Achillion discloses additional data on HCV protease inhibitor ACH-2684

Posted on 5/21/12 via MarketWatch.com. Look what happens when I go away for a week. The CDC changes it's guidelines to include one-time HCV testing for Baby Boomers (FYI, HCV drug developers had a hand in shaping this shift in public policy via the Viral Hepatitis Action Coalition for all you fans of government-corporate relationships) and Achillion continues to shore up their pipeline with decent drugs. OK, so a 3.73 log10 drop isn't exactly Telaprevir-like, but given the right backbone regimen - hopefully one also developed and manufactured by this currently unpartnered company - Achillion could hit it big. 

Achillion Announces Additional Proof-of-Concept Data With ACH-2684 for the Treatment of Hepatitis C

Achieves Up to 3.73 log10 Reduction in Genotype 1 HCV RNA After Three Days of Treatment With Once-Daily 400 mg ACH-2684 in Phase 1b Study

NEW HAVEN, Conn., May 21, 2012 (GlobeNewswire via COMTEX) -- Achillion Pharmaceuticals, Inc. ACHN +10.92% today reported proof-of-concept data from a Phase 1b clinical trial demonstrating that patients with chronic hepatitis C (HCV) genotype 1 (GT 1) treated with ACH-2684, a second-generation protease inhibitor, achieved a mean maximum 3.73 log10 reduction in HCV RNA after three-day 400 mg monotherapy with once-daily (QD) dosing. The compound also demonstrated good safety and tolerability both in healthy volunteers and in patients with HCV.

"We believe ACH-2684, with its potent antiviral activity achieved without boosting and once-daily dosing, is one of the most intriguing protease inhibitors in clinical development for the treatment of HCV," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "As we continue to focus our efforts on advancing our internally developed all-oral, interferon-free HCV regimen consisting of ACH-1625, our next generation protease inhibitor, in combination with ACH-3102, a second generation pan-genotypic NS5A inhibitor, we believe that the profile of ACH-2684 provides a significant strategic and therapeutic option for potential combinations with either ACH-3102 or other direct-acting antiviral agents."

ACH-2684 Phase 1 Clinical Trial

Achillion is evaluating ACH-2684 in a Phase 1 randomized, double-blind, placebo-controlled clinical trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity in healthy subjects and HCV-infected patients. The trial consists of three segments: Phase 1a assessment of single ascending oral doses (SAD) in healthy volunteers, Phase 1a 14-day multiple ascending doses segment (MAD) in healthy volunteers, and Phase 1b evaluation of three days of oral repeat doses in subjects with GT 1 or 3 HCV. The MAD segment of this trial will be initiated during the second quarter and full trial results are expected to be presented at a medical meeting in the fourth quarter of 2012.

During the oral repeat doses segment in subjects infected with GT 1 HCV, a total of 30 patients were enrolled including 6 patients receiving placebo and 24 patients treated with three doses of 100 mg once daily (n=8), 400 mg once daily (n=8), or 400 mg twice daily (n=8) of ACH-2684. No serious adverse events (SAE) were reported and there were no patient discontinuations during treatment. The mean maximum GT 1 HCV RNA decline during therapy for the 100 mg QD, 400 mg QD, and 400 mg BID groups were 3.36 log10, 3.73 log10, and 4.16 log10, respectively, compared to a 0.68 log10 decline for patients receiving placebo. There were no viral breakthroughs observed during ACH-2684 monotherapy. Additional assessments of GT 3 activity are currently under development.

Safety data from the SAD and HCV-infected segments of the trial demonstrated ACH-2684 was well tolerated at all doses evaluated up to and including the maximum total daily dose of 1400 mg. There were no serious adverse events, no clinically significant changes in vital signs, electrocardiograms (ECGs), or laboratory evaluations. All reported adverse events were classified as mild or moderate, and were transient in nature. Dosing in the 14-day MAD segment is being initiated during the second quarter with longer term safety data expected to be available in the third quarter of 2012.

About ACH-2684

ACH-2684 is a next-generation HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-2684 is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and safety profile at high drug exposures. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. ACH-2684 has shown pico-molar potency against NS3 protease that is specific to HCV. It has preclinical activity against the 6 known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 pico-molar. The drug candidate was discovered internally and is being advanced by Achillion.

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, more than twice as widespread as HIV. Three-fourths of the 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.

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 potency, safety, tolerability, effectiveness and other characteristics of Achillion's ACH-2684, ACH-1625 and ACH-3102; Achillion's expectations regarding timing for the commencement, completion and reporting of results of clinical trials of drug candidates including ACH-2684, ACH-1625 and ACH-3102; and Achillion's ability to advance a potentially best-in-class all-oral, interferon-free combination of ACH-1625 and ACH-3102 and ACH-2684 in combination with ACH-3102 or other direct acting antiviral agents. Among the 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 nonclinical studies and clinical trials of ACH-2684, ACH-1625 and ACH-3102; 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, 2011 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 obligation to update any forward-looking statement, except as required by applicable law.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Achillion Pharmaceuticals, Inc.



        CONTACT: Company Contact:
        Glenn Schulman
        Achillion Pharmaceuticals, Inc.
        Tel. (203) 624-7000
        gschulman@achillion.com
        Investors:
        Mary Kay Fenton
        Achillion Pharmaceuticals, Inc.
        Tel. (203) 624-7000
        mfenton@achillion.com
        Media:
        Christin Culotta Miller
        Ogilvy PR
        Tel. (212) 880-5264
        Christin.Miller@Ogilvy.com

Achillion Pharmaceuticals updates investors on HCV protease inhibitor portfolio...

From RTT News: Short blurb on Achillion's HCV protease inhibitor portfolio - ACH-1625 and ACH-2684

Achillion Pharmaceuticals (ACHN) Rose Above Resistance At The Highs
1/10/2012 6:51 AM ET

(RTTNews) - Achillion Pharmaceuticals (ACHN: News ) reported new clinical trial results on its portfolio of protease inhibitors Monday morning. Based upon the results, the company is planning further exploration of ACH-1625 in combination with other oral antiviral agents for the treatment of all HCV genotypes and continues to evaluate ACH-2684 in a Phase 1 clinical trial.

Achillion Pharmaceuticals gapped open higher Monday and climbed further around the middle of the afternoon. The stock finished up by 1.80 at $9.72, with volume at a 6-month high. Achillion broke out of a 2 1/2 week range and set a new high for the year.

Achillion Pharmaceuticals ACH-2684 HCV Pan-Genotype HCV Protease inhibitors goes into the clinic...

Achillion Pharmaceuticals announces first-in-human trials of it's own ACH-2684 HCV protease inhibitor. This is a phase 1 trial designed to study the safety, tolerability, pharmacokinetic profile and antiviral activity of the drug in up to 78 healthy volunteers and up to 40 HCV-infected, genotype 1 & 3 patients. ACH-2684 is said to be active against all six genotypes and offers once-daily dosing


First-in-Human Trial Will Evaluate Safety of Pan-Genotypic Protease Inhibitor in Both Healthy Subjects and Genotype 1 or 3 HCV-Infected Patients


NEW HAVEN, Conn., May 25, 2011 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN), a leader in the discovery and development of small molecule drugs to combat the most challenging infectious diseases, today announced that the Company has begun dosing in a Phase 1 clinical trial of ACH-2684, a novel pan-genotypic protease inhibitor being developed for the treatment of chronic hepatitis C virus (HCV) infection.

The Phase 1 clinical study is a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, pharmacokinetic profile and antiviral activity of ACH-2684. The trial consists of three segments including assessment of single ascending oral doses in healthy volunteers, a 14 day multiple ascending doses segment in healthy volunteers, and evaluation of 3 days of oral ascending repeat doses in subjects with either genotype 1 or genotype 3 hepatitis C infection. The trial will take place in the United States and is designed to enroll up to 78 healthy volunteers and up to 40 HCV-infected patients.

"This first-in-human clinical trial will be instrumental in establishing the safety profile of ACH-2684 in humans," stated Elizabeth A. Olek, D.O., Vice President and Chief Medical Officer of Achillion. "It will also provide Achillion with important preliminary efficacy data against HCV genotypes 1 and 3, and help us to select doses for subsequent clinical development."

"We are very excited to take ACH-2684 into the clinic and advance what we hope will be a unique pan-genotypic, once-daily protease inhibitor," said Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "Furthermore, we expect to shortly launch the 12-week segment of the Phase 2 trial of our lead ACH-1625 protease inhibitor, as well as a Phase 1 trial of our ACH-2928 NS5A inhibitor. We believe we remain poised to deliver a trio of important HCV clinical milestones near the end of this year, namely, 12-week EVR results on ACH-1625 and human proof-of-concept data on both ACH-2684 and ACH-2928. These are all important components in our ultimate strategy of becoming a leader in the development of HCV combination therapies involving our protease and NS5A inhibitors."

About ACH-2684

ACH-2684 is a pan-genotypic HCV protease inhibitor designed and synthesized based on crystal structures of enzyme/inhibitor complex. ACH-2684 is a macro-cyclic, non-covalent, reversible inhibitor of NS3 protease. In preclinical studies, ACH-2684 demonstrated pico-molar potency, excellent pharmacokinetic properties and safety profile at high drug exposures. ACH-2684 also exhibits rapid and extensive partitioning to the liver, as well as high liver/plasma ratios in preclinical studies. ACH-2684 has shown pico-molar potency against NS3 protease that is specific to HCV. It is active against the 6 known genotypes of HCV and exhibits equipotent activity against HCV genotypes 1a and 1b at an IC50 of approximately 100 picomolar. The drug candidate was discovered internally and is being advanced by Achillion.

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 and The American Association of Liver Disease estimates that up to 80% of individuals become chronically infected following exposure to the virus. If left untreated, chronic hepatitis can lead to permanent liver damage, which 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 hepatitis C and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

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 factors, including statements with respect to the potency, safety and other characteristics of ACH-2684, which may not be duplicated in clinical studies and Achillion's expectations regarding timing and duration of clinical trials and reporting of results from clinical trials of ACH-1625, ACH-2684 and ACH-2928. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are: uncertainties relating to results of clinical trials, unexpected regulatory actions or delays, and Achillion's ability to obtain additional funding required to conduct its research, development and commercialization activities. 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, 2010.

All forward-looking statements reflect Achillion's expectations only as of the date of this release and should not be relied upon as reflecting Achillion's views, expectations or beliefs at any date subsequent to the date of this release. Achillion anticipates that subsequent events and developments may cause these views, expectations and beliefs to change. However, while Achillion may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so.

CONTACT: Company Contact:

Glenn Schulman

Achillion Pharmaceuticals, Inc.

Tel. (203) 752-5510

gschulman@achillion.com



Investors:

Mary Kay Fenton

Achillion Pharmaceuticals, Inc.

Tel. (203) 624-7000

mfenton@achillion.com



Media:

Christin Culotta Miller

Ogilvy PR

Tel. (646) 229-5178

christin.miller@ogilvypr.com

Achillion to Raise $50M in Stock Offering for HCV Studies

BioWorld Today - Aug. 20, 2010

Financings Roundup

Achillion Pharmaceuticals Inc. plans to raise about $50 million through the sale of stock and warrants to a select group of investors, money that would be used to advance the company's early stage pipeline of drug candidates for hepatitis C virus (HCV).

At the end of June, the New Haven, Conn.-based company had $20 million in cash resources. With the added funds from the financing, which is expected to close Aug. 20, Achillion hopes to extend its cash through most of 2012.

The financing is intended to take the company's ACH-1625 protease inhibitor to the completion of Phase IIa testing, explained Mary Kay Fenton, Achillion's vice president and chief financial officer.

The Phase II study, which is expected to get under way next month, will have a 28-day segment that is targeted to report data in March 2011 and a 12-week segment that is slated to report results at the end of next year.

"We believe this financing will get us through both of those milestones," Fenton told BioWorld Today.

In addition, Achillion hopes to move its preclinical candidates, ACH-2684, a pan-genotypic protease inhibitor, and ACH 2928, an NS5A inhibitor, through Phase I testing in 2011 . The company also plans to put those candidates in combination studies in 2012 with other HCV assets in development, Fenton said.

ACH-1625, while it has shown promising data in Phase Ib studies, is far behind the front runners in the crowded HCV space. Both Vertex Pharmaceuticals Inc. and Merck & Co. Inc. have their own HCV candidates in Phase III, protease inhibitors telaprevir and boceprevir, respectively. Analysts view both drugs as approvable.

The current standard therapy for HCV is a combination of ribavirin and a pegylated interferon. There are no protease inhibitors currently approved for the infection.

Achillion believes its protease inhibitor, though still in early testing, may stand apart from the others because of its safety and tolerability and sustained viral suppression.

"Based on the early Phase Ib data, we view ACH-1625 as a very promising HCV protease inhibitor in early development," Cowen & Co. analyst Phil Nadeau stated in a research note. He added, "We believe the risk/reward of owning ACHN shares at current levels is highly favorable."

In several dosing cohorts, study patients infected with HCV were dosed for five days and showed a mean maximum drop in viral load of between 3.63 and 4.25 logs. All dosing cohorts also showed a sustained viral suppression in HCV-infected subjects, even after dosing was completed.

"This observation could be an important distinguishing feature and competitive advantage for our compound in comparison to other HCV therapies," Elizabeth Olek, vice president and chief medical officer, said in a Thursday conference call.

A select group of investors, namely venture firms Domain Associates, Clarus ventures, Quaker BioVentures and Pappas Ventures, have agreed to purchase Achillion's stock and warrants in the private placement offering.

While the company's focus is HCV, it also has an HIV candidate elvucitabine, an L-cytosine nucleoside analogue reverse transcriptase inhibitor. Earlier this year, Achillion reported 96-week data showing that the drug had a substantial antiviral effect similar to 3TC (lamivudine, GlaxoSmithKline plc), with 95 percent of patients in the elvucitabine-treated group achieving undetectable viral load compared with 93 percent in the 3TC group.

Achillion is offering 19,755, 101 shares of common stock at a price of $2.49 per share, its consolidated closing bid price reported by NASDAQ Aug. 17.

The warrants to purchase 0.35 shares of common stock for each share of common stock are priced at $0. 125 per warrant share. The warrants, which have a seven-year term from the date of issuance, represent the right to acquire an aggregate of 6,921 ,285 shares of common stock and will be exercisable at a price of $3. 1125 per share.

Shares in Achillion (NASDAQ:ACHN) lost 1 cent, closing at $2.60 Thursday.

Here they grow again: Achillion adds NS5A Inhibitor ACH-2928 to growing stable of anti-HCV candidate compounds

Achillion Pharmaceuticals Announces Nomination of NS5A Inhibitor as a Lead Clinical Candidate for Treatmentof HCV

ACH-2928 Demonstrates Excellent Potency Against HCV RNA Replication, Holds Potential for Combination Therapy

NEW HAVEN, Conn., Jul 22, 2010 (GlobeNewswire via COMTEX News Network) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN), a leader in the discovery and development of treatments for the most challenging infectious diseases, today announced the nomination of a lead clinical candidate in its fourth proprietary program against hepatitis C virus (HCV) infection. The candidate, ACH-2928, is an NS5A inhibitor that in preclinical studies has demonstrated excellent potency against HCV RNA replication, as well as good pharmacokinetic and safety profiles.

"The overall profile of ACH-2928 demonstrates that it is highly active and retains potency against HCV genotypes 1a and 1b, as well as across other genotypes. The compound's high potency, in the picomolar range, and its favorable pharmacokinetic properties strongly suggest once-daily dosing," said Milind S. Deshpande, Ph.D., Executive Vice President and Chief Scientific Officer of Achillion. "Importantly, we believe ACH-2928 is highly effective in combination with NS3 protease inhibitors, NS5B polymerase inhibitors, interferon and ribavirin."

Michael D. Kishbauch, Achillion's President and CEO, stated, "The nomination of this novel NS5A clinical candidate is both exciting and significant. The treatment paradigm for HCV is moving toward combination therapies, and we are now poised to pursue our own combination therapies, putting ACH-2928 together with our highly potent protease inhibitors, ACH-1625 and ACH-2684. The development of our fourth proprietary HCV program underscores the depth of our robust drug discovery expertise in this important therapeutic area. We have initiated IND-enabling testing of ACH-2928, and plan to initiate combination treatment in 2011."

"The nomination of ACH-2928 is further evidence of our expertise in HCV drug discovery and structure-based design. We continue to build discrete intellectual property estates to which we retain all commercial rights," concluded Kishbauch.