Acrivon Therapeutics, Inc. · NASDAQ:ACRV
Acrivon Therapeutics — Investor Day (March 2025)
48 slides from Acrivon Therapeutics's investor day presentation, Mar 25, 2025
Slide 1: Corporate R&D Event March 25, 2025
CORPORATE R&D EVENT March 25, 2025
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 Team Participants
Peter Blume-Jensen, M.D., Ph.D. CEO, President and Founder; Inventor of the AP3 Platform Kristina Masson, Ph.D., M.B.A. Co-Founder and EVP, Business Operations; President and CEO, Acrivon AB William Bradley, M.D. Attending Physician, Department of Radiology, Massachusetts General Hospital; Clinical
Slide 4: Key opinion leader participants
Key opinion leader Participants Mansoor Raza Mirza, M.D. Chief Oncologist at Copenhagen University Hospital, Denmark; Board of Directors, Gynecologic Cancer Inter-Group (GCIG); Medical Director of the Nordic Society of Gynecologic Oncology-Clinical Trial Unit (NSGO-CTU); Vice President of the Europe
Slide 5: Agenda
agenda AP3 Generative Phosphoproteomics: Transforming drug discovery with proteome-wide SAR ACR-368 Phase 2 program update ACR-2316 Phase 1 program update Brief update on preclinical cell cycle program Extended runway guidance Q&A
Slide 6: 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 7: Streamlined AP3-based drug design: integrated AI/ML-driven proteome-wide SAR
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 (>130,000 phospho-sites covering >9,000
Slide 8: AP3 Generative phosphoproteomics platform
AP3 Generative phosphoproteomics platform Proprietary Database Proprietary computational pipeline Drug design and optimization Target ID / Indication Finding MoA / response prediction PD and predictive biomarkers Structured Standardized AI-enabled AP3 Interactome AP3 KSR Predictor AP3 Data Portal AP
Slide 9: 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 ~150,000 phospho
Slide 10: Prediction beyond training - Generative phosphoproteomics
prediction beyond training - Generative phosphoproteomics FOUNDATION MODELS Proprietary AP3 data External data Kinase-Substrate Relationships Protein-Ligand Interactions Properties + + Zero-shot Prediction Available KSR Unavailable KSR AP3 KSR Predictor: Generative AI uncovers kinome-wide substrate
Slide 11: Wee1 and PKMYT1 - critical cell cycle checkpoints in human cancer
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 12: AP3-derived WEE1 substrate ensemble enriched for novel consensus motifs
AP3-derived WEE1 substrate ensemble enriched for novel consensus motifs enabling proteome-based drug design 0 +1 0 -1 0 -2 0 +2 CDK1 Y15 EKIGEGTYGVVYKGR Sub1 Y# XXXXXXXYSXXXXXX Sub2 Y# XXXXXXXYGSXXX 0 -2 0 -2 CDK2 T14 VEKIGEGTYGVVYKA Sub3 S# XXXXXDDSXXXXXXX Sub4 S# XXXXXEDSXXXXXXX Tyrosine centric m
Slide 13: AP3-predicted WEE1 substrates and pathways
AP3-predicted WEE1 substrates and pathways for proteome-wide SAR compound design Y: 80% S: 14% T: 6% WEE1 is primarily a protein Tyrosine kinase Pathway clusters of selected WEE1 substrates Protein domain and function Protein pathway and cell/tissue Pathway enrichment based on key substrates Reactom
Slide 14: AP3-predicted PKMYT1 substrates and pathways
AP3-predicted PKMYT1 substrates and pathways for proteome-wide SAR compound design PKMYT1 is a protein Ser/Thr kinase Clusters of selected PKMYT1 substrates Protein domain and function Protein pathway and cell/tissue Top enrichment from PKMYT1 substrates KEGG:hsa04144, Endocytosis, FDR: 3.74E-06 T:
Slide 15: ACR-2316: uniquely enabled by AP3 to overcome limitations of current inhibitors
ACR-2316: uniquely enabled by AP3 to overcome limitations of current wee1 and pkmyt1 inhibitors AP3-based proteome-wide SAR for desirable pathway effects and suppressing resistance mechanisms ACR-2316: Rationally designed, differentiated WEE1/PKMYT1 inhibitor for superior Therapeutic Index Strong an
Slide 16: Single cell phosphoproteomics pioneered in Olsen lab
Single cell phosphoproteomics pioneered in Olsen lab • Seminal article on revolutionizing and SCP-enabling Astral MS technology >5,000 proteins in individual HeLa cells The first single cell phospho-proteome
Slide 17: ACR-368 Phase 2 update
ACR-368 Phase 2 update
Slide 18: ACR-368-201 Trial design
ACR-368-201 Trial design OncoSignature+ Single Arm Simon 2 Stage Monotherapy Phase 2b with Registrational Intent Single Arm Phase 1b/2 Exploratory Combination with Low Dose Gemcitabine OncoSignature- BM+ BM- ACR-368 monotherapy ACR-368 + LDG combination
Slide 19: 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 20: Demographics and baseline characteristics
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) IV 16 (80) 22 (58) U
Slide 21: Subject disposition
disposition Subject Disposition BM+ BM- Received at least 1 dose* 23 44 Efficacy evaluable (EE) population**, n (%) 20 (100) 38 (100) Efficacy-Evaluable Still on Treatment, n (%) 5 (25) 7 (18) Reason for Discontinuing Treatment, n (%) PD 10 (50) 28 (74) PI Decision 2 (10) 0 Unacceptable Tox 1 (5) 2
Slide 22: 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 23: Best overall response – endometrial BM+ patients
Best overall response* – endometrial BM+ patients OncoSignature accurately predicts tumor drug sensitivity 80% of tumors shrink and 80% DCR in predicted responders Confirmed ORR >2x higher than in last prior line of therapy 35% cORR (95% CI,18 - 57) with ACR-368 versus 15% cORR in last prior line* *
Slide 24: Spider Plot – BM+ patients
Spider Plot – BM+ patients Spider plots based on last RECIST imaging for each patient
Slide 25: Swimmer Plot – BM+ endometrial cancer patients
SWIMMER PLOT – BM+ endometrial cancer patients ⋀ ⋀ Patient #2 had PR per INV and Patient #18 had SD per BICR at second to last imaging mDoT in confirmed responders (not reached) >7.9 months mDoT for all patients = 3.7 months mDoT in previously relapsed patients (not reached) > 5.0 months mDoT in pre
Slide 26: 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; mean) ACR-368 activity in patients refractory to last prior li
Slide 27: AP3-predicted sensitization to ACR-368 by LDG correlates with OncoSignature upregulation
AP3-predicted sensitization to ACR-368 by lDG 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 28: Best overall response – endometrial BM- patients
Best overall response* – endometrial BM- patients BM- patients insensitive to ACR-368 likely benefit from LDG + ACR-368 combination The BOR (cORR = 13%) is comparable to BOR in last prior line (cORR = 17%)** Large tumor shrinkage in some patients with multi-line refractory massive tumor burden *BOR
Slide 29: Case story 1: BM+ patient; BOR = confirmed PR
Case story 1: BM+ patient; BOR = confirmed PR Tx BOR Carboplatin Taxol Dostarlimab CR Dostarlimab PD 67-year-old female with stage IV serous endometrial adenocarcinoma pMMR P53 mutant Biopsy of a hepatic metastasis OncoSignature Positive Tolerated treatment well with only one dosing delay due to mec
Slide 30: Case story 1 (BM+ patient) imaging
Screening Week 8 Week 12 Complete resolution of hepatic target lesions (-100%) (-100%) Case story 1 (BM+ patient) Screening Week 8 and 12 (-100%) Confirmed PR with complete disappearance of more than 10 additional hepatic metastases spanning both lobes and all hepatic segments Demonstrates ACR-368’s
Slide 31: Case story 2: BM+ patient; BOR = SD
Case story 2: BM+ patient; BOR = SD 67-year-old female with stage III endometroid endometrial adenocarcinoma pMMR P53 mutant Biopsy of a vaginal mass OncoSignature Positive Dose reduction and delay due to primarily mechanism related reversible hematological AEs Patient was REFRACTORY to prior lines,
Slide 32: Case story 2 (BM+ patient) imaging
Week 8 Volume 20.9 cm3 (-44%) Screening Longest Diameter: 4.6 cm Volume: 37.2 cm3 Longest Diameter: 4.8 cm (-4.2%) Large volumetric shrinkage (44%) yet not meeting RECIST criteria Case story 2 (BM+ patient)
Slide 33: Case story 3: BM- patient; BOR = confirmed PR
Case story 3: bm- patient; BOR = confirmed PR 73-year-old female with stage IV serous endometrial adenocarcinoma dMMR P53 mutant Biopsy of a hepatic metastasis Oncosignature Negative Tolerated treatment well at reduced dosage with mechanism related reversible hematological AEs BOR in last prior line
Slide 34: Case story 3 (BM- patient) imaging
>50 hepatic metastases occupying 40% of liver Dramatic reduction in size and number Remaining areas consist of residual fibrosis and necrosis, indicating a strong treatment response Screening Week 16 Case story 3 (bm- patient) Confirmed PR with equally strong regression in necrotic lymphadenopathy a
Slide 35: Case story 4: BM- patient; BOR = SD
Case story 4: BM- patient; BOR = SD 69-year-old female with stage IV endometrial adenocarcinoma MMR status unknown P53 status unknown Biopsy of a peritoneal lesion OncoSignature Negative Tolerated treatment well with dose reduction in last 2 doses and only mechanism related reversible hematological
Slide 36: Case story 4 (BM- patient) peritoneal disease reduction
Massive peritoneal disease burden at Screening Volume of disease 1020 cm3 Case story 4 (bm- patient) Profound volumetric reduction in peritoneal disease (1020 cm³ to 168 cm³) RECIST (SD) failing to capture true extent of tumor shrinkage Strongly supports LDG’s role in sensitizing tumors to ACR-368,
Slide 37: Full focus on endometrial cancer; ovarian and bladder cancer being deprioritized
Full focus on endometrial cancer; ovarian and bladder cancer being deprioritized Based on our emerging positive clinical data, competitive positioning, and attractive commercial opportunity, endometrial cancer is prioritized as first potential registration opportunity Tumor type predicted sensitive
Slide 38: Potent synergy of ACR-368 with anti-PD-L1 displays immune memory in mice
Potent synergy of ACR-368 with anti-PD-L1 displays immune Memory in 100% of immunocompetent Mice Average TV at start of treatment in Part I: 43 mm3 (N=8 mice/group) 7 CRs in Part I with combination treatment of ACR-368 + anti-PD-L1 7 CRs in Part II post-rechallenge with MC38 tumor cell inoculation (
Slide 39: ACR-2316 Phase 1 update
ACR-2316 Phase 1 update
Slide 40: Phase 1 Dose Escalation and Expansion Design
Phase 1 Dose Escalation and Expansion Design ~15 Sites 6 Sites (selected solid tumor types)
Slide 41: ACR-2316 program status
ACR-2316 program status Dose level (DL) 1 and DL2 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 already at DL1 using our proprie
Slide 42: AP3 MS Pharmacodynamic PBMC Assay established to support ACR-2316 Phase 1
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 43: Significant 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 44: Preclinical program
Preclinical program
Slide 45: Preclinical Cell Cycle program (Undisclosed Target)
Preclinical Cell Cycle program (Undisclosed Target) Target X – Attractive cancer drug target, no/minimal competitor programs, well-suited for AP3 platform DepMap data suggests target X is an essential gene for cancer cell viability Strong mechanistic target rationale for role in oncogenesis Highly s
Slide 46: AP3-predicted Target X substrates and pathways
AP3-predicted Target X substrates and pathways Target X is a protein Serine kinase Clusters of selected Target X substrates Protein domain and function Protein pathway and cell/tissue Pathway enrichment of key Target X substrates GO:1903047, Mitotic cell cycle process, FDR: 2.66E-21 T: 12% Y: 0 S: 8
Slide 47: 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 Option to Initiate Additional Trials in HPV+ SCC (H&N*, Anal, Cervical), Sarcomas, MDS/MPN** Initial Clinical Data 2H 2025 Update on Registrational
Slide 48: Financial Highlights
FINANCIAL HIGHLIGHTS Cash and Investments $184.6M Projected runway into 2027 Fully Diluted Shares Outstanding 43.8M Current operating plan, assuming no additional financing Balance sheet 31-Dec-2024 Including shares, pre-funded warrants, and equity grants outstanding 31-Dec-2024 Additional runway co