Acrivon Therapeutics, Inc.

Acrivon Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on discovering and developing precision medicines, primarily in oncology, utilizing its proprietary Generative Phosphoproteomics Acrivon Predictive Precision Proteomics, or AP3, platform. The company's core business model revolves around leveraging this platform to quantify drug-regulated pathway activity levels within cells, aiming to accurately match therapies with patients who will benefit, thereby accelerating clinical development and increasing the probability of successful treatment outcomes. The AP3 platform is designed to overcome limitations of genetics-based precision medicine by directly measuring critical tumor-driving pathways, independent of underlying genetic alterations, and is applicable across drug development stages and therapeutic modalities. The company generates revenue from collaboration agreements, which may include upfront fees, license fees, milestone-based payments, and reimbursements for research and development efforts, but has not yet generated revenue from product sales ¹.

The AP3 platform is comprised of a growing suite of internally developed tools, including the AP3 Interactome, the AP3 Kinase Substrate Relationship Predictor, the AP3 Data Portal (designed for generative AI analyses), and the AP3 Chatbot. These tools enable rational drug design optimization for monotherapy activity, identification of drug combinations, identification of clinical biomarkers for predicting patient response, novel target identification, evaluation of potential in-licensing candidates, therapeutic index optimization, and identification of resistance mechanisms. A key application of the AP3 platform is the development of proprietary response-predictive clinical tests called OncoSignature tests, which are drug-tailored, automated, quantitative proteomic tissue imaging tests applied to pretreatment tumor biopsies as a companion diagnostic (CDx) to select patients. The company recently completed and certified a Clinical Laboratory Improvement Amendment (CLIA) laboratory in Watertown, Massachusetts, to perform OncoSignature and other clinical testing in-house ².

Acrivon's pipeline includes its Phase 2b lead program, ACR-368 (also known as prexasertib), an in-licensed precision oncology asset from Eli Lilly & Company (Lilly) that targets CHK1 and CHK2 (CHK1/2). ACR-368 has been dosed in over 400 patients at the recommended Phase 2 dose (RP2D) in past Lilly-sponsored trials, showing deep, durable responses, including complete responses (CRs) and partial responses (PRs), with a generally favorable safety profile. The company identified endometrial cancer (EC) as a particularly sensitive tumor type for ACR-368 using its OncoSignature platform. The ACR-368-201 study, a Phase 2b single-arm clinical trial under an FDA master protocol, includes Arm 1 for OncoSignature-positive (BM+) EC subjects, Arm 3 for biomarker-unselected serous EC subjects with ultra-low dose gemcitabine (ULDG) sensitization, and Arm 4 for biomarker-unselected serous EC subjects with ACR-368 monotherapy. Interim clinical data from Arm 1 for EC showed a confirmed overall response rate (ORR) of 39% ³, and 44% in patients treated with ≤2 prior lines of therapy (pLoT) ⁴. Across pooled BM+ and BM- subjects with serous EC, ≤2 pLoT showed a confirmed ORR of 52% ⁵. An additional interim data extract on December 4, 2025, showed a confirmed ORR of 44% in Arm 1 (BM+ subjects of all histopathologies) ⁶ and 67% in BM+ subjects (N=12) with serous EC ⁷.

The company's internally discovered and developed programs include ACR-2316, a novel, selective, dual WEE1/PKMYT1 inhibitor, which is its second clinical-stage asset. ACR-2316 was rationally designed using the AP3 platform and co-crystallography for enhanced therapeutic index and superior single-agent activity, demonstrating complete tumor regression in preclinical studies. The Phase 1 trial of ACR-2316 is advancing, having established two weekly dosing regimens: 160 mg QD on a 3d on / 4d off schedule and 240 mg QD 2d on / 5d off schedule ⁸. Initial clinical activity includes PRs in EC, SCLC, and sqNSCLC, tumor types not previously sensitive to other WEE1 or PKMYT1 inhibitors. Additionally, ACR-6840, an internally discovered development candidate targeting CDK11, is advancing in IND-enabling studies for a planned IND filing in the fourth quarter of 2026 ⁹.

For the fiscal year ended December 31, 2025, Acrivon reported a net loss of $77.9 million ¹⁰, compared to a net loss of $80.6 million for the year ended December 31, 2024 ¹¹. Total operating expenses for 2025 were $84.114 million ¹², a decrease from $89.199 million in 2024 ¹³. Research and development expenses decreased by $4.0 million to $59.990 million in 2025 ¹⁴ from $63.992 million in 2024 ¹⁵. General and administrative expenses were $24.124 million in 2025 ¹⁶, down from $25.207 million in 2024 ¹⁷. Total other income, net, was $6.209 million in 2025 ¹⁸, a decrease from $8.643 million in 2024 ¹⁹, primarily due to a $2.722 million decrease in interest income ²⁰. As of December 31, 2025, the company had cash, cash equivalents, and investments of $118.6 million ²¹ and an accumulated deficit of $274.9 million ²².

Year-over-year, research and development expenses decreased by $4.002 million ²³. This was primarily driven by an $11.1 million net decrease in costs for ACR-368 due to fewer scheduled milestones and prioritization of EC over other tumor types ²⁴. This was partially offset by a $4.1 million net increase in costs related to ACR-2316 as its clinical trial progressed ²⁵, a $1.7 million net decrease in other drug discovery programs ²⁶, a $3.6 million increase in personnel-related costs (including $0.9 million in stock-based compensation) ²⁷, and a $1.1 million increase in facilities, supplies, and other expenses ²⁸. General and administrative expenses decreased by $1.083 million ²⁹, mainly due to a $0.9 million decrease in payroll and employee-related expenses (including $0.5 million in stock-based compensation) ³⁰ and a $0.2 million decrease in professional fees, facilities, supplies, and other expenses ³¹.

During the reported period, Acrivon announced the completion and certification of its internal CLIA-certified laboratory on February 18, 2026 ³². This led to the mutual termination of the companion diagnostic agreement with Akoya on February 25, 2026, without financial payments, with a transition plan to transfer all related procedures and know-how to Acrivon's in-house CLIA lab ³³. This move provides Acrivon with full control over predictive biomarker identification, CDx development, indication finding, and streamlining co-regulatory approvals. The company also initiated a cohort for ACR-2316 aiming to establish a bi-weekly 2d on / 12d off dosing regimen ³⁴. ACR-6840 is being advanced in IND-enabling studies for a planned IND filing in Q4 2026 ³⁵. In July 2025, Acrivon obtained full release of rights of first negotiation (ROFN) obligations from Lilly for the ACR-368 program, making its rights fully unencumbered ³⁶.

Acrivon Therapeutics expects to continue incurring significant expenses and operating losses for the foreseeable future as it advances its drug candidate pipeline. The company believes its existing cash, cash equivalents, and investments of $118.6 million as of December 31, 2025, will be sufficient to fund operating expenses and capital expenditure requirements into the second quarter of 2027 ³⁷. This estimate is based on assumptions that may prove incorrect, and capital resources could be exhausted sooner. The company anticipates needing substantial additional funding to support its continuing operations and growth strategy, which it expects to finance through equity sales, debt financings, or other capital sources, including potential collaborations or strategic transactions ³⁸.

A major growth area for Acrivon is the continued clinical development of ACR-368. The company is focused on advancing ACR-368 through clinical development and regulatory approval via the accelerated approval pathway in one or more of the three ongoing arms of the ACR-368-201 study: OncoSignature-positive EC subjects (Arm 1) and/or biomarker-unselected serous EC subjects (Arm 3 with ULDG sensitization, and planned Arm 4 with monotherapy) ³⁹. The company plans a confirmatory trial combining ACR-368 with anti-PD-1 versus anti-PD-1 in the maintenance phase of first-line therapy for EC, supported by preclinical synergy data ⁴⁰. Additionally, ACR-368 may exhibit broad synergy with other chemotherapeutic agents, particularly topoisomerase inhibitors in antibody-drug conjugates (ADCs), and the company plans further preclinical and clinical evaluations of this potential ⁴¹. The company is also assessing trial initiation in myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) for ACR-368, based on preclinical observations of sensitivity to CHK1/2 inhibitors due to transcription factor gene mutations ⁴².

Another significant growth area is the advancement of its internally discovered pipeline programs, leveraging the AP3 platform. This includes ACR-2316, a novel, potent, selective dual WEE1/PKMYT1 inhibitor, which is currently in Phase 1 clinical development ⁴³. The Phase 1 study aims to assess safety, tolerability, pharmacokinetic profile, preliminary anti-tumor activity, and determine the recommended Phase 2 monotherapy dose, with dose optimization guided by drug target engagement in alignment with the FDA's Project Optimus ⁴⁴. The company has established two weekly oral dosing regimens for ACR-2316 (160 mg QD on a 3d on / 4d off and 240 mg QD 2d on / 5d off) ⁴⁵ and has initiated a cohort to establish a bi-weekly 2d on / 12d off dosing regimen for enhanced single agent activity and dosing flexibility in future combination studies ⁴⁶. The company plans to generate an OncoSignature for ACR-2316 for dose optimization in Phase 1 and potential individual patient responder prediction ⁴⁷. Furthermore, ACR-6840, an internally discovered development candidate targeting CDK11, is being advanced in IND-enabling studies for a planned IND filing in the fourth quarter of 2026 ⁴⁸.

Operationally, the company expects its research and development expenses to substantially increase as it continues development and manufacturing of ACR-368 and ACR-2316, and conducts discovery and research for preclinical programs, including ACR-6840 ⁴⁹. General and administrative expenses are also anticipated to increase due to headcount growth and costs associated with operating as a public company ⁵⁰. The company's recent establishment of an internal CLIA-certified laboratory and termination of the Akoya agreement are expected to provide enhanced capabilities and efficiencies, including full control over predictive biomarker identification, CDx development, indication finding, and streamlining co-regulatory approvals and co-commercialization ⁵¹.

Acrivon expects to rely on third-party contract manufacturing organizations (CMOs) for the foreseeable future to produce drug candidates for preclinical studies, clinical trials, and future commercial manufacture, if approved ⁵². The company has manufacturing agreements with four CMOs for ACR-368 and one CMO for ACR-2316 ⁵³. It anticipates these CMOs will have capacity for commercial scale production, but no formal agreements are in place yet ⁵⁴. The company believes it can identify and engage additional CMOs without significant disruption if needed ⁵⁵.

The company's capital allocation plans include continued substantial investment in research and development. This encompasses funding ongoing and planned clinical trials for ACR-368 and ACR-2316, discovering and developing additional drug candidates and drug-tailored OncoSignature tests, acquiring or in-licensing other drug candidates and technologies, and maintaining and protecting its intellectual property portfolio ⁵⁶. The company also plans to hire additional clinical and scientific personnel and further refine manufacturing processes ⁵⁷.

Acrivon faces substantial risks, including its status as a clinical-stage biotechnology company with a limited operating history and no commercialized products, leading to significant accumulated losses of $274.9 million as of December 31, 2025 ⁵⁸ and an expectation of continued losses. The company will require additional funding to meet financial obligations and pursue business objectives, with existing cash, cash equivalents, and investments of $118.6 million projected to fund operations only into the second quarter of 2027 ⁵⁹. The business is highly dependent on the successful clinical development and regulatory approval of drug candidates, particularly ACR-368 and ACR-2316, and their associated OncoSignature companion diagnostics, which are lengthy, time-consuming, and unpredictable processes. Failure to obtain regulatory approval for these drug candidates or companion diagnostics, or delays in patient enrollment for clinical trials, would substantially harm the business. Unexpected adverse side effects or safety risks associated with drug candidates could delay or preclude approval, limit commercial potential, or result in significant negative consequences post-approval. The precision oncology space is competitive, with numerous major pharmaceutical and biotechnology companies possessing greater financial resources and expertise, and the company faces competition from existing cancer treatments. Unfavorable pricing regulations, third-party reimbursement practices, or healthcare reform initiatives, such as the Inflation Reduction Act (IRA) allowing Medicare to establish "maximum fair prices" for drugs ⁶⁰ and penalizing price increases faster than inflation ⁶¹, could harm profitability. Reliance on third-party contract manufacturing organizations (CMOs) and contract research organizations (CROs) for supply and clinical trials exposes the company to risks of supply disruption, quality issues, or failure to meet deadlines. Cybersecurity threats, including cyberattacks and data breaches, pose risks to confidential information, intellectual property, and personal data, potentially leading to legal claims, significant regulatory penalties, and reputational damage. Changes in U.S. patent law or the patent law of other countries could diminish the value of patents, impairing the ability to protect future drug candidates.

Management's message to shareholders emphasizes the company's commitment to transforming cancer treatment through its proprietary Generative Phosphoproteomics AP3 platform, which is designed to accurately match therapies with patients. They highlight the platform's ability to overcome limitations of genetics-based precision medicine by directly measuring disease-driving protein activity. A key strategic priority is the expedited clinical development of ACR-368, their CHK1/2 inhibitor, through the ongoing Phase 2 trial in endometrial cancer, with three registrational intent arms: OncoSignature-positive subjects (Arm 1), and biomarker-unselected serous EC subjects with (Arm 3) or without (planned Arm 4) ULDG sensitization. Management also prioritizes the discovery and development of a pipeline of proprietary oncology drug candidates, such as ACR-2316 (a dual WEE1/PKMYT1 inhibitor in Phase 1) and ACR-6840 (a CDK11 target advancing to IND-enabling studies for planned IND filing in Q4 2026 ⁶²), leveraging the AP3 platform for rational drug design. Furthermore, they aim to acquire rights to drug candidates where the AP3 platform can increase clinical success likelihood and opportunistically enter strategic co-development partnerships to maximize the platform's potential. The company believes its existing cash, cash equivalents, and investments of $118.6 million as of December 31, 2025 ⁶³, will fund operating expenses and capital expenditure requirements into the second quarter of 2027 ⁶⁴.