ALS-2200 / J&J, Vertex, BMS - LARVOL DELTA

ALS-2200, a novel once-daily nucleotide HCV polymerase inhibitor, demonstrates potent antiviral activity over 7 days in treatment-naïve genotype 1 (GT1) patients (AASLD 2011) - Presentation time: Nov 11, 2012; 5:15 PM - 5:30 PM; P1, N=76; The plasma PK of ALS-2200 and its metabolites confirmed rapid uptake in the liver; Plasma concentrations of ALS-2200, the prodrug, were generally low with the parent nucleoside observed as the major circulating metabolite; Initial safety data indicates that single doses of ALS-2200 were well tolerated in HV up to 800 mg and with multiple dosing in GT1 CHC subjects in all cohorts dosed so far (up to 100 mg QD)

P1 data • Hepatitis C Virus

Investigational nucleoside and nucleotide polymerase inhibitors and their use in treating hepatitis C virus (Expert Opin Investig Drugs) - "Currently, mericitabine has the most robust data but its efficacy appears to be less than optimal. Other drugs such as ALS-2200 (and its diastereomer VX-135) and BMS-986094 are promising but the data in humans are too scanty to draw conclusions about their future role at this current point in time."

Review • Hepatitis C Virus

A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-135 and Daclatasvir in Subjects With Genotype 1 Chronic Hepatitis C Chronic Hepatitis C (clinicaltrials.gov) - P2; N=23; Completed; Sponsor: Vertex Pharmaceuticals Incorporated; Active, not recruiting -> Completed ; Trial primary completion date: Jul 2015 ->May 2014

Trial completion • Trial primary completion date • Biosimilar • Hepatitis C Virus • Immunology • Inflammation

A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-135 and Daclatasvir in Subjects With Genotype 1 Chronic Hepatitis C Chronic Hepatitis C (clinicaltrials.gov) - P2; N=20; Active, not recruiting; Sponsor: Vertex Pharmaceuticals Incorporated; Recruiting -> Active, not recruiting

Enrollment closed • Biosimilar • Hepatitis C Virus • Immunology • Myositis

A Phase 2 Study to Evaluate the Safety and Efficacy of VX-135 With Ribavirin in Treatment-Naïve Subjects With Chronic Hepatitis C (clinicaltrials.gov) - P2; N=10; Completed; Sponsor: Vertex Pharmaceuticals Incorporated; Active, not recruiting -> Completed ; N=20 -> 10 ; Trial primary completion date: Aug 2013 ->Feb 2014

Enrollment change • Trial completion • Trial primary completion date • Biosimilar • Hepatitis C Virus

First in Human Study of ALS-002200; Single Dose, Food Effect in Healthy Volunteers; Multiple Doses in Chronic Hepatitis C Genotype 1 (clinicaltrials.gov) - P1; N=71; Completed; Sponsor: Alios Biopharma Inc.; Active, not recruiting -> Completed

Trial completion • Biosimilar • Fibrosis • Hepatitis C Virus • Hepatocellular Cancer • Immunology • Inflammation

Wanted: Premier hepatitis C drug developer to partner with Vertex (FierceBiotech) - "Company is in talks with prospective partners for VX-135...one of two experimental therapies picked up in its pact with Alios...the biotech is looking for a marquee-level partner or two to collaborate with on a next-gen cocktail that can keep the money flowing"

Anticipated licensing / partnership • Hepatitis C Virus

Vertex announces key 2012 business objectives as company prepares for planned global launch of KALYDECO in cystic fibrosis (Vertex) - P1 study data of ALS-2200 and ALS-2158 are expected in Q2 2012, which could enable the initiation of P2 proof-of-concept studies to evaluate multiple all-oral, interferon-free combination regimens in the H2 2012; Anticipated P4 study of INCIVEK combination therapy in African Americans with hepatitis C who were not cured with a prior treatment of pegylated-interferon & ribavirin in Q1 2012; Enrollment is expected to begin in Q1 2012 for P2b & 3b clinical studies of INCIVEK combination treatment in people who have recurrent hepatitis C following a liver transplant

Anticipated P1 data • Anticipated P2 enrollment initiation • Anticipated P3 enrollment initiation • Anticipated P4 trial • Hepatitis C Virus

Vertex, Alios start early-stage hepatitis C trials on 2 drugs (San Francisco Business Times) - Alios BioPharma & partner Vertex Pharmaceuticals said that they started two early-stage studies on separate hepatitis C drugs; Safety & tolerability studies of ALS-2200 & ALS-2158 will return data in Q2 2012

Anticipated P1 data • Hepatitis C Virus

Vertex: Q3 2013 Results (Vertex) - Anticipated results from 100mg and 200mg arms of P2 12-week combination therapy trial (VX-135+daclatasvir) in G1 hep C infected patients in early 2014; Anticipated presentation of EU data from P2 12-week combination therapy trial (VX-135+daclatasvir) in G1 hep C infected patients at AASLD (Nov 03, 2013) 

Anticipated P2 data • Hepatitis C Virus

Vertex reports fourth quarter and full-year 2011 financial results (Vertex) - Vertex announced the consolidated financial results for the fourth quarter and full-year ended December 31, 2011; Vertex expects to have on-treatment and SVR4 data from the all-oral, interferon-free arms (VX-222, INCIVEK & ribavirin) of P2 ZENITH study in the Q1 2012; Vertex expects first data from P1 study of ALS-2200 and ALS-2158 in healthy volunteers & genotype 1 pts in Q2 2012; Data from studies in other genotypes are expected later in 2012; Vertex plans to conduct P2 studies to evaluate combination regimens of ALS-2200 or ALS-2158 with INCIVEK or VX-222

Anticipated P1 data • Anticipated P2 data • Anticipated P2 trial • Financial update • Hepatitis C Virus

Vertex announces sustained viral response rate (SVR4) data from all-oral study of VX-135 in combination with daclatasvir in hepatitis C (Vertex Press Release) - P2a, N=23; NCT01842451; Sponsor: Vertex; "...(SVR4) was 83 percent (10 of 12) in treatment-naïve genotype 1 patients who received 200 mg of VX-135 in combination with daclatasvir....The 11 other patients in this arm completed 12 weeks of treatment, and 91 percent (10 of 11) achieved SVR4....100 mg of VX-135 in Combination with Daclatasvir (60 mg)...73 percent (8 of 11) of patients achieved undetectable HCV RNA after 4 weeks of treatment and 73 percent (8 of 11) of patients had undetectable HCV RNA four weeks after the completion of treatment (SVR4)."  

P2a data • Hepatitis C Virus

Vertex reports first quarter 2014 financial results and provides updates on key business priorities (Vertex Press Release) - "The GAAP net loss for the first quarter of 2014 was $(232) million....Vertex today announced that it has amended the terms of its agreement with Alios BioPharma regarding the development and commercialization of the nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor VX-135. Based on the revised agreement and the rapid changes in the hepatitis C treatment landscape following the introduction of new oral therapies, Vertex plans to out-license VX-135 and to end further investment into research and development efforts in hepatitis C."

Licensing / partnership • Sales • Hepatitis C Virus

[Late breaking abstract] An interferon- and ribavirin-free 12-week regimen of once-daily VX-135 and daclatasvir in treatment-naïve patients with genotype 1 HCV infection (EASL 2014) - Presentation time: 10.04.2014, 09:00-18:00; Abstract #P1303; P2, N=23; NCT01842451; Sponsor: Vertex; “…in the VX-135 200 mg/DCV group, SVR4 by intent-to-treat and observed analyses was 83% and 91%, respectively. SVR12 data will be presented…Adverse events (AEs) observed in ≥10% of patients were fatigue (30%), headache (17%), dry skin (13%), and nausea (13%), with incidence similar between treatment groups.”

Anticipated P2 data • P2 data • Hepatitis C Virus

Vertex: Annual Report 2013 (Vertex) - "In July 2013, the FDA placed a partial clinical hold on our ongoing Phase 2 clinical trial in the United States of VX-135 in combination with RBV in patients with genotype 1 HCV infection following observation of reversible elevated liver enzymes in patients who received 400 mg of VX-135 in combination with RBV in a Phase 2 clinical trial in Europe. Until the partial clinical hold has been resolved, we cannot pursue further evaluation of VX-135 in the United States. There is no assurance that the FDA will lift the partial clinical hold or that we will be able to successfully develop VX-135. If we are not able to develop VX-135, or if our progress in developing VX-135 continues to be slowed significantly, our business may be adversely affected."

FDA event • Hepatitis C Virus

ALS-2200, a novel once-daily nucleotide HCV polymerase inhibitor, demonstrates potent antiviral activity in treatment-naïve GT1 chronic hepatitis C patients (APASL 2013) - Presentation time: 08.06.2013, 08:30-17:30; P1, N=98; NCT01590407; Sponsor: Alios Biopharma; "ALS-2200 was well tolerated in HV up to 800mg and with multiple dosing in GT1 CHC patients. AEs reported in CHC patients receiving ALS-2200 were of mild or moderate severity; all AEs resolved without intervention. Most common AEs: headache (4/50), rash with pruritus (3/50) (2 in RBV arm)."

P1 data • Hepatitis C Virus

Vertex: Annual Report 2013 (Vertex) - Anticipated composition of matter patent expiry in US in 2031; Anticipated composition of matter patent expiry in EU in 2031

Anticipated patent expiry • Hepatitis C Virus

The S282T variant is not observed in treatment-naïve patients with genotype 1 HCV infection treated with the nucleotide inhibitor VX-135 in combination with ribavirin (EASL 2014) - Presentation time: 12.04.2014, 09:00-18:00; Abstract #P1225; P2a, N=20; NCT01790100; Sponsor: Alios; “The S282T variant was not observed by population sequencing in any patient (with available data) at any time point.  No additional potential resistant variants were identified in patients who relapsed.  More sensitive sequencing analyses are underway.”

P2a data • Hepatitis C Virus

Credit Suisse Group AG Healthcare Conference (Vertex) - Anticipated initiation of 12 week, once-a-day, combination therapy trial (VX-135 + GSK-805) in HCV in early 2013.

Anticipated new trial