Vital Therapies Announces That Topline Results of VTI-208 Fail to Achieve Primary or Secondary Endpoints of Improvement in Overall Survival Pre-Specified Exploratory Subset Analyses Suggest Efficacy Trends

Vital Therapies, Inc.

, a biotherapeutic company developing ELAD®, a cell-based therapy targeting the treatment of liver failure, today announced that topline results from VTI-208, the Company's phase 3 randomized, controlled, open-label trial, evaluating the ELAD System in subjects with alcohol-induced liver decompensation (AILD) failed to meet the primary endpoint of overall survival through at least 91 days assessed using the Kaplan Meier statistical method. Of 203 total subjects enrolled in VTI-208, 96 were randomized to the treated group and 107 were randomized to the control group. A hazard ratio of 1.027 (slightly favoring the control group) with a log rank p-value of 0.90 (not statistically significant, N.S.) indicated that there was no difference between treated and control subjects in the primary endpoint. Figure 1. Kaplan-Meier Plot of Overall Survival http://media.globenewswire.com/cache/31568/file/36601.pdf The secondary endpoints of proportion of survivors at study days 28 and 91 also showed no difference between the groups (Pearson's Chi-squared p-values of 0.45 (N.S.) and 0.74 (N.S.), respectively). The adverse event profile revealed that treatment emergent serious adverse events were similar between the treated and control groups in the predefined safety population. Table 1. Treatment Emergent Serious Adverse Events (TESAE) Safety Population ELAD N = 95 n (%) Control N = 108 n (%) Total N = 203 n (%) Number (%) of Subjects Reporting Any TESAE 73 (76.8) 75 (69.4) 148 (72.9) Number of TESAEs 156 168 324 Table 2. Subjects Reporting at Least One Treatment Emergent Serious Adverse Event (TESAE) by Preferred Term (Incidence >5%): Safety Population Preferred Term ELAD (N=95) n (%) Control (N=108) n (%) Total (N=203) n (%) Subjects Reporting at Least One TESAE 73 (76.8) 75 (69.4) 148 (72.9) Hepatic failure 13 (13.7) 10 (9.3) 23 (11.3) Ascites 6 (6.3) 13 (12.0) 19 (9.4) Renal failure acute 6 (6.3) 12 (11.1) 18 (8.9) Multi-organ failure 7 (7.4) 10 (9.3) 17 (8.4) Anaemia 8 (8.4) 6 (5.6) 14 (6.9) Hepatic encephalopathy 8 (8.4) 6 (5.6) 14 (6.9) Gastrointestinal haemorrhage 7 (7.4) 6 (5.6) 13 (6.4) Hepatorenal syndrome 3 (3.2) 9 (8.3) 12 (5.9) Pneumonia 2 (2.1) 6 (5.6) 8 (3.9) Respiratory failure 5 (5.3) 2 (1.9) 7 (3.4) The Company is still in the process of analyzing the entire data set in accord with the statistical analysis plan submitted to FDA prior to database lock. Preliminary findings, which remain to be confirmed, include the following: In a 120-subject, pre-specified exploratory subset of the intention-to-treat, or ITT, population with a MELD score of <28 at randomization, a Kaplan-Meier analysis of overall survival approached statistical significance with a hazard ratio of 0.575 and a log-rank p-value of 0.077 (N.S.) in favor of the ELAD group. In the per protocol population for this subset (N = 116), the p-value was 0.059 (N.S.). Furthermore, an analysis of 91-day survival in the ITT cohort revealed ELAD survival of 80.4% versus control survival of 65.2% (Pearson's chi-squared p=0.068, (N.S.)). In subjects with MELD scores of >28 at baseline, outcomes appeared to be worse in the ELAD group compared with the Control group, (p=N.S.), suggesting that future clinical studies should exclude subjects with MELD scores >28. In other respects the ELAD and Control groups appear to be balanced with regard to baseline demographics and key measures of liver disease. Figure 2. Kaplan-Meier Analysis of Overall Survival in Subjects with MELD <28 http://media.globenewswire.com/cache/31568/file/36602.pdf In another pre-specified exploratory analysis of the 101 subject sub-group with age less than the median age of 46.9 years, a Kaplan-Meier analysis of overall survival showed a hazard ratio of 0.634 with a log-rank p-value of 0.167 (N.S.) in favor of the ELAD treated subjects. Furthermore, an analysis of 91 day survival in this cohort revealed ELAD survival of 81.4% versus control survival of 67.2% (p=0.112, N.S.). In subjects with age greater than the median of 46.9 years, outcomes appeared to be worse in the ELAD group compared with the Control group (p=N.S.), suggesting that future study designs may incorporate stratification by age. In other respects the ELAD and Control groups appeared to be balanced for baseline demographics and measures of liver disease. Analyses of data in subjects with either acute kidney injury, defined by serum creatinine greater than 1.5 mg/dl, or evidence of severe coagulopathy, defined by INR >2.5, suggest that these subjects should be excluded from future clinical trials. Of interest, data from laboratory testing of the blood indicators of alcohol consumption in subjects following hospital discharge revealed that there was no apparent relationship between recidivism and survival in either group. The Company will be analyzing the data from the VTI-208 clinical trial during the next several weeks, including data from the pre-specified subset analyses. The Company will stop the VTI-210 and VTI-212 clinical trials, and also plans to meet with the FDA as soon as possible to discuss restructuring its clinical development program, including a potential new trial to confirm the information suggested by the subset analyses. The Company will then give more details on a possible path forward with ELAD. While the overall results are disappointing, the Company is encouraged that a large pre-specified subset of 120 subjects with a MELD score of less than 28 had a hazard ratio of 0.575 and a log-rank p-value of 0.077 (N.S.) in favor of the ELAD group, suggesting that future clinical studies should focus on this cohort with MELD scores less than 28. Separately, a pre-specified subset of 101 subjects under age 46.9 years (the study median age) had a hazard ratio of 0.634 with a log-rank p-value of 0.167 (N.S.) in favor of the ELAD treated subjects, suggesting that future study designs may incorporate stratification by age. Indeed these effects appear to be additive and a subset of 59 subjects with MELD less than 28 and age less than 46.9 years had a hazard ratio of 0.375 in favor of the ELAD group (p=0.085 (N.S.)). Finally, pre-specified analyses suggest that subjects with impaired kidney function and severe coagulopathy may have worse outcomes and therefore future clinical trials will exclude these subjects. With $62.0 million in current cash, the Company believes it could complete a new trial without raising additional capital, although that will depend on discussions with regulatory authorities and the exact design of any new trial. Conference Call Details Vital Therapies will host a conference call to discuss the results of the VTI-208 clinical trial today, August 21, 2015, at 5pm ET, which will be open to the public. The conference call dial-in numbers are (855) 765-5682 for domestic callers and (919) 825-3204 for international callers. The conference ID number for the call is 20307654. Participants may access the live webcast via a link on the Vital Therapies website in the Investor Relations section under "Events" at: http://ir.vitaltherapies.com/. For those unable to dial in at the designated time, a conference call replay will be available for one week following the conference call, from approximately 8:00 p.m. ET on August 21, 2015 to 11:59 p.m. ET on August 28, 2015. The conference call replay numbers for domestic and international callers are (855) 859-2056 and (404) 537-3406, respectively. The conference ID number for the replay is 20307654. Additionally, an archive of the webcast will be available on the Company's website for 90 days.