Arvinas, Inc. · NASDAQ:ARVN
Arvinas — Corporate Update (December 2020)
43 slides from Arvinas's corporate update, Dec 14, 2020
Slide 1: Clinical Program Update: ARV-471 & ARV-110
Clinical Program Update: ARV-471 & ARV-110 14 December 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: 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 † US incidence data from SEER database AR, androgen receptor; ER, estrogen receptor ARV-471 Breast Cancer Estrogen receptor-degrading PROTAC® Initiated Phase 2 ARDENT trial; two potential paths to registration: 3L mo
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: Developing ARV-471 to be the endocrine backbone of choice for ER+/HER2- breast cancer
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) Breast Cancer (~160K) Metastatic Breast Cancer (~50K) Second/Third Line First Line Clinical Limitations En
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 Pharmacokineti
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 Disease progression on CDK4/6 inhibitor ≥ 2 prior endocrine therapies in any setting Up to 3 prior chemotherapy regimens in advanced breast c
Slide 11: ARV-471 Phase 1 patients received extensive prior therapy
ARV-471 Phase 1 patients received extensive prior therapy (N = 21) Patient Characteristics Parameter N (%) Median age (years) 64 ECOG performance status 0 1 10 11 (48) (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
ARV-471 is well tolerated at all dose levels; no Grade 3 adverse events TRAE in ≥ 10% of Patients 30 mg (N=3) 60 mg (N=3) 120 mg (N=7) 180 mg (N=5) 360 mg (N=3) Total (N=21) 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
ARV-471’s PK is dose proportional; exposures far exceed preclinical efficacy thresholds ~ ~ 28 hours Effective half-life (T1/2) The orange line represents the efficacious exposure for tumor regression in preclinical models † Mean ARV-471 AUC24 by Dose (C1D15) ARV-471 Mean Plasma Concentration-Time P
Slide 14: ER degradation observed in patient tumor biopsies
ER degradation observed in patient tumor biopsies Baseline After treatment with 60 mg ARV-471 Red: Estrogen receptor Blue: Nuclei Green: Tumor (cytokeratin) Method: ER immunoreactivity analyzed by quantitative immunofluorescence (QIF) using the automated quantitative analysis (AQUA) method
Slide 15: ARV-471 degraded ER up to 90%
ARV-471 degraded ER up to 90% through the 120 mg dose level † ER immunoreactivity analyzed by quantitative immunofluorescence (QIF) using the automated quantitative analysis (AQUA) method. †† Derived by examining AQUA scores and visually inspecting all samples in the dataset to determine a cut-point
Slide 16: Confirmed RECIST Partial Response in a patient with extensive prior therapy
Extensive prior therapy Confirmed RECIST Partial Response (cPR) in a patient with extensive prior therapy and an ESR1 mutation at 120 mg Baseline CT Scan After 4 Cycles Target 2 Target 2 Target 1 Target 1 51% reduction in target lesions (RECIST partial response) CDK4/6 inhibitor: Palbociclib Endocri
Slide 17: Regression in chest wall lesions in a patient with extensive prior therapy
Regression in chest wall lesions in a patient with extensive prior therapy and multiple ESR1 mutations at 180 mg Baseline (Associated Bleeding) After 4 Cycles (No Bleeding) Extensive Prior therapy CDK4/6 inhibitor: Palbociclib, Abemaciclib Endocrine therapies: 3 Agents Aromatase inhibitors x 2 Fulve
Slide 18: ARV-471 demonstrates promising anti-tumor activity in late line patients
Best Percentage Target Lesion Diameter From Baseline SD SDSD SDSDPDSD (uPR)SD(uPR)PRSD CDK4/6 inhibitor Fulvestrant Investigational SERD Chemotherapy SD SD PD PD 30 mg QD 120 mg QD 180 mg QD 360 mg QD Antitumor Activity in Eligible Patients (N=14)† 0% ARV-471 demonstrates promising anti-tumor activi
Slide 19: ARV-471 achieves a high clinical benefit rate in a heavily pretreated population
Treatment Duration (weeks) Cut off for CBR CDK4/6 Inhibitor Fulvestrant Investigational SERD Chemo Prior Therapies CBR† = 42% (5/12) 30 mg QD 60 mg QD 120 mg QD 180 mg QD PD PD PD SD PD cPR SD PD SD PD SD SD (uPR) Treatment Duration (weeks) and Response in Eligible Patients (N=12)† † Excludes 8 pati
Slide 20: Comparison of ARV-471 profile with Phase 1 data for other SERDs
Comparison of ARV-471 profile with Phase 1 data for preclinical SERDs Source: H3B-6545 SABCS 2020 Poster, ZN-C5 SABCS 2020 Poster, Rintodestrant SABCS 2020, SAR439859 SABCS 2020 Poster, AZD9833 SABCS 2020 and ASCO 2020 Posters, GDC-9545 SABCS 2019 Poster. This comparison utilizes data from different
Slide 21: Characterizing ARV-471 activity across ER+/HER2- breast cancer treatment lines
We aim to characterize the activity of ARV-471 across ER+/HER2- breast cancer treatment lines † SEER database; includes US patient population only, †† E.g., everolimus or alpelisib CDK, cyclin-dependent kinases Pi3Ki; phosphoinositide 3-kinase inhibitor; mTORi: mammalian target of rapamycin inhibito
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 Best-in-Class Profile Superior degradation to fulvestrant and SERDs† Strong efficacy signal in a predominantly ER-independent population Well tolerated Clear Development Path Potential for 2L/3L approval
Slide 23: ARV-110 Clinical Data Update
ARV-110 Clinical Data Update
Slide 24: ARV-110: 40% PSA50 in a molecularly defined subgroup
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† The ongoing Phase 2 ARDENT trial is designed to confirm the potential for accelerated approv
Slide 25: Novel therapies for 2L/3L patients; unmet needs in mCRPC
Novel therapies for 2L/3L patients Non-chemo therapies for 1L patients Key Unmet Needs: Migration of second-generation AR therapies to earlier settings has created substantial unmet need for new treatments in mCRPC Castrate Sensitive (~200k) US Prostate Cancer Treatment Paradigm (# of US patients†)
Slide 26: Our strategy is to develop ARV-110 across treatment settings of prostate cancer
Castrate Sensitive (~200k) Metastatic Castrate Resistant (~40k) 1L2L3L Non-Metastatic Castrate Resistant (~9k) Our strategy is to develop ARV-110 across treatment settings of prostate cancer † SEER database; †† Tombal, Lancet Oncology 2014; ††† de Wit R, N Engl J Med. 2019; Hussain, ESMO 2019. US Pr
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 Patients treated with both abiraterone and enzalutamide 5 82% Patients with non-AR mutations 84% Patients treated with prior chemotherapy 76% Existing AR-directed therapies expected to be ineffective High
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 activity in heavily pre-treated patients with limited treatment options PSA reduction is associated with plasma exposure Activity in wild-type AR patients supports broader use
Slide 29: Exposures exceed the predicted efficacious threshold in a preclinical enzalutamide-resistant model
At 420 mg, exposures exceed the predicted efficacious threshold observed in a preclinical enzalutamide-resistant model Predicted efficacious threshold based on an enzalutamide-resistant prostate cancer model †† Predicted minimum efficacious threshold based on a standard prostate cancer model† Dose A
Slide 30: Increased ARV-110 clinical activity at higher exposures
This threshold is based on preclinical efficacy in an enzalutamide-resistant prostate cancer model This threshold is based on preclinical efficacy in a standard prostate cancer model Increased ARV-110 clinical activity at higher exposures Exposures at levels that overcame enzalutamide resistance†††
Slide 31: Genomic alterations increase over time in mCRPC
TUMOR VOLUME GENOMIC ALTERATIONS OVER TIME TREATMENT 1 TREATMENT 2 TREATMENT 3 Figure adapted from Cancers 2018, 10, 345 Treatment-refractory progression in mCRPC Genomic alterations are known to increase over time and with multiple treatments in mCRPC Genetic context, an important determinant of re
Slide 32: 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) ††† PSA50 PSA30 AR Status Amp T878A, H875Y, L702H Amp WT WT Amp Amp WT Amp W74
Slide 33: Multiple AR mutations could be a signature for continued AR dependence
Multiple AR mutations could be a "signature" for continued AR dependence PSA levels declined even in the presence of significant tumor heterogeneity, AR-V7, and L702H T878/H875 patients are a molecularly defined population for enrichment in our ongoing Phase 2 dose expansion, and represent a potenti
Slide 34: Best PSA Change In Patients with Wild-Type AR
34 Best PSA Change In Patients with Wild-Type AR (N=15)†† PSA50 PSA30 AR Status WT WT WT WT WT WT WT WT WT WT WT WT WT WT WT AR-V7††† + + + + Other Genes Altered (n)† 2 2 1 0 2 0 1 1† 0 2 1 3 0 2 0 PSA50 13% (2/15) ARV-110 is also active in refractory mCRPC patients with tumors expressing wild-type
Slide 35: Strong profile for ARDENT Phase 2 expansion trial
Strong profile for ARDENT Phase 2 expansion trial at 420 mg, oral, once daily Parameter Phase 1 Results Safety Data† P (Well tolerated; no TRAEs Gr >2) Dose Response and Exposure Threshold†† P Efficacy Data†† P Strong signal in molecularly defined patient populations P 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 † Tumors are heterogeneous, so patients may fall into multiple subgroups for post-hoc analysis. Patient Subgroup† Tumor Characteristics T878/H875 T878 and/or H875 AR mutated L
Slide 37: Future migration to earlier lines of therapy
Future migration to earlier lines of therapy, following the path of 2nd-generation AR therapies Castrate Sensitive (~200k) Metastatic Castrate Resistant (~40k) 1L2L3L Non-Metastatic Castrate Resistant (~9k) ARV-110’s planned registrational path aligns with unmet need in mCRPC, and offers potential l
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 Clear Development Path Driving tumor responses and PSA reductions in a molecularly defined, late-line mCRPC population Late-line activity suggests strong potential in CSPC Well tolerated Two potential registrational pa
Slide 39: Conclusion
Conclusion
Slide 40: Arvinas' current pipeline across oncology, I-O, and neuroscience
Arvinas’ current pipeline encompasses a range of validated and undruggable targets in oncology, I-O, and neuroscience Neuroscience Oncology / Immuno-oncology ARVN Program Research IND Enabling Phase 1 Phase 2 Exploratory Indication ARV-110mCRPC ARV-766Other AR indications AR-V7mCRPC ARV-471ER+/HER2-
Slide 41: Anticipated Milestones
Complete Phase 1 data ARDENT Phase 2 interim data Initiation of combination study(s) Full ARDENT Phase 2 data Combination study data Initiation of combination study with CDK4/6i Complete Phase 1 data Initiation of Phase 2 CDK4/6i combination study data Interim Phase 2 data BCL6 Tau Undisclosed (onco
Slide 42: We are well on our way to our 2024 vision
We are well on our way to our 2024 vision Built Arvinas’ Foundation as a Pioneer in Protein Degradation Proved the Concept of Our PROTAC Discovery Engine 2013-2018 2019-2020 Integrated biotech poised for launch Goal to have first PROTAC® degraders proven to benefit patients in registrational studies
Slide 43: Thank You
Thank You