Acrivon Therapeutics, Inc. · NASDAQ:ACRV
Acrivon Therapeutics — Corporate Update (March 2023)
40 slides from Acrivon Therapeutics's corporate update, Mar 13, 2023
Slide 1: Acrivon Predictive Precision Proteomics (AP3): Drug-Tailored Patient Selection for Clinical Success
Exhibit 99.1 Acriv Acrivon on Thera Therapeutics peutics ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3): DRUG-TAILORED PATIENT SELECTION FOR CLINIC AL SUCCESS MARCH, 2023
Slide 2: 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 ACR-368 (Prexasertib) Pipeline - Acrivon’s proprietary - Clinically active (15-20% - Two co-crystallography- and - O
Slide 3: Accomplished Leadership Team
ACCOMPLISHED LEADERSHIP TEAM Rasmus Holm-Jorgensen Erick Gamelin, M.D., Ph.D. Kristina Masson, Ph.D. Peter Blume-Jensen, M.D., Ph.D. Eric Devroe, Ph.D. Chief Financial Officer Chief Medical Officer Co-Founder, CEO, Acrivon AB CEO, Founder Chief Operating Officer EVP Business Operations • Novo Nordis
Slide 4: 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 OUR PROT
Slide 5: 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 6: 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 7: AP3 Platform: Drug Response Prediction in Individual Patients
AP3 PLATFORM: DRUG RESPONSE PREDICTION IN INDIVIDUAL PATIENTS ® PROPRIETARY 3 -STEP WORKFLOW INTEGRATING PROVEN TECHNOLOGIES Drug OncoSignature STEP 1 STEP 2 STEP 3 Predicted Predicted THERAPEUTIC PACKAGE PATIENT RESPONDERS BIOMARKER IDENTIFICATION Non-responder Responder Acrivon drug with predictiv
Slide 8: 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 Endometrial Cancer Second Half 2023 LDG Combinati
Slide 9: 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 10: 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 11: 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 12: 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; k
Slide 13: 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 ® OncoSignature test Biopsy in Automated tumor FFPE Region-of-Interest block biomarker scoring • Pretreatment tumor bi
Slide 14: 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 Fov
Slide 15: ACR-368 OncoSignature Prediction: Biomarker Quantitation 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 Pat
Slide 16: 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 blin
Slide 17: 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 18: Two Attractive ACR-368-Sensitive Cancer Types Identified
TWO ATTRACTIVE ACR -368 -SENSITIVE CANCER TYPES IDENTIFIED Bladder cancer patient samples Endometrial patient samples Pa Pti ae tint 1 L ent 1 O LO W W P Pa at tiie ent nt 2 H 2 HIG IGH H PP aa tite ient 1 L nt 1-LO OW W P Paatti ieent nt 2 H 2-HIG IG H H Class 1 BM Class 1 BM CHK1 S296 Class 2 BM C
Slide 19: 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 20: 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 21: LDG Sensitizes Ovarian Cancer Cell Lines to ACR-368
LDG SENSITIZES OVARIAN CANCER CELL LINES TO ACR -368 Ovarian-Parental OVCAR3-Parental Gemcitabine alone in Ovarian-Resistant OVCAR3-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 100 100 100 Relative IC (uM)
Slide 22: ACR-368 Phase 2 Clinical Trial Has Been Initiated
ACR -368 PHASE 2 CLINICAL TRIAL HAS BEEN INITIATED 3 Cohorts: Ovarian, Endometrial, Bladder Single-Arm Trial Single-Arm Trial OncoSignature Subject Selection on Fresh Tumor ARM 1 OncoSignature Positive ARM 2 OncoSignature Negative Monotherapy Biopsy (≤12 weeks) Combination Therapy Phase 2 Simon 2-St
Slide 23: Internal Pipeline: WEE1 and PKMYT1 - Leveraging AP3
INTERNAL PIPELINE: WEE1 AND PKMYT1 - LEVERAGING AP3 Rationale • Complement to in-licensing, leveraging our AP3 patient selection platform for high clinical POS • Potential within DDR drug target class to pursue combinations (ACR-368, WEE1i, and PKMYT1i) Approach: • Targets with promising clinical ac
Slide 24: WEE1 Program: Ideal for the AP3 Platform
WEE1 PROGRAM: IDEAL FOR THE AP3 PLATFORM • WEE1 is a mitotic cell cycle regulatory kinase; inhibition propagates genomic instability by premature DNA replication and cell cycle progression, resulting in mitotic catastrophe. • Strong preclinical data and emerging clinical data: – AZD1775/MK1775/adavo
Slide 25: Structure- and AP3-Guided Drug Design
STRUCTURE- AND AP3-GUIDED DRUG DESIGN WEE1 and PKMYT1 programs High throughput AP3 profiling Global analysis Pairwise analysis Volcanoplot, FDR=0.05 > 10 k p-sites. ANOVA, HA, FDR=0.05 Lead optimization ongoing in several prioritized series based on high resolution co-crystals (WEE1: 2.1-2.6 Å; PKMY
Slide 26: Acrivon Corporate Priorities
ACRIVON CORPORATE PRIORITIES Clinical IP ® • Advance phase 2 trials in multiple solid tumor • MoU for ACR-368 OncoSignature (filed) ® indications with OncoSignature patient selection • CoM & MoU on all programs Team-building CMC • Key positions to support growth • DS and DP CMC for confirmatory tria
Slide 27: 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 High resolution p-proteomic data enabling: Patient selection for Patient selection for novel Continued
Slide 28: Financial Highlights
FINANCIAL HIGHLIGHTS Cash and marketable securities Projected runway at least into Fully Diluted Shares Outstanding $169.6M 27.0M Q4’24 Balance sheet Current operating plan with no Shares and equity grants 31-December-2022 additional financing outstanding 31-December-2022 Unaudited. 28 ACRIVON THERA
Slide 29: Appendix
APPENDIX 29 ACRIVON THERAPEUTICS
Slide 30: 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 31: 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 multi
Slide 32: Pioneering Phospho-Proteomics Study Identifies Novel PI3K 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 33: 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 34: 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 35: National Cancer Institute Trial in High Grade Serous Ovarian Cancer
NATIONAL CANCER INSTITUTE (NCI) TRIAL IN HIGH GRADE SEROUS OVARIAN CANCER 100 • Single-arm, Phase 2 POC study (Dr. Jung-Min Lee) Best response • N=28 (21 platinum resistant, 6 sensitive, 1 refractory) 50 (N = 24 evaluable patients) • Heavily pre-treated; median of 5 prior systemic therapies • Pretre
Slide 36: Multicenter Clinical Trial in Advanced High Grade Serous Ovarian Cancer
MULTICENTER CLINICAL TRIAL IN ADVANCED HIGH GRADE SEROUS OVARIAN CANCER Study design (Lilly-sponsored) • Multi-center (46 centers, 8 countries), Ph. 2 (N =169) • Pretreatment biopsies mandated N = 169 PATIENTS COHORT DESCRIPTION PERCENT CONFIRMED ORR DURATION OF RESPONSE OVERALL SURVIVAL (OS) IN (95
Slide 37: Single Agent Clinical Activity in Other Tumor Types
SINGLE AGENT CLINICAL ACTIVITY IN OTHER TUMOR TYPES ACR-368 activity in other heavily pretreated tumor types (primarily squamous cell cancer SCC): • 15% ORR in Anal (N = 26), incl. 1 CR; mDoR = 12 mths* • 19% ORR in HPV+ H&N (N=16); 5% ORR in all-comer H&N (N = 57); mDoR = 7 mths • (5% ORR plat-sens
Slide 38: AP3 Phosphoproteomics Proof-of-Concept Study
AP3 PHOSPHOPROTEOMICS PROOF -OF -CONCEPT STUDY Using spatial phosphoproteomics developed in co-founder Jesper Olsen’s lab (Nat. Commun., 2021) Acrivon’s AP3 platform uncovers single agent sensitivity and rational drug combination for treatment with Selinexor, a selective inhibitor of nuclear export,
Slide 39: 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
Slide 40: HPV-Positive Cancers: Strong Rationale and Increasing Potential Market Opportunity
HPV -POSITIVE CANCERS: STRONG RATIONALE AND INCREASING POTENTIAL MARKET OPPORTUNITY • Significant upregulation and tumor dependency on DDR in HPV+ cancers – Strong preclinical evidence demonstrating activation of Chk1 and Chk2 – Durable activity of ACR-368 in in HPV-positive SCCHN and anal cancer •