Acrivon's AP3 Platform and Pipeline - Acrivon utilizes its Acrivon Predictive Precision Proteomics (AP3) platform to overcome limitations of genetics-based precision medicine [2, 7] - The AP3 platform enables exact matching of disease-driving dysregulated pathways with a drug's mechanism of action [8] - Acrivon's pipeline includes ACR-368 (CHK1/CHK2 inhibitor) in Phase 2 trials for endometrial cancer and ACR-2316 (WEE1/PKMYT1 inhibitor) in Phase 1 for AP3-identified tumor types [18] - A novel cell cycle program with an undisclosed target is anticipated to have a development candidate nomination in 2025 [18, 98] - Additional AP3-driven programs are in early discovery for autoimmune/inflammatory candidates [18] ACR-368 and Endometrial Cancer - ACR-368 is being evaluated in a registrational intent Phase 2 single-arm trial based on predicted sensitivity in OncoSignature-positive endometrial cancer patients [18] - In endometrial cancer patients, ACR-368 monotherapy showed a confirmed ORR of 35% in OncoSignature-positive patients [53] - ACR-368 is also being studied with ultra-low dose gemcitabine (ULDG) as a sensitizer in OncoSignature-negative patients [18] - Preclinical data suggests AP3-predicted sensitization to ACR-368 by LDG correlates with OncoSignature upregulation [64] ACR-2316 and WEE1/PKMYT1 Inhibition - ACR-2316 is a novel dual WEE1/PKMYT1 inhibitor designed using the AP3 platform to overcome limitations of benchmark inhibitors [97, 104] - ACR-2316 demonstrated superior preclinical potency versus benchmark WEE1/PKMYT1 inhibitors [111] - Initial clinical activity was observed with ACR-2316 at Dose Level 3, showing approximately 25% tumor shrinkage in a patient with prior chemotherapy and anti-PD-1 therapy [138] Financial Status - As of March 31, 2025, Acrivon had $1648 million in cash and investments, projecting a runway into Q2 2027 [182]

Core Insights - Acrivon Therapeutics is advancing its clinical-stage asset ACR-2316, a selective WEE1/PKMYT1 inhibitor, which has shown superior anti-cancer activity in preclinical studies and is currently in a Phase 1 clinical trial with promising early results [1][2][3] Group 1: Clinical Development - ACR-2316 has completed three dose-escalation cohorts in its Phase 1 trial ahead of schedule, with solid tumor shrinkage observed at dose level three [1][2] - The trial has shown no safety concerns or dose-limiting toxicities (DLTs) at dose levels 1, 2, and 3, with dose level 4 currently enrolling [2] - Initial clinical activity of approximately 25% RECIST tumor shrinkage has been noted, along with a reduction of metastatic lesions in the chest, abdomen, and pelvis at dose level three [2] Group 2: Mechanism of Action - ACR-2316 was designed using Acrivon's AP3 platform to activate CDK1, CDK2, and PLK1 pathways, aiming to induce pro-apoptotic tumor cell death and achieve superior single-agent activity [3][7] - The drug's mechanism is intended to overcome limitations associated with single-target WEE1 and PKMYT1 inhibitors, demonstrating a favorable therapeutic index in preclinical studies [3][7] Group 3: Research and Technology - Acrivon utilizes its proprietary Acrivon Predictive Precision Proteomics (AP3) platform for drug discovery, which measures compound-specific effects on tumor cell protein signaling networks [5][6] - The AP3 platform enables the identification of patients most likely to benefit from Acrivon's drug candidates through OncoSignature companion diagnostics [6][7] - Acrivon is also developing ACR-368, a selective small molecule inhibitor targeting CHK1 and CHK2, which is in a potentially registrational Phase 2 trial for endometrial cancer [6][7]

Core Insights - Acrivon Therapeutics has appointed Dr. Mansoor Raza Mirza as the new Chief Medical Officer, effective April 9, 2025, succeeding Dr. Jean-Marie Cuillerot [1][2] - Dr. Mirza will lead the clinical development of Acrivon's ongoing trials, including the Phase 2b trial of ACR-368 for endometrial cancer and the Phase 1 study of ACR-2316 [1][2] - Acrivon is focused on precision medicine through its Acrivon Predictive Precision Proteomics (AP3) platform, which aims to match drug candidates to patients based on predicted sensitivity [1][7] Company Overview - Acrivon Therapeutics is a clinical stage biopharmaceutical company specializing in precision oncology medicines [7] - The company utilizes its proprietary AP3 platform to discover and develop drug candidates, measuring compound-specific effects on tumor cell protein signaling networks [7][9] - Acrivon's lead candidate, ACR-368, is a selective small molecule inhibitor targeting CHK1 and CHK2, currently in a Phase 2 trial for endometrial cancer [7][8] Clinical Development - ACR-368 has received Fast Track designation from the FDA for its investigation as a monotherapy in endometrial cancer [7] - The ACR-2316 program is also advancing rapidly, showing promising clinical activity during its dose escalation phase [2][8] - Acrivon is developing an OncoSignature test for ACR-368 to identify patients likely to benefit from the treatment, which has received Breakthrough Device designation from the FDA [7] Leadership and Expertise - Dr. Mirza is recognized for his contributions to the clinical development of therapies for ovarian and endometrial cancers, having led multiple successful trials [2][3] - He has authored numerous publications and has been involved in developing national guidelines for managing gynecologic cancers [3][4] - Dr. Mirza's extensive experience includes key positions in various prestigious organizations related to gynecologic oncology [4][5]