CymaBay Therapeutics Inc.

Good day, ladies and gentlemen, and welcome to Syma Bay's fourth quarter and full year 2020 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 Syma Bay website at www.symabay.com. Now I would like to turn the call over to Mr. Dan Mendel, Vice President of Finance at Syma Bay. Mr. Mendel, you may proceed.

Thank you, Operator, and good afternoon, everyone. I hope that you've had a chance to review the press release we issued announcing our fourth quarter and full year 2020 financial results and business updates. You can access that release on our website under the Investors tab. Joining me on the call today are Sujal Shah, Chief Executive Officer, Dr. Chuck McWhirter, Chief Scientific Officer, and Clara Dickinson, Chief Regulatory Officer. Sujal will provide an update on recent progress and plans on the development program for Celadelpar. Chuck will discuss updates to other pipeline opportunities, and I will provide a brief summary of our financials. Following our prepared remarks, we will all be available 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-based expected future performance, business prospects, events or plans, including clinical plans, regulatory approvals, and anticipated timelines and data release dates, and cash runway, are forward-looking statements as defined under the Private Securities Litigation Reform Act 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 CIMA 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 CIMA Bay, and any recording or rebroadcast is expressly prohibited without the written consent of CIMA Bay. At this time, I'd like to turn the call over to Sujil.

Good afternoon, and thank you for joining us. We will spend the majority of our time today discussing the significant progress we are making with Celadalpar, our lead Phase III candidate for patients with the rare autoimmune liver disease, primary biliary cholangitis, or PBC, as well as the other promising opportunities we are actively advancing in our pipelines. It is first important to reflect on all that we have accomplished in 2020 and how those efforts position us for success in the coming year and beyond. After reducing our workforce by 60% at the end of 2019, we started 2020 actively closing down all of our clinical studies and winding down all non-essential activities. We did this to aggressively conserve capital and maximize our ability to execute any number of strategic alternatives we evaluated, including potential in-licensing of assets, mergers, and even liquidation. Importantly, we also launched a rigorous independent evaluation of the potential safety concerns in our Phase II study of Celadalpar in patients with non-alcoholic steatohepatitis, or NASH. By the second quarter, the independent safety review conducted at arm's length by a panel of world-renowned liver experts found no evidence of Celadalpar-related injury in our NASH study, and we quickly submitted complete responses to the FDA clinical holds. In the third quarter, the FDA lifted all clinical holds across the Celadalpar program, and one week later, we announced positive top-line results from our enhanced Phase III study of Celadelpar in PBC. Even though ENHANCE was halted prior to completing its planned 52-week treatment period, results were available for 167 patients who completed at least 12 weeks of treatment. These results, we believe, demonstrated that Celadelpar 10 mg provided patients with a statistically significant benefit on the primary and two key secondary endpoints in the trial. The results for the 55 patients on Celadalpar 10 mg at week 12 revealed a nearly 80% response on the primary composite endpoint, an accepted regulatory approval endpoint when measured at 52 weeks, versus 12.5% for the 56 patients on placebo. Further, there was an almost 30% response on ALP normalization versus none on placebo, and a meaningful and statistically significant placebo-controlled effect on reducing puritis in patients with moderate to severe puritis at baseline, as measured by the numerical rating scale, or NRS. As you may know, puritis is a significant and often debilitating clinical symptom of PBC, reported to affect up to 70% of patients. As we closed out the year, these results were highlighted in a late-breaking presentation at the liver meeting, sponsored by the American Association for the Study of Liver Diseases in November. They were also instrumental in the design for response, our global Phase III registration study that mirrors Enhance. Response will study the same optimal 10 milligram dose of Celadalpar versus placebo in the same patient population with the same primary and two key secondary endpoints. Since our last quarterly update in November, we have been focused on the restart of our global development program for Celadalpar in PBC. It is important to highlight that every element of our program had been either shut down or paused in an effort to conserve capital, including clinical studies and drug manufacturing. A restart of the Cell at LPARP program is a result of the extraordinary efforts our teams made in many behind-the-scenes activities in regulatory, CMC, and quality assurance. In parallel, our clinical operations group has been working tirelessly to enable the initiation of response and our open label long-term study, Assure. It is with great pleasure and excitement that I can announce today that both of these studies are actively recruiting patients. I look forward to providing regular updates on these studies as we progress in the months ahead. For the remainder of our call today, we will outline our plans for the remainder of 2021, including first, Our primary focus on execution of response, assure, and other NDA-enabling clinical and CMC activities for Cell at LPAR and PBC. Second, pre-commercial planning and market research to support investments for launch and lifecycle management for Cell at LPAR in PBC. Third, advancement of our early-stage pipeline and business development opportunities. And finally, fourth, continued management of our capital and human resources. Completing the development of Cell at LPAR for patients with PBC is our top priority. Although Enhance was halted early, its results allowed us to optimize the design and size of response and to leverage our prior experience with clinical sites in more than 20 countries around the world. Our goal is to complete enrollment by the end of this year. despite challenges we are facing with the ongoing COVID-19 pandemic and increased competition for patients. We will have a better indication of enrollment timelines as we move past the middle of this year. In the first quarter, we held investigator meetings in North America, Europe, Latin America, and Asia, where we continue to see enthusiasm and support for Cell at LPAR's return to clinical development. The study is now actively recruiting patients, and with increasing numbers of site activations, we expect screenings and randomizations to accelerate in the coming months. For those not familiar with the design, response is a 52-week placebo-controlled randomized global Phase III registration study evaluating the safety and efficacy of Celadalpar in patients with PBC. It is intended to enroll 180 patients with an inadequate response or intolerance to ursodeoxycholic acid in a two-to-one randomization to oral once-daily Celadelpar 10 mg or placebo. The primary outcome measure is the composite responder rate after 52 weeks. in which a responder is defined as a patient who achieves an alkaline phosphatase level less than 1.67 times the upper limit of normal with at least a 15% decrease from baseline and has a normal level of total bilirubin. Additional key outcomes of efficacy will compare the rate of normalization of alkaline phosphatase at 52 weeks and the change in puritis from baseline to six months for patients with a baseline NRS of four or greater for moderate to severe puritis. Puritis will be assessed using the same numerical rating scale and daily electronic diary as we used successfully in ENHANCE. I can't overstate the value of ENHANCE in determining the size and design of response, which, as I mentioned, once again will evaluate the same patient population the same 10 milligram optimal dose of Celadalpar, and the same primary and two key secondary endpoints. In addition to response, we have also initiated Assure, an open-label, long-term study of Celadalpar in patients with PBC in order to collect additional safety data to support registration. The study will first enroll patients who have participated in our prior studies of Celadalpar and PBC, including the patients who completed the open-label Phase II study and enrolled into our previous long-term study and enhanced. As patients complete response and potentially other future PBC studies with Cell at LPAR, they will also have the opportunity to enroll in Assure. We expect Cell at LPAR to have one of the most robust safety databases in PBC patients ever submitted for an NDA. In the background of these two significant global clinical studies, our teams have also been executing on regulatory and clinical activities for numerous NDA-enabling studies and CMC efforts required to meet our filing and launch timelines. These efforts are often overlooked outside of the company but are highly valued and resourced to succeed as they play a vital role in ultimately enabling the broadest use of Celadelpar to benefit as many patients as possible. On the topic of bringing Celadelpar to patients, I want to highlight some of the important pre-commercial planning and market research work we have been and will continue to conduct through the course of this year. We have been studying Celadelpar in PBC since 2015. having completed four clinical trials studying five doses of Steladalpar in over 300 patients, including in both cirrhotic and non-cirrhotic patients, and with a subset of these having been treated for two years or longer. The 10 milligram dose has consistently shown anti-cholestatic, anti-inflammatory, and anti-puritic activity and good overall safety to date and suggests the potential of Cell at Alpar to provide patients with improvements in biochemical markers of disease and to reduce symptom burden. Our aspiration is to help as many patients as possible achieve the ideal response of normalizing their alkaline phosphatase. We aim to demonstrate that the potential benefits of Cell at Alpar can translate into improved outcomes and quality of life for many patients with CBC. In the U.S. alone, there are approximately 130,000 patients with PBC, with as many as 20 to 30,000 inadequately controlled by or intolerant to first-line treatment with UDCA. There are many more who are not currently considered eligible for second-line treatment, even though they have elevated alkaline phosphatase and may also be at risk of disease progression. There are also many patients who suffer from the symptoms, such as pruritus, with a significant negative impact to their quality of life. Based on current pricing for second-line PBC therapy and the potential to deliver even greater benefit, our early market research with healthcare providers and payers points to the potential for Celadalpar to be the preferred treatment choice for patients and thus an opportunity that may generate significantly greater long-term revenues than Ocala, which according to recent guidance from Intercept, is currently projected to have $325 to $355 million in annual worldwide net sales in 2021. As we mature our market research, we will be providing updates on specific details of our projections. While our core focus remains on completing development of Cell at LPAR in PBC, we continue to evaluate Cell at LPAR and our other early-stage clinical assets for other indications and development opportunities. Let me turn the call over to our Chief Scientific Officer, Dr. Chuck McWherter, to discuss more. Chuck?