ACHN_30%20May%202013(2)
Achillion Pipeline Update
May 30, 2013
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Forward-Looking Statements
This presentation includes forward-looking statements about Achillion Pharmaceuticals, Inc.
and its business, including, without limitation, statements regarding drug discovery, clinical
development, regulatory approval processes, market opportunities, intellectual property,
competition, and financial results. All statements other than statements relating to historical
matters (including statements to the effect that we “believe,” “expect,” “anticipate,” “plan,”
“target,” “intend” and similar expressions) should be considered forward-looking statements.
These forward looking statements are subject to risks and uncertainties that may cause
actual events or results to differ materially from our current expectations. These risks and
uncertainties are detailed in the "Risk Factors" section of our annual report on Form 10-K for
the year ended December 31, 2012, which was filed with the SEC on February 20, 2013.
All forward-looking statements contained in this presentation speak only as of the date
hereof, and we undertake no obligation to update any of these statements, except as
required by law.
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Experienced Management Team
Milind Deshpande, Ph.D.
President, Chief Executive Officer
Gautam Shah, Ph.D.
EVP, Chief Regulatory Officer
Mary Kay Fenton
SVP, Chief Financial Officer
Joseph Truitt
SVP, Chief Commercial Officer
David Apelian, MD., Ph.D.
EVP, Chief Medical Officer
TICE Life Sciences
Built on more than 130 years of health science experience.
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Achillion Pharmaceuticals
HCV Development Portfolio Snapshot
Focused on developing best-in-class compounds and combinations
to form cornerstones of future DAA combinations
Discovery
NS3 Protease Inhibitor Program
Sovaprevir (ACH-1625)
ACH-2684
2 nd Gen NS5A Inhibitor Program
ACH-3102
NS5B Polymerase Program
ACH-3422
Combination Development Program
Sovaprevir / ACH-3102 ± rbv
Preclinical Phase 1 Phase 2
Phase 3
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HCV Therapeutics: Target Profiles
Sovaprevir ACH-3102
ACH-3422
Mechanism of Action NS3 Protease Inhibitor NS5A Inhibitor NS5B Polymerase Inhibitor
Genotype coverage GT 1 - 6 GT 1 - 6 GT 1 - 6
Barrier to resistance
No emergence of ontreatment
PI resistant
mutations seen to date
Higher barrier to
resistance
High barrier to resistance
Combination with DAAs Additive to synergistic Additive to synergistic Additive to synergistic
Safety High safety margins High safety margins
Efficacy (monotherapy) >3 log 10 drop
>3 log 10 drop
(picomolar potency)
Safe through 14-day
animal studies to date
Dosing schedule QD without boosting QD QD
Safety and tolerability
Superior to
1st-generation PIs
Superior to
1st-generation PIs
Abbreviations: DAA, direct-acting antiviral; GT, HCV genotype; PI, protease inhibitor; QD, once daily.
TBD
TBD
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Sovaprevir + ACH-3102
Phase 2: Combination Development Program
2013 2014
1Q 2Q 3Q 4Q 1Q 2Q 3Q
• All trials evaluating
sovaprevir and ACH-3102
• Phase 2 program will have
treated over 400 patients by
3Q14
007- IIa
Gt 1a/b treatment-naïve
(n = 30-50)
No rbv 8/12 wk
(n = TBD)
• First study results expected in
summer 2013
Graphical representation.
Does not indicate specific dates within each quarter
Apollo-C IIb Trial
Worldwide (+rbv)
Gt 1a/b tx-naïve
(n = ~200)
HIV co-infected trial
Gt 1a/b treatment-naïve
(n = TBD)
Non-genotype 1 trial
Gt 2, 3, 4 treatment-naïve
(n = TBD)
Cirrhotic Trial
Compensated cirrhosis
(n = TBD)
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Sovaprevir + ACH-3102 +/- RBV
Phase 2a: -007 Study Overview
Segment 1
Segment 2
RVR EOT
Treatment naive, GT1
N = 15 (10 active/5 placebo)
Sovaprevir (200) + 3102 (150/50) + RBV
Treatment naive, GT1
N = 15 (10 active/5 placebo)
Sovaprevir (400) + 3102 (150/50) + RBV
Treatment naive, GT1
N = TBD
Sovaprevir (TBD) + 3102 (TBD) + RBV
Follow-up
Week 0 Week 4
Week 12
Week 24
• Randomized, double-blind, placebo-controlled, GT1a/1b balanced
• Determine efficacy including RVR, ETR and SVR
• WW study being conducted in the US, Canada, Australia, and NZ
• RVR results anticipated during 3Q13 and SVR during 4Q13
SVR 4
Follow-up
Follow-up
SVR 12
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NS5B Polymerase Inhibitor
ACH-3422
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ACH-3422
NS5B Polymerase Nucleotide Inhibitor
• ACH-3422 is a nucleotide prodrug of uridine analog
• Virology
– Specific for HCV polymerase
– Highly potent (EC 50 : GT 1a 65nM, GT 1b 50 nM, GT 2a 85 nM)
– Highly specific for HCV
– Pan-genotypic activity with a high barrier to resistance
• PK and Metabolism
– Rapid conversion of prodrug to monophosphate in microsomes and
in hepatocytes
– PK profiles suggests once-daily (QD) dosing
• Safety
– 14-day animal tox completed
– High exposure of triphosphate in liver
– No significant findings at the highest dose tested
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ACH-3422
Preclinical Profile
• Potent anti-HCV activity
Inhibitor EC 50 (uM)
• Specific for inhibition of HCV
• Moderate shift in EC 50 in presence of S282T mutation
in NS5B polymerase
– ACH-3422: 5.7-fold shift
– Sofosbuvir: 7.6-fold shift
GT-1b GT-1a GT-2a (JFH-1)
ACH-3422 0.05 0.065 0.085
Sofosbuvir 0.15 0.24 0.091
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ACH-3422
Preclinical Profile
• Rapid conversion of prodrug to monophosphate in
microsomes and in hepatocytes
• Conversion of ACH-3422 to corresponding
triphosphate is comparable to the conversion of
sofosbuvir to triphosphate
– Human hepatocytes/24 h incubation
Inhibitor Parent
Triphosphate
(uM)
Triphosphate
(% of 20uM dose)
ACH-3422 ND 5.15 26
Sofosbuvir ND 5.84 29
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ACH-3422
Preclinical Profile
• Potent in vitro NS5B polymerase inhibition
• Minimal in vitro cytotoxicity
Inhibitor
Inhibitor
IC 50 (uM)
[ 32 P]-CTP [ 32 P]-UTP
ACH-3422-TP 1.15 1.45
Sofosbuvir-TP 1.58 1.11
CC 50 (uM)
HeLa HepG2 Huh-7 CEMss Hepatocytes
(rat)
Hepatocytes
(monkey)
ACH-3422 >50 13.6 32 52 48 88
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Capitalization and Liquidity
Balance Sheet Metrics As of 3/31/2013
Cash and equivalents $200.9 million
Debt obligations $0.6 million
Shares outstanding 96.6 million
Top 5 Shareholders *
Fidelity Management & Research 13.2 million (13%)
QVT Funds 11 million (11%)
Domain Partners 5.8 million (6%)
BlackRock Fund Advisors 5.1 million (5%)
Vanguard Group 4.0 million (4%)
* Based upon most recent SEC filings and confirmed positions
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HCV Development Strategy
• Strategic portfolio that aims to provide optimal
outcomes and treatment duration for all HCV patients
• -007 sova/ACH-3102/rbv 12-wk combination trial for
GT 1 ongoing with interim results anticipated 3Q13
• Modifying existing studies in order to evaluate 8-wk
and 12-wk treatment regimens without rbv expected
to begin summer 2013
• Continue to accelerate development program with
keen focus on initiating Phase 3 in 2H 2014
• Advancing nucleotide NS5B polymerase inhibitor
toward IND 1Q14
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Achillion Pharmaceuticals, Inc.
NASDAQ: ACHN
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