Arvinas, Inc. · NASDAQ:ARVN
Arvinas — 2nd Annual Targeted Protein Degradation Summit (October 2019)
31 slides from Arvinas's conference presentation, Oct 23, 2019
Slide 1: Moving PROTAC Protein Degraders from the Laboratory to the Clinic
Moving PROTAC® Protein Degraders from the Laboratory to the Clinic IAN TAYLOR, PHD 2nd Annual Targeted Protein Degradation Summit OCTOBER 2019 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: Arvinas: Company Overview
Arvinas: Company Overview PIPELINE ARV-110 - Metastatic castration-resistant prostate cancer; Phase 1 initiated 1Q19, and received “Fast Track” designation from FDA in May 2019 ARV-471 - Estrogen receptor-positive / HER2-negative locally advanced or metastatic breast cancer; Phase 1 initiated 3Q19 B
Slide 4: High Potential PROTAC Pipeline, Focused on Cancer and Neurology
High Potential PROTAC® Pipeline, Focused on Cancer and Neurology1 1 Pipeline as of October 23, 2019 Programs [Target] Discovery Lead Optimization IND Enabling Phase 1 Arvinas Owned Oncology Metastatic Castration-resistant Prostrate Cancer ü ü ü Locally Advanced or Metastatic ER+ / HER2- Breast Cance
Slide 5: The Tenets of PROTAC Degraders
The “Tenets of PROTAC® Degraders” Areas where the PROTAC® mechanism of action may be particularly well-suited TENETS OF PROTAC® Degraders
Slide 6: Two Big Questions of the PROTAC Platform
Two Big Questions of the PROTAC® Platform As It Moves From Laboratory to the Clinic TWO BIG QUESTIONS
Slide 7: Asking the Two Big Questions of ARV-110: Androgen Receptor PROTAC
Asking the Two Big Questions of ARV-110: Androgen Receptor PROTAC®
Slide 8: Androgen Receptor Activity Drives Prostate Cancer
Androgen Receptor (AR) Activity Drives Prostate Cancer Current agents work by decreasing androgen levels (abiraterone) or blocking androgen binding to AR (enzalutamide) 15-25% of patients never respond to abiraterone or enzalutamide (intrinsic resistance) Resistance mechanisms to abiraterone and enz
Slide 9: ARV-110 Potently and Rapidly Degrades AR and Inhibits Proliferation
ARV-110 Potently and Rapidly Degrades AR and Inhibits Proliferation Better than Enzalutamide in Preclinical Models In vitro studies ARV-110 degraded 95% to 98% of AR in multiple cell lines typically used in prostate cancer research, including VCaP cells DC50 in VCaP = 1 nM Near-maximal degradation w
Slide 10: ARV-110 Inhibits AR-Dependent Tumor Growth in Xenograft Models
ARV-110 Inhibits AR-Dependent Tumor Growth in Xenograft Models with Oral, Daily Dosing Intact (Non-castrated) VCaP: Dose po, qd Mean AUC0-24 ng*hr/ml† Mean Cmax ng/ml‡ 1 mpk 3628 224 3 mpk 8106 507 Castrated VCaP: mpk = mg/kg Enzalutamide Resistant VCaP: Values represent total drug concentrations †
Slide 11: ARV-110: GLP Toxicology Studies Supported Moving into Clinical Development
MTD, maximum tolerated dose. NOAEL, no observed adverse effect level; mpk = mg/kg ARV-110: GLP Toxicology Studies Supported Moving into Clinical Development Rat Study: Male animals, 20, 60, or 120 mpk per day; Female animals, 20, 40, or 80 mpk per day Overall, ARV-110 was well tolerated at all doses
Slide 12: ARV-110: Phase 1 Study
ARV-110: Phase 1 Study First patient dosed March 2019 Key Objectives: Maximum Tolerated Dose/ Recommended Phase 2 Dose/ Safety Pharmacokinetics Anti-Tumor Activity (PSA, RECIST) Biomarkers Biomarkers: AR degradation in circulating tumor cells (CTCs) and pre- vs post-treatment biopsies (when availabl
Slide 13: ARV-110 Phase 1 Dose Escalation: Pharmacokinetics is Dose Proportional
ARV-110 Phase 1 Dose Escalation—Pharmacokinetics is Dose Proportional Dose po, qd Day 1 AUC0-24 (ng*h/mL) Mean Day 1 Cmax (ng/ml) Mean Day 15 AUC0-24 (ng*h/mL) Meana Day 15 Cmax (ng/ml) Mean 35 mg 160.5 11.1 1701 83 70 mg 300 19.6 2538 141 140 mg 865 54 5023 353 Phase 1 Data a Day 15 AUCs calculated
Slide 14: ARV-110 Phase 1 Dose Escalation: Pharmacokinetics is Dose Proportional
ARV-110 Phase 1 Dose Escalation—Pharmacokinetics is Dose Proportional Dose po, qd Day 1 AUC0-24 (ng*h/mL) Mean Day 1 Cmax (ng/ml) Mean Day 15 AUC0-24 (ng*h/mL) Meana Day 15 Cmax (ng/ml) Mean 35 mg 160.5 11.1 1701 83 70 mg 300 19.6 2538 141 140 mg 865 54 5023 353 Phase 1 Data a Day 15 AUCs calculated
Slide 15: ARV-110 Phase 1 Dose Escalation: Pharmacokinetics is Dose Proportional
ARV-110 Phase 1 Dose Escalation—Pharmacokinetics is Dose Proportional Day 15 AUC Day 15 Cmax Dose po, qd Day 15 AUC0-24 (ng*h/mL) Meana Day 15 Cmax (ng/ml) Mean 35 mg 1701 83 70 mg 2538 141 140 mg 5023 353 a Day 15 AUCs calculated using imputed 24 hour values Orange lines represent AUC and Cmax asso
Slide 16: ARV-110 Phase 1 Dose Escalation: Day 15 Pharmacokinetics
ARV-110 Phase 1 Dose Escalation— Day 15 Pharmacokinetics Tmax† = 4 - 8 hours t1/2‡ = estimated 3 - 7 days † Time of to reach maximum concentration (Cmax) ‡ Effective half-life: rate of accumulation or elimination of a pharmacologic substance 24 hour values are imputed from time zero
Slide 17: ARV-110 Phase 1 Dose Escalation Safety/Tolerability
ARV-110 Phase 1 Dose Escalation Safety/Tolerability: Overall Favorable Profile Observed to Date Dose Levela N Key Safety Findings 35 mg 3 No Dose Limiting Toxicities (DLTs) No Treatment Related Adverse Events (AEs) 70 mg 4 No DLTs No Grade 2/3/4 Treatment Related AEs 140 mgb 3c No DLTs No Grade 2/3/
Slide 18: First-in-Human Androgen Receptor PROTAC ARV-110 Proceeding Through Dose Escalation
First-in-Human Androgen Receptor PROTAC® ARV-110 Proceeding Through Dose Escalation 10 patients with mCRPC treated across three dose levels At doses thus far tested, ARV-110 demonstrating an acceptable safety profile Pharmacokinetics show dose-proportional increase in exposure Dose escalation contin
Slide 19: Two Big Questions, Asked a Second Time: ARV-471 Estrogen Receptor PROTAC
Two Big Questions, Asked a Second Time ARV-471: Estrogen Receptor PROTAC®
Slide 20: ARV-471: ER Degrader for Locally Advanced or Metastatic Breast Cancer
All Breast Cancers1 ~80% ER+ Breast cancer is the second most common cancer in women1 ~268,000 women are expected to be diagnosed with invasive breast cancer in the US in 20191 Metastatic breast cancer accounts for ~6% of newly diagnosed cases2 80% of newly diagnosed breast cancers are estrogen rece
Slide 21: Orally Dosed ARV-471 Shrinks Tumors and Robustly Degrades ER in MCF7 Xenografts
Orally Dosed ARV-471 Shrinks Tumors and Robustly Degrades ER in MCF7 Xenografts WESTERN BLOT PD (18 hours post last dose) % ER REDUCTION 3 mpk 95 10 mpk 97 30 mpk 94 Dose po, qd Mean AUC0-24 ng*hr/ml Mean Cmax ng/ml 3 mpk 658 84 10 mpk 2538 312 30 mpka 5717 962 TGI 85% 98% 124% mpk = mg/kg Values re
Slide 22: ARV-471: GLP Toxicology Studies Supported Moving into Clinical Development
NOAEL, no observed adverse effect level ARV-471: GLP Toxicology Studies Supported Moving into Clinical Development The studies have shown no clinical signs of toxicity following daily oral doses of ARV-471 up to 100 mg/kg/day in rats and 90 mg/kg/day in dogs, nor effects on overall animal health and
Slide 23: ARV-471: Phase 1 Study
ARV-471: Phase 1 Study First patient dosed August 2019 Biomarkers: Key Objectives: Maximum Tolerated Dose/ Recommended Phase 2 Dose/Safety Pharmacokinetics Anti-tumor activity (RECIST, CBR) Biomarkers Biomarkers: ER gene (ESR1) mutational status in ctDNA and/or tumor tissue ER, Progesterone Receptor
Slide 24: ARV-471 Phase 1 Dose Escalation: First Cohort Pharmacokinetics
ARV-471 Phase 1 Dose Escalation— First Cohort Pharmacokinetics Dose po, qd Day 1 AUCTAU (ng*h/mL) Mean Day 1 Cmax (ng/ml) Mean Day 15 AUCTAU (ng*h/mL) Meana Day 15 Cmax (ng/ml) Mean 30 mg 1690 109 4100 224 Phase 1 Data Dose (po, qd) Mean AUC0-24 (ng*hr/ml) Mean Cmax (ng/ml) 3 mpk 658 84 10 mpk 2538
Slide 25: ARV-471 Phase 1 Dose Escalation: First Cohort Pharmacokinetics
ARV-471 Phase 1 Dose Escalation— First Cohort Pharmacokinetics Tmax = 4 hours t1/2 = estimated to be ~24 hours Day 15 24 hour value is imputed from time zero
Slide 26: ARV-471 Phase 1 Dose Escalation: Safety/Tolerability
ARV-471 Phase 1 Dose Escalation—Safety/Tolerability Dose Levela N Key Safety Findings 30 mgb 3 No DLTs No Treatment Related AEs 60 mg 3 TBD b Data not yet 100% source verified Trial update planned in 2nd half 2020 a Orally, once daily First cohort through 28 day dose limiting toxicity evaluation per
Slide 27: Two Big Questions of the PROTAC Platform
Two Big Questions of the PROTAC® Platform TWO BIG QUESTIONS
Slide 28: Two Big Questions of the PROTAC Platform Today
Two Big Questions of the PROTAC® Platform Today: Favorable Initial Clinical Data from PROTAC® Platform: Two Different PROTAC® Degraders Two Different Cancer Indications Two Different Patient Populations TWO BIG QUESTIONS
Slide 29: The Next Big Question: Will a PROTAC Demonstrate Efficacy in the Clinic?
The Next Big Question: Will a PROTAC® Demonstrate Efficacy in the Clinic? Planned Milestone Updates 1H20: Topline Data on Completed ARV-110 Phase 1 Dose Escalation 2H20: ARV-471 Phase 1 Update
Slide 30: Thank You
Thank You The Patients, Their Families and Caregivers Investigators and Clinical Trial Site Staff
Slide 31: And All Arvinas Colleagues!
And All Arvinas Colleagues!
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