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