ACRV

Below are some of these risks, any one of which could materially adversely affect our business, financial condition, results of operations, and prospects: • We are a clinical-stage biotechnology company and have incurred significant losses since our inception.
If we are unable to raise capital when needed, we could be forced to curtail our planned longer-term operations and the pursuit of our growth strategy. • Our business substantially depends upon the successful clinical development of drug candidates using our AP3 platform.
If we are unable to obtain regulatory approval for, and successfully commercialize, drugs developed through the application of our AP3 platform, our business may be materially harmed. • We are highly dependent on the success of ACR-368 and/or ACR-2316, as these are our first drug candidates being developed for clinical development and regulatory approval.
Food and Drug Administration, or FDA, and comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our drug candidates, on a timely basis or at all, our business will be substantially harmed. • For some of our drug candidates, the successful clinical development may depend on the co-approval of an OncoSignature test as a companion diagnostic test.
If we or a companion diagnostic collaborator are unable to obtain regulatory approval for our OncoSignature companion diagnostic tests for such drug candidates, we may not obtain regulatory approval and realize the commercial potential of certain drug candidates. • Our relationships with customers, healthcare providers, including physicians, and third-party payors are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws, health information privacy and security laws and other healthcare laws and regulations.
Overview We are a clinical-stage biopharmaceutical company discovering and developing precision medicines utilizing our proprietary Generative Phosphoproteomics Acrivon Predictive Precision Proteomics, or AP3, platform designed to quantify compound-specific, drug-regulated pathway activity levels inside the intact cell in an unbiased manner, yielding terabytes of proprietary data and delivering rapid, actionable insights.
Our company name, Acrivon, is derived from Greek for “accurate” or “precise”.
We chose it to embody how our AP3 platform can, among other highly actionable discovery and development applications, accurately match our therapies with patients who will benefit.
Our approach is designed to overcome the limitations of genetics-based precision medicine.
We do this by using our precision medicine platform, AP3, to discover and develop our pipeline of innovative oncology drug candidates.
AP3 is engineered to measure compound-specific effects on the entire tumor cell protein, signaling network and drug-induced resistance mechanisms in an unbiased manner and is modality and disease agnostic.
Our AP3 approach is proteomics-based and designed for direct protein measurement of critical tumor-driving pathways and independent of underlying genetic alterations.
By applying our highly specific patient selection approach, and other AP3 applications, to drug development, we seek to both accelerate clinical development and significantly increase the probability of successful treatment outcomes for patients.
Our pipeline includes our Phase 2b lead program, ACR-368, also known as prexasertib, a precision oncology asset in-licensed from Eli Lilly & Company, or Lilly, that targets CHK1 and CHK2, or CHK1/2.
In past Lilly-sponsored trials, ACR-368 was dosed in more than 400 patients at the recommended Phase 2 dose, or RP2D, with reported deep, durable responses, including complete responses, or CRs, in a proportion of patients with solid tumors in past single center and multi-center Phase 2b clinical trials in tumor indications with high unmet need.
While Lilly had explored ACR-368 in many solid tumor types in the above-mentioned studies, they never tested endometrial cancer, or EC.
Using our AP3 platform we generated a protein-based tumor biopsy test, called OncoSignature, designed to prospectively predict treatment benefit of ACR-368 at an individual patient level.
Using the OncoSignature for screening across routine-processed human tumor types (so-called “Indication Finding”) we identified EC as a tumor type which was predicted to be particularly sensitive to ACR-368.
Based on this, we received clearance from the FDA for an IND application to advance ACR-368 in Phase 2b single arm clinical trials in multiple tumor types including EC, conducted under the FDA program known as the master protocol, which was developed to help expedite drug development in multiple tumor types for drugs with an established RP2D within the same overall trial structure.
Subjects in arm 1 of the ACR-368-201 study are stratified for treatment based on OncoSignature-positive, or BM+, predicted sensitivity to ACR-368, across multiple sites in the United States in this registrational intent trial.
Through the use of our OncoSignature test for prospective responder identification, we intend to significantly increase the overall response rate, or ORR, across tumor types sensitive to ACR-368.
Based on interim clinical data from the ACR-368-201 trial we found that the confirmed ORR in Arm 1 for EC was 39%, and 44% in patients treated with ≤2 prior lines of therapy, or pLoT.
Across pooled BM+ and BM- subjects with serous EC, ≤2 pLoT showed a confirmed ORR of 52%.
Serous EC is a very high unmet need and extremely aggressive form of EC, contributing to ~50% of all EC mortality.
Based on this finding, arms 3 and 4 have been added to the study.
Arm 3 is investigating ACR-368 in serous EC subjects with up to two pLoT without the need for pre-treatment tumor biopsy or biomarker stratification (“a serous all comer”), and utilizes ultra-low dose gemcitabine, or ULDG, as a sensitizer.
Arm 4 will investigate the same “serous all comer” subject group but without ULDG sensitization (ACR-368 monotherapy).
These include ACR-2316, our second clinical-stage asset, which is a novel, selective, dual WEE1/PKMYT1 inhibitor designed specifically for enhanced therapeutic index by achieving superior single-agent activity through strong activation of not only CDK1 and CDK2 but also of PLK1 to drive pro-apoptotic cell death, as observed in preclinical studies against benchmark inhibitors, combined with exquisite selectivity.
The Phase 1 trial of ACR-2316 is advancing, with two weekly dosing regimens established.
Initial data has shown a favorable tolerability profile limited to transient, mechanism-based hematological adverse events, predominantly neutropenia and initial clinical activity across AP3-selected solid tumor types, including PRs in EC, as well as SCLC and sqNSCLC, two tumor types which have not shown sensitivity to other clinical WEE1 or PKMYT1 inhibitors currently in development.
In addition, the company is advancing ACR-6840, an internally discovered development candidate targeting CDK11.
In preclinical studies, ACR-6840 has been shown to be pro-apoptotic in aggressive AML cell lines, potently downregulates MCL1, and shown synergy with BCL2 inhibitors.
The agent is being advanced in IND enabling studies for planned IND filing in the fourth quarter 2026.
Our AP3 Platform We have established the proprietary Generative Phosphoproteomics AP3 platform which is designed to allow us to interpret and quantify the drug-regulated compound-specific effects and pathway activity levels inside the intact cell in an unbiased manner.
The platform is comprised of a growing suite of powerful, internally developed tools, including the AP3 Interactome, the AP3 Kinase Substrate Relationship Predictor, the AP3 Data Portal, designed to enable the conversion of multimodal data into structured data amenable for generative AI analyses, and the AP3 Chatbot.
Through the combination of these distinctive tools and capabilities, the platform enables us to go beyond current AI target-centric drug discovery and to rapidly design highly differentiated compounds with high target specificity and optimal, desirable pathway effects on the intracellular signaling network to mechanistically address the underlying molecular cause of disease.
The integrated analyses of our AP3-generated proprietary datasets through a unified computational interface enables streamlined transition from preclinical to the clinical phase, as exemplified by the development of ACR-2316.
Importantly, all drug-regulated effects on the disease-driving, upregulated pathways and active proteins are revealed for each compound that we profile.
We apply these distinctive capabilities of AP3 to streamline discovery and development via rational drug design optimization for monotherapy activity, the identification of drug combinations, identification of clinical biomarkers for predicting patient response, novel target identification, the evaluation of potential in-licensing candidates, identification of potential mechanism based adverse events/therapeutic index optimization, and identification of resistance mechanisms.
One of the aforementioned applications of our AP3 platform are our proprietary response-predictive clinical tests that we refer to as OncoSignature tests.

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Gone since FY2024

Below are some of these risks, any one of which could materially adversely affect our business, financial condition, results of operations, and prospects: • We are a clinical stage biopharmaceutical company and have incurred significant losses since our inception.
If we are unable to raise capital when needed, we could be forced to curtail our planned longer-term operations and the pursuit of our growth strategy. • Our business substantially depends upon the successful clinical development of drug candidates using our AP3 platform and OncoSignature , or OncoSignature companion diagnostics.
If we are unable to obtain regulatory approval for, and successfully commercialize, drugs developed through the application of our AP3 platform and OncoSignature tests, our business may be materially harmed. • We are highly dependent on the success of ACR-368 and/or ACR-2316, as these are our first drug candidates being developed for clinical development and regulatory approval.
Food and Drug Administration, or FDA, and comparable foreign regulatory authorities are lengthy, time consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our drug candidates, on a timely basis or at all, our business will be substantially harmed. • The successful clinical development of some of our drug candidates may depend on the co-approval of an OncoSignature test as a companion diagnostic test.
If we or our companion diagnostic collaborator are unable to obtain regulatory approval for our OncoSignature companion diagnostic tests for such drug candidates, we may not obtain regulatory approval and realize the commercial potential of certain drug candidates. • Our relationships with customers, healthcare providers, including physicians, and third-party payors are subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws, health information privacy and security laws and other healthcare laws and regulations.
Overview We are 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 our proprietary Generative Phosphoproteomics platform, Acrivon Predictive Precision Proteomics, or AP3.
Our approach is designed to overcome the limitations of genomics-based patient selection methods.
We do this by using our precision medicine platform, AP3, to develop our pipeline of oncology drug candidates.
AP3 is engineered to measure compound-specific effects on the entire tumor cell protein signaling network and drug-induced resistance mechanisms in an unbiased manner.
These distinctive capabilities enable AP3’s direct application for drug design optimization 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, which we refer to as patient responders.
We are currently advancing our lead candidate, ACR-368, a selective small molecule inhibitor which targets CHK1 and CHK2 at sub single-digit nM and single-digit nM potency in intact cells, respectively, in a potentially registrational Phase 2 trial focusing on patients with endometrial cancer.
We are continuing enrollment and dosing of patients in this multi-center trial based on AP3-predicted sensitivity to ACR-368 in patients with endometrial adenocarcinoma, a tumor type that was predicted to be sensitive to ACR-368 prior to clinical entry through preclinical AP3-based indication finding, and not previously evaluated in past clinical trials.
Our 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 patients with ovarian cancer treated with ACR-368 in past Phase 2 clinical trials conducted by Eli Lilly and Company, or Lilly, and at the National Cancer Institute, or NCI, providing evidence of robust enrichment of responders through our method.
Moreover, clinical data from the ongoing registrational intent trial in endometrial cancer showed initial validation of the ACR-368 OncoSignature for prospective patient selection (see further details below).
Based on these sets of data, the FDA has granted Breakthrough Device designations for the ACR-368 OncoSignature assay for the identification of endometrial cancer patients and ovarian cancer patients who may benefit from ACR-368 treatment.
Our AP3 approach is proteomics-based and designed to enable identification and treatment of the patients whose tumors are sensitive to a specific drug or drug candidate based on direct protein measurement of critical tumor-driving mechanisms and independent of underlying genetic alterations.
By applying our highly specific patient selection approach to drug development, we seek to both accelerate clinical development and significantly increase the probability of successful treatment outcomes for patients.
Our pipeline includes the Phase 2 lead program, ACR-368, also known as prexasertib, a precision oncology asset that targets CHK1 and CHK2, or CHK1/2.
In past trials, ACR-368 was dosed in more than 400 patients at the recommended Phase 2 dose, or RP2D, with reported deep, durable responses, including complete responses, or CRs, in a proportion of patients with solid tumors in past single center and multi-center Phase 2 clinical trials in tumor indications with high unmet need.
We received clearance from the FDA for an IND application to advance ACR-368 in Phase 2 single arm clinical trials conducted under the FDA program known as the master protocol, which was developed to help expedite drug development in multiple tumor types for drugs with an established RP2D within the same overall trial structure.
Patients are stratified for treatment based on OncoSignature-predicted sensitivity to ACR-368 across multiple sites in the United States in this trial with registrational intent.
Through the use of our OncoSignature test, we believe we can significantly increase the overall response rate, or ORR, observed in previous trials that were conducted without a prospective patient responder identification method.
In September 2024, we reported positive clinical data for endometrial cancer, including a confirmed ORR of 62.5% (95% CI, 30.4 - 86.5).
The data further validated our AP3-based ACR-368 OncoSignature assay, which is used for prospective patient selection in the registrational intent trial, showing a segregation of responders in the OncoSignature-positive, or BM+, versus OncoSignature-negative, or BM-, arms ( p = 0.009 ).
The median duration of treatment was not yet reached, but the duration on study was six months at the time of the data cut.
With the encouraging maturing data in endometrial cancer combined with the competitive positioning given limited treatment options in second line and the potential market opportunity, we are now prioritizing this tumor type.
An interim data extract from the EDC clinical database was done on February 25, 2025, including 20 BM+ endometrial cancer patients treated with ACR-368 monotherapy and 38 BM- treated with ACR-368 plus ultra low dose gemcitabine (LDG) that were efficacy-evaluable by RECIST (2 BM- had treatment discontinued without scan).
All BM+ patients had progressed after prior platinum-based chemotherapy and prior anti-PD-1, and the median and mean prior lines of therapy for these patients were 2 and 2.6, respectively.
In patients that had relapsed after the prior line of therapy (N=6), the confirmed ORR was 50% and the disease control rate (DCR) was 100%.
ACR-368 is also being studied in combination with low dose gemcitabine (LDG) in additional indications, such as squamous cell carcinomas, including squamous cell cancer, or SCC, of head and neck (H&N), or SCCHN, in an Investigator-Initiated Trial (IIT).
Given broad anti-tumor activity observed in past trials in other tumor types, we will potentially study ACR-368 in additional tumor types where there is high unmet need and competitive positioning opportunity.
For example, we are assessing trial initiation in myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN), diseases with high unmet need, based on transcription factor gene mutations rendering these malignancies sensitive to CHK1/2 as observed in various preclinical studies, including studies using ACR-368.
We have previously confirmed in preclinical studies that LDG sensitizes both OncoSignature-negative and BM+ tumors to ACR-368, as predicted by the AP3 platform, and this is consistent with an upregulation of the ACR-368 OncoSignature biomarkers in both human tumor cell lines and in human tumor xenograft mouse models after LDG treatment.
We now have obtained further evidence of such OncoSignature biomarker upregulation in human patient tumors based on serial pre- and post- LDG biopsies in an ongoing Investigator-Initiated Trial at the Moffitt Cancer Center in patients with H&N cancer.
Consistent with this preclinical and now clinical evidence of sensitization by LDG in BM- patients, we are continuing to explore the combination of ACR-368 with LDG in our ongoing endometrial cancer trial.
Preliminary analyses of the 38 BM- patients, who are heavily pretreated (median of 3 prior lines of therapy) show a confirmed ORR of ~13% with the ACR-368 + LDG combination, which is comparable to the best ORR in the last prior line of therapy (median = 3) in these patients, which was 17%.
Based on the totality of the preclinical and observed clinical data, we believe this supports significant LDG sensitization to ACR-368 in BM- patients.
We expect a similar sensitization in BM+ patients which could be explored in a future all-comer study of ACR-368 + LDG.
These include ACR-2316, our second clinical stage asset, a novel, selective, dual WEE1/PKMYT1 inhibitor designed specifically for enhanced therapeutic index by achieving superior single-agent activity through strong activation of not only CDK1 and CDK2 but also of PLK1 to drive pro-apoptotic cell death, as observed in preclinical studies against benchmark inhibitors, combined with exquisite selectivity.
Utilizing AP3 we were able to advance ACR-2316 from being discovered as an initial lead to being dosed in a Phase 1 trial in only 15 months.

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