CymaBay Therapeutics Inc.

Good day, ladies and gentlemen, and welcome to SEMA Bay's third quarter 2021 financial results and business update conference call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for your questions. Please be advised that the call will be recorded at the company's request. It is also being webcast live on the investor section at the SEMA Bay website at www.semabay.com. Now I'd like to turn the call over to Mr. Paul Quinlan, General Counsel at SEMA Bay. Mr. Quinlan, please proceed.

Thank you, Operator, and good afternoon, everyone. I hope that you have had a chance to review the press release we issued announcing our third quarter 2021 financial results and business updates. You can access that release on our website under the Investors tab. Joining me on the call today are Sujul Shah, Chief Executive Officer, Dr. Chuck McWhorter, Chief Scientific Officer, and Dr. Dennis Kim, Chief Medical Officer. Following our prepared remarks, we will open up the call for Q&A. Before we begin, I'd like to remind everyone that statements made during this conference call, including the Q&A session relating to SEMA Bay's expected future performance business prospects, events or plans, including clinical plans, regulatory approval, funding and repayment schedules, anticipated timelines and trial enrollment dates, cash runway, and planning for commercialization of any future products are forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions, actual outcomes and results are subject to risks and uncertainties and could differ materially from those forecast due to the impact of many factors. The company assumes no obligation to update or supplement any forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by applicable law. Participants are directed to the cautionary statements set forth in today's press release, as well as the risk factors set forth in SEMA Bay's quarterly and annual reports filed with the SEC for factors that could cause actual results to differ materially from those anticipated in the forward-looking statements. This conference call is the property of SEMA Bay and any recording or rebroadcast is expressly prohibited without the written consent of SEMA Bay. At this time, I'd like to turn the call over to Sujal.

Thank you, Paul. Good afternoon, and thank you for joining us today. The third quarter marked another period of significant progress at SEMA Bay toward achieving our mission of improving the lives of patients with the rare autoimmune inflammatory liver disease, primary biliary cholangitis, or PBC. Since restarting CELADELPAR development, we have strengthened and grown our team, and in this quarter have achieved many of our operating plan objectives in clinical development, manufacturing, and commercial planning. Our team is working towards completing what we believe is the most extensive development program for any investigational drug in PBC. In addition to our previously completed phase three enhanced and multi-year open label studies, our program is back on track, and we are currently executing five clinical studies with Celadalpar in more than 20 countries and across five continents in support of our plan for a robust NDA submission. The twin pillars of this effort are two global studies in patients with PBC. Response, the primary phase three efficacy and safety study to support marketing approval, and Assure, a long-term safety study to complete a comprehensive patient safety database. Today, our comments will provide a brief summary of our operational progress with our ongoing clinical studies additional data being presented for the first time later this week at the liver meeting sponsored by the American Association for the Study of Liver Diseases, and a summary of our third quarter financials. Before Dennis and Chuck discuss our ongoing studies and upcoming presentations at the liver meeting, I think this is a good time to give those not familiar with CeladalPAR an appreciation for the breadth and depth of our experience in PBC. and the confidence this has given us that Celadelpar has the potential to be a leading treatment option for many patients with PBC. Before discussing the Celadelpar program, let me lay out what we see as the three main unmet needs for patients with PBC. First, many patients need therapies with improved activity against the disease, as evidenced in the incomplete responses commonly observed in their liver lab tests for cholestasis and liver injury. These tests include levels of alkaline phosphatates, bilirubin, and transaminases, biomarkers that have been associated with histological progression and poor outcomes for patients with PBC. It can be argued that offering patients an improved biochemical response and especially the opportunity to potentially achieve the ideal response of biochemical normalization should be a goal of therapy in PBC. Second, many patients with PBC suffer from significant burden of symptoms, including puritis. Currently approved therapies have not addressed this need, and the only approved second-line treatment, abetacolic acid, has been associated with exacerbation or worsening of puritis. A therapy that can provide symptom relief would improve patients' lives, potentially improving acceptability and adherence to therapy as well. Lastly, the majority of PBC patients encompass a spectrum of disease stage ranging from those without cirrhosis to those with compensated cirrhosis, including with portal hypertension. A leading treatment option should be safe across the spectrum of non-cirrhotic and compensated cirrhotic stages of disease. Beginning in 2015, we initiated a series of studies of Celadalpar in patients with PBC that have now included more than 400 participants and has explored a wide range of Celadalpar doses from 2 to 200 milligrams. Over 50 patients in these studies have been treated for two years or more. A remarkably consistent profile has developed across the open-label Phase II studies and the placebo-controlled enhanced Phase III study. The 10 milligram dose emerged as the optimal dose with a pattern of rapid and sustained response with 70 to 80% of patients achieving the primary endpoint, which includes alkaline phosphatase and bilirubin that has been used for accelerated approval of second-line treatment in PBC. Further, up to 30% of patients on Celadalpar normalized their levels of alkaline phosphatase, a potentially significant improvement over available second-line treatment. Significant decreases in transaminases were also found, and we believe that these may be an important difference from other drugs currently in development. As described in our recent publication in the journal Liver International, The 10 milligram dose appears to have improved pruritus, sleep, and fatigue while lowering serum bile acid levels after 52 weeks of treatment. This effect on pruritus was consistent with the data in Enhance, which was measured after three months of treatment using an eDiary collection on the pruritus numerical rating scale. In June, we reported a comparison of the efficacy and safety in a pooled analysis of patients with and without cirrhosis, finding that the biochemical responses and safety profiles were similar in these subpopulations. Taken together, the treatment effects on alkaline phosphatase, bilirubin, transaminases, and puritis across non-cirrhotic and cirrhotic stages support what appears to be a safe and well-tolerated profile and is encouraging for our efforts to confirm this in the response and assure studies as part of the expected NDA submission package. I'd like to ask Dennis to turn our attention to the progress we've made toward enrolling our phase three response and long-term sure studies. Dennis?