Albireo Pharma, Inc.

Good morning, and welcome to the Alvarez Pharma's fourth quarter and year-end 2020 financial results and business update presentation. At this time, all participants are in a listen-only mode. A Q&A session will follow the formal presentation. If anyone should require operator assistance during the call, please press star zero on your telephone keypad. Please note that this conference is being recorded. I'll now turn the call over to your host, Paul Arndt, Managing Director of LifeSci Advisors. Thank you. You may begin.

Thank you, Operator, and good morning, everyone. Thank you for joining today's call. This morning, Alvareo issued a press release highlighting its recent business accomplishments and reporting its financial results for the fourth quarter and year ended December 31, 2020. This press release is accessible via the company's website at www.alvareopharma.com. Before proceeding, we would like to note that management's comments today may include forward-looking statements regarding the company's plans and expectations. These statements are being made under the Private Securities Litigation Reform Act of 1995, and they are subject to various risks and uncertainties. Actual results may differ materially due to various important factors, including those described in the risk factors section of the company's most recent Form 10-K and subsequent SEC filings. These filings can be accessed from the Media and Investor Relations section on the company's website at alvareofarma.com or on the SEC's website. Any forward-looking statements represent management's views as of today, Thursday, February 25, 2021, and should not be relied upon as representing their views as of any subsequent dates. The company undertakes no obligation to update these statements publicly. Now, it is my pleasure to turn the call over to Ron Cooper, Alvareos President and Chief Executive Officer. Ron?

Thank you, Paul, and thank you, everyone, for joining us this morning for Alvareos Q4 and year-end 2020 results and business update. With me today are Simon Harford, our Chief Financial Officer, Dr. Pat Horn, our Chief Medical Officer, and Pamela Stevenson, our Chief Commercial Officer. I'd like to begin today by giving a short review of 2020 and then moving into 2021. 2020 was a transformational year where we delivered against all our stated milestones and commitments as planned. And we're looking at another transformational year in 2021 where we plan to deliver against guidance, starting with becoming a fully commercialized organization with the plan launched to Votavix about expansion beyond PFIC into other rare pediatric conditions, and progressing our pipeline in adult cholestatic and viral diseases. Starting with 2020, the story was overcoming unprecedented challenges. Albareo, like many other companies, worked under new conditions with the global COVID-19 pandemic, new constraints with remote working, and unforeseen challenges conducting clinical trials and manufacturing around the world in a fully virtual manner. Despite these headwinds, our team persevered, overcame the challenges, and ultimately delivered on a very successful 2020 measured by our progress with Odovixibad, our pipeline, and advancing the growth of the company. First, with Odovixibad, we've committed to delivering the PEPFIC 1, Phase 3 study results in PEPFIC. Not only did we deliver those results, but they were strong, hitting both primary endpoints with triple-digit p-values and a solid tolerability profile with low diarrhea rates. On the back of that great data, our team worked in record time to submit for regulatory approvals. We're pleased to announce that both regulatory filings were accepted in the U.S. and Europe with the FDA granting priority review and the EMA granting accelerated review. It is estimated there are approximately 100,000 patients with pediatric cholestatic liver disease around the world. And we've always said Odovixibab is a pipeline in a product with the first indication of PFIC, then allogel syndrome, and belly atresia. Knowing the potential Odovixibab could have in these three indications, we decided to start our first phase three study in PFIC. It is the nature of the disease. We believed it would be easier to validate the dose, tolerability, and our precision pruritus measurement tool, which we did, and the results validated our decision. We have the insight and great confidence from the PETBIC 1 and 2 studies, and we're able to design and initiate two additional phase 3 studies in cholestatic liver disease. With the positive learnings from the PEDVIC program, we've increased our confidence in a positive outcome for our allogel and bilirutresia programs. We committed to starting a bilirutresia study in the first part of the year, and we initiated the BOLD study, which is the world's first and largest prospective randomized placebo-controlled study with an IVAD inhibitor. Bileatresia is the largest pediatric holostatic liver disease with an estimated prevalence of approximately around 45,000 patients around the world. We also committed to starting a third pivotal program in Allergy Ill Syndrome and started the ASSERT trial in the fourth quarter of last year, fulfilling our development commitments and guidance for Odovixibab. Now, looking at our pipeline expansion activities, we completed IND-enabling studies with our novel ASBT inhibitor, A3907 for adult liver diseases, and we made progress with our first NTCP inhibitor, A2342 for viral and cholestatic diseases. Our company matured in many different ways in 2020. From a financial perspective, we made excellent progress, generating over $200 million of both equity and non-dilutive capital. which will take us into 2023 and into the revenue generating period of the company. In parallel, the organization doubled its size and we built new capabilities and a lean infrastructure to drive successful commercialization. Recent hires include our President of the Americas and President of International, both of whom are focused on hiring specialized teams as part of our launch readiness plans, as well as driving our sales and market access strategies and execution in their respective regions. We put medical and access personnel on the ground, and they've been actively engaging with healthcare professionals and payers to gain valuable feedback. As we reflect on 2020 and the unprecedented challenges, we were also fortunate to deliver on unprecedented success. So now looking ahead, in 2021, We're very clear on our goals and expectation for the year as we drive Odovixibet product growth to over $1 billion planned for the second half of the decade. First, we're planning for Odovixibet to be approved in the U.S. and Europe with the issuance of a priority review voucher and deliver commercial sales. Second, we expect further progress in our pipeline with our pivotal phase three studies with the BOLD study in biliary atresia and the ASSERT study in allogilism. BOLD should be well on their way from an enrollment perspective. And third, we plan to characterize our pipeline further. Starting with Odovixibeth, with priority review and a PDUFA date of July 20th in the U.S. and accelerated assessment in Europe, we've engaged in a good dialogue with regulatory authorities and do anticipate an approval and launch in the second half of the year. In preparation, we're gearing up all critical launch activities and steps to ensure we have product to sell. We've executed on the manufacturing plan we agreed with the FDA in the fall of 2018, and we feel confident about the commercial product having used the planned commercial formulation in the PEDFIC Phase III studies. We're also focusing on the supply chain. We've established agreements with 3PLs and specialty pharmacists while also building Albareo Assist, which is a customized in-house patient services program with dedicated care coordinators to help patients navigate their access to Otavix VAT from the start and be with them as they grow. With confidence in regulatory outcomes and drug supply in place, our next priority is access. Regulatory approvals are important around the world, but having a compelling value story is equally important to ensure patients can access the drug. Payers are looking for strong data and a good rationale. The PEDFIC study produced strong positive results from the largest randomized placebo-controlled Phase III study in PFIC. This provides us with compelling Class I evidence, but you also need a full access strategy. As part of the integrated access strategy, we have the natural history data from the NAPID study, which shows that a reduction of bile acids to 65 to 100, depending on the PFE type, by biliary diversion results in long-term NADA survival. Unfortunately, not all patients benefit from biliary diversion surgery and will require liver transplantation for refractory pruritus or end-stage disease. We believe Odovix VAT will be a much better option. In addition, we initiated a burden of disease study to understand the cost and caregiver burden associated with PFIC, and importantly, humanistic data that measures the burden on caregivers and families. So, overall, we feel really good at this time about the comprehensive submission package that we've compiled to support the value of Odovix VAT and ensure patient access globally. The next priority is commercialization, and we are prepared. With our regional heads in the U.S. and Europe in place, they're focused on hiring a highly specialized sales team to call on healthcare providers. In the U.S., our focus has been a fast start at launch. So to deliver on that, we're pleased that we have entered into a new co-promotion agreement with Travere Therapeutics. Travere is a leading rare disease company and marketer of Colbon capsules, which are used by pediatric hepatologists. So why is this important for our commercial strategy? The Travere representatives are highly experienced and have a long-standing relationship with our key HCP prescribers. So they'll be able to help us accelerate our launch and uptake in the U.S. With the Travere sales representatives and our own TAN representatives, will more than double our recent frequency coverage on day one of launch to give us a fast start. Travere will also provide us with valuable insights that their sales representatives have been calling on pediatric hepatologists and their related specialists for more than five years, and they are the main call point for Otavixabab. The co-promotional agreement is set for two years with optionality for extending the relationships. Alvareo will book all revenue and pay Trevier certain fees to compensate its sales representatives for their efforts in selling Odovixibab. We believe this relationship with Trevier will ensure potential prescribers are aware of Odovixibab and understand how to prescribe it for appropriate patients as quick as possible upon FDA approval, which will result in a faster start at lunch. We're also planning on commercializing Otavixibet in other places around the world. In our recent commercial day, we revealed the opportunity for Otavixibet is larger than our initial estimates with 100,000 pediatric liver disease patients around the world, excluding India and China, that could benefit from this therapy. Now, if you look at the data from other rare disease therapies, Many have demonstrated significant opportunity worldwide with more than half of the brand's revenue for each of these coming outside the U.S. just two years after launch. What this means is we anticipate a larger patient population for Odovixibab. Our aspiration is to reach $1 billion of sales for Odovixibab within the second part of this decade through U.S. and international sales. With this in mind, we enter into our first commercial distributor partnership for Otavixibet with Medicine Pharma in Israel. This is the first of multiple plan ex-U.S. commercial distributorships with a focus on countries with high prevalence rates equaling significant commercial opportunities. So overall, it'll be a big year for Otavixibet from an approval, reimbursement, commercialization, partnership perspective, and we are ready to go. Moving on to our key development programs, BOLD, the first, largest, and the only global randomized placebo-controlled Phase III trial of an IBAD inhibitor in biliatresia, has 42 sites activated, and global enrollment continues to be on track. We anticipate having all the sites up and running in the first half of 2021, with top-line data available in 2024. For ASSERT, our pivotal randomized placebo-controlled program in allogeal syndrome, We expect to have all the sites active in the first half of 2021 as well, with top-line data available in 2022. With three pivotal programs for Rotavix about, we're planning a market-leading global approach, focusing on key regions like the U.S., Europe, Turkey, Israel, and Brazil. For PPIC, we anticipate being the first approved and first to market in the majority of the regions. For allogel syndrome, we expect to be first in Europe and ex-U.S. countries pending the results of our Phase III study and a fast follower with the best-in-class profile therapy in the U.S. We also expect to be first in the market for biliary atresia because we have the only Phase III study up and running. The third thing to expect by the end of the year is greater insight into our pipeline beyond pediatric liver disease. We are making tremendous progress with our earlier stage compounds in adult, cholestatic, and viral diseases. We're advancing the development of A3907, our novel ASBT inhibitor, and A2342, which is a novel NTCP inhibitor. The unique properties of A3907, especially the high systemic availability, holds great promise for solving the efficacy high diarrhea challenges observed with IBAD inhibitors in adult cholestatic liver diseases, such as PBC and PSC. For A3907, we're planning a first-in-human Phase I study by the end of first quarter, with top-line data anticipated later this year, and the initiation of Phase II in 2022. We believe A3907 has significant commercial potential in adult cholestatic diseases. We're also excited about developing the first NTCP inhibitor, A2342, for viral and cholestatic diseases. NTCP is a key transporter for bile acids as well as hepatitis B and D viruses. A2342 also has unique properties as it is an oral, potent, small molecule that blocks entry into the liver and should have excellent combinability potential. There really is a good proof of concept for A2342 with a peptide compound called Hepcludex, which is an anti-CV inhibitor approved for hepatitis D in Europe, but given the limitations of a peptide, the maximum dose can only be delivered as a daily sub-Q injection. This product was recently purchased by Gilead for over a billion euros. A2342 is currently in IND-enabling studies with a Phase 1 trial anticipated to start in 2022 and Phase 3 in 23, so Phase 2 in 23. We believe that A2342 could be a valuable treatment for hepatitis B and D and cholestatic diseases. Our research team continues to characterize other novel bile acid modulators. So, to conclude, We're coming off a tremendous year, and we have a great deal of confidence in our ability to deliver in 2021 and beyond. Why? Well, because of our track record at Alvareo, starting with our commercial track record. Not only do we have the building blocks in place, but we have leadership with a demonstrated record of launching. Pamela leads our commercial organization, spent a decade at Pfizer and a decade with Vertex. commercializing products in competitive liver and rare disease markets. Simon, our CFO, has two decades at Lilly and a decade at GSK, and I have over 20 years at BMS. We believe our individual and combined successes at global product launches gives us a market-leading commercialization approach and readiness. Collectively, we have dozens and dozens of successful launches under our belts. Development projects. Alboredo has successfully read out two Phase III programs. First, Alabixa was the first IBAT inhibitor approved anywhere in the world with the approval in chronic constipation, together with EA Pharma, our partner in Japan. And then, of course, the PEPFIC trial results for Odovixibat and PFIC. Odovixibat-PFIC study was the first Phase III study ever conducted in pediatric cholestasis, where there was no precedent on endpoints, trial design, and little natural history. We successfully enrolled and executed the Odovixibab Phase III PETFix study in PFIC. This gives us confidence in our chance for similar success with our BOLD study in bilirutresia and our SIRT study in Allosil syndrome. Preclinical track record. 83907 will be the compound that the preclinical team has progressed into the clinic. This gives us confidence that A2342 will also advance this plan, and there's potential in our other bile acid modulator approaches, allowing for smart pipeline expansion from rare pediatric liver disease and now to adult and liver diseases. So overall, we feel very confident in our ability to deliver against our key objectives in 2021 as we plan to launch Odovixibat, taking us towards our ambition to achieve a billion dollars in sales, progressing our clinical programs in allogel and valeriatresia, and further characterizing our promising preclinical compounds. So now with that, let me turn it over to Simon to give you a quick financial update.