Arvinas, Inc. · NASDAQ:ARVN
Arvinas — Technical Presentation (December 2020)
43 slides from Arvinas's technical presentation, Dec 14, 2020
Slide 1: Clinical Program Update: ARV-471 & ARV-110
Clinical Program Update: ARV-471 & ARV-110 14 December 2020
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: Introduction
Introduction
Slide 4: Agenda
Agenda Topic Participant Introduction John G. Houston, Ph.D. President and Chief Executive Officer ARV-471 Clinical Data Update Ron Peck, M.D. Chief Medical Officer ARV-110 Clinical Data Update Ian Taylor, Ph.D. Chief Scientific Officer Conclusion John G. Houston, Ph.D. President and Chief Executive
Slide 5: ARV-471 and ARV-110: Opportunities to benefit patients in large areas of unmet need
ARV-471 and ARV-110: Opportunities to benefit patients in large areas of unmet need Potential best profile of Potential future endocrine ARV-471 any ER-targeting therapy: • • Tolerability ER degradation therapy of choice in both adjuvant and metastatic settings Estrogen receptor-degrading PROTAC® •
Slide 6: ARV-471 Clinical Data Update
ARV-471 Clinical Data Update
Slide 7: ARV-471: Potential best-in-class estrogen receptor-targeting therapy
ARV-471: Potential best-in-class estrogen receptor-targeting therapy Potential endocrine therapy for ER+/HER2- breast cancer; >200k patients per year in the US alone† Outstanding tolerability profile observed, with potential for adjuvant and metastatic breast cancer settings Better ER degradation th
Slide 8: We are developing ARV-471 to be the endocrine backbone of choice
We are developing ARV-471 to be the endocrine backbone of choice for ER+/HER2- breast cancer treatment US ER+/HER2- Breast Cancer Treatment Paradigm (# of US patients†) Adjuvant (Post-Surgical) Metastatic Breast Cancer (~50K) Breast Cancer (~160K) First Line Second/Third Line Endocrine Aromatase Inh
Slide 9: ARV-471 First-in-Human study is a traditional 3+3 dose escalation study
ARV-471 First-in-Human study is a traditional “3+3” dose escalation study Design • “3 + 3” dose escalation • ARV-471 administered orally, once daily with food • Starting dose: 30 mg Endpoints Primary: • Maximum tolerated dose and recommended Phase 2 dose Key Secondary: • Safety and tolerability • Ph
Slide 10: All Phase 1 patients were post-CDK4/6 inhibitor treatment
All Phase 1 patients were post- CDK4/6 inhibitor treatment; high rate of ER-independent resistance Phase 1 Inclusion Criteria • ER+/HER2- advanced breast cancer • After CDK4/6 inhibitor treatment, ~66% of breast cancers have ER- • Disease progression on CDK4/6 inhibitor independent mechanisms of res
Slide 11: ARV-471 Phase 1 patients received extensive prior therapy (N = 21)
ARV-471 Phase 1 patients received extensive prior therapy (N = 21) Patient Characteristics Parameter N (%) Median age (years) 64 ECOG performance status 0 10 (48) 1 11 (52) Prior visceral disease (liver, lung) 10 (48) Median prior lines of therapy total (range 1-9) 5 (NA) Median number of prior endo
Slide 12: ARV-471 is well tolerated at all dose levels; no Grade 3 adverse events
ARV-471 is well tolerated at all dose levels; no Grade 3 adverse events TRAE in 30 mg (N=3) 60 mg (N=3) 120 mg (N=7) 180 mg (N=5) 360 mg (N=3) Total (N=21) ≥ 10% of Patients Gr 1 Gr 2 Gr 1 Gr 2 Gr 1 Gr 2 Gr 1 Gr 2 Gr 1 Gr 2 N (%) Any - - 2 - 4 - 2 1 2 - 11 (52) Nausea - - 2 - 1 - - 1 1 - 5 (24) Arth
Slide 13: ARV-471's PK is dose proportional; exposures exceed preclinical efficacy thresholds
ARV-471’s PK is dose proportional; exposures far exceed preclinical efficacy thresholds Mean ARV-471 AUC24 by Dose (C1D15) ARV-471 Mean Plasma Concentration-Time Profiles (C1D15) The orange line represents the efficacious exposure for tumor Effective half-life (T1/2) ~~ 28 hours regression in precli
Slide 14: ER degradation observed in patient tumor biopsies
ER degradation observed in patient tumor biopsies Red: Estrogen receptor Blue: Nuclei Green: Tumor (cytokeratin) Baseline After treatment with 60 mg ARV-471 Method: ER immunoreactivity analyzed by quantitative immunofluorescence (QIF) using the automated quantitative analysis (AQUA) method 14
Slide 15: ARV-471 degraded ER up to 90% through the 180 mg dose level
ARV-471 degraded ER up to 90% through the 120 mg dose level ER Expression in Paired Tumor Biopsies† Dose (ESR1 status) 12500 mg (ESR1 30 mg (D538G) D538G) Degradation up to 90%; mg (ESR1 60 mg (Y537S) Y537S) average of 62% 10000 120 mg mg(ESR1 (Y537S)Y537S) ER Expression 120 mg mg(ESR1 (wild type) W
Slide 16: Confirmed RECIST Partial Response in a patient with ESR1 mutation at 120 mg
Confirmed RECIST Partial Response (cPR) in a patient with extensive prior therapy and an ESR1 mutation at 120 mg Extensive prior therapy Baseline CT Scan After 4 Cycles • CDK4/6 inhibitor: Palbociclib • Endocrine therapies: 6 Agents • Aromatase inhibitors x 3 • Tamoxifen • Investigational SERDs X 2†
Slide 17: Regression in chest wall lesions in a patient at 180 mg
Regression in chest wall lesions in a patient with extensive prior therapy and multiple ESR1 mutations at 180 mg Extensive Prior therapy Baseline After 4 Cycles (Associated Bleeding) (No Bleeding) • CDK4/6 inhibitor: • Palbociclib, Abemaciclib • Endocrine therapies: 3 Agents • Aromatase inhibitors x
Slide 18: ARV-471 demonstrates promising anti-tumor activity in late line patients
ARV-471 demonstrates promising anti-tumor activity in late line patients Antitumor Activity in Eligible Patients (N=14)† 30 mg QD 120 mg QD 180 mg QD 360 mg QD 20% 9% Best Percentage Target Lesion 10% SD SD SD SD SD PD SD (uPR) SD(uPR) PR SD 3% Diameter From Baseline 2% 0% 0% 0% SD SD PD PD -10% -5%
Slide 19: ARV-471 achieves a high clinical benefit rate (42%) in heavily pretreated population
ARV-471 achieves a high clinical benefit rate (42%) in this heavily pretreated population through the 180 mg dose level Prior Therapies Treatment Duration (weeks) and Response in Eligible Patients (N=12)† CDK4/6 Investigational Inhibitor Fulvestrant SERD Chemo Cut off for CBR 30 mg QD 001-002 PD 60
Slide 20: Comparison of ARV-471 profile with Phase 1 data for preclinical SERDs
Comparison of ARV-471 profile with Phase 1 data for preclinical SERDs Phase 1 Data Comparison CDK4/6i Mean ER Select TRAEs (> 5% of Patients) Clinical Drug Pretreated Degradation Benefit Gastrointestinal (GI) AEs Other AEs Candidate Patients in Patient Rate (0 – 100%) Tumors Diarrhea Nausea Vomiting
Slide 21: We aim to characterize the activity of ARV-471 across treatment lines
We aim to characterize the activity of ARV-471 across ER+/HER2- breast cancer treatment lines US ER+/HER2- Breast Cancer Treatment Paradigm (# of US patients†) Adjuvant (Post-Surgical) Metastatic Breast Cancer (~50K) Breast Cancer (~160K) First Line Second/Third Line Window of Opportunity (Randomize
Slide 22: ARV-471: Evidence for best-in-class potential in a large area of unmet need
ARV-471: Evidence for best-in-class potential in a large area of unmet need Strong Evidence for Clear Development Large Unmet Need Best-in-Class Profile Path and Opportunity • Superior degradation to • Potential for 2L/3L approval • In the US alone, ER+/HER2- fulvestrant and SERDs† as monotherapy or
Slide 23: ARV-110 Clinical Data Update
ARV-110 Clinical Data Update
Slide 24: ARV-110: 40% PSA50 in a molecularly defined subgroup, and early-line opportunity
ARV-110: 40% PSA50 in a molecularly defined subgroup, and additional opportunity in early-line mCRPC Potential best-in-class therapy for prostate cancer, representing >250k patients per year in the US alone† Well tolerated, escalating through the current dose of 700 mg Continued patient benefit: 40%
Slide 25: Migration of second-generation AR therapies to earlier settings has created unmet need in mCRPC
Migration of second-generation AR therapies to earlier settings has created substantial unmet need for new treatments in mCRPC US Prostate Cancer Treatment Paradigm (# of US patients†) Non-Metastatic Castrate Sensitive Metastatic Castrate Resistant Castrate (~200k) (~40k) Resistant (~9k) First Line
Slide 26: Our strategy is to develop ARV-110 across treatment settings of prostate cancer
Our strategy is to develop ARV-110 across treatment settings of prostate cancer US Prostate Cancer Treatment Paradigm (# of US patients†) Castrate Sensitive Non-Metastatic Castrate Metastatic Castrate Resistant (~40k) (~200k) Resistant (~9k) 1L 2L 3L Near-term opportunities for ARV-110 Expansion opp
Slide 27: ARV-110 is showing early clinical benefit in highly refractory patients
ARV-110 is showing early clinical benefit in highly refractory patients Median prior therapies 5 76% Patients treated with prior chemotherapy Patients treated with both abiraterone and enzalutamide 82% 84% Patients with non-AR mutations Existing AR-directed High tumor therapies expected to heterogen
Slide 28: ARDENT Phase 2 has initiated with a once daily, oral dose of 420 mg
ARDENT Phase 2 has initiated with a once daily, oral dose of 420 mg Design informed by Phase 1 learnings Promising antitumor PSA reduction AR molecular profiling activity is associated with identifies a molecularly in heavily pre-treated plasma exposure defined, late line population patients with li
Slide 29: At 420 mg, exposures exceed the predicted efficacious threshold
At 420 mg, exposures exceed the predicted efficacious threshold observed in a preclinical enzalutamide-resistant model ARV-110 AUC24 Across Total Daily Doses (C1D15/21)††† Predicted efficacious threshold based on an enzalutamide- resistant prostate cancer model †† Predicted minimum efficacious thres
Slide 30: Increased ARV-110 clinical activity at higher exposures
Increased ARV-110 clinical activity at higher exposures Best PSA Change By Preclinical Efficacious Threshold (N=37)† Exposures below minimum Above minimally efficacious exposure; Exposures at levels that efficacious threshold †† below enzalutamide resistant threshold overcame enzalutamide resistance
Slide 31: We have identified ARV-110-sensitive populations despite tumor heterogeneity
We have identified ARV-110-sensitive populations despite significant tumor heterogeneity in our patient population Genomic alterations are known to increase over time and with multiple treatments in mCRPC Treatment-refractory progression in mCRPC • Genetic context, an important determinant TREATMENT
Slide 32: Potential molecularly defined subgroups of patients sensitive to ARV-110
In our late stage, genetically heterogeneous population, we have identified potential molecularly defined subgroups of patients sensitive to ARV-110 Best PSA Change In All Patients Above Minimum Exposure Threshold (N= 28) ††† 100 Best % PSA Change From 75 PSA50 14% (4/28) 50 25 Baseline 0 -25 PSA30
Slide 33: Four of five patients with T878/H875 mutations had PSA reductions
Four of five (80%) patients with T878/H875 mutations had PSA reductions, representing a potential accelerated approval population Best PSA Change In Patients with AR T878/H875 mutations (N=5)†† 100 Best % PSA Change From Baseline 75 PSA50 40% (2/5) 50 • Multiple AR mutations could be a "signature" f
Slide 34: ARV-110 is also active in refractory mCRPC patients with wild-type AR
ARV-110 is also active in refractory mCRPC patients with tumors expressing wild-type AR Best PSA Change In Patients with Wild-Type AR (N=15)†† Best % PSA Change From Baseline 25 PSA50 13% (2/15) 0 -25 PSA30 -50 PSA50 -75 -100 AR Status WT WT WT WT WT WT WT WT WT WT WT WT WT WT WT AR-V7 ††† + + + + O
Slide 35: Strong profile for ARDENT Phase 2 expansion trial at 420 mg
Strong profile for ARDENT Phase 2 expansion trial at 420 mg, oral, once daily Parameter Phase 1 Results Safety Data† (Well tolerated; no TRAEs Gr >2) Dose Response and Exposure Threshold†† Efficacy Data†† Strong signal in molecularly defined patient populations High potential for patient ben
Slide 36: ARDENT will evaluate efficacy in late-line and early-line mCRPC populations
ARDENT will evaluate efficacy in both late-line, molecularly defined patients, and in a broader, early-line mCRPC population Features of the ARDENT Phase 2 Design Potential registrational paths • Enriches T878/H875 for exploration as a potential population for accelerated approval, and retains optio
Slide 37: ARV-110's planned registrational path aligns with unmet need in mCRPC
ARV-110’s planned registrational path aligns with unmet need in mCRPC, and offers potential label expansion into earlier settings Evolving Prostate Cancer US Treatment Paradigm (# of US patients†) Castrate Sensitive Non-Metastatic Castrate Metastatic Castrate Resistant (~40k) (~200k) Resistant (~9k)
Slide 38: ARV-110: Potential to address unmet need across multiple stages of prostate cancer
ARV-110: Potential to address unmet need across multiple stage of prostate cancer Potential for Best- Clear Development Large Unmet Need in-Class Profile Path and Opportunity • Driving tumor responses • Two potential • High unmet need across all and PSA reductions in a registrational paths stages of
Slide 39: Conclusion
Conclusion
Slide 40: Arvinas' current pipeline in oncology, I-O, and neuroscience
Arvinas’ current pipeline encompasses a range of validated and undruggable targets in oncology, I-O, and neuroscience ARVN Program Indication Exploratory Research IND Enabling Phase 1 Phase 2 Phase 3 ARV-110 mCRPC IND 2021 Oncology / Immuno-oncology ARV-766 Other AR indications AR-V7 mCRPC ARV-471 E
Slide 41: ARV-110 and ARV-471 set up Arvinas for a remarkable 2021
ARV-110 and ARV-471 set up Arvinas for a remarkable 2021 Anticipated Milestones 2020 Q4 2021 2022 • Complete Phase 1 data • Full ARDENT Phase 2 data ARV-110 • ARDENT Phase 2 interim • Combination study data (AR data PROTAC®) • Initiation of combination study(s) • Initiation of combination • Complete
Slide 42: We are well on our way to our 2024 vision
We are well on our way to our 2024 vision Integrated biotech poised for launch • Goal to have first PROTAC® degraders proven to benefit patients in registrational studies • Sustainably nominating ≥1 clinical candidate per year 2024 • PROTAC Discovery Engine delivering candidates with Vision tissue-
Slide 43: Thank You
Thank You 43