Acrivon Therapeutics, Inc. · NASDAQ:ACRV
Acrivon Therapeutics — Investor Presentation (September 2023)
49 slides from Acrivon Therapeutics's investor presentation, Sep 5, 2023
Slide 1: Acrivon Predictive Precision Proteomics (AP3): Drug-Tailored Patient Selection
Exhibit 99.2 Acriv Acrivon on Thera Therapeutics peutics ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3): DRUG-TAILORED PATIENT SELECTION FOR CLINIC AL SUCCESS CORPORATE PRESENTATION SEPTEMBER 2023
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
Slide 3: Drug-Tailored Patient Selection Aiming to Overcome Key Attrition Factor
ACRIVON THERAPEUTICS: DRUG -TAILORED PATIENT SELECTION AIMING TO OVERCOME THE KEY ATTRITION FACTOR PREVENTING CLINICALLY ACTIVE DRUGS FROM REACHING MARKET AP3 Platform OncoSignature Test ACR-368 (Prexasertib) Pipeline - Acrivon’s proprietary - Clinically active (15-20% - Monotherapy candidate - Our
Slide 4: Accomplished Leadership Team
ACCOMPLISHED LEADERSHIP TEAM Rasmus Holm-Jorgensen Erick Gamelin, M.D., Ph.D. Kristina Masson, Ph.D., M.B.A Peter Blume-Jensen, M.D., Ph.D. Eric Devroe, Ph.D. Site Head Acrivon AB, Co-Founder Chief Financial Officer Chief Medical Officer CEO, President, Founder Chief Operating Officer EVP Business O
Slide 5: Acrivon Therapeutics at a Glance
ACRIVON THERAPEUTICS AT A GLANCE Development Site (Boston) Precision-Proteomics Site (Lund/Copenhagen) • Drug and clinical biomarker assay development • Early pipeline drug programs • Clinical trials • BM identification and drug profiling • Market access pending approval • Mass spectrometry HQ LOCAT
Slide 6: Acrivon Predictive Precision Proteomics, AP3
ACRIVON PREDICTIVE PRECISION PROTEOMICS, AP3 DNA Genomic Biomarkers are useful for patient selection in the smaller subset of cancers (<10%) with single gene driver mutations or known synthetic lethal context* RNA Protein P Dysregulated CANCER IS CAUSED BY DYSREGULATED PROTEIN ACTIVITY Protein Drug
Slide 7: AP3 Platform Addresses High Unmet Need Beyond NGS-Based Precision Medicine
AP3 PLATFORM ADDRESSES HIGH UNMET NEED BEYOND NGS -BASED PRECISION MEDICINE Acrivon Positioned to Increase Precision Oncology Market Size Current Precision Oncology Approaches Only Scratching the Surface 72 unique approvals Precision Oncology 1.0 51 drugs 31 genomic indications Approved indications:
Slide 8: AP3 Platform: Drug Response Prediction in Individual Patients
AP3 PLATFORM: DRUG RESPONSE PREDICTION IN INDIVIDUAL PATIENTS PROPRIETARY WORKFLOW INTEGRATING PROVEN TECHNOLOGIES STEP 1 STEP 2 STEP 3 THERAPEUTIC PACKAGE PATIENT RESPONDERS BIOMARKER IDENTIFICATION Predicted Predicted Acrivon drug with predictive BM assay Optimal indications and combinations Non-r
Slide 9: Acrivon Pipeline
ACRIVON PIPELINE Anticipated Preclinical Phase 1 Phase 2 Phase 3 Next Milestone Single-Arm Trials Based on OncoSignature Prediction ACR-368 Monotherapy Platinum-Resistant Ovarian Cancer LDG Combination ACR-368 Monotherapy Initial Clinical Readouts in ACR-368 Endometrial Cancer 2H 2023 (CHK1/CHK2) LD
Slide 10: ACR-368: A Clinically Active Phase 2 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) • Good ADME properties, minimal drug-drug interaction (DDI) potential • Discovered by Array Biopharma, acquired by Eli Lilly & Company • CoM patent exp. Oct., 2030; Salt-form exp. Apr.
Slide 11: Clinical Overview of ACR-368 Monotherapy (Past Data)
CLINICAL OVERVIEW OF ACR -368 MONOTHERAPY (PAST DATA) # Indication Trial ORR (confirmed) Median DoR° Reference HGSOC* (BRCA wild type, primarily Phase 2 single center 29% >10 months^ Lee et al, Lancet platinum-resistant) (NCI) Oncology, 2018 HGSOC (BRCA wild type and mutant; Phase 2 multi-center 12.
Slide 12: Past Phase 2 Trials in High Grade Serous Ovarian Cancer
PAST PHASE 2 TRIALS IN HIGH GRADE SEROUS OVARIAN CANCER NCI single-center Phase 2 study (N=28) Lilly-sponsored multi-center (46 center, 8 country) Phase 2 study (N=169) • Heavily pre-treated patients; median 5 prior lines • All lines of prior therapy, BRCA wt and mt, incl. prior PARPi • Pretreatment
Slide 13: Development of AP3-Based Patient Selection OncoSignature Tests
DEVELOPMENT OF AP3-BASED PATIENT SELECTION ONCOSIGNATURE TESTS Technical Validation Functional Validation P-proteomics Cellular MOA (Intended use tissue) (Intended use tissue) Human cancer screening: Quantitative mapping Dose response, BM antibody validation ID of drug-sensitive >20,000 p-sites; kno
Slide 14: OncoSignature Tests: Usage in the Clinic
ONCOSIGNATURE TESTS: USAGE IN THE CLINIC Pretreatment Treatment decision tumor biopsy based on patient stratification Predicted Predicted Sample processing Responder Non-responder Biopsy in Automated tumor FFPE Region-of-Interest block biomarker scoring • Pretreatment tumor biopsy test • Compatible
Slide 15: Consistent ACR-368 OncoSignature Performance Across Preclinical Studies
CONSISTENT ACR -368 ONCOSIGNATURE PERFORMANCE ACROSS PRECLINICAL STUDIES Tissue ID. BM1 BM2 BM3 Fov060265 0.69 0.79 0.73 Fov050855 0.94 0.71 0.67 Fov041300 0.89 0.23 0.55 Fov060380 0.95 0.62 0.51 Fov060050 0.85 0.23 0.51 Fov041285 0.69 0.19 0.5 Fov100142 0.47 0.76 0.47 Fov050764 0.82 0.22 0.47 Fov04
Slide 16: ACR-368 OncoSignature Prediction of Drug Sensitivity Across Patient Samples
ACR -368 ONCOSIGNATURE PREDICTION OF DRUG SENSITIVITY: BIOMARKER QUANTITATION ACROSS HUMAN CANCER PATIENT SAMPLES Class 1 BM Class 2 BM Class 3 BM Tissue ID. BM1 BM2 BM3 Fov060265 0.69 0.79 0.73 Fov050855 0.94 0.71 0.67 Fov041300 0.89 0.23 0.55 Fov060380 0.95 0.62 0.51 Fov060050 0.85 0.23 0.51 Patie
Slide 17: Biopsy Study 1: Response and PFS Benefit in Predicted Responders
BIOPSY STUDY 1: SUBSTANTIAL RESPONSE AND PFS BENEFIT IN PREDICTED RESPONDERS (BLINDED, PROSPECTIVELY DESIGNED STUDY) • Available pretreatment tumor biopsies from past phase 2 trials at NCI with ACR-368 in platinum-resistant ovarian cancer were obtained rd • OncoSignature scores were generated blinde
Slide 18: Two Additional High Unmet Need Solid Cancers Predicted ACR-368-Sensitive
TWO ADDITIONAL HIGH UNMET NEED SOLID CANCERS PREDICTED ACR -368 -SENSITIVE THROUGH HUMAN TUMOR SAMPLE SCREENING HGS Ovarian Sq. NSCLC Bladder cancer Endometrial cancer Tissue ID BM1 BM2 BM3 Tissue ID BM1 BM2 BM3 Tissue ID BM1 BM2 BM3 Tissue ID BM1 BM2 BM3 Fov010719 0.96 0.68 0.78 Rln020132 0.17 0.26
Slide 19: Two Attractive ACR-368-Sensitive Cancer Types Identified
TWO ATTRACTIVE ACR -368 -SENSITIVE CANCER TYPES IDENTIFIED Bladder cancer patient samples Endometrial patient samples Pa Pta ie tint ent 1 1 LO LO W W P Pa at tiie ent nt 2 2 H HIG IGH H PP aa ttie ient nt 1 1-L LO OW W P Paattiieent nt 22 -H HIG IG H H Class 1 BM Class 1 BM CHK1 S296 Class 2 BM Cla
Slide 20: Endometrial and Bladder PDX Models Highly Sensitive to ACR-368
A SUBSET OF ENDOMETRIAL AND BLADDER PDX MODELS ARE HIGHLY SENSITIVE TO ACR -368 Bladder PDX Endometrial PDX 1,500 2,000 2,000 BL001 2,000 BL002 Endo 1 Endo 2 1,500 1,500 1,000 ACR-368-sensitive 1,000 1,000 1,000 500 responders 500 500 0 0 0 0 0 5 10 15 20 25 30 0 7 14 21 0 7 14 21 28 0 5 10 15 20 25
Slide 21: AP3 Uncovers Actionable ACR-368 Resistance Mechanisms
AP3 UNCOVERS ACTIONABLE ACR -368 RESISTANCE MECHANISMS UNBIASED AND INDEPENDENT OF GENETIC INFORMATION T-test significant Proteins, FDR<0.05 Unsupervised Hierarchical Clustering Resistant Parental G1/S CELL CYCLE Upregulated in ACR-368 Resistant Cells Downregulated in ACR- DNA DAMAGE REPAIR 368 Resi
Slide 22: Ultra-Low Dose Gemcitabine Sensitizes Ovarian Cancer Cell Lines to ACR-368
ULTRA -LOW DOSE GEMCITABINE SENSITIZES OVARIAN CANCER CELL LINES TO ACR -368 OVCAR3-Parental Gemcitabine alone in Ovarian-Parental OVCAR3-Resistant Ovarian-Resistant Gemcitabine alone OVCAR3-P and OVCAR3-R 150 150 150 No Gem No Gem 0.53 nM Gem 0.53 nM Gem OVCAR3-P 2.7 nM Gem 2.7 nM Gem OVCAR3-R 100
Slide 23: Enrolling and Dosing ACR-368 in Three High Unmet Need Indications
ENROLLING AND DOSING ACR -368 IN THREE HIGH UNMET NEED INDICATIONS: OVARIAN, ENDOMETRIAL AND BLADDER CANCER • RP2D of ACR-368 based on OncoSignature+ Single Arm Simon 2 Stage Monotherapy predicted sensitivity using our Phase 2b with Registrational Intent ACR-368 OncoSignature Assay Stage 1 St a g e
Slide 24: WEE1 and PKMYT1 Validated Cancer Targets: Ideal for AP3 Approach
WEE1 AND PKMYT1 VALIDATED CANCER TARGETS: IDEAL FOR AP3 APPROACH • WEE1 and PKMYT1 regulate S and G2-M cell cycle checkpoints to ensure proper DNA replication and mitotic completion through phosphorylation and inhibition of CDK2 and CDK1 and CDK1, respectively • WEE1 inhibition propagates genomic in
Slide 25: Internal Pipeline: Advancing ACR-2316 and Other DDR Programs
INTERNAL PIPELINE: ADVANCING DEVELOPMENT CANDIDATE ACR -2316 AND OTHER DDR PROGRAMS - LEVERAGING AP3 Rationale • Leveraging our AP3 patient selection platform for high clinical POS • Potentially optimal profile for monotherapy clinical development and for AP3-identified rational drug combinations Hi
Slide 26: AP3 Platform: Proprietary Pipe for Automated Analyses
Phosphosites AP3 PLATFORM: PROPRIETARY PIPE FOR AUTOMATED ANALYSES WITH ACTIONABLE RESULTS IN ONE DAY Proprietary machine learning algorithms applied to state-of-the-art AP3 MS-based phosphoproteomics for all compound projects Unbiased PD marker identification High throughput MS Dose-response of tar
Slide 27: AP3: Tight, High-Resolution Data with Deep Coverage
AP3: TIGHT, HIGH -RESOLUTION DATA WITH DEEP COVERAGE 25,800 p-sites 16,456 p-sites QC Consensus Data Clean Volcano Hierarchical Kinase Pathway Functional Network QC MS Data Processed Sequence Biomarkers Up Plots Clustering Inference Enrichment Annotation Mapping Data Motif • Filter >60% in at least
Slide 28: AP3 Reveals Drug-Regulated Kinase Activity in Intact Cells
AP3 REVEALS DRUG -REGULATED KINASE ACTIVITY IN INTACT CELLS NOT DETECTABLE BY STANDARD METHODS KinomeScan @ 1µM Substrate motif-inferred kinase activity* ACR-2316 ACR-2316 ACR-2743 ACR-2743 (previous lead candidate) MAPK3K4 PRKCE GAK PKMYT1 PLK1 PLK2 WEE2 PLK3 WEE1 YSK4 Time : 60 minutes Dose : 20 n
Slide 29: AP3 Reciprocal Quenching Reveals Optimal Target Potency Profile
AP3 RECIPROCAL QUENCHING REVEALS OPTIMAL TARGET POTENCY PROFILE FOR DUAL WEE1/PKMYT1 INHIBITOR Sensitive Resistant Sensitive Resistant WEE1i and PKMYT1i dual inhibition synergy Target substrates Target substrate of ACR-368 Target substrate of PKMYT1i Target substrates Optimal potency ratio results i
Slide 30: Dual WEE1/PKMYT1 Inhibitor ACR-2316 Demonstrates Strong Potency and Selectivity
DUAL WEE1/PKMYT1 INHIBITOR ACR -2316 DEMONSTRATES STRONG POTENCY AND SELECTIVITY KinomeScan (106 kinases @ 1000 nM) Benchmark WEE1 inhibitor WEE1 Benchmark Dual inhibitor show potent cell cycle effects compared to benchmark inhibitors PKMYT1 inhibitor PKMYT1 DMSO ACR-2316 (Dual) G1 100 nM, 24 hour D
Slide 31: ACR-2316 Demonstrates Potent Monotherapy Anti-Tumor Activity in Mice
ACR -2316 DEMONSTRATES POTENT MONOTHERAPY ANTI - TUMOR ACTIVITY IN TUMOR -BEARING MICE ACR-2316 anti-tumor activity (QDx7; PO) ACR-2316 anti-tumor activity (5d on/2d off; PO) ACR-2316 causes tumor regression, in contrast to the highest tolerated doses of benchmark WEE1 and PKMYT1 inhibitors, which o
Slide 32: ACR-2316 Favorable Preclinical Profile
ACR-2316 FAVORABLE PRECLINICAL PROFILE Target ACR-2316 MOA • AP3 phosphoproteomics-based, optimized MOA; selective, dual WEE1/PKMYT1 inhibition ü Potency • In vitro kinase activity, IC ≤ 10 nM ü 50 • Potent target engagement in optimized ratio ü • Activity across sensitive human tumor cell lines, CC
Slide 33: ACR-2316 Development: Next Steps
ACR-2316 DEVELOPMENT: NEXT STEPS • Completion of IND-enabling studies • ACR-2316 OncoSignature generation • OncoSignature indication finding and prioritization for clinical development • Planned IND filing Q4 2024, pending IND-enabling studies, in preparation for monotherapy clinical development wit
Slide 34: AP3: Broad Applicability and Untapped Potential
AP3: BROAD APPLICABILITY AND UNTAPPED POTENTIAL DELIVERABLES Patient responder Indication Rational drug Resistance Pharmacodynamic (PD) identification finding combinations mechanisms biomarkers AP3 Patient selection for Patient selection for novel Continued in-licensing Rational drug design SAR broa
Slide 35: AP3 Generates Value Across Multiple Dimensions
AP3 GENERATES VALUE ACROSS MULTIPLE DIMENSIONS Next-Generation Proteomics-Based Precision Medicine Clinical Biomarkers Potential for Predictive Signature Assays Paradigm Shift for Patient Outcomes AP3 Drug Discovery SAR Platform Selectivity Optimization Indication Finding AI + ML enabled Intellectua
Slide 36: The AP3 Approach Is Modality and Disease Agnostic
THE AP3 APPROACH IS MODALITY AND DISEASE AGNOSTIC Therapeutic Oligo/RNA modalities Antibody Bifunctional ADC molecule Small molecule Cancers with DDR stress Oncology Therapeutic Fibrotic and areas inflammatory Autoimmune Current focus Infectious, CNS, and other diseases 36 ACRIVON THERAPEUTICS
Slide 37: Financial Highlights as of Q2 2023
FINANCIAL HIGHLIGHTS AS OF Q2 2023 Cash and marketable securities Projected runway into Fully Diluted Shares Outstanding $151.0M 27.0M 2025 Balance sheet Current operating plan, assuming Shares and equity grants 30-June-2023 no additional financing outstanding 30-June-2023 Unaudited. 37 ACRIVON THER
Slide 38: Acrivon Addressable Markets (US & EU Incidence)
ACRIVON ADDRESSABLE MARKETS (US & EU INCIDENCE) Prioritized indications for single agent ACR-368 Prioritized indications Bladder Cancer (N=742,000) * Endometrial Cancer * + Potential additional HPV SCC 12% indications Ovarian cancer *Currently enrolling * (N = 634,000) and dosing Sarcoma 10% Other c
Slide 39: Appendix
APPENDIX 39 ACRIVON THERAPEUTICS
Slide 40: Team Has Pioneered Outcome-Predictive Quantitative Proteomic Multiplex In Situ Test
TEAM HAS PIONEERED OUTCOME-PREDICTIVE QUANTITATIVE PROTEOMIC MULTIPLEX IN SITU TEST Prostate cancer 8-marker biopsy test developed and launched by Founding team Raw Image Epithelium Classified Nuclei Classified ROI: Malignant Epithelium A B C D Protein Current Ideal test multiplex CDx in situ test t
Slide 41: Proof-of-Concept for Protein Biomarker Signature: Marketed Multiplex Cancer Test
PROOF -OF -CONCEPT FOR PROTEIN BIOMARKER SIGNATURE: MARKETED, OUTCOME -PREDICTIVE MULTIPLEX CANCER TEST (2015) • Third-party blinded clinical validation, bioinformatic analysis (U. Montreal) • Validation of locked ProMark™ test on single institution biopsy cases (N=274) • Secondary validation on mul
Slide 42: Pioneering Phospho-Proteomics Study Identifies Novel PI3'K Pathway Inhibitor Biomarkers
PIONEERING PHOSPHO -PROTEOMICS STUDY IDENTIFIES NOVEL PI3’K PATHWAY INHIBITOR BIOMARKERS Sci Transl Med 2: 1-14 (2010) Editorial Highlights: TOWARD CUSTOMIZING TUMOR TREATMENT Just as our view of Earth has become increasingly global, cells are now seen as complex networks of interacting and intersec
Slide 43: Olsen Lab: Examples of Deep Proteomics Drug Profiling
OLSEN LAB -EXAMPLES OF DEEP PROTEOMICS DRUG PROFILING Science Signaling (2018) Nature Communications (2020) Cell Systems (2017) Highest throughput, sensitivity, and scalability to date ALK-i : LDK378, TAE684, crizotinib, lorlatinib. Deepest proteome resolution of a human cell to date Cell Reports (2
Slide 44: Advisors and Collaborators
ADVISORS AND COLLABORATORS SAB David Berman, M.D., Ph.D. George Demetri, M.D., Robert Abraham, Ph.D. Timothy Yap, M.B.B.S., FACP, FASCO, FAACR Ph.D., F.R.C.P. Professor, Director, EVP, Head Cancer Biology, Queen’s Cancer Res. Inst., Professor, Harvard Med. Associate Prof., MD Odyssey Therapeutics On
Slide 45: AP3 Is Applicable Across Drug Development Stages
AP3 IS APPLICABLE ACROSS DRUG DEVELOPMENT STAGES Approval & Target ID Hit ID Lead Opt IND Enabling Early Clinical Late Clinical Commercialization ID druggable AP3 drug profiling: AP3 is also applicable in preclinical phase driver targets Unbiased drug target engagement & PD biomarkers Resistance Mec
Slide 46: Optimized Dual Inhibitors Show Shared and Differentiated Pathway Effects
OPTIMIZED DUAL INHIBITORS SHOW SHARED AND DIFFERENTIATED PATHWAY EFFECTS Optimized dual WEE1 and PKMYT1 inhibitors affect cell cycle and canonical MAPK pathways in desirable manner Benchmark* WEE1 + PKMYT1 Substrate motif-inferred ACR-2743 ACR-2316 Inhibitors in combination kinase activities Kinase
Slide 47: AP3-Derived Dual Potency Optimization to Overcome WEE1 Inhibitor Resistance
AP3 -DERIVED DUAL POTENCY OPTIMIZATION TO OVERCOME WEE1 INHIBITOR RESISTANCE: RECIPROCAL QUENCHING Cell cycle and cancer Protein set name PUJANA_CHEK2_PCC_NETWORK DNA DNA damage homology Sensitive responses Resistant repair PKMYT1i WEE1i PUJANA_BRCA1_PCC_NETWORK Mitotic regulation WEE1i PKMYT1i REAC
Slide 48: AP3 Reveals Single Agent Sensitivity Context and Rational Drug Combinations
AP3 REVEALS SINGLE AGENT SENSITIVITY CONTEXT AND RATIONAL DRUG COMBINATIONS INDEPENDENT OF GENETIC INFORMATION Using spatial phosphoproteomics (Nat. Commun., 2021) Acrivon’s AP3 platform can uncover single agent sensitivity and rational drug combinations for targets with complicated mechanism of act
Slide 49: Eli Lilly ACR-368 High Level License Terms
ELI LILLY ACR -368 HIGH LEVEL LICENSE TERMS • In-licensing completed 27 January 2021 – WW exclusive rights with rights to sub-license – $5M up front and low single digit percentage equity subject to ordinary dilution going forward – Aggregate development and commercial milestone payments of up to $1
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