Acrivon Therapeutics, Inc. · NASDAQ:ACRV
Acrivon Therapeutics — Investor Presentation (September 2025)
57 slides from Acrivon Therapeutics's investor presentation, Sep 5, 2025
Slide 1: Acrivon Predictive Precision Proteomics (AP3) Corporate Presentation
ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3) NEXT GENERATION PRECISION MEDICINE CORPORATE PRESENTATION SEPTEMBER 2025 Exhibit 99.1
Slide 2: Forward-looking statements
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 o
Slide 3: Acrivon Therapeutics – a next-generation precision medicine company
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 ≈
Slide 4: Acrivon Therapeutics overview
Development Site (Boston) Drug development and clinical biomarkers ML/AI-driven AP3 analyses Clinical leadership and trial oversight Precision-Proteomics Site (Lund/Copenhagen) Early pipeline drug discovery programs BM identification and drug profiling Mass spectrometry Acrivon therapeutics OVERVIEW
Slide 5: Accomplished leadership team
Accomplished leadership team Peter Blume-Jensen, M.D., Ph.D. CEO, President, Founder Eric Devroe, Ph.D. Chief Operating Officer Erick Gamelin, M.D., Ph.D. Chief Development Officer Executive Serono, Merck & Co., Daiichi Sankyo CSO Metamark - Marketed prostate proteomic test ProMark® Inventor Acrivon
Slide 6: Acrivon Pipeline
Acrivon Pipeline Anticipated Next Milestone Phase 3 Phase 2 Phase 1 Preclinical ACR-368 (CHK1/CHK2) Single-Arm Trials Based on OncoSignature Prediction Other Trials Ongoing/Under Consideration: HPV+ SCC (H&N*, Anal, Cervical), Sarcomas, MDS/MPN Initial Clin Data 2H 2025 Registrational Trial and Conf
Slide 7: AP3 generative phosphoproteomics platform
AP3 Generative phosphoproteomics platform Proprietary computational pipeline Structured Standardized AI-enabled AP3 Interactome AP3 KSR Predictor AP3 Data Portal AP3 Chatbot MS-proteomics Genomics Internal Multi-modal AP3 MS-proteomics Proprietary Public Validate Design + Insight Proprietary Databas
Slide 8: AP3-based drug discovery and clinical development
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 sel
Slide 9: AP3 approach is modality and disease agnostic
Infectious, CNS, and other diseases Oncology Fibrotic and inflammatory Autoimmune DDR and Cell Cycle Therapeutic areas Therapeutic modalities Small molecule Bifunctional molecule Antibody ADC Oligo/RNA The AP3 Approach is modality and disease agnostic Current pipeline Next
Slide 10: OncoSignature: drug response prediction in individual patients
Oncosignature: 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.
Slide 11: ACR-368: a clinically active CHK1/2 inhibitor
ACR-368: a clinically active phase 2 CHK1/2 inhibitor ATP-competitive inhibitor of CHK1 (0.9 nM) and CHK2 (8 nM) Acrivon holds full, unencumbered global rights to the asset Exclusively in-licensed from Eli Lilly & Company (WW rights); originally discovered by Array (Pfizer) Balanced inhibition of bo
Slide 12: ACR-368 OncoSignature test: prospective patient stratification
ACR-368 oncosignature test: prospective patient stratification Pretreatment tumor biopsy test Compatible with 5 business days turn-around Offered by CDx partner under exclusive license from Acrivon Pretreatment tumor biopsy Treatment decision based on patient stratification OncoSignature-positive On
Slide 13: ACR-368-201 trial protocol
ACR-368-201 trial protocol A Phase 2 Study of ACR-368 Therapy in Subjects with Endometrial Cancer Subjects with endometrial cancer who have relapsed after prior platinum-based chemotherapy and one prior line of anti-PD-(L)1 therapy OncoSignature Stratified Cohort (Positive or Negative) Subjects with
Slide 14: Endometrial cancer is an AP3-predicted tumor type
Endometrial cancer is an AP3-predicted tumor type 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 OncoSigna
Slide 15: Evolving treatment landscape for advanced or recurrent endometrial cancer
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 approval in dMMR and pMMR – C/P + Pembrolizumab (NRG GY018) - C/P + Dostarlimab (
Slide 16: Endometrial patient demographics and baseline characteristics
Endometrial patient Demographics and baseline characteristics Subject Demographics BM+ N = 20 BM- N = 38 Median Age (range) 65.0 (54, 76) 67.5 (42, 80) Race, n (%) White 14 (70) 22 (58) Black/African American 4 (20) 9 (24) Asian 1 (5) 5 (13) Unknown/Other 1 (5) 2 (5) Stage, n (%) III 4 (20) 14 (37)
Slide 17: Encouraging safety profile
Encouraging safety profile Treatment-Related Adverse Events, n (%) BM+ (N=26) BM- (N=51) All Grades Grades 3/4 All Grades Grades 3/4 Thrombocytopenia 14 (54) 4 (15) 30 (59) 18 (35) Anemia 13 (50) 7 (27) 29 (57) 23 (45) Neutropenia 8 (31) 7 (27) 14 (28) 12 (24) Leukopenia 5 (19) 3 (12) 11 (22) 10 (20
Slide 18: Best overall response – endometrial BM+ patients
Best overall response* – endometrial BM+ patients PD PD PD PD PD PD PD PD PD PD PD N = 20 Best Overall Response in last prior line of therapy: *BOR of either BICR or INV EDC data extract Feb 25, 2025 OncoSignature accurately predicts tumor drug sensitivity 80% of tumors shrink and 80% DCR in predict
Slide 19: ACR-368 activity in relapsed and refractory patients
RELAPSED REFRACTORY 17 4 11 7 6 14 10 8 18 2 3 1 19 15 12 16 5 OT OT OT OT BoR on Treatment CR PR SD PD NE ACR-368 activity in patients relapsed after last prior line 50% ORR mDoR > 10 mo (not reached) 100% DCR** DoT > 8.5 mo (not reached) ACR-368 activity in patients refractory to last prior line 3
Slide 20: AP3-predicted sensitization to ACR-368 by ULDG
AP3-predicted sensitization to ACR-368 by UlDG correlates with OncoSignature upregulation BM2 BM3 Quantified BM scores Pre/Post ULDG Tumor from H&N IIT patient A427 human lung tumor xenograft BM1 Pre- LDG Post- LDG Preclinical data Clinical data
Slide 21: Deep, rapid responses in BM+ patients
Screening Week 8 Week 12 Complete resolution of hepatic target lesions (-100%) (-100%) Deep, rapid responses in BM+ patients with aggressive endometrial tumors Screening Week 8 and 12 (-100%) Confirmed PR with complete disappearance of >10 additional hepatic metastases spanning both lobes ACR-368 si
Slide 22: Development path for ACR-368 in endometrial cancer
Development path for ACR-368 in endometrial cancer Accelerated approval pathway Ongoing single arm registrational intent Phase 2 monotherapy in BM+ patients Single arm 2nd line all-comer study ACR-368 + ULDG in all-comer patients based on ULDG MOA and clinical data in 2nd line ULDG is confirmed to n
Slide 23: Synergy of ACR-368 with anti-PD-L1 displays immune memory
Potent synergy of ACR-368 with anti-PD-L1 displays immune Memory in 100% of Mice Complete tumor regression Immune memory Immune memory independent of CD8 Immune memory independent of CD4 Immune memory requires both CD4 + CD8 Legends:
Slide 24: ACR-368 with anti-PD-L1 is well tolerated
ACR-368 with anti-pd-l1 is well tolerated consistent with non-overlapping toxicities Legends:
Slide 25: Confirmatory trial option: first line expansion as switch maintenance
Confirmatory trial option: First line expansion as switch maintenance – a significant market potential Anti-PD-1 IV Q3W + CT (paclitaxel + carboplatin) 6 cycles pMMR patients (~80%) with measurable stage III/IVA, stage IVB, or recurrent endometrial cancer Anti-PD-1 IV Q6W up to 14 cycles Median PFS
Slide 26: ACR-368 potential in other high unmet tumor types
ACR-368 potential in other high unmet tumor types Myelodysplastic Syndrome (MDS) and Myeloproliferative Neoplasms (MPN): Prevalent (~50%) mutations in splicing factor (SF) genes resulting in hyperactivated CHK1,2 Preclinical murine transplant studies of SF3B1-mutated human HSCs show potent ACR-368 s
Slide 27: ACR-368 combination opportunities in all-comer populations
ACR-368 combination opportunities in all-comer populations supported by strong rationale and data Anti-PD-(L)1 inhibitors ACR-368 is strongly synergistic with anti-PD-(L)1 and the two agents also have non-redundant activity Opportunity for frontline expansion in high unmet need tumors with significa
Slide 28: Internal pipeline: AP3-based drug discovery
Internal pipeline: AP3-based drug discovery potential first- and best in class candidates Streamlined AP3-based drug discovery AP3 used for biologically relevant selectivity profiling Program 2: Preclinical cell cycle program (undisclosed target) No known competitive programs Strong preclinical evid
Slide 29: Streamlined AP3-based drug design
Streamlined AP3-based drug design: integrated AI/ML-driven proteome-wide SAR Peptide clean up Direct DIA analysis Drug treatment Proteolysis P-peptide enrichment Ultra high resolution P-proteomic profiling Week 0 Week2 Turn-around <2 weeks Quantitative mapping (>150,000 phospho-sites covering >13,00
Slide 30: AP3: proprietary high-resolution data
AP3: proprietary HIGH-RESOLUTION DATA for streamlined biological drug design and development Acrivon proprietary compound data (>150 million data points per experiment) Several hundred samples (quadruplicates) in each experiment; >100 compounds profiled Miniaturized, high throughput, scalable: <2 we
Slide 31: WEE1 and PKMYT1 – critical cell cycle checkpoints
Wee1 and PKMYT1 - critical cell cycle checkpoints in human cancer WEE1 and PKMYT1 regulate S and G2-M cell cycle checkpoints to ensure proper DNA replication and mitotic completion Defective DNA repair is highly prevalent in cancers, creating a dependency on checkpoint proteins Only known substrate
Slide 32: ACR-2316: enabled by AP3 to overcome limitations of benchmarks
ACR-2316: uniquely enabled by AP3 to overcome limitations of benchmark wee1 and pkmyt1 inhibitors Drug Design by AP3-based SAR for desirable pathway effects and suppressing resistance mechanisms ACR-2316: Rationally designed, differentiated WEE1/PKMYT1 inhibitor for superior Therapeutic Index Comple
Slide 33: ACR-2316 is a potentially best- and first-in-class agent
Acr-2316 is a potentially best- and first-in-class agent designed using Acrivon’s ap3 platform Program Goals Demonstrated Results Superior single agent activity High selectivity and potency Streamlined clinical development Favorable ADME-PK, Therapeutic Index, and safety profile Broad preclinical th
Slide 34: ACR-2316 demonstrates strong potency and selectivity
Dual wee1/pkmyt1 inhibitor ACR-2316 demonstrates strong potency and selectivity DNA content 100 nM, 24 hour ACR-2316 exerts potent cell cycle effects with pronounced S-G2/M accumulation KinomeScan (468 kinases @ 1mM) DMSO Azenosertib Lunresertib ACR-2316 94% 41% 58% 50% ACR-2316 is highly selective
Slide 35: AACR 2025: AP3 uncovers tumor cell death through CDK1, CDK2, PLK1
AACR 2025: Generative Phosphoproteomics AP3 uncovers robust tumor cell death through cdk1, cdk2, and plk1 Poster link here
Slide 36: ACR-2316 results in strong activation of CDK1
Acr-2316 results in strong activation of cdk1 across cell lines Unbiased quantitation of ACR-2316-regulated CDK1 substrate p-sites (308) in intact cells based on CDK1 consensus recognition motif (Acrivon proprietary hybrid database approach) across multiple experiments Actionable insight into driver
Slide 37: ACR-2316 is highly potent across tumor cell lines and ex vivo models
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
Slide 38: Superior activity of ACR-2316 over WRN inhibitors
SUPERIOR ACTIVITY OF ACR-2316 oVER WRN INHIBITORS IN BOTH MSI HIGH AND MSS CELL LINES HRO761 is a noncovalent allosteric inhibitor of WRN (Novartis); VVD-133214/ RO7589831 is a covalent allosteric WRN inhibitor (Roche); ACR-2316 is more potent than both WRN inhibitors even in the optimal MSI high co
Slide 39: ACR-2316 induces complete tumor regression
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
Slide 40: Synergy of ACR-2316 with anti-PD-L1 displays immune memory
Potent synergy of ACR-2316 with anti-PD-L1 displays immune Memory in 100% of Mice Legends: Complete tumor regression Immune memory Immune memory independent of CD8 Immune memory independent of CD4 Immune memory requires both CD4 + CD8
Slide 41: ACR-2316 with anti-PD-L1 is well tolerated
ACR-2316 with anti-pd-l1 is well tolerated consistent with non-overlapping toxicities Legends:
Slide 42: ACR-2316 Phase 1 enrollment and dosing ongoing
ACR-2316 phase 1 PATIENT enrollment and dosing ongoing ACR-2316-101: Phase 1 study of ACR-2316 in subjects with specific advanced solid tumors Aiming for streamlined clinical development: ACR-2316 advanced in 15 months from initial lead into Phase 1 uniquely enabled by AP3 AP3-based indication findi
Slide 43: ACR-2316 clinical trial status
ACR-2316 clinical trial status Dose level (DL) 1, DL2 and DL3 cleared without safety concerns or DLTs by the safety review committee Preliminary PK data indicate approximate dose proportionality in the first 2 DL cohorts Significant drug target engagement observed in human PBMCs at DL1 and even deep
Slide 44: AP3 MS pharmacodynamic PBMC assay
AP3 MS Pharmacodynamic (PD) PBMC Assay established to support ACR-2316 Phase 1 study Blood draw PBMC isolation LC-MS analysis Quantitative PD result PBMCs isolated from ACR-2316 Phase 1 trial patients Non-invasive liquid biopsy for pharmacodynamic biomarkers Exhaustive depth: ∼8,000 proteins and ∼ 2
Slide 45: Drug target engagement observed in PBMCs at dose level 1
significant drug target engagement observed in pBMCs already at dose level 1 CDK1 CDK2 CDK5 PLK1 AKT1 AKT2 Drug-regulated P-sites (paired t-test : p-value < 0.05) (xxxxxxxS/TPxK/RxxSx) (QxxxxxxS/TPxxKxxx) (xTxxxxxS/TPxxxxEx) (xxxxRxxS/TxSxxxxx) (xxxxLDxS/TxxExxxx) (xxRxRxxS/TxSxxxxx) N=32196 N=2229
Slide 46: Preclinical cell cycle program (undisclosed target)
Preclinical Cell Cycle program (Undisclosed Target) Potential for first- and best-in-class program Attractive cancer drug target, no/minimal competitor programs, well-suited for AP3 platform Strong mechanistic target rationale for critical role in oncogenesis DepMap data suggests target X is an esse
Slide 47: AP3-predicted substrates and pathways
AP3-predicted substrates and pathways Target is a protein Serine kinase Clusters of selected substrates for cell cycle drug target Protein domain and function Protein pathway and cell/tissue Pathway enrichment of key substrates GO:1903047, Mitotic cell cycle process, FDR: 2.66E-21 T: 12% Y: 0 S: 88%
Slide 48: AP3 interactome data analysis infrastructure
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 Machine-Learning Filtering Batch effects Normalization Imputation ~164,000 phospho
Slide 49: AP3 reveals drug-regulated kinase activity not detectable by standard methods
AP3 reveals drug-regulated kinase activity in intact cells not detectable by standard methods Time : 60 minutes Dose : 20 nM KinomeScan @ 1mM ACR-2316 Drug-regulated kinase activity* in intact cells ACR-2743 (previous lead candidate) *Kinase activity based on substrate motif analysis using a proprie
Slide 50: Optimized dual inhibitors show desirable pathway effects
Optimized dual inhibitors show desirable pathway effects Activity (NES) -5 0 5 Substrate motif-inferred kinase activities Kinase activity based on proprietary PTM-SEA-based hybrid workflow and analyses Optimized dual WEE1 and PKMYT1 inhibitors affect cell cycle and canonical MAPK pathways in desirab
Slide 51: AP3 reciprocal quenching identifies PKMYT1 as WEE1 inhibitor resistance mechanism
AP3 Reciprocal quenching identifies PKMYT1 as a key wee1 inhibitor-induced resistance mechanism Induced Suppressed Enrichment Score (NES) 500 5 Protein set size Mitotic regulation Cell cycle and cancer DNA homology repair DNA damage responses Sensitive Resistant WEE1i PKMYT1i PKMYT1i WEE1i PUJANA_BR
Slide 52: Reciprocal quenching reveals optimal potency profile for dual inhibitor
AP3 reciprocal quenching reveals optimal target potency profile for dual WEE1/PKMYT1 inhibitor PKMYT1i WEE1i PKMYT1i WEE1i Sensitive Resistant HCL, Euclidean 1043 p-sites from 298 proteins 4 -4 Centered log2FC (treated vs. DMSO) Target substrate of ACR-368 Target substrate of PKMYT1i Optimal potency
Slide 53: ACR-2316 induces activation of pro-apoptotic mitotic kinases
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
Slide 54: Inhibition of CDK1 consensus substrate Y15 by ACR-2316
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
Slide 55: AP3-based compound design in intact cells
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
Slide 56: Data driven execution and value creation
data driven execution and value creation Recent Accomplishments (Last 12 Months) Anticipated Next Milestones (2025) Positive ACR-368 data (ESMO 2024 and April 2025 Corporate R&D Event) in registrational intent endometrial cancer trial Dose level (DL) 1, DL2 and DL3 for ACR-2316 cleared without safet
Slide 57: Financial highlights
FINANCIAL HIGHLIGHTS Cash and Investments $147.6M Projected runway into Q2 2027 Fully Diluted Shares Outstanding 45.2M Current operating plan, assuming no additional financing Balance sheet 30-Jun-2025 Shares, PFW, and equity grants outstanding 30-Jun-2025 Notes: Unaudited.
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