Acrivon Therapeutics, Inc. · NASDAQ:ACRV
Acrivon Therapeutics — Investor Presentation (January 2024)
60 slides from Acrivon Therapeutics's investor presentation, Jan 8, 2024
Slide 1: Acrivon Predictive Precision Proteomics (AP3) Corporate Presentation January 2024
ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3) OVERCOMING LIMITATIONS OF GENETICS-BASED PRECISION MEDICINE CORPORATE PRESENTATION JANUARY 2024 Exhibit 99.1
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 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-causing, dysregulated pathways with a drug’s mechanism of action (Acrivon meaning ≈
Slide 4: 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 5: Acrivon: next generation precision oncology
Acrivon: next generation precision oncology overcoming limitations of genetics-based precision medicine Experienced team focused on execution with cash runway into 2H 2025 ACR-368 (Phase 2) CHK1/2 inhibitor in registrational intent trials in multiple solid tumor types ACR-2316 (IND-enabling) Dual WE
Slide 6: Accomplished leadership team
Accomplished leadership team Peter Blume-Jensen, M.D., Ph.D. CEO, President, Founder Eric Devroe, Ph.D. Chief Operating Officer Erick Gamelin, M.D., Ph.D. Chief Development Officer Executive Serono, Merck & Co., Daiichi Sankyo CSO Metamark - Marketed prostate proteomic test ProMark® Inventor Acrivon
Slide 7: Acrivon Therapeutics at a glance
Development Site (Boston) Drug and clinical biomarker assay development Clinical trials Market access pending approval Precision-Proteomics Site (Lund/Copenhagen) Early pipeline drug programs BM identification and drug profiling Mass spectrometry Acrivon therapeutics at a glance Peter Blume-Jensen C
Slide 8: Acrivon predictive precision proteomics, AP3
Acrivon predictive precision proteomics, AP3 *Oncogenic Kinase Signaling: Blume-Jensen, P. and Hunter, T. Nature (2001) Synthetic lethality as an engine for cancer drug target discovery: Huang, A. et al. NatRevDrugDisc (2020) Genomic Biomarkers are useful for patient selection in the smaller subset
Slide 9: 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 Sources: Company Filings, ACS, CDC, NCI, Wall Street Research (2022) Precision Oncology 1.0 Predictive Precision Proteomics Aiming to make targeted therapeutic sol
Slide 10: 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 11: 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 Q4 2024 Clinical Data at Major Medical Conference
Slide 12: 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) 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., 2037 AC
Slide 13: Clinical overview of ACR-368 monotherapy (past data)
Clinical overview of ACR-368 monotherapy (past data) Dosing and Administration IV q14d (RP2D = 105 mg/m2) Safety summary Acceptable safety profile in >1,000 patients - No clinical or regulatory holds imposed across all clinical studies to date Primary adverse events ≥ grade 3 were hematological (man
Slide 14: Past phase 2 trials in high grade serous ovarian cancer
past phase 2 trials in high grade serous ovarian cancer Lee et al; Lancet Oncology: 2018 Past trials suggest unenriched all-comer ORR in HGS ovarian cancer is ~15-20% Durable clinical activity in most responders No predictive biomarkers identified, need for alternative biomarker approach (ideal for
Slide 15: Development of AP3-based patient selection OncoSignature tests
Development of AP3-based patient selection oncosignature tests Quantitative mapping >20,000 p-sites; 25% drug-related Drug-regulated phospho-sites and biological processes Literature and database mining P-proteomics Technical Validation (Intended use tissue) BM antibody validation by quantitative IF
Slide 16: OncoSignature tests: usage in the clinic
oncosignature tests: usage in the clinic Pretreatment tumor biopsy test Compatible with 5 business days turn-around Offered by CDx partner under exclusive license from Acrivon Pretreatment tumor biopsy Treatment decision based on patient stratification Predicted Responder Predicted Non-responder Sam
Slide 17: Consistent ACR-368 OncoSignature performance across preclinical studies
Consistent ACR-368 oncosignature performance across PRECLINICAL studies Prediction of treatment outcome in human PDX models ORR enrichment to ≥ 55%; AUC of 0.88 and 0.9 Two separate, prospectively designed, blinded studies of biopsies from past Phase 2 trials with ACR-368 in patients with platinum-r
Slide 18: 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 19: 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 OncoSignature scores were generated blinded to tr
Slide 20: Two additional cancers predicted ACR-368-sensitive through human tumor screening
Two additional high unmet need solid canceRS predicted ACR-368-sensitive through human tumor sample screening OncoSignature-positive = 30-50% OncoSignature-positive = 30-40% OncoSignature-positive = 0% (ORR in past trial: 0%) OncoSignature-positive = 30% (ORR in past trials: 12+% and 29%) HGS Ovaria
Slide 21: Two attractive ACR-368-sensitive cancer types identified
Two attractive ACR-368-sensitive cancer types identified Bladder cancer patient samples Endometrial patient samples Class 1 BM Class 2 BM Class 3 BM Predicted Non-Responders Predicted Responders Predicted Non-Responders Predicted Responders ACR-368 OncoSignature screening of human cancer samples Pat
Slide 22: ACR-368-sensitive responders in endometrial and bladder PDX models
ACR-368-sensitive responders A subset of endometrial and bladder PDX models are highly sensitive to ACR-368 Endometrial PDX Bladder PDX BM1 BM2 BM3 PDX-L PDX-H Predicted Non-Responders Predicted Responders
Slide 23: AP3 uncovers actionable ACR-368 resistance mechanisms
G1/S CELL CYCLE Unsupervised Hierarchical Clustering T-test significant Proteins, FDR<0.05 Parental Resistant Upregulated in ACR-368 Resistant Cells Downregulated in ACR-368 Resistant Cells DNA DAMAGE REPAIR AP3 uncovers actionable ACR-368 resistance mechanisms unbiased and independent of genetic in
Slide 24: Low dose gemcitabine sensitizes ovarian cancer cell lines to ACR-368
low dose gemcitabine sensitizes ovarian cancer cell lines to ACR-368 Prexasertib Abs EC50 + 0 nM Gem: >10 uM + 0.53 nM Gem: 100 nM + 2.7 nM Gem: 6 nM Prexasertib Abs EC50 + 0 nM Gem: 15 nM + 0.53 nM Gem: 2.7 nM + 2.7 nM Gem: 0.2 nM Bliss Synergy score: <-10: Drug interaction is likely antagonistic -
Slide 25: 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 OncoSignature+ Single Arm Simon 2 Stage Monotherapy Phase 2b with Registrational Intent Stage 1 (N= 23 per cohort) Stage 2 (N= 48 per cohort) Phase 1b (N= ~21) Phase 2 Expansion (N= 33 per coho
Slide 26: Encouraging initial clinical observations
Encouraging Initial clinical observations Consistent with the extensive experience and tolerability profile from past trials, drug-related adverse events are primarily hematological, reversible, and manageable In the limited number of patients evaluated by imaging, preliminary evidence of clinical a
Slide 27: WEE1 and PKMYT1 validated cancer targets: ideal for AP3 approach
Wee1 and PKMYT1 validated cancer targets: ideal for AP3 approach Ghelli Luserna di Rorà et al. J. Hematol Oncol, 2020 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, r
Slide 28: Internal pipeline: advancing ACR-2316 and other DDR programs
Internal pipeline: advancing development candidate acr-2316 and other ddr programs - leveraging AP3 >40 high resolution co-crystals (1.5-3.1 Å) and AP3-driven SAR Novel WEE1- and PKMYT1-selective structural series and lead candidates Optimal selectivity profiles generated based on AP3 profiling ACR-
Slide 29: Executive summary: ACR-2316 development candidate
Executive summary: ACR-2316 development candidate Superior activity across human tumor cell lines and in mouse tumor models, vs clinical benchmark WEE1 and PKMYT1 inhibitors Favorable in vitro ADME, PK, and oral bioavailability with safety MTD/DRF studies consistent with predicted desirable human ex
Slide 30: ACR-2316 shows attractive profile in ongoing preclinical studies
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 31: 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 32: ACR-2316 shows superior activity vs benchmarks across tumor cell lines
ACR-2316 SHOWS SUPERIOR ACTIVITY VS BENCHMARKS across all human tumor cell lines tested Example: Ovarian human cancer cell lines 19 ovarian and other human tumor cell lines tested to date
Slide 33: ACR-2316 is highly potent across cell lines and ex vivo tumor 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 ACR-2316 Azenosertib Lunresertib Adavosertib Debio 0123 CTG-0703 CTG-3383 CTG-2733 CTG-2884 CTG-1703 CTG-0956 CTG-1448 CTG-1498 CTG-3226 CTG-16
Slide 34: ACR-2316 shows potent anti-tumor activity compared to clinical inhibitors
Efficacy (5 ON / 2 OFF) Tolerability (5 ON / 2 OFF) ACR-2316 shows potent anti-tumor activity compared to clinical wee1 or pkmyt1 inhibitors
Slide 35: ACR-2316 shows deep regression in tumors progressing on a WEE1 inhibitor
ACR-2316 shows deep regression in tumors progressing on a benchmark wee1 inhibitor Anti-tumor activity Tolerability
Slide 36: ACR-2316 emerging safety profile from preclinical animal studies
ACR-2316 emerging safety profile from preclinical animal studies appears promising Mice: ACR-2316 is well-tolerated at target doses up to ≤60 mg/kg daily oral dosing resulting in tumor regression in xenograft mouse models Reversible, mechanism-based hematological effects; moderate reticulopenia, mon
Slide 37: Streamlined AP3-based biological SAR optimization
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 Week2 Turnaround <2 weeks Quantitative mapping (>35,000 phospho-
Slide 38: AP3: tight, high-resolution data with deep coverage
AP3: TIGHT, HIGH-RESOLUTION DATA WITH DEEP COVERAGE Acrivon proprietary compound data (~30 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 39: AP3 reveals drug-regulated kinase activity in intact cells
AP3 reveals drug-regulated kinase activity in intact cells not detectable by standard methods Time : 60 minutes Dose : 20 nM KinomeScan @ 1mM ACR-2316 Drug-regulated kinase activity* in intact cells ACR-2743 (previous lead candidate) *Kinase activity based on substrate motif analysis using a proprie
Slide 40: 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 41: AP3-derived dual potency optimization to overcome WEE1 inhibitor resistance
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 42: AP3 reciprocal quenching reveals optimal 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 43: 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 Demonstrated preclinical superiority vs. benchmark WEE1 and PKMYT1 compounds Stronger preclinical anti-tumor activity vs. benchmark WEE1 and PKMYT1 co
Slide 44: AP3 is broadly applicable across drug discovery and development
AP3 is broadly applicable across drug discovery and development Predicted Responder AP3 Clinical Biomarkers Predictive OncoSignature tests Indication Finding Sensitive tumor types Resistance Mechanisms Rational drug combinations Drug Discovery SAR Optimal target selectivity PD Markers ~6,000 per com
Slide 45: Financial highlights
FINANCIAL HIGHLIGHTS Cash and marketable securities $142.1M Projected runway into H2’25 Fully Diluted Shares Outstanding 27.6M Current operating plan, assuming no additional financing Balance sheet 30-Sept-2023 Shares and equity grants outstanding 30-Sept-2023
Slide 46: Acrivon addressable markets (US & EU incidence)
Acrivon Addressable markets (US & EU incidence) Prioritized indications for single agent ACR-368 All cancers US and Europe Est. >6.3M cases/year Potential additional indications (N = 634,000) US cancer stats are based on ACS 2022 publication and subtype estimation from literature; EU cancer stats ar
Slide 47: Appendix
‘| APPENDIX ACRIVON THERAPEUT
Slide 48: Team has pioneered outcome-predictive quantitative proteomic test ProMark
Team has pioneered outcome-predictive quantitative proteomic multiplex in situ test ProMark®: Marketed, automated in situ proteomic test for human outcome prediction included under NCCN guidelines Founding team: Has pioneered p-proteomics and quantitative multiplex imaging including double-blinded c
Slide 49: Validation of ProMark 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-center biopsy cohort (N=359) for clinical use indication Marketed test included under NCCN Guidelines and M
Slide 50: Pioneering phosphoproteomics study identifies PI3K pathway inhibitor biomarkers
pioneering phospho-Proteomics study identifies novel pi3’k pathway inhibitor biomarkers Sci Transl Med 2: 1-14 (2010) TOWARD CUSTOMIZING TUMOR TREATMENT Just as our view of Earth has become increasingly global, cells are now seen as complex networks of interacting and intersecting signaling pathways
Slide 51: Olsen Lab examples of deep proteomics drug profiling
OLSEN LAB-EXAMPLES OF DEEP PROTEOMICS DRUG PROFILING ONGOING (MULTICENTER): Profiling of DDR and core kinase pathway inhibitors (>45) ALK-i : LDK378, TAE684, crizotinib, lorlatinib. SHP2-i: SHP099 -allosteric inhibitor. CHK1-i: SCH900776, ATM-i: KU55933 CDK7-i: THZ-1 JNK p38a DNAPK ATM CHK1 ATR Scie
Slide 52: Advisors and collaborators
advisorS anD collaborators GU Pathologist; bladder cancer expert Expert on protein biomarkers and quantitative tissue imaging Academic lead on ProMark® David Berman, M.D., Ph.D. Professor, Director, Queen’s Cancer Res. Inst., Ontario Canada George Demetri, M.D., FACP, FASCO, FAACR Professor, Harvard
Slide 53: AP3 is applicable across drug development stages
AP3 is APPLICABLE across drug development stages Target ID Hit ID Lead Opt IND Enabling Early Clinical Late Clinical Approval & Commercialization Indication Finding: OncoSignature patient sample screening AP3 drug profiling: Unbiased drug target engagement & PD biomarkers OncoSignature patient respo
Slide 54: ACR-2316 meets pre-specified development candidate criteria
ACR-2316 meets pre-specified development candidate criteria Target ACR-2316 MOA AP3 phosphoproteomics-based, optimized MOA; selective, dual WEE1/PKMYT1 inhibition ü Potency In vitro kinase activity, IC50 ≤ 10 nM Potent in cell target engagement in optimized ratio Activity across sensitive human tumo
Slide 55: Key data: ACR-2316 versus benchmarks
Key data: ACR-2316 versus benchmarks Assay ACR-2316 Adavosertib Azenosertib Debio123 Lunresertib Biochemical Wee1 Binding IC50 1 nM 1 nM 2 nM 1 nM 31 nM PKMYT1 Binding IC50 27 nM 155 nM 337 nM 2 µM 10 nM Cellular Target Engagement WEE1 EC50 (Y15) 2 nM 19 nM 16 nM 109 nM >10 µM PKMYT1 EC50 (T14 Alpha
Slide 56: AP3 analysis: ACR-2316 vs benchmark WEE1 inhibitor
AP3 analysis: ACR-2316 regulates cell cycle and mitosis more potently than benchmark wee1 inhibitor Resistant WEE1 inhibitor ACR-2316 Sensitive 60min 200nM Induced Suppressed Enrichment Score (NES) Significant Not significant p value Cell cycle RTK-MAPK HDR Mitotic pathways SREBP GTPases Mitotic pat
Slide 57: AP3 analysis: ACR-2316 vs benchmark PKMYT1 inhibitor
AP3 analysis: ACR-2316 regulates cell cycle and mitosis more potently than benchmark pkmyt1 inhibitor Induced Suppressed Enrichment Score (NES) Significant Not significant p value Cell cycle RTK-MAPK HDR Mitotic pathways SREBP GTPases Tight junction Autophagy Post-synaptic transmission
Slide 58: Comprehensive kinome selectivity profiling
Comprehensive kinome selectivity profiling ACR-2316 468 kinases @ 1mM Adavosertib Azenosertib Lunresertib Debio0123 WEE1 PKMYT1 WEE1 WEE1 WEE1 PKMYT1 KinomeScan
Slide 59: AP3 uncovers single agent sensitivity and rational drug combinations
Cell Reports, August 9, 2022 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 action AP3 reveals single agent sensitivity context and rational drug combinations in
Slide 60: 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 $168M, of w
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