ACHN_30%20May%202013(2)

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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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