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NACF Investor Event Slide Deck.pptx
Transcript of NACF Investor Event Slide Deck.pptx
©2014 Vertex Pharmaceuticals Incorporated
The Science of Possibility: Reaching More CF Patients and Enhancing Benefit
NACF Conference | October 9, 2015
Jeff Leiden, M.D., Ph.D. President & CEO
Paul Negulescu, Ph.D. SVP & San Diego Site Head
Jeff Chodakewitz, M.D. EVP & Chief Medical Officer
Stuart Arbuckle EVP & Chief Commercial Officer
Ian Smith EVP & Chief Financial Officer
©2015 Vertex Pharmaceuticals Incorporated
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Safe Harbor Statement
This presentation contains forward-looking information pertaining to KALYDECO®, ORKAMBI®, the ongoing discovery, development and commercialization of Vertex’s
product candidates and the Company’s future financial performance. While the
Company believes that these forward-looking statements are accurate, these
statements are subject to risks and uncertainties that could cause actual outcomes
to differ materially from the Company’s current expectations. These risks and
uncertainties include, among others, the risk that data from the Company's
development programs may not support registration or further development of its
compounds due to safety, efficacy or other reasons, the risk that in vitro responses may not be predictive of clinical results, and the risks and uncertainties listed in the
Company’s October 8, 2015 press release and under Risk Factors in the Company’s
10-K and other filings with the SEC.
©2015 Vertex Pharmaceuticals Incorporated
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Agenda
Jeff Leiden, M.D., Ph.D., President & CEO Executing on the Strategy
Paul Negulescu, Ph.D., SVP & Site Head, San Diego Commitment to Patients: Reaching More People and Enhancing the Benefit in the Future
Jeff Chodakewitz, M.D., EVP & Chief Medical Officer Highlights from the Meeting and Our Development Programs
Stuart Arbuckle, EVP & Chief Commercial Officer Reaching More Patients Who Can Benefit Today
Q&A moderated by Ian Smith, EVP & Chief Financial Officer
©2015 Vertex Pharmaceuticals Incorporated
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2014 – 2015 ü Maximize the potential of KALYDECO ü Launch ORKAMBI ü Progress a portfolio of medicines to reach more patients with CF ü Enhance the pipeline through internal and external investments
2016 + • Significant revenues from launching multiple high-value medicines • An operating expense profile that supports earnings growth • A pipeline of transformational medicines in CF and beyond
Vertex Strategy G
row
th Build foundation for long-term growth
Sustained revenue and earnings growth
2012 – 2013 ü KALYDECO approval and launch ü Advance CF pipeline ü Invest in research outside CF
Invest to build core business
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CF Strategy and Opportunity Maintaining Leadership in CF
Add
ress
able
Cys
tic F
ibro
sis
popu
latio
n
Vertex regimens APPROVED OR SUBMITTED CLINICAL TRIALS UNDERWAY
KALYDECO (ivacaftor) ORKAMBI (lumacaftor + ivacaftor) Dual or triple combination
US
R117H & Peds G551D & Ga(ng
US Residual Fn &
EU R117H & Peds
F508del Homozygous
ages 6-11
Vast Majority of all CF patients
US F508del Homozygous
ages 12+
F508del/ Minimal Fn
Ex-US F508del Homozygous
ages 12+
Ex-US Residual Fn
Ongoing clinical trials: • Ph 3 VX-661 • Ph 3 F508del homozygous
ages 6-11 • Next-Gen Correctors
>60,000 2016 & Beyond
Today >25,000
>3,400 June 2015
>2,600 Oct 2014
©2015 Vertex Pharmaceuticals Incorporated
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3
1
Today: CF Complexity Requires Multiple Regimens Multiple CF Medicines and Combinations for Different Patient Populations
Gating Mutations
Homozygous F508del/F508del
ORKAMBI
Potentiator + VX-661 (in trials) +
Next-Gen Corrector(s) (planned)
KALYDECO Heterozygous F508del/Minimal Fn
©2015 Vertex Pharmaceuticals Incorporated
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Future: Triple Combinations Have Potential to Treat Vast Majority of CF Patients
Nonsense Mutations and others
KALYDECO Monotherapy (no F508del)
Anyone with ≥1 F508del Mutation (Next-Gen Corrector + VX-661 + ivacaftor)
Gating & Residual Fn Mutations
MAXIMIZE THE NUMBER OF PATIENTS TREATED
INCREASE THE BENEFIT FOR ALL and GOAL:
Homozygous F508del/F508del
Heterozygous F508del/Minimal Fn
©2015 Vertex Pharmaceuticals Incorporated
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Other Approaches Such as ENaC Inhibitors Could Provide Additional Benefit
ENaC inhibitor
Next-Gen Corrector + VX-661 + ivacaftor Anyone with ≥1 F508del Mutation
Gating & Residual Fn Mutations
(Next-Gen Corrector + VX-661 + ivacaftor)
MAXIMIZE THE NUMBER OF PATIENTS TREATED
INCREASE THE BENEFIT FOR ALL and GOAL:
Homozygous F508del/F508del
Heterozygous F508del/Minimal Fn
Nonsense Mutations
and others
©2015 Vertex Pharmaceuticals Incorporated
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Agenda
Jeff Leiden, M.D., Ph.D., President & CEO Executing on the Strategy
Paul Negulescu, Ph.D., SVP & Site Head, San Diego Commitment to Patients: Reaching More People and Enhancing the Benefit in the Future
Jeff Chodakewitz, M.D., EVP & Chief Medical Officer Highlights from the Meeting and Our Development Programs
Stuart Arbuckle, EVP & Chief Commercial Officer Reaching More Patients Who Can Benefit Today
Q&A moderated by Ian Smith, EVP & Chief Financial Officer
©2015 Vertex Pharmaceuticals Incorporated
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Enhancing CFTR Protein Function with Next-Gen Correctors: Expanding to Treat More Patient Groups and Enhancing Potential Benefit
Hypothesis: Any CF Patient with at least one F508del mutation should benefit
Mechanism: Next-Gen correctors act with VX-809 or VX-661 to get more CFTR protein to the cell surface
Progress: Vertex is moving 2 Next-Gen correctors, VX-152 and VX-440, into Phase 1 studies in healthy volunteers in 2015
Heterozygous F508del/Minimal Fn
Homozygous F508del/F508del
F508del/Gating F508del/Residual Fn
EXPAND ENHANCE ENHANCE
©20
15 V
erte
x P
harm
aceu
tical
s In
corp
orat
ed
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Triple Combinations Show Enhanced CFTR Function In Vitro
3 Donor Bronchi 5 Donor Bronchi
Chl
orid
e tr
ansp
ort (
%N
orm
al C
FTR
func
tion)
VX-152
Lumacaftor – – – Ivacaftor –
VX-440
80
70
60
40
20
10
30
50
VX-661
Ussing Chamber studies using bronchial epithelial cells expressing the genotypes indicated; Top of bar charts represent EC90 concentrations
ORKAMBI Untreated ORKAMBI Untreated
+++
F508del F508del
Homozygous
F508del Minimal CFTR function allele
Heterozygous
+++
+++
+++
©2015 Vertex Pharmaceuticals Incorporated
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1
2.9
2.5
0
1
2
3
4
F508del/F508del
Fold Increase in Chloride Transport Over ORKAMBI in F508del/F508del and F508del/Minimal Function HBE cells
ORKAMBI
VX-152 +VX-661
+ IVA VX-440
+VX-661 +IVA
Triple Combinations Show Enhanced CFTR Function In Vitro
Fold
incr
ease
rela
tive
to O
RK
AM
BI
Bar charts represent EC90 concentrations
1
3.3
2.8
0
1
2
3
4
F508del/Minimal Fn
ORKAMBI
VX-152 +VX-661
+ IVA VX-440
+VX-661 + IVA
©2015 Vertex Pharmaceuticals Incorporated
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Triple Combinations Show Enhanced Cilia Beat Frequency in HBE Cells In Vitro
©2015 Vertex Pharmaceuticals Incorporated
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In epithelial cells • CFTR transports chloride ions out
• ENaC transports sodium ions in
• Balance between CFTR and ENaC activity regulates hydration of the airway surface
In Vitro, Inhibiting ENaC Shows Potential to Amplify Effect of CFTR Modulators in the Lung
Lung Epithelial Cell
Cl-
Na+
H20
CFTR ENaC
©2015 Vertex Pharmaceuticals Incorporated
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VX-371 Significantly Amplified Cilia Beat Frequency in F508del Homozygous HBE Cells In Vitro
0.3
1
2
0
1
2
3
VX-371 ORKAMBI ORKAMBI + VX-371
F508del/F508del – HBE Cells (Fold increase in cilia beat frequency @ 72 hours in vitro)
Fold
incr
ease
rela
tive
to O
RK
AM
BI
F508del F508del
Homozygous
©2015 Vertex Pharmaceuticals Incorporated
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Research Activity Supports Our Pipeline Progression
• Two next-gen CFTR correctors advancing into the clinic in 2015 with potential to extend treatment to all CF patients with the F508del mutation
• ENaC blocker VX-371 (P-1037) increases cilia beating and airway surface liquid when combined with CFTR modulation in F508del homozygous airway cells
• Vertex is continuing internal research to identify additional correctors
©2015 Vertex Pharmaceuticals Incorporated
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Agenda
Jeff Leiden, M.D., Ph.D., President & CEO Executing on the Strategy
Paul Negulescu, Ph.D., SVP & Site Head, San Diego Commitment to Patients: Reaching More People and Enhancing the Benefit in the Future
Jeff Chodakewitz, M.D., EVP & Chief Medical Officer Highlights from the Meeting and Our Development Programs
Stuart Arbuckle, EVP & Chief Commercial Officer Reaching More Patients Who Can Benefit Today
Q&A moderated by Ian Smith, EVP & Chief Financial Officer
©2015 Vertex Pharmaceuticals Incorporated
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Development Plans for VX-152 and VX-440 and Triple Combinations
Results and regulatory input
Phase 2 Triple combination
Phase 1 Monotherapy and triple combination
Healthy volunteers Multiple CF patient groups, including F508del/minimal function
Single and multiple doses up to 14 days
Up to 28 days treatment duration
Initiate Nov 2015 Anticipated 2H 2016 Initiation
©2015 Vertex Pharmaceuticals Incorporated
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VX-371 (P-1037) Phase 2 Development Plan
VX-371 vs. Saline
ANY CFTR MUTATION 120 patients, Age 12+
14 Days
Follow-up
F508DEL HOMOZYGOUS PATIENTS 150 Patients, Age 12+
ORKAMBI + VX-371 vs. ORKAMBI alone
28 Days, Crossover Design
Follow-up
Data anticipated mid-2016
• Safety • Absolute change
in ppFEV1
Key Outcome Measures Recruiting (conducted by Parion)
Starting in 2016 (conducted by Vertex) • Safety • Absolute change
in ppFEV1
• Other exploratory measures
Key Outcome Measures
Vertex plans to explore ENaC inhibition in several other pulmonary indications
©2015 Vertex Pharmaceuticals Incorporated
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VX-661 + Ivacaftor: Potential to Treat Multiple CF Patient Groups
Phase 3 studies are evaluating efficacy and safety in CF patients 12 and older across 4 groups:
F508del/F508del “homozygous” ~500 patients, 6 months of treatment vs. placebo
F508del/Gating ~200 patients, 8 weeks of treatment vs. ivacaftor
F508del/Residual function ~300 patients, 8 weeks of treatment, crossover design
F508del/minimal function “heterozygous” Initially enroll ~150 patients for 12 weeks of treatment, Potential expansion to 300 patients based on futility analysis
Studies expected to complete enrollment in mid-2016* * Expect to complete enrollment by mid-2016 in first three studies, and in first part of fourth (F508del/Min Fn) study
©2015 Vertex Pharmaceuticals Incorporated
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KALYDECO sNDA Submission for Residual Function Accepted for Priority Review
sNDA for use of KALYDECO in people with CF ages 2+ who have one of 23 Residual Function mutations accepted for Priority Review by FDA
• KALYDECO currently approved in US to treat patients as young as 2 years old with one of 10 mutations*
• sNDA based on:
o Preclinical data for ivacaftor in the 23 residual function mutations
o The established clinical profile of KALYDECO, and
o Previously reported data from an exploratory Phase 2a study
• >1,500 people in the US have one of these mutations; PDUFA date of February 6
* G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H
©2015 Vertex Pharmaceuticals Incorporated
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Key Clinical Goal: Understand Value of Starting Treatment Early
• KALYDECO approved in US to treat patients as young as 2 years old with one of 10 mutations*
• Initiating study in 1Q16 to evaluate the safety of treating infants and toddlers <24 months
KALYDECO
ORKAMBI
• ORKAMBI approved in US to treat patients who are F508del homozygous as young as 12 years old
• Studies ongoing to evaluate the safety and efficacy of treating F508del homozygous patients age 6 – 11
• Planning a study to evaluate the safety of treating ages 2 – 5
CLINICAL DEVELOPMENT PLANS
* G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H
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17 Data Presentations at NACFC
HIGHLIGHTS
Long-Term Safety Data on Ivacaftor Treatment • Annual risk of death, organ transplantation, hospitalization and frequency of pulmonary exacerbation
were all significantly lower in the ivacaftor group compared to matched controls from the CF Patient Registry (Poster #246)
Rate of Lung Function Decline Not Associated with Acute Improvements in ppFEV1 in PERSIST Study • Results indicate that KALYDECO produces separate and independent effects on lung function: acute
improvement in ppFEV1, and a reduction in the rate of ppFEV1 decline (Poster #221)
Reduction in Pulmonary Exacerbations in Traffic and Transport Studies Not Correlated to Acute Improvements in Lung Function • ORKAMBI pulmonary exacerbation benefit was independent of the acute change in lung function at Day
15 (Poster #241)
Improvements in Lung Function, Pulmonary Exacerbations and BMI Observed Across Sub-Groups in TRAFFIC and TRANSPORT Studies, Regardless of Baseline Lung Function • Efficacy and safety of ORKAMBI were generally similar across lung function subgroups (Poster #245)
The effects of CFTR modulators on treating the underlying cause of disease can be measured in multiple ways
©2015 Vertex Pharmaceuticals Incorporated
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Agenda
Jeff Leiden, M.D., Ph.D., President & CEO Executing on the Strategy
Paul Negulescu, Ph.D., SVP & Site Head, San Diego Commitment to Patients: Reaching More People and Enhancing the Benefit in the Future
Jeff Chodakewitz, M.D., EVP & Chief Medical Officer Highlights from the Meeting and Our Development Programs
Stuart Arbuckle, EVP & Chief Commercial Officer Reaching More Patients Who Can Benefit Today
Q&A moderated by Ian Smith, EVP & Chief Financial Officer
25
CF Strategy and Opportunity Maintaining Leadership in CF
Add
ress
able
Cys
tic F
ibro
sis
popu
latio
n
Vertex regimens APPROVED OR SUBMITTED CLINICAL TRIALS UNDERWAY
KALYDECO (ivacaftor) ORKAMBI (lumacaftor + ivacaftor) Dual or triple combination
US
R117H & Peds G551D & Ga(ng
US Residual Fn &
EU R117H & Peds
F508del Homozygous
ages 6-11
Vast Majority of all CF patients
US F508del Homozygous
ages 12+
F508del/ Minimal Fn
Ex-US F508del Homozygous
ages 12+
Ex-US Residual Fn
Ongoing clinical trials: • Ph 3 VX-661 • Ph 3 F508del homozygous
ages 6-11 • Next-Gen Correctors
>60,000 2016 & Beyond
Today >25,000
>3,400 June 2015
>2,600 Oct 2014
©2015 Vertex Pharmaceuticals Incorporated
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KALYDECO Reaching More Patients Based on Geographic and Label Expansion
US: • Patients ages 2+ with Gating mutations*
• R117H (approved Dec 2014)
Ex-US: • Strong Australian uptake in Gating patients
following reimbursement in late 2014 • International reimbursement approval for
non-G551D Gating mutations received in Italy, France, UK and the Netherlands during 2Q15
• R117H (ages 18+) and G551D/Gating (ages 2-5) CHMP positive opinion received Sept 2015
o Marketing Authorization expected in EU in 4Q15
Our goal is to provide access to KALYDECO as quickly as possible for patients who may benefit
Approval of the Residual Function sNDA in the US for ages 2+ could potentially benefit >1,500 additional patients
* G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R
©2015 Vertex Pharmaceuticals Incorporated
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ORKAMBI Has Potential to Benefit Many More People with CF Homozygous for F508del
• US FDA approval received July 2 for patients ages 12+ who are homozygous for the F508del mutation
• EU MAA decision expected in 4Q15
o CHMP Positive Opinion in Sep
o Country-by-country reimbursement discussions to follow
• Planned sNDA submission for ages 6-11 in US in 2016
~5,500 6-11 in US + EU
~12,000 12+ in EU
~8,500 12+ in US
©2015 Vertex Pharmaceuticals Incorporated
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2014 – 2015 ü Maximize the potential of KALYDECO ü Launch ORKAMBI ü Progress a portfolio of medicines to reach more patients with CF ü Enhance the pipeline through internal and external investments
2016 + • Significant revenues from launching multiple high-value medicines • An operating expense profile that supports earnings growth • A pipeline of transformational medicines in CF and beyond
Vertex Strategy G
row
th Build foundation for long-term growth
Sustained revenue and earnings growth
2012 – 2013 ü KALYDECO approval and launch ü Advance CF pipeline ü Invest in research outside CF
Invest to build core business