and ACR-2316 Synergies with Immune Checkpoint Inhibitors and ADC Payloads, Revealing Broad Clinical Development Opportunities (GlobeNewswire) - "Potent preclinical efficacy with durable immune memory observed in combinations of either ACR-368 or ACR-2316 with anti-PD-L1 and strong synergy of ACR-368 with Topoisomerase 1 (Topo 1) inhibition. Data supports potential for frontline clinical combinations of ACR-368 and ACR-2316 with immune checkpoint inhibitors and of ACR-368 with Topo 1 antibody-drug conjugates (ADCs)."

Preclinical • Solid Tumor

Detailed mechanistic understanding of ACR-2316, a novel, clinical-stage WEE1/PKMYT1 inhibitor, rationally designed for superior single-agent activity through potent activation of CDK1, CDK2, and PLK1 using Acrivon's machine learning-driven AP3 platform (AACR 2025) - "The unique capabilities of our generative AI-driven AP3 platform used to rationally design ACR-2316 enabled a comprehensive analysis of ACR-2316-regulated CDK1/2-and PLK1-induced pathways underlying its differentiated, potent anticancer activity, as demonstrated in head:head preclinical studies against clinical benchmark inhibitors. ACR-2316 has advanced into the clinic ahead of schedule uniquely enabled by AP3 and is currently in a Phase 1 clinical trial in subjects with AP3-selected advanced solid tumors. Acrivon anticipates reporting initial ACR-2316 clinical Phase 1 data second half of 2025."

Clinical • First-in-human • Machine learning • Oncology • Solid Tumor • CDK1 • CDK2 • PKMYT1 • PLK1

Anticipated Upcoming Milestones (Acrivon Press Release) - "Provide additional update on Arm 1 and initial clinical data from Arm 3 of the ACR-368 Phase 2 trial in mid-2026; Achieve readiness for Phase 3 confirmatory trial for ACR-368 in combination with PD-1 therapy in mid-2026....Report additional ACR-2316 Phase 1 clinical data in weekly and bi-weekly dosing regimens and transition into dose expansion in select tumor types in 1H 2026....Initiate additional internal programs utilizing AP3 platform in 2H 2026."

P1 data • P2 data • Endometrial Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Initial data from Phase 1 dose escalation (N=33) for ACR-2316, a potential first-in-class WEE1/PKMYT1 inhibitor, showed favorable tolerability; two weekly oral dosing regimens (160 mg QD, 3d on/4d off and 240 mg QD, 2d on/5d off) established with a bi-weekly regimen initiated (Acrivon Press Release) - "A subject with high grade Mullerian EC (BRCA1/2 wt) enrolled at the 120 mg dose level, who had previously received prior platinum-based chemo and tamoxifen and second-line pembrolizumab-lenvatinib, had confirmed PR and was on therapy for 42 weeks; A subject with SCLC (MSS) enrolled at the established 160 mg dose level, who had previously received cisplatin/durvalumab, second-line tarlatamab and radiation therapy, achieved an unconfirmed PR (50% tumor shrinkage) at first scan (with subsequent scan showing further shrinkage (69%) of target lesion, but progression of liver metastases in non-target lesions after the date of EDC extract); A subject with squamous NSCLC (BRCA1 mutated) enrolled at the 240 mg dose level, but reduced to 200 mg in the first cycle, had previously received platinum-based chemo with durvalumab followed by three other immune therapies."

P1 data • Endometrial Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Acrivon Therapeutics...announced it will be providing ACR-368 and ACR-2316 clinical data and other updates in January 2026. (The Manila Times) - "Topics will include: Updated interim ACR-368 clinical data from the ongoing registrational-intent Phase 2b study as well as an update on the additional recently initiated tumor biopsy-independent Phase 2b arm, and the planned confirmatory Phase 3 trial; Initial clinical data from the ongoing Phase 1 study of ACR-2316, a potential first- and best-in-class WEE1/PKMYT1 inhibitor, including safety data, dosing regimen, and early clinical activity across AP3-prioritized solid tumor types; Nomination of new preclinical development candidate, including target disclosure, for Acrivon’s AP3-driven cell cycle program."

Clinical data • Pipeline update • Endometrial Adenocarcinoma • Squamous Cell Carcinoma of Head and Neck

ACR-2316 is a novel, differentiated, clinical-stage WEE1/PKMYT1 inhibitor designed by Acrivon's Generative Phosphoproteomics AP3 Platform for optimal pro-apoptotic pathway effects in tumor cells resulting in superior preclinical activity (AACR-NCI-EORTC 2025) - "In cellular TE assays, ACR-2316 displayed more potent WEE1 TE than all benchmark WEE1 inhibitors (azenosertib, adavosertib, Debio0123), while simultaneously targeting MYT1... WEE1 inhibitor-induced MYT1 activation constitutes a resistance mechanism that may limit the clinical efficacy of WEE1 inhibition. ACR-2316 is a potent, selective WEE1/MYT1 inhibitor that displays superior preclinical efficacy via its differentiated profile optimized by AP3 pathway-based structure-activity relationships in the intact cell. Acrivon's ongoing Phase 1 ACR-2316 monotherapy trial in solid tumors has already demonstrated clinical activity during dose escalation prior to reaching Recommended Phase 2 Dose."

Preclinical • Tumor cell • Oncology • Solid Tumor • BRAF • CDK1 • CDK2 • PKMYT1 • PLK1

Global pharmacodynamic effects uncovered with AP3 phosphoproteomic profiling of novel WEE1/PKMYT1 inhibitor ACR-2316 reveals the critical importance of PLK1 for ACR-2316's superior preclinical activity and differentiated mechanism of action (AACR-NCI-EORTC 2025) - "The clinical WEE1 inhibitors azenosertib and Debio0123, and the PKMYT1 inhibitor lunresertib were administered in parallel at maximum tolerated/formulable doses... ACR-2316 is a potential first- and best-in-class dual inhibitor of WEE1 and PKMYT1, rationally designed using Acrivon's proprietary AP3 platform to deliver superior single-agent efficacy. Potent activation of PLK1, together with CDK1/2, is essential for the superior activity of ACR-2316. ACR-2316 has shown clinical activity in its ongoing Phase 1b monotherapy trial in solid tumors during dose escalation."

PK/PD data • Preclinical • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • CDK1 • PKMYT1 • PLK1 • RRM2 • WEE1

Acrivon Therapeutics' generative ensemble model (KaiSR) accurately predicts and expands proprietary, actionable kinase-substrate relationships globally for the human kinome (AACR-NCI-EORTC 2025) - "AP3 was recently used for designing the in-house discovered, potentially first- and best-in-class compound ACR-2316, a WEE1/PKMYT1 dual inhibitor currently in a phase 1b trial...In conclusion, Acrivon's AP3 platform and generative AI model KaiSR uncover kinome-wide signaling networks generating unprecedented insights enabling a unique approach to target identification, streamlined drug discovery, and clinical development. Acrivon continues to leverage KaiSR and the full suite of its AP3 Generative Phosphoproteomics platform to expand and progress its proprietary pipeline of novel therapeutic candidates."

Clinical • Oncology • CDK1 • CDK2 • PKMYT1 • PLK1

Acrivon Therapeutics Reports First Quarter 2025 Financial Results and Business Highlights (Yahoo Finance) - "Anticipated Upcoming Milestones: (i) Provide update on registrational-intent trial and confirmatory trial design for ACR-368; (ii) Report initial clinical data from the Phase 1 clinical study of ACR-2316 in the second half of 2025; (iii) Advance a new potential first-in-class cell cycle drug discovery program for an undisclosed target towards development candidate nomination in 2025."

Clinical protocol • P1 data • Pipeline update • Solid Tumor

Acrivon Therapeutics to Reveal the Molecular Mechanisms Driving Strong Single-Agent Activity of ACR-2316, its AP3-Enabled Clinical Stage WEE1/PKMYT1 Inhibitor, at the AACR Annual Meeting 2025 (GlobeNewswire) - "Acrivon Therapeutics, Inc...announced it will present data from AP3 Generative Phosphoproteomic analyses of ACR-2316-regulated CDK1-, CDK2-, and PLK1-induced pathways at the American Association for Cancer Research (AACR) Annual Meeting taking place April 25-30, 2025 in Chicago."

Clinical • Oncology • Solid Tumor

Acrivon Therapeutics Provides Program Updates and Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "Anticipated Upcoming Milestones: Provide update on registrational intent trial and confirmatory trial design for ACR-368; Report initial clinical data from the Phase 1 clinical study of ACR-2316 in the second half of 2025."

Clinical protocol • P1 data • Solid Tumor

Acrivon stops developing Lilly castoff for ovarian and bladder cancers to switch focus to endometrial (FierceBiotech) - P1b/2b | N=390 | NCT05548296 | Sponsor: Acrivon Therapeutics | "The Watertown, Massachusetts-based biotech had been evaluating the CHK1/2 inhibitor, called prexasertib or ACR-368, in a phase 2b trial of patients with endometrial cancer....Based on an interim data extract, Acrivon was able to show that the OncoSignature 'accurately identified patients whose tumors are sensitive to ACR-368,' with 80% of these individuals seeing their tumor shrink to some extent, according to Acrivon. This cohort saw a confirmed overall response rate of 35%....The company had already made endometrial cancer its top priority but used yesterday's filing to announce that it had now 'officially deprioritized ovarian and bladder cancers' as targets for ACR-368....The clinical resources for these two indications will be redirected to testing ACR-368 in endometrial cancer as well as toward Acrivon’s other clinical-stage candidate, ACR-2316."

P2b data • Pipeline update • Bladder Cancer • Endometrial Cancer • Ovarian Cancer

Acrivon Therapeutics Reports Third Quarter 2024 Financial Results and Business Highlights (GlobeNewswire) - "Provide program updates from our ongoing registrational-intent Phase 2b trial of ACR-368 in patients with gynecological cancers prospectively predicted sensitive to ACR-368 in the first half of 2025; Report initial data from the Phase 1 clinical study of ACR-2316, which is enriched for tumor types predicted to be sensitive to monotherapy through AP3-based indication finding, in the second half of 2025...Research and development expenses were $18.9 million for the quarter ended September 30, 2024 compared to $10.3 million for the same period in 2023. The difference was primarily due to the continued development of ACR-368..."

Commercial • P1 data • Trial status • Gynecologic Cancers • Oncology • Solid Tumor

Rational design of a superior single agent active, potential best-in-class WEE1/PKMYT1 inhibitor using Acrivon Predictive Precision Proteomics (AP3) (EORTC-NCI-AACR 2024) - "WEE1 inhibitors azenosertib and Debio0123, or the PKMYT1 inhibitor lunresertib, had a best response of stable disease at maximum achievable dose... ACR-2316 is a potent, selective dual inhibitor of WEE1 and PKMYT1, uniquely designed using Acrivon's AP3 platform for superior single agent activity through potent activation of CDK1, CDK2, and PLK1, and is on track for IND submission in Q3 2024 and first-in-human dosing in Q4 2024."

Oncology • Ovarian Cancer • Solid Tumor • CASP3 • CDK1 • CDK2 • PKMYT1 • PLK1

Acrivon Therapeutics to Present Data Demonstrating Deployment of its AP3 Platform for Streamlined Drug Discovery and Clinical Development at Two Scientific Conferences - Human Proteome Organization World Congress and EORTC-NCI-AACR Symposium (GlobeNewswire) - "Acrivon Therapeutics, Inc....announced the company will be presenting data on the ability of its AP3 platform to uniquely enable the clinical development of ACR-368 and the discovery and design of ACR-2316 at two upcoming scientific congresses: Human Proteome Organization (HUPO) World Congress taking place from October 20-24, 2024 in Dresden, Germany and EORTC-NCI-AACR (ENA) Symposium taking place from October 23-25, 2024 in Barcelona, Spain."

Clinical data • Oncology • Solid Tumor

Acrivon Therapeutics to Present Data Demonstrating Deployment of its AP3 Platform for Streamlined Drug Discovery and Clinical Development at Two Scientific Conferences - Human Proteome Organization World Congress and EORTC-NCI-AACR Symposium (GlobeNewswire) - "Acrivon Therapeutics, Inc...today announced the company will be presenting data on the ability of its AP3 platform to uniquely enable the clinical development of ACR-368 and the discovery and design of ACR-2316 at two upcoming scientific congresses: Human Proteome Organization (HUPO) World Congress taking place from October 20-24, 2024 in Dresden, Germany and EORTC-NCI-AACR (ENA) Symposium taking place from October 23-25, 2024 in Barcelona, Spain."

P2b data • Preclinical • Oncology • Solid Tumor

Phase 1 Study of ACR-2316 in Specific Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Acrivon Therapeutics

Metastases • New P1 trial • Oncology • Solid Tumor

Acrivon Therapeutics Announces Initial Patient Dosing in Phase 1 Trial of ACR-2316, a Novel WEE1/PKMYT1 Inhibitor Designed Using AP3 for Superior Single-Agent Activity (GlobeNewswire) - "Acrivon Therapeutics, Inc...today announced that the first patient has been dosed in its Phase 1 clinical trial evaluating ACR-2316, the company’s internally discovered, potent, selective WEE1/PKMYT1 inhibitor, designed by AP3 to overcome the limitations of single-target WEE1 and PKMYT1 inhibitors. ACR-2316 is initially being developed in selected solid tumors identified by AP3...'We look forward to progressing this trial and expect to report initial clinical data in the second half of 2025.'"

P1 data • Trial status • Oncology • Solid Tumor