Acrivon Therapeutics, Inc. · NASDAQ:ACRV
Acrivon Therapeutics — Investor Day (April 2024)
42 slides from Acrivon Therapeutics's investor day presentation, Apr 24, 2024
Slide 1: Corporate R&D Event: Acrivon Predictive Precision Proteomics (AP3)
CORPORATE R&D EVENT APRIL 24, 2024 ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3) OVERCOMING LIMITATIONS OF GENETICS-BASED PRECISION MEDICINE
Slide 2: Forward-looking statements
Forward-looking statements -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 pl
Slide 3: Outline
outline Acrivon Therapeutics and AP3 overview 5 minutes Initial ACR-368 Phase 2 trial data 25 minutes AP3-based drug design: Dual WEE1/PKMYT1 inhibitor ACR-2316 and pipeline 20 minutes AP3 Interactome 5 minutes Live Q&A 20 minutes For a comprehensive corporate deck, please visit: https://Acrivon.com
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: 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 IND Filing in Q3 2024 Trial Initiation Q4 2024 Clinical Data 1
Slide 6: Acrivon Therapeutics – overview
Acrivon Therapeutics – overview Next-generation precision medicine; Foundational team pioneers in phosphoproteomics-based R&D AP3-based prospective patient responder identification Acrivon in-licensed ACR-368 (Prexasertib) a Lilly flagship program (durable single agent activity across solid cancers,
Slide 7: ACR-368 clinical data
ACR-368 clinical data Initial data from the ACR-368 prospective patient selection Phase 2 clinical trial in gynecological cancers Data cut as of April 1, 2024
Slide 8: 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 9: ACR-368 OncoSignature prediction of drug sensitivity
ACR-368 OncoSignature prediction of drug sensitivity: Biomarker quantitation across human Cancer patient samples Predicted Responder Patient with drug target dependency Class 1 BM Class 2 BM Class 3 BM Patient High Predicted Non-Responder Patient with no drug target dependency efficiently excluded C
Slide 10: Therapeutic bar for platinum-resistant ovarian and endometrial cancer
Therapeutic bar for High grade platinum-resistant ovarian and endometrial cancer new approvals Platinum-resistant ovarian cancer: ≥2nd line SOC* ~12% ORR, mDoR 3.7 – 5.7 months Mirvetuximab: Post 1-3 prior lines, FRa-high PROC (~35% of patients; ORR ~35%, PFS = 5.6 months) ~85% of patients with PROC
Slide 11: ACR-368-201 status – ovarian and endometrial
ACR-368-201 status – ovarian and endometrial (locked oncosignature thresholds, prospective trial) 12 weeks confirmatory scan on 11/27. PR confirmed (-30.16%). Clario reported SD (-23% and SD (-28%) 28 weeks scan expected on 3/18 21 patients awaiting 8-week scan 13 patients awaiting 8-week scan OncoS
Slide 12: OncoSignature+ gyn patients – tumor shrinkage
Oncosignature+ gyn patients – tumor shrinkage (Locked thresholds, prospective evaluation per protocol) BOR = Best overall response BOR PD PD SD SD SD PR PR uPR PR PR 105-004 102-010 124-001 166-003 141-002 102-012 120-011 143-002 120-007 143-004 * *Since data cut off, the one unconfirmed PR has been
Slide 13: OncoSignature-positive monotherapy GYN summary
OncoSignature-positive phase 2 monotherapy GYN summary– prospective data with locked thresholds ^ Agresti-Coull -Ovarian: The 95% CI^ for ORR = (12%, 77%). For reference, ovarian SOC ~12%. -Endometrial: The 95% CI^ for ORR = (23%, 88%). For reference, endometrial SOC ~ 9% Data cut as of April 1, 202
Slide 14: ACR-368 OncoSignature prospectively predicts sensitivity to monotherapy
ACR-368 OncoSignature prospectively predicts sensitivity to monotherapy in ongoing phase 2 trial ORR BM+ (ARM 1) ACR-368 monotherapy BM- (ARM 2) ACR-368 + ULDG Patients (N) Ovarian 40% (2/5) 0% (0/11) 16 Endometrial 60% (3/5) 0% (0/5) 10 Combined 50% (5/10) 0% (0/16) 26 Notes: (non-parametric bootst
Slide 15: 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 16: OncoSignature+ (Arm 1) Spider Plots
Oncosignature+ (ARM 1) Spider Plots – locked Thresholds Arm 1 – All GYN Subjects Arm 1 – Ovarian Arm 1 – Endometrial Note: mDoR established in past Phase 2 ACR-368 monotherapy RP2D trials (>200 patients) is between 5.6 months to >10 months (Konstantinopoulos et al, Gyn Oncol (2022); Lee et al, Lance
Slide 17: OncoSignature-negative summary (GYN indications)
Oncosignature-negative summary (GYN indications) – prospective data with locked thresholds Clear ULDG sensitization and activity (see waterfall plot), but no PRs to date with locked thresholds Data cut as of April 1, 2024
Slide 18: OncoSignature-negative (Arm 2) best overall response
oncosignature-negative (arm 2)- best overall response (Locked thresholds, prospective evaluation) RP2D of ULDG = 10 mg/m2 104-026 166-002 152-002 120-008 124-002 104-023 171-001 109-015 119-002 152-001 113-002 104-028 104-027 148-001 153-004 BOR = Best overall response; One PD subject censored for l
Slide 19: Treatment-Related Adverse Events – OncoSignature-positive (Arm 1)
Treatment-Related Adverse Events by Indication – OncoSignature-positive (Arm 1) Treatment-related AEs in >15% of subjects, locked thresholds; RP2D (ACR-368 105 mg/m2) ARM 1 Endometrial Ovarian Urothelial ALL (Arm 1) N = 7 N = 14 N = 2 N = 23 All Gr 3/4 All Gr 3/4 All Gr 3/4 All Gr 3/4 Anemia 2 (29)
Slide 20: Treatment-Related Adverse Events – OncoSignature-negative (Arm 2)
Treatment-Related Adverse Events by Indication – OncoSignature-negative (Arm 2) Treatment-related AEs in >15% of subjects, locked thresholds, RP2D (ACR-368 105 mg/m2; ULDG = 10 mg/m2) ARM 2 Endometrial Ovarian Urothelial ALL (Arm 2, 10 mg/m2 Gem) N = 11 N = 22 N = 5 N = 38 All Gr 3/4 All Gr 3/4 All
Slide 21: ACR-368 Manufacturing Status
ACR-368 Manufacturing Status Registration and validation campaigns complete with release of all batches 21.9 kg of GMP API in stock (enough for >100k doses) Registration campaign complete with all three batches released and yield ~95% Active Pharmaceutical Ingredient Drug Product
Slide 22: AP3-enabled drug discovery: ACR-2316 and pipeline
AP3-enabled drug discovery AP3-based drug design: ACR-2316, a potential first-in-class, dual WEE1/PKMYT1 inhibitor and pipeline
Slide 23: Streamlined AP3-based biological SAR
Streamlined AP3-based biological SAR OPTIMIZATION FOR SINGLE AGENT ACTIVITY OF PRECLINICAL PROGRAMS 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 (>35,000 phospho
Slide 24: AP3: Tight, high-resolution data with deep coverage
AP3: TIGHT, HIGH-RESOLUTION DATA WITH DEEP COVERAGE Acrivon proprietary compound data (~50 million data points per experiment); dozens of compounds profiled Miniaturized, high throughput, scalable: <2 weeks turn-around, automated AI computational analyses in 1 day Actionable results: Resistance mech
Slide 25: ACR-2316 – uniquely enabled by AP3 to overcome limitations of WEE1 and PKMYT1 inhibitors
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 single agent activity (AP3) AP3-guided design to overcome WEE1 and PKMYT1 single inhibitor resistance through balanced dual inhibition High selectiv
Slide 26: ACR-2316 relative performance vs benchmark inhibitors
ACR-2316 ++++ ++ ++++ ++++ ++++ Adavosertib ++ - ++ +++ ++ Azenosertib ++ - +++ ++ ++ Debio0123 + - ++++ + + Lunresertib - +++ + + + WEE1 cellular drug target engagement PKMYT1 cellular drug target engagement In vivo efficacy Kinome selectivity Relative performance Human tumor cell viability Acr-231
Slide 27: Dual WEE1/PKMYT1 inhibitor 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 28: 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 29: ACR-2316 potently activates CDK1 and drives mitotic catastrophe
ACR-2316 potently activates CDK1, regulating >300 CDK1 consensus substrates and driving mitotic catastrophe 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 multipl
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 tumor models Human tumor cell lines Breast Lung Ovarian Prostate Renal Medulloblastoma Glioblastoma
Slide 31: ACR-2316 induces potent cell death compared to benchmarks
ACR-2316 induces potent cell death compared to benchmark wee1 and pkmyt1 inhibitors CellTox-Green Assay Most Cytotoxic ACR-2316 Adavosertib Azenosertib Debio 0123 Lunresertib
Slide 32: ACR-2316 induces potent caspase 3/7 cleavage
Acr-2316 induces potent caspase 3/7 cleavage compared to benchmark wee1 or pkmyt1 inhibitors Caspase 3/7-Glo Assay ACR-2316 Adavosertib Azenosertib Debio 0123 Lunresertib Highest Caspase Activity
Slide 33: 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 34: Expediting ACR-2316 towards clinical monotherapy development
Expediting ACR-2316 towards clinical monotherapy development A novel, AP3-enabled, internally discovered dual WEE1 / PKMYT1 inhibitor Rational Design Potent anti-tumor activity across human tumor cell lines and in tumor-bearing mice vs benchmarks Superior Profile Optimized via AP3 AP3-enabled design
Slide 35: AP3-derived dual potency optimization: reciprocal quenching
AP3-derived dual potency optimization to overcome wee1 inhibitor resistance: Reciprocal quenching 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_
Slide 36: AP3 reciprocal quenching reveals optimal dual target potency profile
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 37: AP3 Interactome v.1 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 50,000 phosphosites 20,000 phosph
Slide 38: Cell cycle regulatory pipeline program (undisclosed target)
cell cycle regulatory pipeline program (undisclosed target) Target X – an exciting cancer drug target, no/minimal competitor programs, perfectly suited for AP3 platform DepMap data suggest suggest target X is an essential gene for cancer cell viability Strong mechanistic target rationale for role in
Slide 39: Financial Highlights – March 31, 2024 Pro-Forma
FINANCIAL HIGHLIGHTS – March 31, 2024 PRO-FORMA Cash and marketable securities ~$234M Projected runway into H2’26 Fully Diluted Shares Outstanding ~43.8M Current operating plan, including PIPE Not including additional financing Pro-forma as of Mar-31-2024 Including net proceeds from recent PIPE Pro-
Slide 40: Key take-aways
Key take-aways Initial clinical data (cut-off date April 1, 2024) have demonstrated prospective validation of our AP3 platform and our key objectives 50% confirmed overall response rate observed in patients with OncoSignature-positive gynecological (ovarian and endometrial) cancers Enrichment of ORR
Slide 41: 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 42: Q&A session
¢ Q&A session ACRIVON THERAPEUTICS )