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
Acrivon Therapeutics (NASDAQ: ACRV) announced upcoming data presentation at AACR Annual Meeting 2025 regarding their clinical-stage drug candidate ACR-2316, a selective WEE1/PKMYT1 inhibitor. The Phase 1 trial is progressing ahead of schedule, with three dose-escalation cohorts completed without safety concerns.
Key highlights include:
- ~25% RECIST tumor shrinkage observed at dose level 3
- Drug target engagement confirmed at dose levels 1 and 2
- No dose-limiting toxicities reported
- Currently enrolling dose level 4
The presentation will reveal how ACR-2316, developed using their AP3 Generative Phosphoproteomic platform, induces mitotic and replicative tumor cell death. The drug has shown superior anti-cancer activity in preclinical studies compared to benchmark inhibitors.
Acrivon Therapeutics (NASDAQ: ACRV) ha annunciato la prossima presentazione dei dati al AACR Annual Meeting 2025 riguardante il loro candidato farmaco in fase clinica ACR-2316, un inibitore selettivo di WEE1/PKMYT1. Lo studio di Fase 1 procede in anticipo rispetto ai tempi previsti, con tre coorti di dose-escalation completate senza problemi di sicurezza.
Punti salienti:
- Riduzione del tumore del ~25% secondo i criteri RECIST al livello di dose 3
- Confermata l’attivazione del bersaglio farmacologico ai livelli di dose 1 e 2
- Assenza di tossicità dose-limitante
- Attualmente in corso il reclutamento per il livello di dose 4
La presentazione mostrerà come ACR-2316, sviluppato con la piattaforma AP3 Generative Phosphoproteomic, induca la morte delle cellule tumorali mitotiche e replicative. Il farmaco ha dimostrato un’attività anticancro superiore negli studi preclinici rispetto agli inibitori di riferimento.
Acrivon Therapeutics (NASDAQ: ACRV) anunció la próxima presentación de datos en la Reunión Anual AACR 2025 sobre su candidato a fármaco en fase clínica ACR-2316, un inhibidor selectivo de WEE1/PKMYT1. El ensayo de Fase 1 avanza antes de lo previsto, con tres cohortes de escalada de dosis completadas sin preocupaciones de seguridad.
Puntos clave:
- Reducción tumoral del ~25% según RECIST en el nivel de dosis 3
- Confirmada la interacción con el objetivo farmacológico en los niveles de dosis 1 y 2
- No se reportaron toxicidades limitantes de dosis
- Actualmente se está reclutando para el nivel de dosis 4
La presentación mostrará cómo ACR-2316, desarrollado con la plataforma AP3 Generative Phosphoproteomic, induce la muerte de células tumorales mitóticas y replicativas. El fármaco ha mostrado una actividad anticancerígena superior en estudios preclínicos en comparación con inhibidores de referencia.
Acrivon Therapeutics (NASDAQ: ACRV)는 임상 단계 약물 후보인 ACR-2316에 관한 2025년 AACR 연례회의 데이터 발표를 예고했습니다. ACR-2316은 선택적 WEE1/PKMYT1 억제제입니다. 1상 임상시험은 예정보다 빠르게 진행 중이며, 세 개의 용량 증량 코호트가 안전 문제 없이 완료되었습니다.
주요 내용은 다음과 같습니다:
- 3단계 용량에서 약 25% RECIST 종양 축소 관찰
- 1단계 및 2단계 용량에서 약물 표적 결합 확인
- 용량 제한 독성 보고 없음
- 현재 4단계 용량 모집 중
발표에서는 AP3 Generative Phosphoproteomic 플랫폼을 사용해 개발된 ACR-2316이 유사분열 및 복제 중인 종양 세포 사멸을 어떻게 유도하는지 설명할 예정입니다. 이 약물은 전임상 연구에서 기준 억제제 대비 우수한 항암 효과를 보였습니다.
Acrivon Therapeutics (NASDAQ : ACRV) a annoncé la prochaine présentation des données lors de la réunion annuelle AACR 2025 concernant leur candidat médicament en phase clinique ACR-2316, un inhibiteur sélectif de WEE1/PKMYT1. L’essai de phase 1 progresse plus rapidement que prévu, avec trois cohortes d’escalade de dose complétées sans problèmes de sécurité.
Points clés :
- Réduction tumorale d’environ 25 % selon RECIST au niveau de dose 3
- Engagement de la cible confirmé aux niveaux de dose 1 et 2
- Aucune toxicité limitante liée à la dose rapportée
- Recrutement en cours pour le niveau de dose 4
La présentation dévoilera comment l’ACR-2316, développé grâce à leur plateforme AP3 Generative Phosphoproteomic, induit la mort des cellules tumorales mitotiques et en phase de réplication. Le médicament a démontré une activité anticancéreuse supérieure dans les études précliniques par rapport aux inhibiteurs de référence.
Acrivon Therapeutics (NASDAQ: ACRV) kündigte die bevorstehende Datenpräsentation auf dem AACR Annual Meeting 2025 zu ihrem klinischen Wirkstoffkandidaten ACR-2316 an, einem selektiven WEE1/PKMYT1-Inhibitor. Die Phase-1-Studie verläuft schneller als geplant, mit drei abgeschlossenen Dosis-Eskalationskohorten ohne Sicherheitsbedenken.
Wichtige Highlights:
- ~25 % Tumorverkleinerung nach RECIST bei Dosisstufe 3
- Wirkstoffbindung an Zielmoleküle bei Dosisstufen 1 und 2 bestätigt
- Keine dosislimitierenden Toxizitäten gemeldet
- Derzeit Rekrutierung für Dosisstufe 4
Die Präsentation wird zeigen, wie ACR-2316, entwickelt mit der AP3 Generative Phosphoproteomic-Plattform, den mitotischen und replizierenden Zelltod von Tumoren induziert. Das Medikament zeigte in präklinischen Studien eine überlegene krebshemmende Wirkung im Vergleich zu Referenzinhibitoren.
- Early clinical efficacy with 25% tumor shrinkage at dose level 3
- No safety concerns or dose-limiting toxicities in first three cohorts
- Confirmed drug target engagement at initial dose levels
- Trial progressing ahead of schedule
- Current dose level 3 is well below projected recommended Phase 2 dose, indicating potential need for higher doses
Insights
ACRV's ACR-2316 shows promising early efficacy with 25% tumor shrinkage in Phase 1 at low doses, demonstrating target engagement with clean safety profile.
The preliminary Phase 1 data for Acrivon's WEE1/PKMYT1 inhibitor ACR-2316 represents a significant early clinical validation of their approach. Three dose cohorts have been completed without dose-limiting toxicities, and the fourth is enrolling - importantly, this is ahead of the expected timeline. What's particularly compelling is the observation of ~25% tumor shrinkage at dose level 3, which is substantially below the projected recommended Phase 2 dose. This suggests a potentially wide therapeutic window.
The drug's mechanistic profile targeting both WEE1 and PKMYT1 represents a differentiated approach compared to single-target inhibitors. Their proprietary AP3 platform appears to be providing two crucial advantages: first, in the drug design itself through their "Generative Phosphoproteomic" approach, and second, in patient selection by identifying tumor types predicted to be sensitive to ACR-2316.
Target engagement biomarkers were detected even at the lowest dose levels (1 and 2), with evidence of dose proportionality in pharmacokinetic analyses. This pharmacodynamic confirmation supports that the drug is working as designed mechanistically. The upcoming AACR presentation will provide deeper insights into how ACR-2316 induces mitotic and replicative tumor cell death through CDK1, CDK2, and PLK1 pathways - mechanisms that appear central to its differentiated activity profile observed in preclinical studies.
The early clinical activity observed with ACR-2316 deserves attention from a clinical oncology perspective. Observing ~25% RECIST tumor shrinkage and reduction of metastatic lesions throughout multiple anatomical sites (chest, abdomen, pelvis) at just the third dose level signals potentially meaningful anti-tumor activity. While this doesn't yet meet the formal RECIST threshold for partial response (≥30%), it's remarkably close for such an early stage in dose escalation.
The dual inhibition of WEE1 and PKMYT1 represents a sophisticated approach to cell cycle checkpoint modulation. By targeting both kinases simultaneously, ACR-2316 appears designed to achieve more complete inhibition of the G2/M checkpoint than single-target approaches. Cancer cells often rely on these checkpoints when DNA damage occurs, and comprehensive inhibition forces damaged cells into mitosis, triggering cell death.
What's scientifically intriguing is Acrivon's use of their AP3 platform to analyze phosphoproteomic changes induced by their compound, revealing downstream effects on CDK1, CDK2, and PLK1 pathways. This level of mechanistic understanding is uncommon in early clinical development and suggests a highly rational design approach. The absence of dose-limiting toxicities through three cohorts is encouraging from a safety perspective, as cell cycle inhibitors can sometimes exhibit narrow therapeutic windows due to effects on normal proliferating tissues. The presence of clinical activity well below the projected recommended Phase 2 dose indicates potential for optimizing the efficacy-toxicity balance.
Presentation to highlight how AP3 Generative Phosphoproteomic analyses uncover how ACR-2316 induces mitotic and replicative tumor cell death, and the mechanisms underlying its superior potency observed preclinically
Phase 1 trial of ACR-2316 ahead of schedule with three dose-escalation cohorts completed; solid tumor shrinkage already observed at dose level three, well below the projected recommended Phase 2 dose
WATERTOWN, Mass., April 25, 2025 (GLOBE NEWSWIRE) -- Acrivon Therapeutics, Inc. (“Acrivon” or “Acrivon Therapeutics”) (Nasdaq: ACRV), a clinical stage precision medicine company utilizing its Acrivon Predictive Precision Proteomics (AP3) platform for the discovery, design, and development of drug candidates through a mechanistic match to patients whose disease is predicted sensitive to the specific treatment, 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.
ACR-2316 is a selective WEE1/PKMYT1 inhibitor, which has shown differentiated and superior anti-cancer activity in preclinical studies against clinical benchmark inhibitors and is currently in an ongoing Phase 1 monotherapy clinical study. Using AP3-based Indication Finding and AP3-based analyses of in-house and publicly available data, the company is enrolling patients in the clinical trial with certain high unmet need solid tumor types selected based on predicted sensitive to ACR-2316. Dose levels (DLs) 1, 2 and 3 have been cleared without safety concerns or dose-limiting toxicities (DLTs) by the safety review committee, and DL4 is now enrolling. Drug target engagement was observed already at DLs 1 and 2 using the company’s clinical mass-spectrometry-based AP3 profiling, with evidence of approximate dose proportionality based on plasma pharmacokinetic analyses. Notably, initial clinical activity of ~
“ACR-2316 was rationally designed through AP3-based SAR to induce desirable anti-tumor pathway effects inside a cell and to overcome the limitations of single-target WEE1 and PKMYT1 inhibitors. Our Phase 1 study of ACR-2316 is advancing rapidly, and we are excited about these encouraging observations, including early clinical activity,” said Peter Blume-Jensen, M.D., Ph.D., chief executive officer, president, and founder of Acrivon Therapeutics. “Uniquely enabled by our Generative Phosphoproteomics AP3 platform, ACR-2316 is optimized to achieve superior single-agent activity, complete tumor regression and pro-apoptotic tumor cell death with a favorable therapeutic index, as demonstrated in preclinical studies. At AACR, we look forward to sharing exciting data which show how signaling pathways acted upon by ACR-2316 mechanistically deliver potent activity.”
Poster Details:
| Poster Title: | 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 Generative Phosphoproteomics AP3 platform |
| Abstract Number: | 357 |
| Poster Section / No: | 17 / 1 |
| Session Category: | Experimental and Molecular Therapeutics |
| Session Title: | Cell Cycle Effects of Anticancer Drugs |
| Presenter: | Lei Shi, Ph.D. |
| Date and Time: | Sunday, April 27 | 2:00-5:00 p.m. CT |
About Acrivon Therapeutics
Acrivon is a clinical stage biopharmaceutical company discovering and developing precision oncology medicines for patients whose tumors are predicted to be sensitive to each specific medicine by utilizing its proprietary Generative Phosphoproteomics platform, Acrivon Predictive Precision Proteomics, or AP3. The AP3 platform is engineered to measure compound-specific effects on the entire tumor cell protein signaling network and drug-induced resistance mechanisms in an unbiased manner yielding terabytes of high resolution proprietary quantitative data for pathway-based drug design, indication finding, and response prediction. These distinctive capabilities enable AP3’s direct application for streamlined rational drug discovery for monotherapy activity, the identification of rational drug combinations, and the creation of drug-specific proprietary OncoSignature companion diagnostics that are used to identify the patients most likely to benefit from Acrivon’s drug candidates. Acrivon is currently advancing its lead candidate, ACR-368 (also known as prexasertib), a selective small molecule inhibitor targeting CHK1 and CHK2 in a potentially registrational Phase 2 trial, focusing on endometrial cancer. The company has received Fast Track designation from the Food and Drug Administration, or FDA, for the investigation of ACR-368 as monotherapy based on OncoSignature-predicted sensitivity in patients with endometrial cancer. Acrivon’s ACR-368 OncoSignature test, which has not yet obtained regulatory approval, has been extensively evaluated in preclinical studies, including in two separate, blinded, prospectively-designed studies on pretreatment tumor biopsies collected from past third-party Phase 2 trials in patients with ovarian cancer treated with ACR-368. The FDA has granted Breakthrough Device designations for the ACR-368 OncoSignature assay for the identification of patients with endometrial cancer who may benefit from ACR-368 treatment.
In addition to ACR-368, Acrivon is also leveraging its proprietary AP3 precision medicine platform for developing its co-crystallography-driven, internally discovered pipeline programs. These include ACR-2316, the company’s second clinical stage asset, a novel, potent, selective WEE1/PKMYT1 inhibitor designed for superior single-agent activity through strong activation of not only CDK1 and CDK2, but also of PLK1 to drive pro-apoptotic cell death, as demonstrated in preclinical studies against benchmark inhibitors. In addition, the company has a preclinical cell cycle program with an undisclosed target.
Acrivon has developed its AP3 Interactome, a proprietary, computational analytics platform driven by Generative Phosphoproteomics machine learning for integrated comprehensive analyses across all large, in-house AP3 phosphoproteomic drug profiling data sets to advance its in-house research programs.
Forward-Looking Statements
This press release includes certain disclosures that contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 about us and our industry that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this press release, including statements regarding our future results of operations or financial condition, preclinical and clinical results, business strategy and plans and objectives of management for future operations, are forward-looking statements. In some cases, you can identify forward-looking statements because they contain words such as “anticipate,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would” or the negative of these words or other similar terms or expressions. Forward-looking statements are based on Acrivon’s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks and uncertainties that are described more fully in the section titled “Risk Factors” in our reports filed with the Securities and Exchange Commission. Forward-looking statements contained in this press release are made as of this date, and Acrivon undertakes no duty to update such information except as required under applicable law.
Investor and Media Contacts:
Adam D. Levy, Ph.D., M.B.A.
alevy@acrivon.com
Alexandra Santos
asantos@wheelhouselsa.com
FAQ
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