Albireo Pharma, Inc.

Good day and welcome to the Alvareo Pharma First Quarter 2021 Earnings Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference over to Mr. Paul Arndt. Please go ahead, sir.

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 first quarter ended March 31, 2021. This press release is accessible via the company's website at www.albareofarma.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 such including those described in the risk factors section of the company's most recent form, 10-K, and the subsequent SEC filings. These filings can be accessed from the media and investor section of the company's website at www.albareofarma.com or on the SEC's website. Any forward-looking statements represent management's views as of today, Thursday, May 6, 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?

Right. Thank you, Paul, and thank you, everyone, for joining us this morning for Alvareos Q1 2021 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. Our themes for today are commercial readiness and corporate growth. At the start of the year, we laid out a plan of how we would expand to a global organization to reach the large 100,000 pediatric cholestatic patient opportunity around the world and realize our aspiration to exceed $1 billion in the second half of the decade. To deliver on this aspiration, we must build a strong global commercial organization to successfully launch Bilvay Otavixibat in PFIC, expand beyond PFIC into other rare pediatric conditions, and progress our pipeline in adult cholestatic and viral liver diseases. So what I'll do is I'll take you through the progress and achievements as we continue to deliver on our objectives and make plans in support of our ambitions. In the short term, our priorities remain. Number one, bring Belvay Otavixibab over the line with product approvals in the U.S. and Europe with the issuance of a priority review voucher and a fast start in approved markets. Number two, focus on the global opportunity in cholestatic liver disease, progressing our market-leading global commercialization approach in the top 25 markets to reach the 100,000 patients with rare cholestatic liver disease. Three, continue to enroll patients in our two gold standard global pivotal phase three studies in biliary atresia, BOLD, and allogeal syndrome, ASSERT. And number four, advance A3907 through phase one and into phase two. Move A2342 into the clinic and characterize our other novel bile acid modulators. Commercial readiness. Starting with our commercialization strategy and launch readiness, with a 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 anticipate an approval and launch in the second half of the year. Plainly, we need to be ready to launch at any time and are encouraged by the ongoing discussions and progress with U.S. and E.U. regulatory bodies on the path to gaining product approvals. Now, part of launch readiness is making sure that you have a brand name that is simple and consistent around the world. We are very pleased to announce that Bilvay is the brand name for Rotavixibat. That has been accepted by the EMA and has been provisionally accepted by the FDA. Having one global name is important for brand recognition and it's just not easy to achieve. The name BILVE supports our brand positioning and it's tested well with physicians and patients on multiple parameters. So we're really excited to unveil it now and then officially upon anticipated product approvals. Day one readiness is a core focus within our organization. And Pamela and her team are driving ahead on both the U.S. and EU launches and the rest of the world commercial partnerships, having made great strides and significant progress in hiring, onboarding, and training of people who are highly specialized in their respective geographies, functions, and in rare and liver disease markets. In the U.S., the sales team is onboarding and are surveying U.S. HCPs on their current management of PFIC patients in preparation for launch. At the same time, we're actively engaging with Travere Therapeutics to operationalize the planning for our combined efforts for the U.S. launch. Also on track are our customized in-house patient support services through Alvareo Assist. We have the entire care coordinator team in place, training alongside our commercial and medical teams, and working on perfecting the customized patient support services to help families navigate their access to Billabay from the start and be with them when they grow. In Europe, Germany is an early launch country and it has the largest market potential. So we have prioritized and completed hiring of the full team in Germany, including commercial, medical, and operations. We're also replicating our patient support services and localized for in-country needs and regulations. So Alvareosis Germany will soon be a reality, providing support services to optimize patient outcomes and support long-term adherence to bilve. In both the U.S. and Europe, we know we have a compelling bilve value story, including the PETFIC-1 randomized placebo-controlled trial, PETFIC-2 open-lasal data with patients on drunk beyond two years, NAPID natural history data, and the Caregiver Disease Burden Study. This compelling package of evidence should be an advantage in our mission to gain broad access of Build Bay across a wide range of patients. We have confidence in our comprehensive submission package and country-level plans that we have compiled to support the value of Build Bay and ensure patient access globally. Outside the U.S. and Europe, a key component of our commercialization strategy is a solid partnership network with leading rare disease companies. This is particularly important to regions such as Turkey and the Middle East that have an increased prevalence of PFIC, making them top 10 markets for commercial opportunities. So we're thrilled to share the completion of two ex-U.S. commercial partnerships for Bell Bay. The first with Genelash, or GEN, a leading specialty pharmaceutical company in Turkey with more than 20 years of experience, partnering with global pharmaceutical companies to bring innovative therapies and rare solutions to the community. GEN will be responsible for regulatory filings, reimbursement submissions, medical and commercial support for Build-A-Day. The second partnership is with GenPharm Services, a privately held regional pharmaceutical company focused on rare diseases, specifically in Saudi Arabia and the Gulf. Now, unlike other countries, the number one reason for pediatric liver transplants in Saudi Arabia is PFIC, making the region important for helping patients and commercial opportunities. Similar to our arrangement with GEN, GEN Pharma will be responsible for regulatory filings, reimbursement submissions, medical and commercial support for Bill of Rights. As part of both agreements, Alvareo net sales will be recognized on sales to each partner. Adding, again, and GenPharm agreements to the one signed in the first quarter with medicine, we now have three solid commercial distributorships in place. Each company is a rare disease market leader in its respective region, and each of the regions have some of the highest PFIC prevalence rates. These agreements are a demonstration of advancement of our well-laid plans as part of our global strategy for the commercialization of BuildAid. Now, as we look ahead to the longer-term commercialization readiness and expanding beyond PFIC, we continue to progress our pediatric development programs that will enable additional indications for current unmet cholestatic liver disease patients. The Global Pivotal Phase III Study of Bilve and Allergy Illness Syndrome, or CERT study, continues to enroll and dose patients, tracking to have all sites active in the first half of 2021, with top-line data available next year. The BOLD study, which is the first and only pivotal Phase III trial of an IVAD inhibitor in biliary atresia, continues to be on track, and we're meeting our patient enrollment goals with 48 global site activations, including 18 in the U.S. and 30 sites ex-U.S. Valeriatria is the largest pediatric cholestatic liver disease with an estimated prevalence of approximately 45,000 patients around the world. We anticipate top-line data in 2024. A positive data readout will lead to a major global expansion opportunity and a potential treatment that could make and impact on many families. Corporate growth, R&D. Looking at our early stage in preclinical work, our focus remains on smart pipeline expansion efforts, most recently solidifying progress in rare pediatric liver disease to adult and viral liver diseases. In March, we announced the initiation of our Phase I study with A3907, The first highly bioavailable ASBT inhibitor to enter the clinic, which we're planning to develop for adult cholestatic liver diseases, such as primary sclerosing cholangitis, PSE, and primary biliary cholangitis, PBC. This is significant. We dosed the first patients in the first inhuman study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral formulation. The unique properties of A3907, especially the high systemic availability, holds great promise for increasing dose to gain additional efficacy while minimizing the diarrhea dose-limiting effects observed with IPAD inhibitors in this patient population. Now that we have the Phase I study in progress, we're looking at the top-line data later this year and the initiation of Phase II in 2022. We're also pleased with the issuance of a U.S. composition of matter and method of use patent which provides exclusivity into 2040, not including patent term extension. We believe that A3907 has significant commercial potential in adult cholestatic liver diseases. We're also excited about ongoing preclinical studies and modeling for A2342, the first oral NTCP inhibitor for viral and cholestatic diseases. NTCP is a key transport 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 really excellent combinability potential. Hepcludex, a daily sub-Q NTCP inhibitor purchased by Gilead, for over a billion euros, provides both good scientific and financial value proof of concept. A2342 is currently in I&E enabling studies with a phase one trial, anticipate to start in 2022. Overall, we continue to expand our pipeline, delivering on the promise of scientific leadership. For context, A3907 is the third compound that the preclinical team has progressed into the clinic which continues to give us great confidence that A2342 will also advance this plan. There's also potential in our other bile acid modulator approaches the research team continues to work on. Enterprise strength. Beyond the outstanding hiring we've completed in the U.S., Europe, and most specifically Germany, U.K., and Italy, we are adding top-level leadership strength as part of the enterprise team. We recently established appointed Joan Connolly as Chief Technology Officer, who joined the organization to oversee drug substance and product development, clinical supply distribution, commercial supply chain, and quality. Joan's career spans manufacturing management, regulatory filing, CMC, and product commercialization, as well as supply chain, logistics, sourcing, and procurement. Most recently, Joan led technical operations at Stemline Therapeutics, where she was responsible for taking their lead product from the IND stage through to commercialization. And before that, Joan had held senior roles in Inclone Systems and Bristol-Myers Squibb. So we're fortunate to add Joan's expertise that spans early drug development through product launches, which is key as we prepare for launch while progressing our clinical and preclinical programs in pediatric and adult liver diseases. Geo's deep expertise and experience in end-to-end drug development and commercialization only strengthens our capabilities as we continue to progress our pipeline and prepare for the market. So, in summary, we feel very confident as we plan to launch BuildBay, taking us towards our ambition to achieve a billion dollars in BuildBay sales in the second part of the decade. progressing our clinical programs in allogene and bilirutresia, and further characterizing our promising preclinical compounds. We have the right vision, strategy, approach, and people as we continue to deliver on our corporate objectives and build Alvareo into a fully commercialized organization that will deliver on a successful product launch. Now let me turn it over to Simon to give you a quick financial update. Simon?

Thank you, Ron. Let me quickly summarize our financial results for Q1 2021. Revenues were $2 million for the first quarter of this year compared to $1.5 million for the first quarter of 2020. The higher revenue was due to the estimated royalty revenue received from EA Pharma for elabixabat for the treatment of chronic constipation. The royalty revenue, as always, is passed on to healthcare royalty partners. R&D expenses were $19.9 million for the first quarter of 2021 compared to $16.1 million for the first quarter of last year. The higher expenses were principally due to personnel expenses as we continue to increase our headcount and program activities. The increase in program activities was primarily due to Bill VEI for the regulatory submission in PFIC, and the additional indications for biliary atresia and allergy syndrome as we continue to drive our development programs. In addition, we increased spend for aid 3907 as the drug progresses in phase one. These increased expenses were partially offset by the fact that we are no longer developing elabixibat and due to lower spend in preclinical programs. General and administrative expenses were $15.3 million for the first quarter of the year, compared to $8.2 million for the same quarter last year. The increase is due to headcount and activities in a number of areas, such as marketing, field force preparations in the U.S. and Europe, and infrastructure to support commercialization in PFIC once anticipated approval is received. Net loss for the first quarter of 2021 was $43.7 million, or a loss of $2.29 per share, compared to a net loss of $31.5 million, or a net loss of $2.23 per share for the first quarter of 2020. As of March 31, 2021, we had cash and cash equivalents of $217.1 million, which compares to $251.3 million at December 31, 2020. The company has sufficient cash runway to fund the planned launch of Odovic Sabat in PIVIC and its development programs into 2023. Additionally, we plan to monetize a priority review voucher at an appropriate time if received upon approval. We have revised guidance for the 2021 operating cash firms which is now anticipated to be in the range of $130 to $135 million. The increase is primarily due to acceleration of the pipeline. For example, A3907 Phase 1 started earlier than originally planned, and to further bolster the fast-start Bilvey launch efforts. 2021 revenue from Bilvey is anticipated to be in the low single-digit U.S. dollar millions. With that, let me turn the call back over to Ron for closing remarks. Super.

Thank you, Simon. We started the year strong and marching toward the potential launch of BuildVay while progressing our pipeline, proving our ability to deliver our guidance. We need to bring BuildVay over the line in the U.S. and Europe with the issuance of a proprietary voucher and a fast start in the approved markets. So to recap our top priorities, number one, we're focusing on the global cholestatic liver disease opportunities in the top 25 markets, starting with PFIC regulatory approvals, patient access, and commercial distributorship agreements. Two, we will continue to enroll patients in our two global phase three studies in biliary atresia and allogel syndrome, as well as expand beyond PFIC. R&D will advance with A307 Phase 1 underway while moving A2342 into the clinic and characterize our other novel biolacin modulators. Overall, our global commercial strategy is solid with Bilvay's robust value proposition, our high level of readiness, and our actions to expand beyond PFIC into other diseases. In the coming months, we look forward to announcing the approval of Bilvay in both the U.S. and Europe in updating you on our launch efforts. So more to come on that. Thank you, everyone, for joining us, and we're pleased to open the call now for Q&A. Operator, over to you.

Thank you. If you would like to ask a question, please signal by pressing star 1 on your telephone keypad. If you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, press star 1 to ask a question. and we'll take our first question from N. Yang with Jefferies. Please go ahead.

Thank you. So a couple of questions. So I think for PFIC in the past, you mentioned that about 500 to 700 addressable patients in the U.S., most of them have been identified. So in the U.S., the question is, what would be the kind of gating factors to reach the patients and get them on the drug? And second question is on the European pricing side. So in the U.S., you know, at your commercial day, you talked about pricing range. But in EU, obviously Germany – would have the highest pricing. But overall, what do you think a pricing band would be? Thank you.

Hi, it's Pamela. To answer, I'll take the first question that you asked first around the gating factors in the U.S. with the estimated PFIC prevalence. You had mentioned that we shared on commercial day the 500 to 700 addressable patients in the U.S. The gating factors to reach this market potential, you know, I'd say are twofold. You know, one is ensuring that patients have access to therapy, and what we're doing there is with the payers, ensuring that they are educated around PFIC. And secondly, with Alvareo Assist, our customized patient support program, which will help individual patients navigate through reimbursement. And so to answer your question, we will be working as quickly as possible, and we know that payers, it takes time to move through that process, right, through the reimbursement process for each individual payer. So we'll be moving quickly to ensure we are addressing that gaining factor. On your second question around European pricing, we've done a lot of work. And as you know, in Europe, the reimbursement process, including Germany, is dependent on your ability to show the value of the product and be able to demonstrate efficacy through your clinical data, especially robust clinical data. And as we've looked across Europe, you know, we're confident in the pricing band that other rare disease analogs have been able to secure. So if you look across these analogs, it's quite, you know, well within the range. Typically we see a list prices that are within, you know, 20% to 30% of what you're going to see in the U.S., and that's the analogs that we're looking at. just closing. You know, we're excited. We're ready to go. And, you know, both in Europe and in the U.S.

Thank you.

Thanks for the question, Ewan. You know, just to add, you know, as Pamela said, probably the biggest issues for uptake is access. And as Pamela said, we're working actively here in the U.S., but also right around the world with our submissions. So what we would like to do as quickly as possible is get to the estimated between 2,300 and 2,800 available patients, right? And so that's where our focus is. But as Pamela says, it's access here in the U.S. and access in Europe as well. Thanks for the question, June.

We'll take our next question from Ritu Baral with Cohen. Please go ahead.

Good morning, guys. Thanks for taking the questions. And I'm going to beg your forgiveness as a jaded analyst who has been dealing with the FDA this last six months. Given your upcoming PDUFA date in July, have there been any new questions or submissions to the agency submitted that you think could drive a three-month extension of the PDUFA like we have, like we've seen all around. And then right now, as far as you know, without disclosing anything you can't, our labeling discussions plan to start on a relatively timely basis per usual schedules.

Ritu, thanks for the question. I'm sure that that's been a challenge for you on multiple fronts. As you can appreciate, I can't really get into the specifics on our dialogue with the FDA. Suffice to say that PFIC has high medical need. There's no approved drug. Our data in the PETFIC-1 and PETFIC-2 studies are great efficacy and great tolerability. And thus far, I think we've enjoyed a good dialogue with the agency. You know, they've been engaged and timely. So we feel pretty confident about our July 20th PDUFA date and the subsequent launch for BILVE in the U.S.

Got it. Thanks for addressing that. I guess as you think about your hires, as you mentioned, Alvareo Assist seems to be hired up and your field force is in place. Can you talk about, well, can you just reiterate sort of the headcount in both of those? And then who are the hires that you have made in those positions? What's their experience? Where are they from? And do they have preexisting relationships with you? pediatric hepatologists or those, you know, specialist centers.

Yeah, thanks for the question, Ritu. And I'll let Pamela talk about a little bit of the background. But, you know, in terms of numbers, you know, what we've said is we anticipate about 10 representatives in the U.S. In addition to the dozen representatives with Travera Therapeutics as a partner, we haven't really given – given the details in terms of the care coordinators, but suffice to say the care coordinators, there'll be enough individuals there to deal with any patients, all the prescriptions, and help those patients navigate through the process of getting access to Bill. Pamela, maybe you can talk a little bit about the background of our teams.

Yes, sure. So on our sales team, we've had the good fortune of just being able to recruit and attract really high-caliber, experienced sales professionals who have been working in, you know, I'd say there's two different things we're looking for that we've been able to achieve. The first is experience in the hepatology space. So to your point, they know the hepatologists. They have great experience, really understand and have existing relationships. And then the second would be the rare disease. So being able to understand how, you know, in an environment where you're going into sort of the targeted 60 centers, understanding and knowing how to sort of scale through the entire center. And so those two attributes, I would say, are the most important things, and we've been successful in being able to have those attributes on our team. And then, as Ron mentioned, that's bolstered by our partnership with because they have those existing relationships as well, and they're very experienced. And then the final thing is recency of experience. So we're taking people right out of the field right now who have been selling through the COVID environment, and so they have the virtual selling skills. So that's the makeup of our sales team. And then on the care coordinator side, again, we have hired care coordinators who have been doing this their entire career. have been working from highly experienced companies that have their own in-house patient support programs, who are very skilled at speaking with patients and families, as well as understanding how to navigate the complex reimbursement environment in the U.S. So really pleased and excited by the caliber of people we've been able to attract.

So the care coordinators have had rare disease, that sort of rare disease.

Absolutely, long history. We targeted rare disease companies, yep.

Super. And, sorry, last question that I want to speak in. Any last allowances for the COVID roll-off period that you're going to be launching into? We've heard from other companies that patient-doctor interactions have been down across a number of disease states. I'm just wondering how much of that – is applicable for pediatric post-static diseases, and do you see any trends in that sort of patient-clinician interaction thus far in the first half?

We find that in the serious, you know, rare diseases like this, that the interactions between the patients and the physicians has remained quite strong, either through in-person visits and or virtual visits. So we don't anticipate an impact in terms of patients being able to see their providers, you know, primarily because of the severity of this disease.

Got it. Thanks for letting me tweak that one and taking the rest.

Thanks, Richa.

And we'll take our next question from Leona Mosadas with Wedbush Securities. Please go ahead.

Thank you for taking my questions, and congratulations on your progress. For the label, are there any, do you expect a broad label or are there any bogeys that could happen or likely?

Well, Leanna, as you can appreciate, I really can't comment directly on our regulatory interactions. Suffice to say that we've submitted all five modules, both the FDA and the EMA, We submitted the PETFIC data, which you know hit both primary endpoints and showed good tolerability. We also submitted the PETFIC 2 open label data as well, an interim cut. And within that, we have PETFIC 1, 2, and 3 patients. So they have all the information. We're in active dialogue with them, and we're looking forward to sharing with you more details as we get past the PDUFA date of July 20th.

Thank you.

And we'll take our next question from Brian Scorney with Baird. Please go ahead.

Hey, good morning, everyone. Thank you for taking my question. I just want to kind of get a little help in trying to think through the near-term guidance on bull day sales and just kind of how to think about it a little bit on a medium term. And so for the near term, you know, how do we kind of think about that in terms of sort of new, entirely new starts versus patients on the expanded access program? And can you discuss at all the size of the expanded access program sample right now and the sort of timeline we should think about for converting those from the program to commercial form? And then on the medium term side of things, when you think about that 600 patient available U.S. market, you know, can you contextualize how many patients are there really ID'd and under care? And if I look at something like the launch of a Kalydeco, it basically had 90% of the ID'd patients on treatment about a year in. This is a bit of an outlier, but how should we be thinking about PFAC in that context and the differences you see in the markets that would sort of anticipate sort of a longer route to higher penetration?

Thanks. All right, great, Brian. Let me try and characterize how we see this year going. I think the way to think about this year is there's still a lot of variables that aren't quite clear as yet. And that's why we've given guidance for sales in the low single-digit million. So what's not good? We don't know exactly the date of approval, right? And remember that that's approval for both the U.S., the PDUFA date of July 20th, but also Europe. And remember, what we're trying to do is access the 2,300 to 2,800 patients, right, from a global perspective that are available. And these are people that are eligible for treatment right now. So what are the things that we have to have? First of all, we have to have an approval. So both the U.S. and Europe are pretty important. And we're still working on our European approval. So we don't know exactly when that's going to occur, but we feel confident that's going to occur in the second half of the year. The second thing is the sequencing of access, right? As Pamela has spoken about, we've been in dialogue with insurance companies in the US, but it does take time for them to process as well. We're in active dialogue with payers within Europe as well, and that will take some time as well. So we've got to work our way through that. So think of this year as the year of where we sort of sort through the access part of things, we sort through the regulatory process, right? And then your question about EAP patients and open label patients, part of that is these people are in different countries, right? So think about those patients as sort of correlating with that time of when we get approval and we get access. So as we think about this year, the patients that we are talking about here, the 2,300 to 2,800 available patients, these are patients that are available for therapy. They are in various stages of early diagnosis or waiting for treatment, and we'll try and access them as quickly as possible. Get access for them. Get them into Alvareo Assist. Put nice white gloves around them and take care of them and help them grow into being stronger and healthier children. Thanks, Brian. Thank you.

And we'll take our next question from Ed Ars with HCU Wainwright. Please go ahead.

Great. Thanks for taking my questions, and congrats on the continued progress across the pipeline. A couple of questions for me, probably first for Pamela. We're just a little over two months away from the PDUFA date now, and of course you've mentioned that your reps are onboarded. and doing the appropriate outreach, as well as, you know, the team at Travere, as well as your Alvareo Assist. It seems like everything is in place. I'm wondering what is the focus between now and PDUFA as, you know, the last few weeks in terms of, you know, what still may need to get done for that day one readiness?

So hi, Ed. Thanks for the question. Yeah, we're two months away from the PDUFA date, but we're ready to go now. So as mentioned, you know, we've hired, we've trained, we're onboarding. And so we are ready to go from an operational perspective, from a team perspective. And the one outstanding, you know, item is the final FDA-approved label. So between now and then, as we get more insight on that label, We keep training and training and training and fine-tuning, but we're ready to go. There's really nothing left. We could launch tomorrow. We've gone through all of the critical tasks that need to get done. So, yeah, from a commercial perspective, we're ready to go. We're just waiting for the approval.

Yeah, I think the way to think about it, Ed, is the team has just been practicing, right, and practicing what it looks like. you know, how we generate prescriptions, how we deliver drug, right, and how we make sure that throughout radio assist that the patients have a really great experience. So, you know, there's just some things you just can't do until you get the final label, right? And so once we get the final label, we'll be moving very quickly. Of course.

Right. So just one follow-up for me. On these commercial partnerships, as you mentioned, You just recently signed your second and third. I know there's 25 markets that you're focused on globally. Wondering if you could help us understand which of those are, you know, most likely amenable to partnerships either on a regional basis or country-by-country basis as you, you know, continue to march forward.

Hi, Ed, this is Simon. So as we've looked at regional partnerships, our approach has really been to say, let's focus first and foremost on those major markets where we will be able to launch relatively quickly following US and European anticipated approval. So if you look at top 10 markets overall, several countries come into the top 10 outside of Europe and the US. And those include Turkey, Saudi Arabia, and parts of the Gulf region, as well as Brazil in Latin America. So we've really tried to focus on some of those key top markets, because they typically allow for fairly early access in and of themselves as markets as well as being a good opportunity. And as we discussed on our commercial day, yeah, more than 50% of revenue typically in similar analogs in rare diseases comes from markets outside of the U.S. Then we have, for the longer term, we also are sort of looking at the opportunity for China As we said on commercial day, that's not in our top 25 markets currently of what we sort of projected going forward. But that is a good opportunity, particularly for biliary atresia longer term. But to go to a market such as that, we would want to make sure that we have the right milestones in place and that we are getting appropriate value from an opportunity such as that. But near-term focus... Turkey, Saudi, two of the top ten markets, and then Brazil is another important one.

Great. That's very helpful laying out the timeline. I appreciate it. Congrats again. Thank you, Ed.

And once again, if you would like to ask a question, please press star 1. We'll take our next question from Tim Lugo with William Blair. Please go ahead.

Thanks for the question, and I know everyone's probably excited about another regulatory question, but just following up on some of the, I guess, anxiety from the analyst community, you know, last year the agency had difficulty in kind of executing manufacturing inspections because of the pandemic, but, you know, hopefully that Not as much of an issue now with the U.S. opening back up. Can you just update us on your manufacturing status and how confident you are from a regulatory perspective?

I know there's anxiety out there, but to be honest, I'm not anxious. I think we feel really confident from a manufacturing perspective. As I said, we submitted the full module, the full CMC module, In our phase three study, we used the plan commercial formulation in that we spoke to, we had a good dialogue with the FDA a couple of years ago when we're executing on that plan, right? And that seems to be on track. So we feel pretty confident again about our approval around our PDUFA date of July 20th. And as Pamela said, we're ready to go from all fronts.

That's great to hear. Then, you know, let's kind of look forward into 2022 when hopefully we're all less anxious. You know, given the patient dynamics from the U.S. with your partner Travere, but also, you know, what should be a European approval, you know, knock on wood, hopefully by then, do you expect a significant apportionment of revenues in 2022 could be coming from Europe and maybe even a larger portion than what we would be seeing from the U.S.?

You know, again, as I said in my earlier response, there are multiple unknowns in this case, right? So the exact date of our U.S. approval, we think it's going to be the PDFA date of the 20th of July. We're in good dialogue with Europe, so the exact date of that. And then also, how these regional partnerships click in, and how access clicks in. So that's one of those ones we'll see. But frankly, we're focused on the global opportunity for Onivixima. We're building a pediatric cholestatic liver disease drug. We want to get at around 100,000 individuals around the world. And when it comes to PFIC, that range of 2,300 to 2,800 individuals, we're going to try and get to them as quickly as possible. And given that there are more patients outside the U.S., it's quite possible that we'll be seeing a higher than anticipated contribution from Europe, but it's really too early to say.

All right, great. Thank you for all the color.

Thanks.

We'll take our next question from Yasmeen Rahimi. Please go ahead. Hi, Tim.

Thank you so much for sharing all the updates. A couple questions for you. Maybe the first one would be, can you shed light into with PEDSIC to, you know, continuing to enroll and have patients on, have you been able to collect event rates, event rates meaning, you know, coming off of transplantation list or liver risk, Is there a potential that regulators could ask for those type of data points? And it may even require a separate, you know, study to be conducted. So I would love to hear your thoughts on that. And then maybe the second one is on the PRV. So, you know, what is, in your view, the likelihood of being granted the PRV, update approval, and then I have a follow-up.

So this is Pat, and I can take the one on the PET-FIC-2 study. So that is our ongoing study looking at the long-term safety and efficacy of Otavixibab in patients with all types of PFIC. And there we are really collecting those long-term outcomes. We're looking at time to biliary diversion surgery, time to liver transplant, whether patients can come off surgery list either from the biliary diversion surgery or liver transplantation. So that is an ongoing study. It's continuing as planned. The plans for that study are well known to both of the regulatory agencies. And in terms of post-marketing commitment, you know, certainly those will be part of the discussion with ongoing regulatory agencies.

And then I guess to add to that, Yasmeen, and answer your question about the PRV, when we were in dialogue with both regulatory agencies, the FDA and EMA, we had confirmed at that time that PEDFIC 1, on its own, was all that we needed to do from a submission perspective for approval, much like the single study of BOLD and the single study of ASSERT is needed for approval. The additional data that we gave for PEPFIC 2 gives additional color, the interim cut. And so those are the types of things we'll continue to talk through in terms of post-approval commitment, as Pat's indicated. Now, as it relates to the PRV, we announced a couple years ago that, in fact, the FDA has deemed Odovixabat as being PRV eligible. So we are PRV eligible. And I think the way you need to think about that is that approval pretty much equals PRV being granted, right? So we have to fulfill the requirements of the PRV, which is doing the PEDFix study and submitting the drug. There are some administrative pieces that have to occur, you know, on approval, but we feel pretty confident that the PRV will be issued on approval, and as you know, those are quite valuable. We sit in a very good cash position, so we have the luxury of, and we don't need the PRV, so we plan to monetize it, and we'll monetize it at the right time.

Thank you, Ron, and thank you, Pat, for the color. Maybe a follow-up. Germany may be one of the largest market opportunities there, and also you can go in with no pricing requirements, being able to get market access faster. Can you help us understand sort of how many patients have been identified in Germany, just to kind of help us understand more granularly on some of the larger opportunities, like how many patients that are at least in Germany alone that could be available for therapy? Thank you.

Thanks for that question. We're pretty excited about Germany because, as you said, there is a fair amount of people that immigrated into Germany with the disease, so I think it has a pretty good level of disease. We really are keeping leader support, and as you said, it has good pricing. At this time, we're not giving country-by-country detail in terms of numbers, but suffice to say, that in terms of patients that are available for treatment, you know, ex-US, we anticipate somewhere between 1,700 and 2,100 patients, so pretty significant opportunity there as well.

Thank you, Ron, for taking my question.

Thank you, Yasmeen.

As a reminder, please press star 1 to ask a question, and we'll take our next question from Joseph Stringer with Needham & Company. Please go ahead.

Hi, everyone. Good morning. Thanks for taking our questions. Just one on the kind of the competitive side of things. So you'd likely be first to market in the U.S. for PFIC and in Europe, you know, things go well, likely first to market. But could be a competitor coming to market in the first part of 2022 in PFIC in Europe. And just wanted to get your thoughts on You know, how do you see that affecting your current, you know, commercial prep and discussions around reimbursement and things in Europe? And maybe would there be any sort of, you know, read-through to your U.S. prep and launch discussions? Thank you.

Yeah, I think what we're really excited about, Joey, is that, you know, we're taking a leadership approach with Bilvay with all diseases right around the globe, right? So, you know, when you think about the PETFix study, the BOLD study, the ASSERT study, these are all gold standard, double-blind, placebo-controlled studies, right? And so they should help us gain approval, you know, if the latter two are successful, in multiple regions around the world, right? So we feel really good about our leadership approach though. But that's not only about regulatory approval, that also is from an access perspective, right? And so that will actually, that is level one, class one type information. Now we're gonna supplement that with an app and natural history database and a burden of care study. And we put together a pretty compelling access package. And when you consider in the PEPFIC data, we have both PFIC 1, 2, and 3 patients. So there's a lot of really interesting data there. So as a result, we believe that we will have a leadership approach, you know, for both regulatory approvals and access across multiple indications for Build Bay and building Build Bay into what we believe will be, you know, a billion-dollar product in the second part of the decade.

Great. Thanks for taking our questions.

Thanks, Joy.

It appears there are no further questions at this time. I'd like to turn the conference back to CEO Ron Cooper for any additional or closing remarks.

Great. Thanks, operator. Well, first of all, thank you all for attending today's conference call. As we continue to ready for approval, we'll update you on our regulatory filings and launch planning, as well as the advancement of our clinical programs as part of our growth strategy. Really appreciate your attention today. We have a lot of exciting near-term milestones ahead of us, and our strong financial position will enable us to continue to advance Alpareo's mission, which is to provide hope to families of patients with liver disease and the entire liver community. Thanks again to all of you for your continued support. Have a great day.

This concludes today's call. Thank you for your participation. You may now disconnect.