Arvinas, Inc. · NASDAQ:ARVN
Arvinas — Technical Presentation (May 2020)
30 slides from Arvinas's technical presentation, May 29, 2020
Slide 1: ARV-110 Phase 1/2 Dose Escalation: Interim Update
ARV-110 Phase 1/2 Dose Escalation: Interim Update 29 May 2020 Exhibit 99.2
Slide 2: Safe harbor and forward-looking statements
Safe harbor and forward-looking statements This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the development and regulatory status of our pr
Slide 3: ARV-110 data validates the potential of our PROTAC platform
ARV-110 data validates the potential of our PROTAC® platform, a completely novel therapeutic modality Preclinical profile translating to patient benefit Potential for genetically defined development pathway Efficacy signal in humans ARV-110 is the first PROTAC degrader with an efficacy signal in hum
Slide 4: Today's presentation
Today’s presentation Preclinical Profile of ARV-110 ARV-110 Clinical Data Update Pipeline Update
Slide 5: Today is a significant milestone for PROTAC protein degraders
Today is a significant milestone for PROTAC® protein degraders First proof of concept for PROTAC® protein degraders Benefitting patients where traditional inhibitors have failed Validates our confidence in this novel therapeutic modality and our pipeline
Slide 6: Preclinical Profile of ARV-110
Preclinical Profile of ARV-110
Slide 7: New approaches are needed to target the androgen receptor, a critical driver of mCRPC
New approaches are needed to target the androgen receptor, a critical driver of mCRPC Androgen Receptor (AR) activity drives prostate cancer Prostate cancer is the second leading cause of cancer death in men in the US1 Current agents work by decreasing androgen levels (abiraterone) or blocking andro
Slide 8: ARV-110 is a PROTAC protein degrader that targets AR in preclinical models
ARV-110 is a PROTAC® protein degrader that targets AR in multiple preclinical models of prostate cancer mCRPC, metastatic castration-resistant prostate cancer 1Ledet E, The Oncologist 2019 AR MitoC 1 2 3 5 4 6 7 1 2 4 3 5 ARV-110, 10 mpk Vehicle 6 2 4 3 5 ARV-110, 3 mpk 1 6 ARV-110 targets wildtype
Slide 9: In October, ARV-110 was well-tolerated with exposures consistent with preclinical efficacy
In October, we showed that ARV-110 was well-tolerated and had reached exposures consistent with preclinical efficacy †Orally, once daily ‡Not including 1 non-evaluable patient (discontinued on day 1; patient’s condition had worsened in the interval from screening to the morning of treatment initiati
Slide 10: Three questions facing PROTAC protein degraders
THREE QUESTIONS Today, we will address the third critical question facing PROTAC® protein degraders as a new therapeutic modality First addressed in October 2019 Will a PROTAC be safe in humans? Will a PROTAC be efficacious in humans? Will a PROTAC have drug-like properties in humans? To be initiall
Slide 11: ARV-110 Clinical Data Update
ARV-110 Clinical Data Update
Slide 12: ARV-110 is a traditional 3+3 dose escalation study in mCRPC
Our study of ARV-110 is a traditional “3+3” dose escalation study in patients that have received ≥2 prior systemic therapies for mCRPC Design “3 + 3” dose escalation; starting dose = 35 mg, orally, once daily with food Dose increases dependent on toxicities Range 25% to 100% based on severity of AEs
Slide 13: Enrolled patients (N=22) have been highly pretreated at baseline
Enrolled patients (N=22) have been highly pretreated at baseline Patient characteristics Parameter N (%) Median age (years) 67.5 ECOG Performance Status 0 1 15 7 (68) (32) Number of prior regimens in mCRPC ≥2 Mean Median (range, 2-9) 22 5 6 (100) (NA) (NA) Prior 2nd generation AR treatment Abiratero
Slide 14: ARV-110 has been generally well tolerated; potential drug-drug interaction with rosuvastatin
ARV-110 has been generally well tolerated; potential drug-drug interaction in the two patients taking concomitant rosuvastatin †Patients on rosuvastatin (N=2) Related TEAE in ≥ 10% of patients (N=22) 1 of 22 patients had a DLT with ALT/AST Grade 3/4 and renal failure (280 mg) Related TEAE 35 mg (N=3
Slide 15: Clinical observations of patients receiving concomitant rosuvastatin
Clinical observations 2 of 22 patients received concomitant rosuvastatin First patient with DLT: Grade 3/4 ALT/AST and renal failure Second patient with Grade 3 ALT/AST; re-challenge off rosuvastatin supported contribution of rosuvastatin. Patient continues on ARV-110 with no further toxicity Pharma
Slide 16: ARV-110 exposures are dose-proportional with drug-like pharmacokinetics
ARV-110’s exposures are dose-proportional and continue to demonstrate drug-like pharmacokinetics; half-life supports QD dosing 1Upper line based on enzalutamide-resistant vertebral cancer of the prostate (VCaP) models. Lower line based on castrated and non-castrated VCaP model QD, once per day. AUC,
Slide 17: ARV-110 degrades AR in tumor tissue, first proof of mechanism
ARV-110 degrades AR in tumor tissue, demonstrating the first proof of mechanism for PROTAC® protein degraders 2.5X 10X BASELINE ON-TREATMENT Decreased AR protein levels in an AR wildtype/amplified tumor from a patient following 6 weeks of ARV-110 dosing (280 mg)
Slide 18: Best percent change of PSA from baseline in evaluable patients (N=20)
Best percent change of PSA from baseline in all patients evaluable for safety (N=20)1 1Two of 22 patients were not evaluable: 1 patient had 1 dose and discontinued trial, and 1 patient had PSA less than 1 ng/ml and eligibility by radiographic progression; 2Treatment discontinued after 2 weeks due to
Slide 19: Duration of therapy
Duration of therapy ABI ENZA Chemo (any) ‡ DLT PCWG3 minimum PSA follow-up (Scher JCO 2016)† Prior therapies Data as of April 20, 2020 †PCWG3, Prostate Cancer Working Group 3; ‡Dose reduced for non-safety reasons; ◊PSA50 responder; ◊◊PSA50/RECIST responder Duration of therapy increases in patients a
Slide 20: AR biomarker status and best % PSA change at ≥140 mg (N=12)
AR biomarker status and best % PSA change in patients at ≥140 mg (N=12)1 AR-V7 L702H Wild-type or with point mutations known to be degraded by ARV-1102 Confirmed PSA50 responses Confirmed RECIST response T878A H875Y T878A H875Y In patients without L702H or AR-V7, 2 of 7 had PSA decreases >50% 1Exclu
Slide 21: Confirmed PSA responder; non-evaluable by RECIST
Confirmed PSA responder; non-evaluable by RECIST 1Jernberg E, Endocrine Connections, 2017 Response PSA: 74% decline No radiographic progression Duration of ARV-110: 30 weeks and ongoing Patient history 69 y.o. male Extensive bone metastases including the sternum, left first rib, T3, T10 vertebral bo
Slide 22: Confirmed RECIST partial response with PSA response
Response RECIST: 80% reduction in tumor measurements Duration of ARV-110: 18 weeks and ongoing PSA: 97% decline Patient history 72 y.o. male Extensive disease involving adrenal gland, aortocaval nodes, multiple cone metastases Prior therapy included Bicalutamide Enzalutamide Provenge Abiraterone Cab
Slide 23: Exciting path forward
Exciting path forward Unequivocal efficacy signal in first-in-human dose escalation study Deep, durable, and ongoing responses Heavily pretreated population Patients resistant to standard of care Clear path ahead 420 mg cohort dosed Backfilling patients at 280 mg while dose escalating Adding new sit
Slide 24: Pipeline Update
Pipeline Update
Slide 25: Our high potential PROTAC pipeline is focused on cancer and neuroscience
Our high potential PROTAC® pipeline is focused on cancer and neuroscience ARV-110 Androgen Receptor ARV-766 (AR Backup) Androgen Receptor AR Variant Degrader AR-V7 ARV-471 Estrogen Receptor Multiple Indications Undisclosed Targets CENTRAL NERVOUS SYSTEM Prostate Cancer Breast Cancer Additional I-O a
Slide 26: Preclinical profile translating into clinical benefit
Preclinical profile translating into clinical benefit Signals of efficacy in a heavily pretreated patient population with high unmet need, where traditional inhibitors have failed Proves the concept of PROTAC targeted protein degradation, validating our confidence in our pipeline of degraders Arvina
Slide 27: For More Information
For More Information PRESS/MEDIA pr@arvinas.com INVESTORS ir@arvinas.com BUSINESS DEVELOPMENT bd@arvinas.com CAREERS careers@arvinas.com
Slide 28: Appendix
Appendix
Slide 29: PROTAC protein degraders function inside cells
PROTAC protein degraders function inside cells Formation of trimer complex and ubiquitination of target protein Multiple ubiquitin molecules “tag” target protein for degradation Targeted protein is degraded by the proteasome Iterative PROTAC degrader activity PROTAC® E3 Ligase Target Protein Ubiquit
Slide 30: AR biomarker status and best % PSA change at ≥140 mg (excludes DLT patient)
AR biomarker status and best % PSA change in patients at ≥140 mg (excludes DLT patient; N=12)1 1One patient discontinued after 2 weeks due to DLT associated with rosuvastatin; AR status based on assays from Epic Sciences, Foundation Medicine (RUO), and OHSU/KDL AR Status: AR-V7 Wildtype Amplif. Wild