Acrivon Therapeutics, Inc. · NASDAQ:ACRV
Acrivon Therapeutics — Investor Day (May 2023)
34 slides from Acrivon Therapeutics's investor day presentation, May 1, 2023
Slide 1: AP3: Drug-Tailored Patient Selection for Clinical Success
Exhibit 99.1 A Acr criv ivon on T T h h e e r r a a p p e e u u t t ii c c s s ACRIVON PREDICTIVE PRECISION PROTEOMICS (AP3): DRUG-TAILORED PATIENT SELECTION FOR CLINIC AL SUCCESS INVESTOR EVENT MAY 01, 2023
Slide 2: Forward-Looking Statements
F O R W A R D - L O O K I N G S T A T E M E N T S 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
Slide 3: Outline
O U T L I N E • Company overview • Acrivon Predictive Precision Proteomics (AP3) platform update • Preclinical pipeline update • Clinical trial enrollment progress • Corporate updates • Q & A 3 A C R I V O N T H E R A P E U T I C S
Slide 4: Drug-Tailored Patient Selection: Overcoming Key Attrition Factor
A C R I V O N T H E R A P E U T I C S : D R U G - T A I L O R E D P A T I E N T S E L E C T I O N 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 activ
Slide 5: 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 6: AP3 Platform: Drug Response Prediction in Individual Patients
AP3 PLATFORM: DRUG RESPONSE PREDICTION IN INDIVIDUAL PATIENTS ® P R O P R I E T A R Y 3 - S T E P W O R K F L O W I N T E G R A T I N G P R O V E N T E C H N O L O G I E S Drug OncoSignature S T E P 3 S T E P 1 S T E P 2 Predicted Predicted THERAPEUTIC PACKAGE PATIENT RESPONDERS BIOMARKER IDENTIFICA
Slide 7: AP3 Applicable Across Drug Development Stages
A P 3 I S A P P L I C A B L E A C R O S S D R U G D E V E L O P M E N T S T A G E S 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 engage
Slide 8: AP3 Reveals Single Agent Sensitivity and Rational Drug Combinations
A P 3 R E V E A L S S I N G L E A G E N T S E N S I T I V I T Y C O N T E X T A N D R A T I O N A L D R U G C O M B I N A T I O N S I N D E P E N D E N T O F G E N E T I C I N F O R M A T I O N Using spatial phosphoproteomics (Nat. Commun., 2021) Acrivon’s AP3 platform can uncover single agent sensi
Slide 9: Example: Druggable CDC Inhibitor Resistance Mechanism
E X A M P L E : D R U G G A B L E C D C 7 I N H I B I T O R R E S I S T A N C E M E C H A N I S M ( 5 1 4 2 P - S I T E S S I G N I F I C A N T L Y R E G U L A T E D ) Enriched kinase motif p-value CDK1,2,4,6 kinase substrate motif 1.65E-08 Cdc2 kinase substrate motif 8.29E--09 CDK kinase substrate
Slide 10: AP3 Uncovers Actionable ACR-368 Resistance Mechanisms
A P 3 U N C O V E R S A C T I O N A B L E A C R -368 R E S I S T A N C E M E C H A N I S M S U N B I A S E D A N D I N D E P E N D E N T OF G E N E T I C I N F O R M A T I O N T-test significant Proteins, FDR<0.05 Unsupervised Hierarchical Clustering Resistant Parental G1/S CELL CYCLE Upregulated in
Slide 11: Ultra-Low Dose Gemcitabine Sensitizes Ovarian Cancer Cell Lines to ACR-368
U L T R A - L O W D O S E G E M C I T A B I N E S E N S I T I Z E S O V A R I A N C A N C E R C E L L L I N E S T O A C R -368 OVCAR3-Parental Gemcitabine alone in OVCAR3-Resistant Ovarian-Parental Ovarian-Resistant OGe VCAR3m -P ac ndi t Oa VCbi ARne 3-R alone 150 150 150 No Gem No Gem 0.53 nM Gem
Slide 12: 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, WEE1, and PKMYT1 inhibitors) High throughput AP3 profiling WEE1 an
Slide 13: WEE1 and PKMYT1 Programs: Ideal for AP3 Approach
W E E 1 A N D P K M Y T 1 P R O G R A M S : I D E A L F O R A P 3 A P P R O A C H • 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 prop
Slide 14: 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 15: Profiles of Benchmark WEE1 and PKMYT1 Inhibitors
P R O F I L E S O F B E N C H M A R K W E E 1 A N D P K M Y T 1 I N H I B I T O R S Assays WEE1 inhibitor A WEE1 inhibitor B WEE1 inhibitor C PKMYT1 inhibitor Target IC50 1.2 nM 2.0 nM 1.0 nM 9.8 nM Target Engagement IC50 18.6 nM 15.9 nM 109.0 nM 10 nM Cell Viability IC50 31.9 nM 49.2 nM 318.0 nM 87
Slide 16: In Vitro Kinase Profiling Does Not Predict Drug-Regulated Kinase Activity
I N V I T R O K I N A S E P R O F I L I N G D O E S N O T N O T P R E D I C T D R U G - R E G U L A T E D K I N A S E A C T I V I T Y I N I N T A C T C E L L S PTM-SEA – 60min & 200nM Not Active Active ompound 1 ompound 1 ompound 2 KinomeScan Kinase Activity* ompound 2 ompound ompound Time : 60 minu
Slide 17: Proprietary Pipeline for Automated AP3 Data Analyses
Phosphosites P R O P R I E T A R Y P I P E F O R A U T O M A T E D A P 3 D A T A A N A L Y S E S Proprietary machine learning algorithms applied to state-of-the-art AP3 MS-based phosphoproteomics for all compound projects Unbiased PD marker identification • Automated quantitation of EC50s for 5- 6,0
Slide 18: Tight, High-Resolution Data with Deep Coverage
T I G H T , H I G H - R E S O L U T I O N D A T A W I T H D E E P C O V E R A G E 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 Mot
Slide 19: WEE1 Inhibitors Are More Different Than Similar
WEE1 INHIBITORS ARE MORE DIFFERENT THAN SIMILAR Drug-regulated phosphorylation sites Pathway enrichment analysis Unique and shared drug-regulated sites (unsupervised hierarchical cluster) Cell cycle Mitosis apoptosis Shared on target mechanisms Clinically actionable drug-specific effects FDR < 0.5 &
Slide 20: WEE1 Inhibitor-Regulated Global Phosphoproteome Reveals Differentiated Effects
W E E 1 I N H I B I T O R - R E G U L A T E D G L O B A L P H O S P H O P R O T E O M E R E V E A L H I G H L Y D I F F E R E N T I A T E D E F F E C T S Drug-regulated phosphosites Compound 1 Compound 2 Compound 3 Mean log2FC -5 0 5 FDR < 0.5 & abs(Fold Change) > 1.5 Differentiated WEE1 inhibitor-s
Slide 21: Functional Pathway Network Effects by WEE1 and PKMYT1 Inhibitors
F U N C T I O N A L P A T H W A Y N E T W O R K E F F E C T S B Y W E E 1 A N D P K M Y T 1 I N H I B I T O R S A R E H I G H L Y D I S T I N C T Compound 1 Compound 2 Compound 3 Compound 4 Sensitive tumor cell RTK-MAPK axis Phosphoinositides Mitotic regulation Cell cycle TLR Insensitive and signali
Slide 22: Benchmark WEE1 Inhibitors Have Differentiated Pathway Modulation
B E N C H M A R K W E E 1 I N H I B I T O R S H A V E D I F F E R E N T I A T E D C O M P O U N D - S P E C I F I C D I S E A S E P A T H W A Y M O D U L A T I O N Drug regulation of pathway activity states Drug-regulated phosphorylation sites (substrate consensus motif enrichment analysis) (unsuper
Slide 23: Differential WEE1 Inhibitor-Regulated Pathway Activity
D I F F E R E N T I A L W E E 1 I N H I B I T O R - R E G U L A T E D P A T H W A Y A C T I V I T Y Shared on target CDK1/2 activation and compensatory activation of CHK1 and ATR Substrate motif-inferred kinase activities Compound 1 Compound 2 Compound 3 1 2 Activity (NES) -3 0 3 Time : 60 minutes D
Slide 24: WEE1 Inhibitor Regulation of Pathway Activity (4h)
W E E 1 I N H I B I T O R R E G U L A T I O N O F P A T H W A Y A C T I V I T Y ( 4 H ) Drug-regulated kinase activities calculated based on consensus motif enrichment analysis * = FDR < 0.05 ** = FDR < 0.01 ***= FDR < 0.005 0.32 1.6 8 40 200 1000 0.32 1.6 8 40 200 1000 0.32 1.6 8 40 200 1000 Compou
Slide 25: Differential Regulation of PLK Activity
D I F F E R E N T I A L R E G U L A T I O N O F P L K 1 A C T I V I T Y – P O T E N T I A L I M P A C T O N P A T I E N T T R E A T M E N T O U T C O M E (4 hours) Compound 3 Compound 1 Compound 2 WEE1 WEE1 WEE1 CDK1 CDK1 CDK1 AURKA AURKA AURKA PLK1 PLK1 PLK1 Mitotic Mitotic Possible catastrophe cat
Slide 26: ACR-368 Is Synergistic with and Overcomes Resistance to WEE1 Inhibitor
ACR-368 (nM) ACR-368 (nM) ACR -368 IS SYNERGISTIC WITH AND OVERCOMES RESISTANCE TO WEE1 INHIBITOR WEE1 inhibitor 125 1000 nM 333 nM 100 111 nM 37 nM Human 12.3 nM 75 Combo synergy correlates to 4.12 nM endometrial 1.37 nM WEE1 inhibitor resistance 50 tumor cell 0 nM line 15 25 r = 0.93 0 0 p = 0.007
Slide 27: Actionable Findings and Conclusions
A C T I O N A B L E F I N D I N G S A N D C O N C L U S I O N S • AP3 enables unbiased measurement of compound-specific on- and off-target effects • WEE1 inhibitors all demonstrate activation of CDK1/2 and cell cycle machinery • Benchmark WEE1 inhibitor AP3 profiles can be leveraged for rational dru
Slide 28: WEE1 and PKMYT1 Program Status
W E E 1 A N D P K M Y T P R O G R A M S T A T U S • Hundreds of compounds designed and synthesized across multiple lead series • High resolution co-crystal structures generated for >30 compounds in complex with Wee1 or PKMYT1 (resolution from about 1.5Å to <3Å) Crystal structure of adavosertib:Wee1
Slide 29: Exemplary PKMYT1 and WEE1 Dual-Selective Lead Compound Profiles
E X E M P L A R Y P K M Y T 1 A N D W E E 1 A N D D U A L - S E L E C T I V E L E A D C O M P O U N D P R O F I L E S Compound CMPD-2655 CMPD-2714 CMPD-2707 CMPD-2743 (A) Wee1 IC 451 nM 251 nM 410 nM 1.3 nM 50 PKMYT1 IC 6.5 nM 2.9 nM 1.8 nM 20.6 nM 50 17 nM (Wee1) TE EC 118 nM (PKMYT1) 47.1 nM (PKMY
Slide 30: ACR-368 Clinical Trial
A C R - 3 6 8 C L I N I C A L T R I A L • We reconfirm our guidance and timeline of initial clinical readouts of our Phase 2 3 Cohorts: and Phase 1b/2 clinical trial in H2 2023 Ovarian, Endometrial, Bladder Single-Arm Trial Single-Arm Trial OncoSignature • Enrolling and dosing patients at the Subjec
Slide 31: 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 32: Financial Highlights
FINANCIAL HIGHLIGHTS Cash and marketable securities Projected runway at least into Fully Diluted Shares Outstanding $159.5M 27.0M Q4’24 Balance sheet Current operating plan assuming no Shares and equity grants 31-March-2023 additional financing outstanding 31-March-2023 Unaudited. 32 ACRIVON THERAPE
Slide 33: 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 34: 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 34 ACRIVON THERAPEUTICS