www.hivandhepatitis.com

Two New Nucleotide HCV Polymerase Inhibitors Enter Clinical Trials

A pair of hepatitis C virus (HCV) nucleotide analog NS5B polymerase inhibitors, ALS-2200 and ALS-2158, are now entering Phase 1 human trials, according to a recent announcement.

The candidates were discovered by Alios BioPharma and are being jointly developed with Vertex. The 2 new trials will evaluate the safety of the compounds in healthy volunteers before progressing to people with genotype 1 chronic hepatitis C. Ultimately the companies are aiming for all-oral regimens that may include telaprevir (Incivek) or the investigational non-nucleoside polymerase inhibitor VX-222.

Below is an edited excerpt from an Alios/Vertex press release describing the trials.

Vertex and Alios BioPharma Begin Clinical Studies of Nucleotide Drug Candidates ALS-2200 and ALS-2158 for the Treatment of Hepatitis C

• Studies to evaluate safety and effects on viral kinetics in people with chronic genotype 1 hepatitis C
• Data expected in second quarter of 2012 could enable initiation of interferon-free, nucleotide-based combination studies in the second half of 2012

Cambridge, Mass. -- (BUSINESS WIRE) -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) andAlios BioPharma, Inc.today announced the initiation of two clinical studies for the nucleotide analogues ALS-2200 and ALS-2158, which are inhibitors of the hepatitis C NS5B polymerase. The studies will evaluate the safety and tolerability of ALS-2200 and ALS-2158 in healthy volunteers followed by a seven-day evaluation to observe the effects on viral kinetics in people with chronic genotype 1 hepatitis C.

Data are expected in the second quarter of 2012, which could enable the initiation of studies to evaluate multiple all-oral, interferon-free combination regimens for chronic hepatitis C in the second half of 2012. Vertex has worldwide development and commercialization rights for ALS-2200 and ALS-2158, which were discovered by Alios BioPharma. Alios and Vertex are jointly conducting the Phase 1 studies announced today.

"These studies are an important step in our ongoing efforts to strengthen our leadership position in hepatitis C by developing all-oral regimens that could further improve the future treatment of this disease," said Peter Mueller, PhD, Executive Vice President, Global Research and Development, and Chief Scientific Officer for Vertex. "The studies of ALS-2200 and ALS-2158 announced today are designed to generate data that may provide the opportunity to rapidly advance into Phase 2 development where we could evaluate a number of nucleotide-based regimens beginning in the second half of next year, including regimens with Incivek or VX-222."

Study Design

The two Phase 1 studies announced today will be randomized, double-blind, placebo-controlled studies. The primary goals are to evaluate the safety and tolerability of single ascending doses of ALS-2200 and ALS-2158 in healthy volunteers and of multiple ascending doses in people with chronic genotype 1 hepatitis C. A secondary objective will be to evaluate the effects on viral kinetics of ALS-2200 and ALS-2158 during seven days of dosing in people with hepatitis C.

Dosing is now underway for the study of ALS-2200, and dosing is expected to begin next week for the study of ALS-2158. Vertex and Alios BioPharma expect to have complete data, including seven-day viral kinetic data, from each trial in the second quarter of 2012, which could enable the initiation of all-oral, interferon-free Phase 2 combination studies in the second half of 2012. These Phase 2 studies are expected to evaluate combination regimens of ALS-2200 or ALS-2158 with Incivek (telaprevir) or VX-222, potential dual nucleotide regimens and other interferon-free combination regimens that may also include ribavirin. Incivek is Vertex's FDA-approved protease inhibitor for chronic genotype 1 hepatitis C, and VX-222 is Vertex's investigational hepatitis C non-nucleoside polymerase inhibitor. The combination studies will be designed to generate sustained viral response (SVR or viral cure) data.

About ALS-2200 and ALS-2158

ALS-2200 and ALS-2158 are highly potent pan-genotypic nucleotide analogues that appear in in vitroand non-clinical studies to have a high barrier to drug resistance and the potential to be dosed orally once-daily. Both compounds are designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Each compound is structurally distinct and has its own unique mechanism of action, which supports the potential for developing these compounds together as a dual nucleotide regimen and as part of combination therapy regimens, including regimens with Incivek (telaprevir) and VX-222. Data from in vitro studies showed that both ALS-2200 and ALS-2158 had a synergistic effect when combined together and with Incivek and VX-222. Additionally, in thosein vitro studies,both compounds showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.

Vertex gained worldwide rights to ALS-2200 and ALS-2158 through an exclusive worldwide licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that will focus on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, rheumatoid arthritis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada. Today, Vertex has more than 1,900 employees around the world, and Sciencemagazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

For more information, see www.vrtx.com.

About Alios BioPharma

Alios BioPharma is a biotechnology company located in South San Francisco, California, that is developing novel medicines aimed at the treatment of viral diseases. Alios has an innovative team of highly experienced scientists and clinical researchers who are developing direct acting antiviral agents against several human viral pathogens of public health importance including, hepatotropic and respiratory viruses and other chronic, acute and emerging viral diseases. The overall goal for the Alios therapeutic platform is to maximize patient benefits in areas of high unmet medical need through optimization of potency, safety and tolerability. Alios is the recipient of the 2011 BayBio Pantheon Outstanding Partnering Award.

For more information, see www.aliosbiopharma.com.

12/13/11

Source

Vertex and Alios BioPharma. Vertex and Alios BioPharma Begin Clinical Studies of Nucleotide Drug Candidates ALS-2200 and ALS-2158 for the Treatment of Hepatitis C. Press release. December 9, 2011.