CymaBay Therapeutics Inc.

Good day, ladies and gentlemen, and welcome to SEMA Bay's fourth quarter and full year 2021 financial results and business update conference call. At this time, all participants are in 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've had a chance to review the press release we issued announcing our fourth quarter and full year 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, Dan Minold, VP Finance, Dr. Chuck McWhorter, Chief Scientific Officer, Dr. Dennis Kim, Chief Medical Officer, and Louis Stewart, Chief Commercial Officer. Following our prepared remarks, we will open 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 CIMA Bay's expected future performance, business prospects, events or plans, including clinical plans, regulatory approvals, funding and repayment schedules, anticipated timelines and trial enrollment dates, cash runway, and planning for commercialization 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 on reasonable assumptions, actual outcomes and results are subject to risks and uncertainty 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 statement 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 Sujil.

Thank you, Paul. Good afternoon, and thank you for joining us. Today, we will discuss highlights of our 2021 accomplishments and review recent progress we have made advancing the development of Celadalpar, our lead phase three candidate for patients with the rare autoimmune liver disease primary biliary cholangitis, or PBC. and on the key milestones we believe we are well positioned to achieve in 2022 and beyond. Highlights of our accomplishments in 2021 include many important areas impacting our primary objective of improving the lives of patients with PBC. These include the initiation and advancement of our global phase three clinical development program, presentation and publication of data at important medical meetings and in peer-reviewed journals, execution of two successful financings, and the addition of experienced, dedicated team members across the organization. At the beginning of 2021, we reinitiated what we believe is the most extensive program for any investigational drug currently in development for treatment of PBC. In addition to several NDA-enabling studies, we initiated 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. These studies draw from the extensive experience we gained from our prior phase two and phase three development, where data has continued to support the potential for Celadalpar to address many of the unmet needs faced by patients with PBC. The presentations and publications we made in 2021 highlight the potential for Celadalpar to address three important unmet needs for patients with PBC. First, many patients need therapies with improved activity against the disease, as exhibited in the incomplete responses commonly observed in their 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. We believe that offering patients an improved biochemical response, and especially the opportunity to achieve biochemical normalization, should be the aspiration 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 pruritus. A therapy that can provide symptom relief would improve patients' lives, potentially improving acceptability and adherence to therapy. Lastly, 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 this spectrum of non-serotic and compensated serotic stages of disease. During 2021, we had the opportunity to present new analyses at the annual meetings hosted by the European Association for the Study of Liver Diseases, or EASL, in June, and the American Association for the Study of Liver Diseases, or ASLD, in November. In one presentation at EASL, we shared a retrospective analysis of data from our prior phase 2 and phase 3 studies that demonstrated Celadalpar appeared to be safe and well-tolerated and showed meaningful and dose-dependent improvement in biochemical response in PBC patients with prior treatment with abetacolic acid, the only approved second-line treatment for PBC, or fibrates. which are sometimes used off-label in patients with PBC. At EASL, we also shared pooled analysis of cirrhotic patients from the open-label Phase II study and a placebo-controlled enhanced study reporting on three-month efficacy and safety of 5 or 10 milligrams of Celadalpar. After three months, the efficacy, tolerability, and safety in patients with compensated cirrhosis had a consistent pattern and magnitude of biochemical response in liver biochemistry to that of non-cirrhotic patients, and importantly, was accompanied by a similar safety profile. As increased attention has emerged on the significance of portal hypertension in cirrhotic PBC patients, we updated this pooled analysis later in the year at ASLD. examining the cirrhotic patients with and without portal hypertension compared to those without cirrhosis. Again, there were comparable profiles for efficacy, tolerability, and safety. Portal hypertension in cirrhotic patients with PBC is estimated to comprise about half of all patients who have compensated cirrhosis and is a significant risk factor for progression to decompensation. Understanding the safety and efficacy of Celadalpar in cirrhotic patients with and without portal hypertension will be an ongoing part of the Celadalpar program with the goal of understanding if Celadalpar is an appropriate treatment option for this currently unserved population. Perhaps the most meaningful dataset last year was the oral presentation at ASLD, where we shared an analysis on the efficacy and safety of Celadalpar over two years of treatment in patients with PBC. Treatment of more than 50 patients with Celadalpar over two years appeared safe and well-tolerated and led to sustained and progressive reductions in biomarkers of cholestasis and hepatocellular injury throughout the second year of treatment. Almost 80% of patients achieved the composite endpoint based on ALP and bilirubin and over 40% of patients normalized ALP at two years. We believe that Celadalpar is the only drug in development for PBC as an add-on therapy to UDCA that has safety and efficacy results of this duration. In addition to these presentations, data from a Phase II study demonstrating improvements in measures of pruritus, sleep, and fatigue and decreased serum bile acids in patients with PBC was published as a full manuscript in Liver International last year. Puritis baseline intensity correlated with serum bile acid levels and puritis improvement over 52 weeks correlated with decreases in a specific set of serum bile acids. This paper also reported improvements in patient reported sleep disturbance using two different questionnaires and improvements in fatigue scores using the PBC40 questionnaire. Collectively, these data illustrate CeladalPAR's treatment effects on alkaline phosphatase, bilirubin, transaminases, and puritis across non-serotic and serotic 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 in support of our planned NDA submission. In the midst of significant challenges in the capital markets of mid to late 2021 that continue to this day, we executed two successful financings that have provided the capital we forecast to support our operating plans through the end of 2023. Under the terms of the non-dilutive risk sharing development funding transaction with Abingworth, we have already received $75 million to support the Celadal PAR development program for PBC since closing of the agreement in July of last year. We have the option to receive an additional $25 million within approximately two months of the completion of enrollment of response. Commonly, Risk sharing funding agreements in biotech are for programs that are commercial or at least have regulatory approval. We believe the strategic funding committed by Abingworth prior to the completion of the phase three response registration study reflects a shared view around the potential for Celadalpar to address unmet needs for patients with PBC. We are excited to have Abingward's support as they have deep scientific, operating, and financial experience in biotech. In November of last year, we also completed a $75 million equity offering that included both existing and new investors. Our balance sheet now lets us fully concentrate on completing the NDA package for Cell at LPAR, including delivering the top line results for response planned for mid-2023. Dan will review our financials later in the call, but we start 2022 with a very strong balance sheet, having brought in multiple experienced quality biotech investors in these two financings. While establishing the value proposition of Cell at Alpar and funding its development were necessary, our future success depends on having a team with the talent and experience to take us through approval and commercial preparation. In 2021, I'm pleased to say we did this up and down the organization, building out functional teams, adding key executives, and adding to our board. In the first half of the year, we appointed Dr. Dennis Kim as Chief Medical Officer and Louis Stewart as Chief Commercial Officer. These seasoned biotech executives come with considerable talent and energy to apply their leadership and experience as we move into a period in which we plan to complete development and regulatory submissions for Cell at LPAR and begin pre-commercial preparation. We strengthened the entire organization with the addition of key talent across functions that will form the foundation of our plans to deliver an NDA submission for Cell at LPAR and bring it to the market in order to provide patient access and create value for our stakeholders. At the board level, we were fortunate to bring on biopharma veteran Tom Wiggins and commercial leader Janet Dorling. Tom and Janet bring complementary skills and experiences to the board. and in particular our seasoned biotech executives who have guided teams through development to commercialization. In addition, earlier today we announced the appointment of Dr. Eric Lefebvre to the board. Eric is currently the Chief Medical Officer at Pliant Therapeutics. He has extensive experience in the pharmaceutical industry as an executive focused on clinical development, medical affairs, business development, and lifecycle strategy, and more than 10 years of experience developing drugs and liver disease indication. We look forward to Eric helping guide us through our next phase of development and commercialization. 2021 was a year filled with significant accomplishment and progress, despite multiple headwinds we and others in our industry faced. The pandemic impacted participation in clinical studies, timelines for regulatory and ethics committee approvals of study protocols, and vital resources at clinical sites. Since our last quarterly call in November, we faced new challenges as the Omicron variant has surged more rapidly than any other strain of COVID-19 at the end of the year through the first few months of 2022. Now we find ourselves thinking of the many innocent people impacted by the Russian invasion of Ukraine, including those involved in our PBC clinical studies in both countries. Our primary focus is on their safety, as we hope for resolution and peace. Through all of these challenges, we have worked to focus on those things that are in our control. We expanded our global phase three registration study response to more countries and more sites. We offered services to patients and clinical sites, providing concierge transportation, home health, and temporary staffing where possible. We invested in additional advertising and targeted programs to raise awareness of our study and support screening and enrollment. We have also increased the frequency of our interactions with principal investigators and their staff around the world, both virtually and in person, where permitted. Although we cannot predict new challenges we may face, we remain committed to completing enrollment in response in the first half of this year. Excluding Ukraine and Russia, response is active in 20 countries across more than 120 clinical sites. In parallel to response, our open-label long-term safety study, Assure, has also advanced significantly since the end of last year. As you may recall, Assure is open to PBC patients enrolled in previous studies of Celadalpar. We have seen a high level of interest in Assure, where we have now enrolled more than 120 PBC patients from our prior PBC clinical studies. The progress we have made in both response and assure, despite many global challenges, continues to highlight the significant unmet needs that persist for PBC patients today. Before we open the call for questions, I'll ask Dan to review key financials for the fourth quarter and full year 2021. Dan?