Achillion Presents New Data on ACH-3102 to Treat Hepatitis C at the International Liver Congress

April 23, 2013

- Phase 1 Results Further Demonstrate Potency of ACH-3102 in Genotypes 1a and 1b and Against Resistant HCV-

- Study Shows ACH-3102 and Sovaprevir Can be Co-Administered Without Interaction -

- Total of Six Poster Presentations to be Made During EASL -

AMSTERDAM, The Netherlands, April 23, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN)today announced the presentation of new data demonstrating the efficacy, safety, tolerability, and combinability of ACH-3102, a second-generation, pan-genotypic NS5A inhibitor, at the 48^th Annual Meeting of the European Association for the Study of the Liver (EASL) during the International Liver Congress 2013. ACH-3102 and sovaprevir are currently in Phase II combination development for the treatment of patients with chronic Hepatitis C infection (HCV). During the upcoming poster presentations, data will be reported that demonstrates ACH-3102 achieves a reduction in HCV RNA despite the presence of resistant variants. In addition, ACH-3102 demonstrates no drug-drug interaction with sovaprevir, Achillion's second-generation protease inhibitor.

Data highlights include:

Poster No. 876: A Second Generation NS5A Inhibitor, Demonstrates Potent Antiviral Activity in Patients with Genotype 1A HCV Infection Despite the Presence of Baseline NS5A-Resistant Variants. Friday, April 26, 2013: Poster Session — Category 08c: Viral Hepatitis C: Clinical (therapy).

• Treatment naïve patients with genotype 1 chronic HCV infection, patients received a single dose of ACH-3102 at various doses (Group 1: 50 mg, n=4; 150 mg, n=4; 300 mg, n=4 or placebo, n=2) or placebo and were evaluated for baseline NS5A-resistant viral variants, which was present in the majority of patients. Based on the robust anti-viral effect observed in Group 1, a lower dose (25 mg, n=6) of ACH-3102 or placebo (n=3) was studied in Group 2.
• All tested doses of ACH-3102 were safe and well-tolerated in subjects with chronic HCV Genotype 1 infection.
• Robust, rapid and sustained suppression of plasma HCV RNA levels was observed in all doses (mean reduction of 4.04 log₁₀, 3.78 log₁₀, 3.52 log₁₀, and 3.93 log₁₀ IU/mL for 25 mg, 50 mg, 150 mg and 300 mg doses, respectively, versus reduction of 0.68 log₁₀ IU/mL for placebo). Plasma HCV RNA levels sharply declined within the first two days post-treatment, and remained lower than baseline for at least 14 days.
• ACH-3102 retains potent anti-viral activity against both wild-type and NS5A-resistant viral variants, differentiating it from first-generation NS5A inhibitors.

Poster No. 1201: No Clinically Significant Pharmacokinetic Interaction between Sovaprevir and ACH-3102 in Healthy Volunteers. Saturday, April 27, 2013. Poster Session — Category 08d: Viral Hepatitis C: Clinical (new compounds, resistance).

• In a 24-patient healthy volunteer study, there was no clinically significant pharmacokinetic interaction between ACH-3102 and sovaprevir, Achillion's 2^nd generation NS3 Protease Inhibitor (PI), when co-administered with or without food.
• Co-administration of ACH-3102 and sovaprevir was deemed safe and well-tolerated and the results support a combination Phase 2 study which is currently underway

Poster No. 1199: Findings from Clinical Virology Studies on ACH-3102 are Consistent with Preclinical Observations on its Improved Potency Against Genotype-1A HCV and Resistant Variants. Saturday, April 27, 2013: Poster Session — Category 08d: Viral Hepatitis C: Clinical (new compounds, resistance).

• Single doses of ACH-3102 at 25 mg - 300 mg have previously shown robust antiviral activity in Genotype 1a patients, with reductions in HCV RNA observed in presence of baseline mutations associated with viral resistance to NS5A inhibitors.
• These results show that ACH-3102 administered in 50 mg, 150 mg, and 300 mg doses reduced viral load by 3.98-4.60 log₁₀ IU/mL in four patients with Y93C/D/H mutation, 3.35-4.02 log₁₀ IU/mL in four patients with M28T/V mutation, and 3.40 log₁₀ IU/mL in one patient with L31M mutation.
• Also in GT-1a patients, a comparison of 1-150 NS5A versus full-length NS5A showed less than five-fold differences in their susceptibility to ACH-3102, compared with up to a greater than 358-fold differences in susceptibility to daclatasvir.
• ACH-3102 retained potency (EC₅₀0.042 nM) in GT-1b patients with pooled NS5A mutations, all of whom carried the L31M and Y93H double mutation. In contrast, daclatasvir potency was reduced 2,200-fold (EC₅₀ 22 nM).

"The high barrier to resistance observed with ACH-3102 to date continues to confirm our view that ACH-3102 is unique from other NS5As and has the promise to be a cornerstone therapy in the treatment of Hepatitis C," said Milind Deshpande, Ph.D., President of Research and Development and Chief Scientific Officer of Achillion. "The unique characteristics of ACH-3102, combined with the unique profile of our 2nd generation PI, sovaprevir, which also has a higher barrier to resistance than typical PIs, make for what we believe is a high potential combo, competitive against both current and emerging combinations."

Additional Poster Presentations at EASL:

Friday, April 26, 2013: Poster Session — Category 08c: Viral Hepatitis C: Clinical (therapy).

• Lawitz E., et al. ACH-2684 Demonstrates Potent Viral Suppression in Genotype 1 Hepatitis C Patients with and without Cirrhosis: Safety, Pharmacokinetic, and Viral Kinetic Analysis. Pres. #847.
• Agarwal A., et al. Viral Kinetics Modeling to Predict cEVR and Aid in Dose Selection Decisions for Phase 2/3 Clinical Trials. Pres. #784.

Saturday, April 27, 2013: Poster Session — Category 08d: Viral Hepatitis C: Clinical (new compounds, resistance).

• Fabrycki J., et al. Findings from Clinical Virology Studies on Sovaprevir, a Phase 2 HCV NS3A Protease Inhibitor, Indicate a High Pharmacological Barrier to Viral Resistance. Pres. #1200.

About ACH-3102

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. ACH-3102, Achillion's second generation NS5A inhibitor, has demonstrated potent activity against all HCV genotypes in vitro and in preclinical studies achieved additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, interferon and ribavirin. In preclinical studies, ACH-3102 demonstrated excellent potency, in the pico-molar range, against wild type HCV RNA replication, as well as potency against resistant mutants that have been identified in clinical studies. ACH-3102 was deemed to be safe and well-tolerated in Phase 1 development and achieved mean maximal reductions in HCV RNA of 3.78 log₁₀ after a single dose. ACH-3102 has been granted fast track designation by the FDA and is currently being evaluated in Phase 2 for the treatment of HCV.

About Sovaprevir

Sovaprevir, previously referred to as ACH-1625, is a pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. Sovaprevir is an open chain, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, sovaprevir demonstrated high potency, unique pharmacokinetic properties and an excellent safety profile at high drug exposures. Sovaprevir has rapid and extensive partitioning to the liver, as well as high liver/plasma ratios, and has shown low single-digit nanomolar potency that is specific to HCV. It is equipotent against HCV genotypes 1a and 1b at IC₅₀ of approximately 1nM. Sovaprevir is currently in Phase 2 clinical development and has shown clinical antiviral activity against genotypes 1 and 3. Fast Track status was granted to sovaprevir in 2012 for the treatment of chronic HCV.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including more than 5 million people in the United States, making HCV more than twice as widespread as HIV. Three-fourths of the global HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000 begin_of_the_skype_highlighting 1-203-624-7000 end_of_the_skype_highlighting.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the expected potency, safety, tolerability, effectiveness, combinability and other characteristics of sovaprevir and ACH-3102; and Achillion's expectations regarding timing for the commencement, completion and reporting of results of its clinical trials of both ACH-3102 in combination with ribavirin and sovaprevir in combination with ACH-3102. We may use words such as "expect," "anticipate," "project," "intend," "plan," "believe," "seek," " estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage clinical trials of sovaprevir, ACH-3102 and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2012 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

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