Slide 1: Corporate R&D Event: Acrivon Predictive Precision Proteomics (AP3)
CORPORATE R&D EVENT September 14, 2024 ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3) OVERCOMING LIMITATIONS OF GENETICS-BASED PRECISION MEDICINE Exhibit 99.2
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: Outline
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 prop
Slide 4: 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 5: AP3 developed to overcome critical challenges facing biopharma industry
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-ena
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 Option to Initiate Additional Trials in HPV+ SCC (H&N*, Anal, Cervical) and Sarcomas Trial Initiation Q4 2024 Multiple Program Updates Q3 (ESMO) and
Slide 7: Newly disclosed ACR-368 clinical data
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
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 platform: Drug response prediction in individual patients
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.
Slide 10: 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) 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 CHK
Slide 11: Endometrial cancer is an AP3-predicted ACR-368-sensitive tumor
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-
Slide 12: High grade advanced stage endometrial cancer opportunity
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-
Slide 13: ACR-368-201 trial and enrollment in endometrial cancer
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-
Slide 14: Demographics and subject disposition (N=35)
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) 1
Slide 15: Significant ACR-368 responder enrichment in efficacy-evaluable subjects
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
Slide 16: Clinical activity in BM+ patients progressed on prior anti-PD-1
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%) w
Slide 17: Ongoing confirmed responses in BM+ subjects across subtypes
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 an
Slide 18: Confirmed responses in subjects who all progressed on prior anti-PD-1
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 C
Slide 19: Deep, rapid responses seen in patients with large tumor lesions
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
Slide 20: Evidence of LDG sensitization in BM- subjects
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
Slide 21: Encouraging safety profile
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 ch
Slide 22: Market research: endometrial cancer significant opportunity for ACR-368
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
Slide 23: KOL market research suggests ACR-368 profile attractive
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 deve
Slide 24: 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 Approved in the dMMR and pMMR populations - C/P + Pembrolizumab (NRG GY018) - C/P
Slide 25: 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 endometrial cancer trial represents the first potential approval opportunity for ACR-368 Confirmatory trial strategy Evaluating options to potentially move tow
Slide 26: ACR-368 potential in high unmet tumor types beyond endometrial
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 c
Slide 27: ACR-2316, dual WEE1/PKMYT1 inhibitor
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
Slide 28: Streamlined AP3-based design of compounds
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
Slide 29: ACR-2316: uniquely enabled by AP3 to overcome limitations
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
Slide 30: 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 31: ACR-2316 induces complete tumor regression across models
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 32: ACR-2316 favorable preclinical safety profile
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, DR
Slide 33: ACR-2316 IND cleared and initial clinical sites activated
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 OncoS
Slide 34: ACR-2316 potentially best-in-class agent designed using AP3
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
Slide 35: AP3 Interactome v.2: proprietary interactive 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 Filtering Batch effects Normalization Imputation ~150,000 phosphosites ~50,000 pho
Slide 36: 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 37: Potent inhibition of CDK1 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 38: CDK1 Y15 inhibition by ACR-2316 vs comparators
Robust potent inhibition of CDK1 consensus substrate Y15 by ACR-2316 vs comparators 60min and 200nM in ACHN 3 -3 log2FC
Slide 39: CDK1 Y15 inhibition vs comparators: dose-dependent
Robust potent inhibition of CDK1 consensus substrate Y15 by ACR-2316 vs comparators Dose-dependent comparison @ 60min in ACHN 3 -3 log2FC
Slide 40: CDK1 Y15 inhibition vs comparators: time-dependent
Robust potent inhibition of CDK1 consensus substrate Y15 by ACR-2316 vs comparators Time-dependent comparison @ 200 nM in ACHN 3 -3 log2FC
Slide 41: 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 42: Financial highlights
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
Slide 43: Key take aways
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%),
Slide 44: The AP3 approach is modality and disease agnostic
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
Slide 45: Q&A session
¢ Q&A session ACRIVON THERAPEUTICS @