Slide 1: AR Franchise Update: Bavdegalutamide and ARV-766
AR Franchise Update Bavdegalutamide and ARV-766 October 22, 2023
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 potential advantages, therapeutic benefits
Slide 3: Bavdegalutamide and ARV-766 both show strong profiles in mCRPC; ARV-766 broader efficacy
In the clinic, bavdegalutamide and ARV-766 both show strong profiles in mCRPC; ARV-766 has shown broader efficacy and superior tolerability • Bavdegalutamide has proven the concept for a PROTAC® AR degrader in prostate cancer • Updated Phase 2 data demonstrate 11.1 months rPFS in patients with AR 87
Slide 4: Phase 1/2 trial with bavdegalutamide, an oral PROTAC AR degrader
Phase 1/2 trial with bavdegalutamide, an oral PROTAC® AR degrader European Society for Medical Oncology (ESMO) 2023 4
Slide 5: Bavdegalutamide has proven the concept of a PROTAC AR degrader in mCRPC
Bavdegalutamide has proven the concept of a PROTAC® AR degrader in mCRPC Existing options leave unmet need in post-NHA mCRPC • NHA retreatment is associated with limited benefit (e.g., rPFS ~ 4 months)(1-4) • Emerging non-AR agents have better outcomes (e.g., rPFS 7-9 months post-taxane therapy), bu
Slide 6: Bavdegalutamide's ARDENT Phase 2 trial design
Bavdegalutamide’s ARDENT Phase 2 trial has explored efficacy in patients with tumors that retain AR dependency Part A: Phase 1 Dose Escalation Part B: Phase 2 Dose Expansion (ARDENT) RP2D = 420 mg once daily AR LBD Biomarker Dose Defined Groups Screening Screening Escalation (n=~140) (n=71) 35 mg to
Slide 7: Patients enrolled in the Phase 1/2 trial were NHA-experienced and heavily pretreated
Patients enrolled in the Phase 1/2 trial were NHA-experienced and included heavily pretreated patients (median prior therapies = 4) Table 1: Baseline characteristics Total at 420 mg QD AR LBD patients1 Parameter (n=153) (n=45) Age, median (range), y 73 (48–91) 72 (51–83) ECOG PS, n (%)2 0 81 (53) 25
Slide 8: Bavdegalutamide's tolerability has been shown to be manageable in mCRPC
Bavdegalutamide’s tolerability has been shown to be manageable in patients with mCRPC TRAEs reported in ≥10% of patients treated with • The most common bavdegalutamide 420 mg QD in the Phase 1/2 trial (n=153) treatment-related adverse Total n (%) Grade 1 Grade 2 Grade 3 events (TRAEs) with Any TRAE
Slide 9: Bavdegalutamide demonstrated robust rPFS of 11.1 months in NHA-experienced mCRPC
In clinical settings, bavdegalutamide has demonstrated a robust rPFS of 11.1 months in an NHA-experienced mCRPC patient population Population Median PFS PSA50 AR 878/875† 11.1 months 14/26 (54%) (n=26) (95% CI: 7.1–NR) 10 events in 26 patients No. at risk AR 26 25 17 16 13 13 11 11 9 6 6 6 3 3 3 3 3
Slide 10: Bavdegalutamide's efficacy profile is differentiated from non-AR agents
Bavdegalutamide’s efficacy profile is differentiated from those of non- AR agents Cross-trial benchmarks are not based on head-to-head studies Clinical Activity Safety Profile Trial Name Route of Addressable Patient Drug Prior taxane Discontinuation status Administration Segment Median rPFS Grade ≥3
Slide 11: AR L702H mutations diminish the efficacy of bavdegalutamide
The presence of AR L702H mutations diminishes the efficacy of bavdegalutamide Mutation status PSA50 rate AR 878/875 alone (n=26) 54% AR 878/875 with co-occurring L702H (n=11) 9% Any tumor with AR L702H (n=24) 8% Bavdegalutamide’s diminished efficacy in patients harboring tumors with AR L702H may lim
Slide 12: Bavdegalutamide has proven the concept for a PROTAC AR degrader in AR LBD mCRPC
Bavdegalutamide has proven the concept for a PROTAC® AR degrader in AR LBD mCRPC • In clinical settings, bavdegalutamide achieved a robust efficacy in post-NHA patients with most AR LBD mutations, with particularly strong responses in patients with tumors harboring AR 878/875 mutations alone • Bavde
Slide 13: ARV-766 Clinical Update
ARV-766 Clinical Update 13 Arvinas Confidential and Proprietary
Slide 14: ARV-766 is a pan-AR PROTAC degrader designed to degrade wild-type AR and all mutations
ARV-766 is a pan-AR PROTAC® degrader designed to degrade wild- type AR and all clinically relevant AR mutations, including L702H • The prevalence of AR LBD mutations is increasing, especially L702H • L702H is estimated at ~11% of mCRPC in 20233 • In total, the prevalence of AR LBD mutations in mCRPC
Slide 15: ARV-766 has potential to be first- and best-in-class PROTAC AR degrader in mCRPC
ARV-766 has the potential to be first- and best-in-class PROTAC® AR degrader in mCRPC June • Strong activity (42% PSA50) in post-NHA patients across all LBD 2023† disclosure (including L702H) mutations (N=47) • Low rates of Grade 2 and 3 TRAEs; 1 discontinuation, 2 dose reductions • Activity remains
Slide 16: ARV-766's tolerability profile surpasses that of bavdegalutamide
ARV-766’s excellent tolerability profile surpasses that of bavdegalutamide in the clinical setting TRAE ≥10% Bavdeg ARV-766 Bavdeg ARV-766 n (%)1 (n=1532) (n=84†) (n=1532) (n=84†) Any Grade Any Grade Grade 3+ Grade 3+ Any TRAE 135 (88) 55 (66) 24 (16) 7 (8) Fatigue 53 (35) 24 (29) 1 (1) 2 (2) Nausea
Slide 17: ARV-766: 41% of patients with AR LBD mutations achieve PSA50
ARV-766: 41% of patients with AR LBD mutations achieve PSA50 (n=17†) 100 PSA50=41% Continuing treatment 75 Best % PSA Change From Baseline 50 25 0 -25 PSA30 -50 PSA50 -75 -100 AR = androgen receptor; LBD = ligand-binding domain; PSA = prostate-specific antigen; QD = once daily; PSA30 = best PSA decl
Slide 18: ARV-766 shows improved efficacy signals in tumors harboring AR L702H
ARV-766 is demonstrating improved signals of efficacy in patients with tumors harboring AR L702H mutations compared to bavdegalutamide in the clinical setting PSA50 rates (%) Bavdegalutamide† ARV-766‡ Patients with tumors 8% (2 of 24) 50% (4 of 8) with L702H • 41% PSA50 (7 of 17) in patients with an
Slide 19: Deep PSA decline in wild-type AR patient supports development in pre-NHA settings
Deep PSA decline in patient with mCRPC with wild-type AR supports development in pre-NHA settings, including mCSPC AR = androgen receptor; PSA = prostate-specific antigen; mCSPC = metastatic castrate-sensitive prostate cancer; mCRPC = metastatic castrate-resistant prostate cancer; 19 NHA = novel hor
Slide 20: ARV-766 could reach 3X more patients in mCRPC, with additional mCSPC opportunity
ARV-766 has the potential to reach 3X more patients in mCRPC than bavdegalutamide, with additional opportunity in mCSPC Potential addressable patient populations in mCRPC† ~35,000 ARV-766: • Strong signals of efficacy and excellent tolerability All LBD (25%) in a population representing ~25% of mCRP
Slide 21: Arvinas believes ARV-766 will be a better choice than bavdegalutamide
Based on current clinical data, Arvinas believes ARV-766 will be a better choice than bavdegalutamide for patients with both early- and late-line prostate cancer Potential for PROTAC® AR degrader to improve outcomes in patients with Bavdegalutamide ARV-766 prostate cancer Degrades wild type and ampl
Slide 22: Path Forward for PROTAC AR Degraders in mCSPC and mCRPC
Path Forward for PROTAC® AR Degraders in mCSPC and mCRPC 22 Arvinas Confidential and Proprietary
Slide 23: Arvinas will prioritize ARV-766 in mCSPC and mCRPC
Arvinas will prioritize ARV-766 in mCSPC and mCRPC • Arvinas is committed to advancing the best treatment for patients in both early- (mCSPC) and late-line (mCRPC) disease • Based on our current clinical data, we believe that ARV-766 will be superior to bavdegalutamide in each setting, and can enrol
Slide 24: Q&A
Q&A • John Houston, Ph.D, President and Chief Executive Officer, Arvinas • Ron Peck, M.D., Chief Medical Officer, Arvinas • Daniel P. Petrylak, M.D., Professor of Medicine (Medical Oncology) and of Urology; Chief, Genitourinary Oncology; at Yale School of Medicine • Investigator: bavdegalutamide Pha