ACRV Acrivon Therapeutics Inc

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Exhibit 99.1

 

Acrivon Therapeutics Reports Positive Endometrial Cancer Data from Ongoing ACR-368 Registrational Intent Phase 2 Study at ESMO, Advancement of ACR-2316 into Clinic Ahead of Timelines, and Progress on its AP3 Interactome for Proprietary Data Analysis

-  Confirmed overall response rate (ORR) = 62.5% (95% CI, 30.4-86.5) observed in prospectively-selected ACR-368 OncoSignature-positive (BM+) patients with endometrial cancer

-  Achieved statistically significant segregation of responders in BM+ vs BM- subgroups based on OncoSignature patient selection (p-value = 0.009)

-  ACR-368 endometrial cohort data maturing with all responders still on therapy; mDoR not yet reached (~6 months at time of data-cut)

-  Endometrial cancer now anticipated to be the first tumor type with potential for ACR-368 accelerated regulatory approval

-  IND clearance and initial sites activated ahead of timelines for ACR-2316 with first-in-human dosing anticipated in Q4 2024

-  AP3 Interactome generating proprietary, actionable insights, leveraging in-house data and delivering algorithm-based machine learning-enabled pathway and biomarker analyses

-  Acrivon to host a webcast joined by endometrial cancer key opinion leader Dr. Ramez N. Eskander today, Saturday, September 14 at 9:00 a.m. ET

WATERTOWN, Massachusetts, September 14, 2024 – 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, today presented additional positive clinical data at ESMO from the ongoing registrational intent, multicenter Phase 2 trial of ACR-368 in patients with locally advanced or metastatic, recurrent endometrial cancer. The company has also disclosed that the Investigational New Drug (IND) application for its next clinical candidate, ACR-2316, has been cleared by the FDA with initial clinical sites now activated, and first-in-human dosing for the Phase 1 study expected in the fourth quarter of 2024.

“We are very excited to provide several significant, positive updates across our rapidly advancing clinical pipeline since our last R&D event in April,” said Peter Blume-Jensen, M.D., Ph.D., chief executive officer, president, and founder of Acrivon. “First, at ESMO earlier today, we presented an updated interim efficacy and safety data cut of our registrational intent

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ACR-368 Phase 2 study, which showed a confirmed ORR of 62.5% in endometrial cancer patients. Notably, endometrial cancer is a tumor type that we predicted to be sensitive to single agent ACR-368 with our AP3 indication finding screening approach which we have now confirmed in the clinic. The maturing data is particularly encouraging as the lower bound of the 95% confidence interval is now 30%, above our targeted goal for this metric. Moreover, while median duration of response has not yet been reached, it is now approximately 6 months with all responding patients on therapy at time of data cut-off. Given the strength of the data we believe endometrial cancer might provide the first potential approval opportunity for ACR-368. We are actively evaluating potential confirmatory trial designs, including front line, for a potential future label expansion. We are also excited to disclose that the FDA has cleared the IND for our second clinical program, ACR-2316, well ahead of original timeline projections. Clinical trial sites have been activated and are now actively screening patients for enrollment into a Phase 1 study. Today’s update further strengthens the validation of our prospective OncoSignature patient selection method and of our differentiated AP3 platform delivering actionable data across discovery and development.”

ACR-368 Updates and Highlights

 

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Presented data at ESMO from the ongoing, registrational-intent, multicenter Phase 2 trial of ACR-368 in patients with high grade endometrial cancer. Importantly, all patients enrolled must have progressed on prior anti-PD-1 therapy, unless ineligible. The data were based on 35 safety-evaluable subjects, of which 23 (8 BM+ and 15 BM-) were efficacy-evaluable with at least one on-treatment scan (data cut off July 25, 2024).

 

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Reported a confirmed ORR (RECIST 1.1) of 62.5% (95% CI, 30.4-86.5) observed in the cohort of prospectively-selected OncoSignature-positive (BM+) patients who were efficacy-evaluable. Endometrial cancer is a tumor type that was predicted to be sensitive to ACR-368 by AP3-enabled indication screening before any clinical data was generated.

 

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Median duration of response (mDOR) was not yet reached (~6 months at time of data cut-off); all responding patients still on therapy

 

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Best overall response (BOR) in last prior line predominantly progressive disease (PD) in confirmed ACR-368 responders

 

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Confirmed responses were observed across molecular and histological subtypes

 

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Demonstrated the ability of the AP3-based ACR-368 OncoSignature assay to prospectively predict patients sensitive to ACR-368 monotherapy based on updated data that showed a clear segregation of responders in the BM+ versus OncoSignature-negative (BM-) arms (p-value = 0.009)

 

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Observed further evidence of sensitization to ACR-368 by ultra-low dose gemcitabine (ULDG) in a proportion of BM- subjects, with an initial disease control in 8 out of 15 subjects, including 1 confirmed complete response (CR)

 

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Consistent with past trials and earlier reported data from this trial, the ACR-368 treatment-related adverse events observed were limited, predominantly transient, reversible, mechanism-based hematological AEs, which typically occurred during the first 1-2 cycles of therapy. There was a notable absence of long-lasting myelosuppression, or the typical more severe non-hematological AEs commonly seen with ADCs and chemotherapy.

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Company conducted a blinded third-party KOL market research study which showed strong interest in the emerging clinical profile of ACR-368 (product name blinded) as an important potential therapy in the rapidly evolving treatment landscape of endometrial cancer where second line options are now limited due to anti-PD-1 and chemotherapy having been approved in front line therapy

 

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An estimated ~30K new cases of high-grade, locally advanced or metastatic, recurrent (progressed on anti-PD-1 and chemotherapy) endometrial cancer per year

 

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~90% of these patients will progress to second line

 

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The recent approval of pembrolizumab plus chemotherapy as a first-line treatment leaves a significant unmet need in the second-line, where the bar from reported chemotherapy efficacy in second-line is an ORR of 14.7% and mPFS of 3.8 months (Makker et al; N Engl J Medicine, 2022)

 

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The ESMO poster presentation is available on Acrivon’s website in the “Science and Publications” section

ACR-2316 Updates

 

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The company today disclosed that the FDA has cleared the IND for its novel, dual WEE1/PKMYT1 inhibitor ACR-2316, ahead of projected timelines

 

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Multiple clinical sites have been activated for the Phase 1 dose optimization study

 

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Initial patient dosing expected in fourth quarter 2024 in selected tumor types

AP3 Interactome Updates

 

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Proprietary, computational analytics platform leveraging machine learning now further advanced for integrated comprehensive analyses across all large, in-house AP3 phosphoproteomic drug profiling data sets.

 

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Integration enables quantitative analyses to generate actionable insights for rational drug design, predictive biomarkers, resistance mechanisms, and indication finding to be implemented in the clinic

 

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AP3 Interactome has been deployed to enable indication finding and patient responder identification for ACR-368 and to generate the novel dual WEE1/PKMYT1 inhibitor ACR-2316

Company Webcast and KOL Participation

The company will host a webcast today, Saturday, September 14 at 9:00 a.m. ET to further discuss these data and pipeline updates. A link to the webcast can be found on the investors page of www.acrivon.com.

In addition to company executives, Ramez N. Eskander, M.D., assistant professor of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, CA, a key opinion leader in endometrial cancer will participate in the webcast. Dr. Eskander is the lead author on the influential paper “Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer” (N Engl J Med (2023) 388(23):2159-2170).

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About Acrivon Therapeutics

Acrivon is a clinical stage biopharmaceutical company developing precision oncology medicines that it matches to patients whose tumors are predicted to be sensitive to each specific medicine by utilizing Acrivon’s proprietary proteomics-based patient responder identification 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. 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. 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 across multiple tumor types. 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 platinum-resistant ovarian or 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 designation for the ACR-368 OncoSignature assay for the identification of ovarian cancer patients 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 potent, selective WEE1/PKMYT1 inhibitor designed for superior single-agent activity as demonstrated in preclinical studies against benchmark inhibitors. The company is also progressing internally- developed preclinical programs, including a cell cycle program with an undisclosed target.

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

CORPORATE R&D EVENT September 14, 2024 ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3) OVERCOMING LIMITATIONS OF GENETICS-BASED PRECISION MEDICINE Exhibit 99.2

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Forward-looking statements Certain information contained in this presentation includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding our future results of operations or financial condition, business strategy and plans and objectives of management for future operations. 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. Our forward-looking statements are based primarily on our current expectations and projections about future events and trends that we believe may affect our business, financial condition and results of operations. The outcome of the events described in the forward-looking statements is subject to risks and uncertainties, including the factors described in our filings with the U.S. Securities and Exchange Commission. New risks and uncertainties emerge from time to time, and it is not possible for us to predict all risks and uncertainties that could have an impact on the forward-looking statements contained in this presentation. The results, events, and circumstances reflected in the forward-looking statements may not be achieved or occur, and actual results, events, or circumstances could differ materially from those described in the forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this presentation. We undertake no obligation to update any forward-looking statements or to reflect new information or the occurrence of unanticipated events, except as required by law.

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outline Acrivon Therapeutics and AP3 overview Data update on the prospective ACR-368 registrational intent Phase 2 trial in endometrial cancer Update on ACR-2316, an AP3-derived dual WEE1/PKMYT1 inhibitor cleared for Phase 1 Intro to AP3 Interactome v.2: Real-time actionable analyses of Acrivon proprietary AP3 data Live Q&A For a comprehensive corporate deck, please visit: https://Acrivon.com

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Acrivon Therapeutics – a next-generation precision medicine company Neurological Cancer Inflammatory Fibrosis Drug P Metabolic Acrivon Predictive Precision Proteomics (AP3) Enables an exact match between the disease-driving, dysregulated pathways with a drug’s mechanism of action (Acrivon meaning ≈ exact, accurate) Broadly applicable in R&D (biological SAR, resistance, patient responders); leveraged for internal pipeline DNA RNA Protein Dysregulated Protein Dysregulated Pathways + OncoSignature® Blume-Jensen, P & Hunter, T: Oncogenic kinase signaling Nature (2001) Olsen, JV et al: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks Cell (2006); Andersen, JN et al: Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors Sci Transl Med (2010)

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AP3 developed to overcome Critical challenges facing biopharma industry Discovering potent compounds suitable for clinical monotherapy Determining which patients will benefit from those drugs Preventing or reducing resistance to maximize response durability AP3 is a proprietary, machine learning-enabled internal R&D engine that effectively addresses these challenges, driving rapid advancement of our pipeline Challenge Acrivon Predictive Precision Proteomics (AP3) Optimal target/pathway selectivity for rapid generation of single agent active compounds Identification of drug-sensitive indications and patients for actionable precision medicine Ability to rapidly identify and overcome resistance mechanisms

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Acrivon Pipeline Anticipated Next Milestone Phase 3 Phase 2 Phase 1 Preclinical ACR-368 (CHK1/CHK2) Single-Arm Trials Based on OncoSignature Prediction Option to Initiate Additional Trials in HPV+ SCC (H&N*, Anal, Cervical) and Sarcomas Trial Initiation Q4 2024 Multiple Program Updates Q3 (ESMO) and Q4 2024 Endometrial Cancer Bladder Cancer OncoSignature-Predicted Monotherapy Sensitive Tumors Future Development Candidates Additional AP3-driven co-crystallography programs ACR-368 Monotherapy LDG Combination Registrational intent Phase 2 single arm trials based on predicted sensitivity to ACR-368 monotherapy in OncoSignature-positive patients Exploratory Phase 1b/2 single arm trials of ACR-368 in combination with low dose gemcitabine, or LDG, in OncoSignature-negative patients LDG Combination ACR-368 Monotherapy Fast Track Designation ACR-368 Monotherapy LDG Combination ACR-2316 (WEE1/ PKMYT1) Phase 1 Activated OncoSignature-Predicted Monotherapy Sensitive Tumors Cell cycle program (undisclosed target) Development Candidate Nomination 2025 Discovery *Investigator-Initiated Trial (IIT) activated at Moffitt Cancer Center Platinum-Resistant Ovarian Cancer ACR-368 Monotherapy Breakthrough Device & Fast Track Designations LDG Combination

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Newly disclosed ACR-368 clinical data ESMO 2024: Interim data from the registrational intent Phase 2 prospective clinical trial in endometrial cancer Data cut as of July 25, 2024 Poster available on Acrivon’s website: https://acrivon.com/science/#publications-posters

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AP3-based drug discovery and clinical development in predicted sensitive subjects and tumor types Predicted Responder AP3 Clinical Biomarkers Predictive OncoSignature tests Indication Finding Sensitive tumor types Resistance Mechanisms Rational drug combinations Drug Discovery SAR Optimal target selectivity PD Markers ~6,000 per compound Informs in-licensing AP3 profiling of candidates Streamlined Clinical Development Predicted sensitive indications with informed dose optimization

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AP3 platform: Drug response prediction in individual patients “Disease Pathway-Based Method to Generate Biomarker Panels Tailored to Specific Therapeutics for Individualized Treatments”: EP 2 229 589, issued June 10, 2015; US2017/0067877A9, pending. OncoSignature® is a Registered Trademark: US Reg. No. 5,718,472; Int. Cl. 5, 42. Intl. Reg. 1382289 PROPRIETARY WORKFLOW INTEGRATING PROVEN TECHNOLOGIES STEP 1 STEP 2 STEP 3 BIOMARKER IDENTIFICATION THERAPEUTIC PACKAGE Acrivon drug with predictive BM assay PATIENT RESPONDERS Optimal indications and combinations AP3 DRUG PROFILING Resistant Sensitive BIOMARKER VALIDATION HIGH RES PROTEOMICS BY MS CELL LINES, PDX, HUMAN TISSUE CLINICAL SIGNATURE ASSAY 3-6 BIOMARKERS PROSPECTIVE RESPONSE PREDICTION ON PRETREATMENT BIOPSY No benefit Benefit Predicted Non-responder Predicted Responder Patients without biomarkers critical for drug sensitivity efficiently excluded + OncoSignature® CLASS 1 BM CLASS 2 BM CLASS 3 BM AI-DRIVEN

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ACR-368: a clinically active phase 2 CHK1/2 inhibitor ATP-competitive inhibitor of CHK1 (0.9 nM) and CHK2 (8 nM) Exclusively in-licensed from Eli Lilly & Company (WW rights); originally discovered by Array (Pfizer) CoM patent exp. Oct., 2030; Salt-form exp. Apr., 2037 Balanced inhibition of both CHK1 and CHK2 believed important for RECIST monotherapy activity ACR-368 (MW): 365.4 DRUG TARGET PROFILE AT TIME OF IN-LICENSING Durable monotherapy activity: Platinum-resistant ovarian and squamous cell cancers (Anal and H&N) Large safety database, favorable safety profile: >1,000 patients treated (~50% mono, ~50% in combination) Ideal for AP3 method: Proven clinical activity, but requires patient responder identification to achieve sufficient ORR G1/S-defective cancers rely on CHK1-regulated cell cycle checkpoints CHK1 pauses cell cycle to enable DNA repair G2/M Checkpoint S Phase Checkpoint M G1 S Cancer Cell Cycle G2 CHK1/2 CHK1/2 Defective G1/S Checkpoint

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Endometrial cancer is an AP3-predicted ACR-368-Sensitive tumor ACR-368 OncoSignature-based indication finding prior to trial entry ACR-368 OncoSignature imaging demonstrates addiction to CHK1/2 DDR axis Confirmation of predicted sensitivity in genetically non-modified PDX models Confirmation of ACR-368 OncoSignature prediction in PDX tumor tissues pretreatment in >1,000 cancer patients treated with ACR-368 in Lilly-sponsored trials, endometrial cancer was not tested

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High grade advanced stage endometrial cancer opportunity has opened for ≥ 2nd line (post anti-PD-1) ACR-368 Target Indication: High grade, locally advanced or metastatic, recurrent endometrial cancer Significant unmet need, attractive commercial potential Must have recurred after prior chemo and PD-1/PD-L1 inhibitor therapy1 Irrespective of molecular (MMR, p53, other) alterations and subtype (serous, endometrioid, clear cell, carcinosarcoma) SOC: ≥2nd line (post-PD-1 + chemo) ~14.7% ORR, mPFS 3.8 months2 ≥3rd line ~9% ORR, mPFS 2.8 months3 ACR-368 Target Product Profile: ≥25% ORR with CI lower bound >20%; mDoR ≥5.5 months 1Unless ineligible for PD-1/PD-L1 therapy 2Eskander R et al, NEJM, 2023; Mirza MR et al, NEJM, 2023; Makker V et al, NEJM, 2022 3Ray-Coquard I et al, BJC, 2013

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ACR-368-201 Trial and enrollment in endometrial cancer April 2024 Corporate R&D Event1 ESMO 20242 Endometrial Cancer BM+ BM- Total BM+ BM- Total Safety-Evaluable (enrolled ≥1 dose) 7 11 18 12 23 35 Efficacy-Evaluable (≥1 on-treatment scan) 5 5 10 8 15 23 BM+% (enrolled BM+/Total) 38.9% 34.3% BM+ BM- https://clinicaltrials.gov/study/NCT05548296 1https://ir.acrivon.com/news-events/events-presentations 2https://acrivon.com/science/#publications-posters Enrollment in Endometrial Cancer ACR-368-201 Trial Ongoing enrollment in ovarian and bladder cancer cohorts with update planned for future date

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Demographics and subject disposition (N=35) Subject Demographics BM+ N = 12 BM- N = 23 Median Age (range) 66 (60-76) 68 (42-78) Race (%) White 8 (67) 16 (70) Black/African American 3 (25) 3 (13) Asian 0 (0) 3 (13) Other 0 (0) 1 (4) Unknown 1 (8) 0 (0) Current Stage (%) III 3 (25) 12 (52) IV 9 (75) 10 (43) unk 0 (0) 1 (4) Histology (%) Serous 8 (67) 7 (30) Endometrioid 3 (25) 7 (30) Carcinosarcoma 1 (8) 3 (13) Clear Cell Carcinoma 0 (0) 2 (9) Other 0 (0) 4 (17) ECOG Status at Baseline (%) 0 5 (42) 10 (43) 1 7 (58) 13 (57)  Subject Disposition BM+ N = 12 BM- N = 23 Median Prior Lines (range) 2 (1-4) 3 (1-4) Prior PD-1/PD-L1 Therapy (%) Yes 12 (100) 22 (96) No 0 (0) 1 (4)* Discontinued Study Drug (%) 3 (25) 13 (57) Reason for Discontinuing Study Drug (%) PD 2 (17) 10 (43) PI Decision 1 (8) 0 (0) Unacceptable Tox 0 (0) 1 (4) Subject Decision 0 (0) 1 (4) Subject Withdrawal of Consent 0 (0) 1 (4) Survival Status (%) Alive^ 10 (83) 14 (61) Deceased 2 (17) 7 (30) Unknown 0 (0) 2 (9) *Subject deemed ineligible for anti-PD-1therapy. ^1 BM+ and 4 BM- subjects are still on study for follow-up, but no longer receiving study drug. Data current as of 25July2024 and includes all subjects enrolled with registrational intent BM- includes all subjects treated with ACR-368 + low dose gemcitabine (LDG) at RP2D (105 mg/m2 and 10 mg/m2, respectively).

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significant ACR-368 responder enrichment in efficacy-evaluable subjects1 (N=23) in registrational intent phase 2 trial Overall Response BM+ Monotherapy BM- LDG Combination Total N = 8  N = 15 N=23   N (%) N (%) N (%) CR 0 (0) 1 (7) 1 (4) cPR 5 (63) 0 (0) 5 (22) uPR 0 (0) 1 (7) 1 (4) SD 1 (13) 6 (40) 7 (30) PD 2 (25) 7 (47) 9 (39) cORR (95% CI) 62.5% (30.4, 86.5) 6.7% (0.84, 31.8) 26% (12.3,46.8) OncoSignature BM+ vs BM- Segregation P = 0.009 Prospective initial validation of the AP3-based ACR-368 OncoSignature now achieved for endometrial cancer (P = 0.009 vs P = 0.083) Confirmed ORR in BM+ subjects now 62.5% with the lower bound of 95% C.I. 30.4% (vs. 22.9%) Confirmed ACR-368 responders still on therapy; mDoR not yet reached (~6 months at time of data-cut vs ~2 months) 1Subjects with ≥1 on-treatment scan 2https://ir.acrivon.com/news-events/events-presentations Meaningful positive data maturation since April R&D Event2

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Clinical activity in BM+ patients who have all progressed on prior anti-pd-1 therapy Data current as of 25July2024, includes all BM+ subjects Percent Change from Baseline (sum of diameters) cPR SD PD Still on Treatment Confirmed ORR = 62.5% 95% C.I. (30.4%, 86.5%) Significant disease control (75%) with most RECIST responses occurring early

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Ongoing confirmed responses in BM+ subjects across subtypes Data current as of 25July2024 Months on Treatment 4 – BOR on last prior line 5 – BOR on ACR-368 1 – Subtype 2 – MMR Status mDOR not yet reached (~6 months at time of data cut-off) Durable responses in patients who all progressed on prior anti-PD-1 and whose BOR in last prior line was mostly PD Most patients are pMMR and p53 mutant, consistent with their prevalence in high grade endometrial cancer ACR-368 OncoSignature prediction is independent of molecular (incl. MMR) and histological subtype 3 – p53 Status 1 2 3 4 5

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Confirmed responses in subjects who all progressed on prior anti-PD-1 Endometrial subtype # Prior Lines Last Prior Therapy (LPT) BOR on LPT BOR on ACR-368 Serous 3 Pembrolizumab/Lenvatinib PD cPR Serous 2 Pembrolizumab/Lenvatinib PD cPR Endometrioid 4 Cisplatin PD cPR Serous 1 Pembrolizumab SD cPR Carcinosarcoma 2 Pembrolizumab/Lenvatinib PR cPR Serous 4 Liposomal doxorubicin PD SD Serous 3 Pembrolizumab/Lenvatinib UNK PD Serous 3 Pembrolizumab/Lenvatinib NA PD BOR = Best Overall Response, UNK = unknown, NA = not applicable, NT = not tested Data shown current as of 25Jul2024 and includes all efficacy-evaluable (at least one scan on-treatment) BM+ subjects All confirmed responders progressed on prior PD-1 therapy and majority had BOR = PD on last prior line of therapy Only 1 RECIST response amongst 6 patients with BOR data from LPT

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Deep, rapid responses seen in patients with large tumor lesions Screening Week 8 Week 16 Superior vaginal cuff Inferior vagina 0 mm 72-yo female with Stage III serous endometrial carcinoma (pMMR) PD on last prior line (pembrolizumab/lenvatinib) Confirmed PR at Week 16 73% overall decrease in sum of target lesions from baseline

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Evidence of LDG sensitization in proportion of BM- subjects in exploratory phase 1b/2 trial Best Overall Response Initial disease control (1 cCR, 1 uPR, and 6 SD) observed in a proportion of BM- subjects LDG sensitization may potentially increase ORR across BM+ and BM- patients 1 2 3 4 Data current as of 25July2024, includes all BM- subjects enrolled at RP2D for LDG (10 mg/m2). 1– Histology; 2 – MMR; 3 – BOR on most recent prior line; 4 – BOR on ACR-368 + LDG PR SD PD Still on Treatment CR Confirmed Response Time on Treatment (Weeks) Percent Change from Baseline (sum of diameters) Percent Change from Baseline (sum of diameters) Months on Treatment

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Encouraging safety profile Limited, predominantly transient, reversible, mechanism-based hematological AEs, which typically occurred during the first 1-2 cycles of therapy Notable absence of long-lasting myelosuppression or the typical more severe non-hematological AEs commonly seen with ADCs and chemotherapy ACR-368 data current as of 25July2024 and includes the safety population of endometrial carcinoma subjects (any subject who has received at least one dose of ACR-368) enrolled (BM+ and BM-) and at the RP2D for LDG (BM-). Prophylactic G-CSF encouraged in BM+ and mandated in BM- subjects (compatible with q14d dosing regimen). Treatment-Related Adverse Events of Note ACR-368 (BM+) ACR-368 + LDG (BM-) N = 12  N = 23 All (%) Gr 3/4 (%) All (%) Gr 3/4 (%) Thrombocytopenia 6 (50) 2 (17) 12 (52) 8 (35) Anemia 4 (33) 3 (25) 12 (52) 9 (39) Neutropenia 3 (25) 3 (25) 7 (30) 7 (30) Febrile Neutropenia 0 0 3 (13) 3 (13) Fatigue 3 (25) 0 7 (30) 0 Vomiting 3 (25) 0 2 (9) 0 Diarrhea 2 (17) 0 2 (9) 0 Infusion Reaction 0 0 1 (4) 0 Hypertension 0 0 1 (4) 1 (4) Dyspnea 0 0 2 (9) 0

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blinded KOL Market research underscores endometrial cancer represents significant opportunity for acr-368 Endometrial cancer (EC) projected to be the third most prevalent cancer and the fourth leading cause of cancer-related death among women by 20401 Incidence = 67,880, prevalence = 865,000 in the US (2023)*; Incidence increasing by 1-3% per year Mortality = 13,250 in the US (2023); 5-year survival ~ 80%* High grade EC accounts for majority of EC deaths each year Second line (2L) now represents a high unmet need New cases of high grade, recurrent EC (progressed on anti-PD-1 + chemo) ~30K patients/year 90% of cases believed to progress to 2L therapy Recent front-line approvals of anti-PD-1 plus chemo followed by anti-PD-1 only1,2 for high grade EC reduces/eliminates pembro + lenvatinib3 as viable 2L option for most patients Reported chemotherapy efficacy in 2L is ORR = 14.7% and mPFS = 3.8 months3 *SEER database 1Eskander et al, NEJM 2023; 2Mirza et al, NEJM 2023; 3Makker et al, NEJM 2022

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Blinded Kol market research suggests acr-368 profile attractive to gynecologic oncologists Themes Implications Representative quotes Significant SOC gap and unmet need exists in 2L opportunity for ACR-368 Huge unmet need still exists in endometrial cancer treatment, especially pMMR ”People that develop recurrence almost invariably do not survive their endometrial cancer.” “That's really where there is the biggest opportunity is – in 2L.” “I would say that you would really want to see something with a response rates north of 30% to really get people excited about that but really the bar is above 20% and would be interesting.” “I know the FDA is very interested in companion diagnostics. I think that they really want to see that the work is being done to understand the responders.” Biomarker driven approach highly attractive and justified for high ORR “I believe that in pMMR the contribution of immune therapy is modest.” “If you had a 20% or 25% response rate, that would be pretty good” “If you could predict which patients would respond so that the patients that you chose would be higher, then I think you'd be in like Flynn.” “I think everybody's struggling with what to do for 2L therapy.” Clinicians eager to embrace new therapeutic options especially in challenging to treat molecular sub-groups “Those patients (pMMR) we know they don't have as robust as response as those patients that are mismatch repair deficient. Certainly, that's a big unmet need.” Recent changes to standard of care leaves opportunity for significant penetration with new 2L therapies That ACR-368 OncoSignature is independent of genetic background or histology further favorably differentiates the agent Source: Single blinded, proprietary third-party market research with endometrial KOLs conducted August-September 2024 “Over 60% ORR? I hope such a compound really exists!”

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Symptoms (i.e. bleeding, pain) Evolving Treatment Landscape for the Management of Advanced Stage or Recurrent Endometrial Cancer Diagnosis Surgical Staging Carboplatin + Paclitaxel + Immune Checkpoint Inhibition US FDA Approved in the dMMR and pMMR populations - C/P + Pembrolizumab (NRG GY018) - C/P + Dostarlimab (RUBY/GOG 3031) NCCN Compendium Listed - C/P + trastuzumab (HER2+ serous and carcinosarcoma) - C/P alone MAINTENANCE Pembrolizumab Dostarlimab ------------ Trastuzumab Progression-Free Survival (9-13 months in the pMMR EC population) Progression Lenvatinib + Pembrolizumab -------------- C/P + IO -------------- US FDA approval of T-Dxd In HER2 3+ Other Lines of Therapy and Clinical Trials Post-Progression Survival (12-18 months) No Prior-IO Prior-IO Single agent vs combination Chemotherapy -------------- US FDA approval of T-Dxd In HER2 3+ Progression With chemotherapy: ORR 15%; mPFS 3.8 mo Potential alternate strategies: hormonal therapy, single agent IO, T-Dxd in HER 2 2+ (NCCN) Courtesy Dr. R. Eskander

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Development path for ACR-368 in endometrial cancer Accelerated approval pathway Ongoing single arm registrational intent Phase 2 monotherapy endometrial cancer trial represents the first potential approval opportunity for ACR-368 Confirmatory trial strategy Evaluating options to potentially move towards new front line setting Randomization anti-PD-1 vs anti-PD-1 + ACR-368 post C/P + anti-PD-1 (sub-group analysis; MMR status in all-comer)* Potential ≥2nd line options: ACR-368 + ULDG in all-comer patients *Based on current clinical data showing cPRs in patients progressing on prior anti-PD-1 together with a strong rationale for, and preclinical data demonstrating additive/synergistic activity of ACR-368 and anti-PD-1 (Refs: Lyer et al, Cancer Disc 2021; McGrail et al, Sci Transl Med 2021; Sen et al, Cancer Disc 2019)

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ACR-368 potential in high unmet tumor types beyond endometrial, ovarian, and bladder cancer Enrollment is continuing in our ongoing multicenter phase 2 trials in ovarian and bladder cancer with planned update at a future date ACR-368 has also shown promising clinical activity in HPV+ squamous cell cancers (SCC), and sarcomas* HPV+ SCC are of increasing incidence (~50,000-60,000 new cases per year in the US) and includes ~70-80% of oropharyngeal H&N, ~20% of esophageal, ~90% of cervical, and 95% of anal cancers** SCCHN: Dr. C Chung, MD, Chair, Moffitt Cancer Center has begun an investigator-initiated trial with ACR-368 + ULDG in both HPV+ and HPV- SCCHN post anti-PD-1. IND cleared and site is activated HPV+ SCC represent tumor types of high unmet need and attractive option for next Acrivon-sponsored trial(s) with ACR-368 *Hong et al, CCR 2018, Slotkin et al, ASCO Annual Meeting 2022 **CDC 2023; ICO/IARC Information Centre on HPV and Cancer 2023; Gribb et al, Dela J Public Health 2023, NCI 2023

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ACR-2316, a potent, novel, dual WEE1/PKMYT1 inhibitor optimized for superior single agent activity and therapeutic index IND CLEARED AND FIRST CLINICAL SITES ACTIVATED AHEAD OF SCHEDULE AP3-BASED DRUG DISCOVERY

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Streamlined AP3-based design of compounds for superior single agent activity and therapeutic index Peptide clean up Direct DIA analysis Drug treatment Proteolysis P-peptide enrichment Ultra high resolution P-proteomic profiling Week 0 Week 2 Turnaround <2 weeks Quantitative mapping (>105,000 phospho-sites covering >10,000 proteins) Drug-regulated phospho-sites and biological process enrichment Drug-regulated pathway activity mapping and reconstitution P P AP3 enables pathway-based drug design for optimal drug properties High resolution and throughput MS-based P-proteomics

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ACR-2316: uniquely enabled by AP3 to overcome limitations of current wee1 and pkmyt1 inhibitors Zhu et al, J. Med. Chem. (2017) Program goals (superior therapeutic index): Superior single agent activity (AP3) Potent activation of CDK1, CDK2, and PLK1 and quenching of resistance through balanced WEE1/PKMYT1 inhibition to ensure robust pro-apoptotic tumor death High selectivity for minimal AEs (co-crystallography) Structure-guided design to limit adverse events (AEs) to be strictly mechanism-based, transient, short-lived Streamlined clinical development (ACR-2316 OncoSignature) To identify/prioritize sensitive indications prior to clinical start and for drug target engagement-based dose optimization during Phase 1 AP3 used for pathway-based optimization to achieve superior single agent activity Co-crystallography for drug design and selectivity ACR-2316: Rationally designed WEE1/PKMYT1 inhibitor Superior anti-tumor efficacy with complete tumor regression across models High selectivity ensures transient, short-lived, mild AEs Potent WEE1 inhibition, balanced PKMYT1 inhibition, overcomes resistance and enables robust activation of CDK1, CDK2, and PLK1 for mitotic catastrophe

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ACR-2316 is highly potent across human tumor cell lines and patient-derived ex vivo tumor models Patient-derived ex vivo ovarian tumor models Human tumor cell lines (not genetically selected) Breast Lung Ovarian Prostate Renal Medulloblastoma Glioblastoma Pancreatic WEE1i PKMYT1i

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ACR-2316 induces complete tumor regression across models and dosing regimens 5d on/2 d off Model 1 5d on/2 d off Model 2

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ACR-2316 - favorable preclinical safety profile Mice: ACR-2316 was well-tolerated, resulting in tumor regression in xenograft mouse models at multiple dosing regimens (qw, 2qw, 3d on/4d off, 5d on/2d off, and qd) Transient, reversible, mechanism-based hematological adverse events Rat and dog MTD, DRF, and GLP tox studies: GLP tox studies (31 days) completed in rat and dog with the planned human dosing regimen achieving exposure required for tumor regression Adverse events were mechanism-based, short-lived, reversible and limited to dividing myeloid progenitors and gastrointestinal tract We believe the broad therapeutic index observed across all our preclinical studies conducted with the planned dosing regimen is consistent with the target human exposure required for anti-tumor activity and anticipated reversibility of mechanism-based AEs

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ACR-2316 IND cleared and initial clinical sites activated ACR-2316-101: Phase 1 study of ACR-2316 in subjects with advanced solid tumors Aiming for streamlined clinical development: Multiple sites currently activated and screening, first dosing expected shortly AP3-based indication finding and OncoSignature development ongoing Dose optimization to be guided by drug target engagement aligned with Project Optimus Dose Expansion RP2D determination in 2 selected tumor types Dose Escalation (N ≤ 42 patients) In selected solid tumor types

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Acr-2316 is a potentially best-in-class agent rationally designed using Acrivon’s ap3 platform Program Goals Demonstrated Preclinical Results Superior single agent activity High selectivity and potency Streamlined clinical development Favorable safety profile Broad preclinical therapeutic index and anti-tumor activity across dosing regimens 5-20-fold more potent* in preclinical models than clinical benchmarks High selectivity results in adverse events limited to transient, short-lived, mechanism-based, reversible Superior* single agent anti-tumor activity through robust CDK1, CDK2, and PLK1 activation and elimination of dominant resistance mechanisms through balanced WEE1 and PKMYT1 inhibition AP3-Enabled SAR AP3-based identification of PD biomarkers and prioritization of promising indications 1 2 3 4 *Head-to-head preclinical studies against benchmarks with clinical data

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Data completeness Peptide IDs CV Pearson Correlation PCA Hierarchical Clustering DEPs Volcano Plots ANOVA Hierarchical clustering Consensus Sequence Motif Kinase Inference Pathway Enrichment Network Mapping Biomarkers Filtering Batch effects Normalization Imputation ~150,000 phosphosites ~50,000 phosphosites Ap3 interactome v.2: Proprietary Interactive Data analysis infrastructure Actionable data across all AP3 experiments accessible for all Acrivon scientists Fully scripted, algorithm-based machine learning-enabled pathway and biomarker analyses

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Acr-2316 induces potent activation of pro-apoptotic mitotic kinases in sensitive tumor cells Robust activation of CDK1with ACR-2316 exemplified by enrichment of 206 upregulated substrates of CDK1 ACR-2316 @60min and 200nM in ACHN

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Robust potent inhibition of CDK1 consensus substrate Y15 by ACR-2316 AP3 interactome enables real time quantitative computational analyses of proprietary AP3 drug profiling data across different conditions and experiments Comparison @60min and 200nM in ACHN Time-dependent comparison @ 200nM in ACHN Dose-dependent comparison @ 60min in ACHN ACR-2316 ACR-2316 3 -3 log2FC 3 -3 log2FC 3 -3 log2FC

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Robust potent inhibition of CDK1 consensus substrate Y15 by ACR-2316 vs comparators 60min and 200nM in ACHN 3 -3 log2FC

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Robust potent inhibition of CDK1 consensus substrate Y15 by ACR-2316 vs comparators Dose-dependent comparison @ 60min in ACHN 3 -3 log2FC

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Robust potent inhibition of CDK1 consensus substrate Y15 by ACR-2316 vs comparators Time-dependent comparison @ 200 nM in ACHN 3 -3 log2FC

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AP3-based compound design in intact cells: optimal activation and inhibition of critical pathways CDK1, CDK2, and PLK1 top activated kinases critical for potent pro-apoptotic tumor cell death (mitotic catastrophe) top inhibited kinases involved in resistance to WEE1 inhibitors

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FINANCIAL HIGHLIGHTS Cash and marketable securities $220.4M Projected runway into H2’26 Fully Diluted Shares Outstanding 43.9M Balance sheet 30-June-2024 Current operating plan, assuming no additional financing Including shares, pre-funded warrants and equity grants outstanding 30-June-2024

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Key take aways Significant clinical advancements and continued prospective validation of our AP3 platform since last R&D update in April Interim registrational intent Phase 2 clinical data for ACR-368 endometrial cancer cohort*, with confirmed ORR (63%) and lower bound of confidence interval (~30%), solidifying endometrial cancer as likely first indication for potential approval Statistically significant segregation of responders in BM+ vs BM- subgroups based on prospective OncoSignature patient selection (p-value = 0.009) ACR-368 endometrial cohort data maturing with all responders still on therapy; mDoR not yet reached (~6 months at time of data-cut) IND clearance of ACR-2316, a potential best-in-class, dual WEE1/PKMYT1 inhibitor rationally designed using AP3; clinical sites activated and screening patients for enrollment in a Ph1b study AP3 Interactome generating proprietary, actionable insights, leveraging in-house data and delivering fully scripted, algorithm-based machine learning-enabled pathway and biomarker analyses 1 2 3 4 5 Cash and marketable securities ~$220M with runway projected into second half of 2026 6 * Data cut as of July 25, 2024 Actively evaluating potential confirmatory trial designs for a potential future label expansion 7

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Infectious, CNS, and other diseases Oncology Fibrotic and inflammatory Autoimmune Cancers with DDR stress Therapeutic areas Therapeutic modalities Small molecule Bifunctional molecule Antibody ADC Oligo/RNA The AP3 Approach is modality and disease agnostic Current focus

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Q&A session

v3.24.3

Document and Entity Information	Sep. 14, 2024
Cover [Abstract]
Amendment Flag	false
Entity Central Index Key	0001781174
Document Type	8-K
Document Period End Date	Sep. 14, 2024
Entity Registrant Name	Acrivon Therapeutics, Inc.
Entity Incorporation State Country Code	DE
Entity File Number	001-41551
Entity Tax Identification Number	82-5125532
Entity Address, Address Line One	480 Arsenal Way
Entity Address, Address Line Two	Suite 100
Entity Address, City or Town	Watertown
Entity Address, State or Province	MA
Entity Address, Postal Zip Code	02472
City Area Code	(617)
Local Phone Number	207-8979
Written Communications	false
Soliciting Material	false
Pre Commencement Tender Offer	false
Pre Commencement Issuer Tender Offer	false
Security 12b Title	Common Stock, $0.001 par value
Trading Symbol	ACRV
Security Exchange Name	NASDAQ
Entity Emerging Growth Company	true
Entity Ex Transition Period	false

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