Intercept Pharmaceuticals, Inc.

Ladies and gentlemen, thank you for standing by. Your conference call shall begin momentarily. Thank you. Thank you. Thank you for standing by and welcome to Intercept Pharmaceuticals Q1 2022 earnings conference call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question at that time, please press star then one on your touchtone telephone. As a reminder, today's call is being recorded. I will now turn the conference to our host, Mr. Narek Subgerian, so you may begin.

Thank you. Good morning, and thank you for joining us on today's call. This morning, we issued a press release announcing our first quarter 2022 results and business updates, which is available on our website at interceptpharma.com. Before we begin our discussion, I'd like to note that during our call, we will be making forward-looking statements, including statements regarding our food product and clinical development program, certain regulatory matters, and our strategy, prospects, financial guidance, and future commercial and financial performance. Listeners are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this call, and we undertake no obligation to update such statements except as required by law. These forward-looking statements are based on estimates and assumptions that, although believed to be reasonable, are inherently uncertain and subject to a number of risks and uncertainties. Some, but not necessarily all, are the risk factors that could cause our actual results to differ materially from our historical results, or those anticipated or predicted by our forward-looking students are discussed in this morning's press release and in our periodic public findings with the SEC. Today's call will begin with prepared remarks from our President and CEO, Jerry Durso, our Chief Commercial Officer, Linda Richardson, President of Research and Development and Chief Medical Officer, Dr. Michelle Berry, and Chief Financial Officer, Andrew Say. We will then open the call to take questions. Please limit yourself to one initial question in order to allow time for all questions to be addressed. Let me now turn the call over to our CEO, Jerry Dosso.

Thanks, Narek, and good morning, everyone. Thank you for joining us on our first quarter 2022 earnings conference call. As we proceed through this transformational year for Intercept, I'm pleased with the progress that our team made in the first quarter. We reported $88.6 million in worldwide Ocaliba net sales, representing 8% growth, compared to the first quarter of 2021. While Ocaliba continued to deliver revenue growth on a worldwide basis in the U.S., as we expected, we saw a slower growth rate versus previous quarters given the cumulative impact of COVID-19 and last year's label update. Overall, our quarterly performance was in line with our expectations. With more than 20,000 patient years of experience for Ocaliba and PBC, we're strategically focused on generating and sharing compelling long-term data to support adoption of Ocaliba. Given the substantial number of patients with PBC who could benefit from second-line treatment, I remain confident in our ability to continue to grow this business over the long term. Turning to NASH, we're nearing completion of the new top-line data analysis from our Phase III Regenerate study, which will include a significantly larger data set than our interim analysis in 2019. NASH is the most rapidly growing cause of liver transplantation in the U.S., and people living with advanced fibrosis due to NASH urgently need an approved therapy. As the first company with positive Phase III data in NASH, we look forward to delivering these new data analyses and furthering our understanding of OCA's potential role in treating this disease. We continue to target a potential pre-submission meeting with the FDA in June. Our second Phase III trial in NASH reversed, evaluating OCA in patients with compensated cirrhosis due to NASH, is on track for a top-line readout in the third quarter. Our team has also made progress on our earlier stage pipeline programs, which Michelle will elaborate on later in this call. Turning now to the announcement we made yesterday. As you saw from our press release, Advance Pharma has acquired the rights to our international operations, including the rights to commercialize Ocala in PBC in markets outside the U.S., Also under the terms of the agreement, we'll receive royalties on any future ex-U.S. net sales of Obetacolic and NASC should Advanced Pharma pursue marketing authorization for this indication. Upon the closing of this transaction, Intercept will continue to be responsible for the manufacturing and supply of Obetacolic acid globally, and Advanced Pharma will be responsible for the packaging, distribution, and commercialization of the therapy in all markets outside the U.S., Intercept will maintain an office in the U.K. to manage our global supply chain, support our global clinical trials, and our quality organization, though the majority of current Intercept employees outside the U.S. will transfer to Advanced Pharma. Importantly, this transaction is consistent with the focus that we've been employing over the last year and a half. Since I've assumed the role of CEO, we've been laser focused on strengthening our financial foundation to support multiple pathways for future growth. Ultimately, this transaction was a financially strategic move for our organization, and the proceeds of the deal will significantly strengthen the company's balance sheet, increase our ability to invest in our core business priorities, including the support for a potential launch of NASH should we be successful in the U.S., and also allow us to continue to advance and expand our pipeline. I want to thank our international colleagues for their contributions to Intercept. I'm inspired by their commitment to bettering the lives and building a healthier tomorrow for people throughout the world with progressive non-viral liver diseases. We know that Advance Pharma will be positioned to drive growth of Ocaliba outside the U.S., and this will ultimately benefit the international PBC community. We look forward to working closely with the Advance Pharma team to ensure a seamless transition. Now, before we continue with the rest of our quarterly earnings recap, Andrew will now provide additional financial details around the agreement. Andrew?

Thanks, Jerry, and good morning, everyone. To provide a bit more color on this, under the terms of the agreement with Advance Pharma, Intercept will receive consideration in the amount of $405 million uptrend subject to customary working capital and other adjustments. We will receive an additional $45 million from Advance Pharma contingent upon receipt of an extension of pediatric orphan exclusivity in Europe. Subject to customary legal and regulatory approvals and other closing conditions, we expect to close in two to three months. As a result, we are suspending our financial guidance as we assess the impact and timing of this transaction on our organization. We anticipate providing revised 2022 financial guidance after the close of the transaction, likely during our second quarter earnings call. Ultimately, and as Jerry mentioned, this agreement reflects our commitment to a strong balance sheet and gives us the ability to invest in our strategic priorities, including support for a potential launch of NASH in the U.S. should we be successful. It also gives us flexibility to manage our debt obligations. With that, I'll turn the call over to Linda. Linda?

Thanks, Andrew, and good morning, everyone. I'm pleased to share that we continue to drive sales growth in our PBC business in the first quarter of this year. We delivered worldwide Ocalibur net sales of 88.6 million, which is comprised of U.S. sales of 59.2 million and ex-U.S. sales of 29.4 million, aligned with our expectations. In the U.S., we historically see evidence of seasonality in Q1 performance caused by benefit verification requirements and patient migration to new plans, which occur at the start of the year. this pattern was further exacerbated by a large number of national employers and health plans that migrated to new network specialty pharmacies, and this lengthened the time to process new prescriptions. In Q1 2022, we are also seeing the effect of last year's U.S. label update on reducing the number of patients eligible for Ocaliba. I would remind everyone that Q1 2021 included decompensated PBC patients, and those with evidence of portal hypertension, both in total prescriptions and entering as new Ocala patients. We believe that this will be just a transient phase and growth will return as we replenish the patient pipeline over the next few quarters. Current U.S. market dynamics show that nearly 90% of our physician interactions are now in person, patient visits are trending up in recent weeks, and we've seen a much quicker turnaround in patients moving through the enrollment process in March. Moving on to our international regions. In the first quarter, we saw continued growth driven by strong new patient starts. Our net sales were 21% higher than the same period last year, with all countries performing above budget. I would like to take a moment to acknowledge the many contributions and outstanding performance that the international team has made to the overall business, especially over the last 15 months when I have had the opportunity to work closely with them. In closing, we remain confident in our ability to drive growth, increase market penetration, and maintain a positive long-term outlook for our PBC business. While we recognize that lowering ALP has been a longstanding marker of improvement in PBC, optimizing care includes additional considerations. We believe outcomes data in PBC will become an important consideration for prescribers and patients as it addresses the higher goals of avoiding liver transplantation and improving morbidity and mortality. We are committed to generating and evaluating this type of data for Ocaliba, which we believe will be highly differentiating. As we move through 2022, new data from COBALT, additional real-world evidence, information from PBC registries, and the publication of the data we presented at AASLD last year will provide a continuous flow of messages on the important role Ocala plays as the only approved second-line therapy for patients with PBC. I'll now turn the call over to Dr. Michelle Berry. Michelle?

Thank you, Linda, and good morning, everyone. Today I'll be providing a few updates on our continued work to generate evidence supporting Ocala and PBC, as well as updates on our NASH development program and on our pipeline. Looking first at PBC, as we mentioned last quarter, we are focused on completing the analyses for the phase four cobalt study and leveraging real-world data sets to help show the clinical benefits of long-term therapy with Ocaliba beyond biochemical measures. The ultimate goal of therapy and PBC, those events that make a difference to someone living with PBC, is to prevent progression to end-stage liver disease, liver transplantation, and death. And we are generating substantial evidence from multiple different sources on the positive benefits of Ocaliba on these clinical outcomes. To that end, we were pleased to present pilot data last year at the liver meeting from the phase three POISE trial open label extension, which showed that individuals receiving Ocaliba for PBC in a clinical trial setting had statistically longer transplant-free survival when compared to individuals from external databases who were eligible but who did not receive Ocaliba. These data, which we expect to publish later this year, continue to generate very positive feedback from physicians regarding their impact on clinical decision-making and on the PBC community. Importantly, these data will be included as support for our post-marketing study, COVALT, and regulatory submissions to both FDA and EMA in the second half of this year. As we've previously communicated, we've closed our COVALT study because of challenges associated with retaining patients in a multi-year placebo-controlled study, especially when there's a commercially available therapy. we are compiling the final available placebo-controlled data from COVALT, including a new expanded primary endpoint that includes earlier clinical events that indicate progression toward decompensation. The new primary endpoint has a higher sensitivity for demonstrating Ocala's clinical benefit than the original primary endpoint of hospitalization for liver events, liver transplant, and death. We are working on completing top-line data analyses in the coming weeks and look forward to sharing them when available. Additionally, our data compilation from COBALT will include a pre-specified comparison of randomized patients who received Ocaliba with patients from external data sets. For the same reasons behind the closure of our COBALT study, we've initiated two retrospective real-world studies collectively called HEROES. which leverage real-world evidence to assess Ocala's impact on important clinical outcomes. Along with data from the phase three POIS trial open label extension and outcomes from COBALT, we intend to include these data as supportive evidence in our regulatory submissions later this year. Now on NASH. We're excited to be nearing completion of the new data analyses from our phase three Regenerate study and look forward to sharing these results. As a reminder, these new analyses will now include more than 8,000 patient years of safety data compared to around 2,400 in the prior submission and nearly 1,000 patients who've reached four years in Regenerate. The comprehensive assessment of the safety database will therefore provide a much more robust insight on OCA's benefit-risk profile in NASH. A pre-submission meeting with the FDA is currently scheduled for June, and we intend to continue the discussion on the structure and content of the potential submission. Although FDA has expressed interest in the totality of our data in NASH, which will include over 2,000 subjects with non-invasive tests, or NITs, We recently received additional feedback on our final data analysis plan, including details on the different populations of interest for a potential resubmission. The primary population for histology will mirror the original interim analysis population of 931 subjects. Additional analyses will consider the entire histology population, which includes the new 500 subjects. As with any FDA review, the agency can evaluate any patient population within a submission. We are also continuing to work toward a top line data readout from our base rate reverse study, the only active late stage study in compensated cirrhosis due to NASH. We anticipate delivering top line data from reverse in the third quarter. We will assess the role of these data in our ongoing dialogue with the agency once we have the results in hand. Overall, the amount of data we are generating in NASH, which regenerate and reverse, is unprecedented. And ultimately, upon completion of these analyses, we will have accumulated the largest phase three clinical trial data set in the field. Moving on to our pipeline, we continue to screen patients and add clinical sites in our U.S.-based phase two study of our OCA-fezofibrate-fixis combination for PBC. In addition, we continue to enroll our international Phase II study that is evaluating different dosing regimens of the OCA-VEZA combination. Our large Phase I study in the U.S. to better characterize the exposure data and any potential drug-drug interactions of the fixed-dose combination remains ongoing. Together, these three studies will inform the dose selection and study design for a Phase III trial. Our comprehensive phase one study for our next generation FXR agonist, INT787, is ongoing, and we are on track to have an open IND in the coming weeks. We look forward to sharing additional information about our intended indication and development plans for INT787 later this year. I will now turn the call over to Andrew for a financial update. Andrew?

Thank you, Michelle. Please refer to our press release issued earlier today for a summary of our financial results for the first quarter ended March 31, 2022. In the first quarter, we recognized $88.6 million in worldwide Ocala net sales, representing 8% growth over the prior year quarter. Our worldwide Ocala net sales were comprised of U.S. net sales of $59.2 million and ex-U.S. net sales of $29.4 million. In the U.S., as anticipated, we experienced a typical seasonality in Q1 patients as Q1 patients were impacted by the resetting of insurance plans and Medicare coverage gaps at the beginning of the year. Our gap operating expenses and non-gap adjusted operating expenses for the quarter were $98.9 million and $91.8 million, respectively. This was a decrease of $12.1 million and $9.9 million versus the prior year quarter as we continue to focus on cost management. As a reminder, our non-GAAP adjusted operating expenses excludes stock-based compensation and depreciation. Non-GAAP adjusted operating expenses is a non-GAAP financial measure under SEC regulations. Please refer to our press release issued earlier this morning for a full explanation and reconciliation of this measure. Our cost of sales was $0.8 million, and the quarters ended March 31, 2022 and 2021. Our cost of sales for the quarters ended March 31, 2022 and 2021 consisted primarily of packaging, labeling, materials, and related expenses. Our selling general and administrative expenses were $50 million in the first quarter of 2022, down from $59.3 million in the prior year quarter. The decrease was primarily driven by our ongoing efforts to manage our operational costs and to run the business as efficiently as possible. Our research and development expenses were $48.1 million in the first quarter of 2022, down from $50.8 million in the prior year quarter, as we continue to drive efficiencies while progressing our NASH program. Interest expense for the quarter ended March 31, 2022, with $6.7 million. We expect cash interest expense to be approximately $23.5 million for the full year based on our current capital structure. In the first quarter of 2022, we reported a net loss of $17.3 million, a decrease compared to a net loss of $40.4 million in the first quarter of 2021. As of March 31, 2022, we were well positioned with cash, cash equivalents, restricted cash, and investment debt securities available for sale of $406.9 million. In summary, I am pleased with our commercial performance, which is on track in the first quarter, and our continued cost management during this important time in Intercept's history. We are well positioned to continue investing in the growth of OCALVA and PBC, supporting our NASH development program and regulatory process with the FDA, and furthering our pipeline. With that, I'd now like to turn it over to the operator for any questions. Operator?

Thank you. Again, ladies and gentlemen, if you'd like to ask a question, please press star then 1 on your touch-tone telephone. Our first question comes from Yasmine Rahimi of Piper Sandler. Your line is open.

Good morning, team, and thank you for taking the questions, and congrats on the new partnership with Advanced Pharma. Two quick questions for you. One is directed to Michelle. Maybe I'll start off with, are we going to be seeing the interim data after you've had your meeting with the FDA in June, or are you planning to meet with the FDA first? and then come back and release the data and kind of provide a comprehensive overview of data as well as the next steps. And then the second question is in regards to advanced pharma deal, what do they want to see in order to motivate them to partner for a national ex-US geographies? And thank you so much for taking my questions.

Okay, thanks, Yaz. We'll flip it right to Michelle on the first question, and then I'll come back with the question on the deal.

Great. Good morning, Yaz. So on the data, as you're aware, as soon as we have the data, that certainly is material for the company. So we would be releasing those top line data as soon as we have those and they're ready to share. We do have the pre-submission meeting calendar with the FDA. You don't have to have those data in hand to have the meeting. And actually, there are some companies that have their pre-submission meetings planned well before they have data in hand, because the majority of those conversations, frankly, are around the structure of the submission and making sure that the company and the agency are aligned. on the different populations of interest so that you can get all of your tables, listings, figures lined up and ready to submit. So we, again, we will have those data released as soon as we have those in hand. Can't say much more specifically about that at the moment, but you'll hear about it.

Yeah, and on the considerations around NASH, as Advanced Pharma has the rights to commercialization in the territory, they would be determining whether or how to pursue on a regulatory basis in NASH. Obviously, as the global developer, we would have the data. We would provide them with the data that we're in preparation for now, and then they would make a decision. We did think it was important in the structure of this deal that we were able to benefit from a potential upside in NASH outside of the U.S., so we felt good about the inclusion of a strong double-digit royalty should ADVANZ pursue and be successful with securing availability of OCA and NASH outside of the U.S.

Thank you, Tim, and I'll jump back in the queue.

Thanks.

Thank you. Our next question comes from Ritu Baral of Taiwan. Your line is open.

Good morning, everyone. Thanks for taking the question. Could we just go through exactly what will be part of the resubmission to the FDA, just as far as patient numbers? Michelle, am I sort of reading this right? You're going to have 1,400 patients at the primary endpoint. And can you tell us, I guess, how many total discrete patients have been treated with drug? And then I've got a question about reverse.

Okay. Thanks, Ritu.

Sure. Hi. Good morning, Ritu. So, in the submission, we've, again, been in a lot of dialogue with the FDA about specifically which populations they wanted to see. As we've talked a lot about over the last year or so, their main area of interest is looking at the primary population of that mirrors what was part of the original submission in 2019. So the 931 patients that were part of that ITT analysis read by central readers. So as long as we mirror that population, we don't use any alpha. So that's really critical. They, of course, are interested in looking at all of the histology data that we have for subjects that have both a baseline and a month 18. And that includes the new 500. So that would be part of another analysis. But the group that has both the central read from the original analysis and both that and the new consensus pathology reads would be the primary submission will be the top line. We also have subjects who are out at 4,800. That's the total safety population that we've talked about. We have 1,000 subjects who are now out to 48 months. So that's what comprises our safety population with over 8,000 patient years of data. So again, a substantially more robust package. than what was submitted in 2019. I know it gets a little complicated. This is certainly not a straightforward submission. It is an accelerated approval with a surrogate endpoint, with several surrogate endpoints, including the non-invasive test, as well as, you know, continuing to move toward that full primary indicate, primary analysis for clinical endpoints. This submission, is a resubmission on an interim analysis using a new methodology, but importantly, is focused on that same population that mirrors the original submission from 2019. Got it.

Okay. And then you mentioned FDA was interested in a few different populations. Was there any mention of a subpopulation that encompasses potential FAST progressors? We've heard a lot of that over the years from KOLs.

We'll certainly be looking at that. I don't anticipate that we will have that with our top line data, but we have multiple populations that will be assessed following the availability of those top line data.

Got it. And then just going back to reverse and the primary endpoint on that. Any, or just the analysis, other companies have moved to moving their endpoint to something more biomarker-based, maybe ELF, and other companies are incorporating AI into some of their fibrosis assessments. Any plans to either amend the various endpoints to include AI quantification or, I guess, promote the importance of ELF within the analysis?

So, we do have secondary endpoints that include all of these other non-invasive tests, including the wet biomarkers, as well as the non-invasive fiber scan, et cetera, that will be included as secondary analyses. And apologies, we're going to ask folks to stick to one question and then to let everybody get through the queue. Those data will be available in the third quarter. Thanks, Richie.

Thank you. Our next question comes from Thomas Smith of the SBB. Your line is open.

Hey, guys. Good morning. Thanks for taking the questions. Just on... On the advance deal, can you comment on how much visibility advance has into the ongoing regenerate reanalyses and the reverse trials they were conducting, their diligence? And then can you also provide, I guess, any additional details on just thinking financially, you know, the split of your operational spend that's currently ex-UF relative to the global total? Thanks. Thanks.

Thanks, Thomas. Appreciate the question. You know, obviously, Advance did a deep, diligent process, as you can imagine. Can't really comment much further than that, except that, you know, they have done a deep dive on the company. Andrew, maybe you want to comment on Thomas. As I understand your question, it was kind of color around commercial investment by territory. Was that kind of what you were trying to get at there?

Correct, yeah, operational spend ex-U.S.

Yeah, Thomas, thanks for the question. Look, you know, we don't break out our profitability by segment, but what I can tell you is that both segments, the international business unit, commercial unit, and the U.S. business unit are very profitable. So you can see the gross margin that we have on the top of our P&L. Just by virtue of the U.S. being sized, the majority of our profits come through the U.S. business. Having said that, the international business is also a terrific business. It's showing terrific growth, and we think Advans is getting a great asset. This made sense for us and on the strategic level, so we think it's a very fair, good transaction for both sides. And, yes, we do keep the majority of the profits generated by Ocala just by nature of the U.S. business being larger.

Okay, great.

Thanks.

I appreciate you taking the question. Yeah, that's helpful. Thanks.

Thank you. Again, ladies and gentlemen, we please ask that you please limit yourself to one question, and then you may return to the queue to follow up. Thank you. Our next question comes from Mayank Mantani of B. Raleigh. Your line is open. Okay.

Thank you. Thanks for taking our questions and congrats on the advance, dude. So just maybe a quick clarification question on PPC and then I do have a Nash question also. So on the U.S. component of the previously issued guidance, have you, has there any underlying assumptions changed? I know your guidance was suspended, but relative to the last time you issued, has anything changed there? And then the HERO study that You just initiated, can you just clarify the timeline for that data and whether that would be part of the PBC submission? And then lastly, just on NASH, now that you're out four years with some patients, is there an event rate analysis that has been done, even in a blinded manner, that at least informs you how you're tracking relative to your initial prediction? Thanks for taking our question. Okay.

All right, so maybe we start with the question around guidance and sales, which we have suspended the guidance pending closing and an ability to come back later with an update.

Yeah, sure. With regard to guidance, nothing has fundamentally changed in the business. You know, had the advance transaction not taken place, we're very comfortable with the guidance that we issued earlier in the year. And we likely would have reiterated we're on track. We're very happy with where sales were in the first quarter, both in the U.S. and internationally. Expenses are very under control. You know, we're suspending largely due to the fact that we just can't impact the timing of the transaction. We just think it makes sense to reissue in Q2. But, no, nothing fundamentally has changed.

Michelle, maybe on HEROES?

Yes, so you'll recall at the liver meeting last year we presented the pilot study from the POIS Open Label Extension compared with a large external database and showed the impact of Ocalibut on improved and highly statistically significant improved transplant-free survival. We are now turning to two larger external databases to pull data from the over 20,000 patient years of data that we know of in Ocala and PBC to support the data from our cobalt study. We will be submitting the primary analyses from cobalt to both the FDA and EMA, but we will be supporting those data with these two large databases, one patient registry and one that's a claims database that we hope will also continue to show this transplant-free survival as we showed in the data last year.

Thanks for the question.

Thank you. Our next question comes from John Willadin of JMP Securities. Your line is open.

Hey, thanks for taking the question and the updates today. Michelle, just hoping for clarification for the confusing feedback from FDA. When you use the word mirrors, I just wanted to clarify, are they primarily just wanting you to reread the biopsies from the 931 patients from the interim analysis with your new methodology using three readers? Is that their primary focus for the new data package?

Yes, sir, just to start off. Yes, we are rereading all of those subjects, but importantly, their primary focus for this resubmission of interim analysis is on those 931 patients that mirrored the original interim analysis and that were read by central, the two central readers. This is using the new methodology as we've been talking about for almost a year now. It's really important for the FDA to learn from this very large database. So we're excited to be providing them with those data. But certainly every patient who has been willing to provide us with a liver biopsy will be included in this database, both for the interim analysis and in the eventual analysis of the full data set. But again, this second interim analysis of the same data set, that's what I was referring to with the mirrored primary analysis.

Thank you. Our next question comes from Brian Abrams from RBC Capital Markets. Your line is open.

Hey, guys. Good morning. Thanks for taking my question, and congratulations on the licensing deal. So I guess just kind of along the lines on Regenerate, maybe another question for you, Michelle. So just given that you won't be able to or you won't be including those additional 500 biopsies in the primary histology endpoint that, you know, may have helped broaden the overall database, do you believe that you'll need to show a wider delta on the primary endpoint? or is a comparable effect to what you showed in the interim with the more reliable methodology now, coupled with the larger long-term safety database that you'll have, do you think that'll be sufficient?

That's a great question. And again, remember the draft guidance had recently been issued in which the FDA stated that they wanted to look at a consensus methodology. So they want to make sure that they're looking at the same patient population that was previously analyzed using central readers. So they have an apples to apples comparison of that same data set to see if that addresses their prior concerns with discordance between two readers. However, they will be looking at the full data set, certainly ethically. Any patient who undergoes a liver transplant will be included in these analyses, and they're going to want to see every single patient included in one of the analyses. But for that first analysis, they wanted to make sure it was mirroring the original patient population.

Thank you. Our next question comes from Michael Yee of Jefferies. Your line is open.

Hi, thanks. Good morning. I appreciate the questions. Hi, Mike. Our question relates to maybe the timing of the transaction, literally right ahead of the regenerate, reread, and in front of the reverse cirrhosis study, just from the concept of if someone's getting all the rights to this drug outside the United States, wouldn't they want to have some insight into that? and how you thought about the timing of that personally, given if it was all positive this quarter and next quarter, then the whole value of the whole asset, including OUS, would go up. So maybe you could just talk a little bit about that and the second part of that, which is literally the same thing. How do they decide whether they want to file in OUS or not, and is that their NDA or NAA, not yours? They fully control all that. Thank you.

Thanks, Mike. Appreciate the questions. You know, we've talked and we've been focused as we looked at the transformational period that we're in and will be in as we look at this about ensuring that the financial foundation is as strong as possible and as we consider the potential next steps for Intercept as on a strategic basis getting as much optionality as we can. And so the level of value here we felt comfortable with at this time, and I think when we think ahead to creating the right kind of optionality, I think the strengthening of our balance sheet will allow us, in all scenarios, frankly, to move the company forward and ensure that whichever path we're on, we have strong ability to invest and make the right financial choices. So, again, based on The strength of the deal, we felt it was in the best interest to do the deal. And again, I think to the good optionality, whichever we pursue. It's difficult for me to speculate on advances thinking they will have the decision-making ability to decide whether or not to file. And according to the rights they gained, they will be the regulatory interactor in the territories that they own. So again, that would be their decision. We would, as the global developer, give them access to the data that we generate and the history of our discussion and how it continues in the U.S. on the regulatory side, but it would be their call.

Thank you. Our next question comes from Jay Olson of Oppenheimer. Your line is open.

Hey, congrats on the deal with ADVANCE, and thank you for taking my question. Can you talk about the... Can you talk about the process for selling the ex-U.S. Ocala business to Advans? Was that a competitive process with multiple bidders? And did that process also contemplate selling the U.S. Ocala business? And does that deal include the rights to the OCA Bezafibrate combo, or do you retain those rights ex-U.S.? Thank you.

So, as a reminder, our rights to Bezafibrate and our development plan for Bezafibrate is a U.S.-specific plan. The agreement with ADVANZ is specific to Ocala in PBC. And, obviously, if they pursue OCA monotherapy in NASH, they have the rights to pursue that, as well with the royalty I mentioned earlier from $1 sales if they if they succeed there. There was another part to your question. Oh, the process. Yes, there were multiple parties involved in the process.

Thank you. Our next question comes from Brian Scornier-Baird. Your line is open.

Hey, good morning, everyone. My question is really on what your level of commitment to completing Regenerate is as designed. This deal gives you a substantial cash possession, but it just seems like if the FDA doesn't allow OCA to get a review based on this reanalysis, the cost of running this fully out to 2025 or later might be kind of too much to bear. So I guess why not just stop the study now and see what you have? How many events have occurred at this point And in between any trends and events, 1,000 four-year biopsies, 2,500 72-week biopsies, and 8,000 patient years of safety. If this reanalysis isn't sufficient, is that the most likely option of what you would do to move forward?

Yeah, maybe I'd start on that, and Michelle can add some color on the work that will continue. So, you know, we've said that we are focused in the interactions with the agency and obviously with the data centers. sets that we're in the process of generating exclusively on the potential of OCA and NASH on an accelerated approval pathway. That's where our focus is. Obviously, the data and the subsequent interactions will define the right next steps, but we are exclusively focused on the accelerated pathway, which is one of the reasons why it's been so important for us, as I mentioned, a bit earlier to make sure that the foundation financially was as strong as possible so that we do have good optionality regardless of the strategic path that we choose here. Michelle, any color on the outcomes piece, just that we continue to accumulate the data set if we are able to succeed on the accelerated approval pathway? We'll need that data eventually.

The only thing I'd add on that, Jerry, is that both the histology endpoint and the noninvasive tests are considered potential surrogate markers, and both of those would need to be validated against the clinical outcomes. So, without clinical outcomes, neither have been validated to date. So, I do believe that the agency continues to have much interest in looking at that that potential correlation with those clinical outcomes. But as Jerry said, this interim analysis is focused on the month 18 surrogate analysis of histology, and certainly all those secondary non-invasive tests will be part of the package to be submitted.

Thank you. Our next question comes from Steve Seedhouse of Raymond James. Your line is open.

Good morning. Thank you. In your prepared comments, you sounded confident that you have not, in fact, peaked in PBC in terms of penetration. I guess it's unclear from slide four how much U.S. growth could be expected going forward. So I wanted to ask about volume growth, specifically in the U.S. and PBC year over year. What was that this quarter? And what do you expect you can achieve in terms of volume growth post-cobalt data, assuming that's positive? Thanks.

So I think that we're very confident in our ability, remember, we need to come through a period where we lost 5 to 7% of our business based on a label change. So, we'll look at moving forward, replenishing that part and, you know, new patient starts are very fundamental to that. And as I said in the opening comments, we believe that we have a pipeline of data coming that will help with, you know, publications and our resubmission for full approval. in the U.S. that will allow us to be highly differentiated and offering value unmatched. With the amount of time that we've been on the market, these are the others, we're going to be in great stead. So that's our kind of plan and a long-term plan. Focus, though, is get back to growing the underlying business. And if we look at even units, frankly, units are up because we are going from smaller scripts that could be for those patients who were only taking two, three, you know, four twice a week for four weeks, you know, that's low volume. Now that we're on the 30-day regimens and we're moving forward in that capacity, we actually have higher volume.

The only other additional point I'd make is just a reminder that, you know, we estimate only about one-third of the potential candidates for Alava, according to the label, have been on treatment. So there is still a significant pool of patients who qualify for treatment who are within the label and who Ocaliba would be the only indicated option for as second-line patients. So we'll continue the good work ahead on Ocaliba in the U.S.

And we're seeing, we're continuing with our strategy of expansion to community gastros. We're continuing to see new prescribers come in, to the market. And as we said before, new visits are up again. Patients are back in and seeing their physicians. So I think this kind of combination of new prescribers, patient visits, and new data really does give us a positive path forward.

Thank you. Our next question comes from Joseph Stringer of Needham and Company. Your line is open.

Hi, good morning. Thanks for taking our questions. Just a quick one on 787, just given the mechanism of action, FXR agonist follow-on, would you consider NASH as an indication or would you look to explore other types of indications for that? Thank you.

All right. Great question. Happy to talk about 787. We look forward to sharing more about this molecule. Very excited about it and look forward to rolling out all of the preclinical data that we now have on this molecule, how it differentiates from OCA, and the potential indications that we are pursuing later this year. So we look forward to sharing all of that. Again, a really exciting molecule. I think, you know, we are continuing to push forward on that. I think that our commitment there with OCA Certainly can't be questioned, but I think we are looking at a molecule that does differentiate and gives us a lot of exciting optionality. We look forward to talking about that later on this year.

Thank you. Our next question comes from Ellie Merle of UBS. Your line is open.

Hey, guys. Thanks for taking the question. Just in terms of the updated data, could you provide maybe some more color From the safety perspective in NASH, I guess what we'll be getting, particularly as it pertains to potential longer-term safety updates, and if any sort of, you know, liver events such as, say, progression to cirrhosis would be included as, say, a safety event ahead of a potential longer-term outcome data read. Thanks.

Thanks for the question, Ellie. Michelle?

Yep, so on safety, we will be giving the, with the top line, we are happy that we will be able to include all the adjudications there as well. So, you may recall with this much larger, more robust safety database, we did specifically have an independent committee looking at adjudicated cases for hepatic safety events, but not clinical outcomes for this analysis. at cardiovascular safety and at renal safety, given that this patient population has a higher incidence of type 2 diabetes, et cetera, that puts them at increased risk there. So need to make sure that the hepatic, cardiovascular, and kidney safety are all fully adjudicated. So we will be planning to share that with the top line data. Certainly, all the details along those will be shared later at a scientific conference. The hepatic outcomes will be part of the final analysis for this. Those events are also being adjudicated, and that will include the month 48 histopathology, which should represent over half, maybe even over two-thirds of those cases of progression to cirrhosis.

Thank you. Our next question comes from Salveen Richter of Goldman Sachs. Your line is open.

Hey, thanks for taking the question. This is Matt on for Salveen. I just want to see if there's anything special we should consider as we model this transaction. Will the $405 million roughly be recorded in the next month or two, you said? And then the royalties, you said these are double digits. Are these flat or tiered? And then... In terms of, I'm assuming there's no milestone payments attached to that either. But just wondering if there's anything else we should consider. Thank you very much.

Yeah, sure. Happy to take that. So, yeah, the $405 million is, you know, as described, it's a cash payment upfront that's going to be net of working capital and other fees on the transaction. That will come through immediately upon close, which, as we've said, we expect to be in the next two to three months, depending upon regulatory. We're hoping to get that in by the end of June, but, you know, you can't control the regulatory process. In terms of the royalty, the upfront 405 and subsequent 45 is really related to just the Ocala PBC business. The royalty is for any new indications in territories outside the U.S. So that would only kick in in the event that they get essentially a NASH indication in any of the ex-US territories. That royalty, as Jerry mentioned, is sort of a strong double-digit royalty. It goes down to zero dollars. It's not tiered. So it starts at sales one and stays flat, you know, throughout the sales process for NASH. Is that helpful?

Thank you. Our next question comes from Jeff Meacham of Bank of America. Your line is open.

Good morning. This is Jason on for Jeff. Thank you so much for taking our question, and let me also extend my congratulations on the outlicing deal as well. I wanted to return to Nash. Appreciating that safety is obviously a primary focus on the resubmission, do you have a sense of how critical or at least how much of a focus the additional efficacy data will be, especially given kind of the biopsy outcomes. I guess along these lines, could you see reverse being potentially part of the resubmission package? Thanks.

Hi, Jason. Thanks for the question. So certainly the CRL previously was focused on the benefit-risk, and this now much more robust safety database will play a key role there. As I've mentioned in prior calls, I think with a compound that is likely to be used for life after initiation of therapy, once patients have progressed to advanced fibrosis for sure, that it's important to have long-term safety data. We'll be presenting those data with our top line, showing especially those cardiovascular, hepatic, and renal safety parameters On the efficacy side, we do have an increased patient population with the new 500, but as I've mentioned before, with this new methodology, the FDA has been clear that they want a comparison of the prior analyses with the central reader versus the new consensus panel methodology. So that will be the first. analysis, but clearly we want to include all of those subjects and the FDA as well has expressed their interest in the total weight of the evidence for the molecule. With regard to reverse, yes, I do expect that that would be an additional data set that will be critical, especially because this will be the first readout that we have in any large study in an advanced phase three setting in patients with compensated cirrhosis. So I think that will be of great interest certainly to all of us to see where these patients are who are really beginning to get more advanced in their disease process. So we'll be looking to have those conversations with the agency about As I mentioned earlier, the content and the structure of the potential resubmission. Thanks for the question.

Thank you. Our next question comes from Ritu Barra of Cowan. Your line is open.

Hi, guys. Thanks for taking the follow-up. I did want to just ask about any inclusion of AI on reverse or how you're thinking about that endpoint Michelle, I think you did, no, sorry, that was unpoised when you were saying we were going to include earlier events for the Phase 4 resubmission. I guess that was my second follow-up question, if you have time. Thanks.

Yeah, yeah, thanks for your patience on those, Richie. So, yes, in the NASH setting, we are looking at some exploratory and secondary endpoints, looking at AI. Those are certainly growing in interest, either as a way to assist with a human pathologist, and sort of funny, we have to specify that those are human reads now, but there is increasing interest there in sort of addressing some of the concerns that the FDA had had about variability in human interpretation of histopathology and how AI can be helpful. We've certainly seen that in other therapeutic areas where AI can be particularly helpful in those outcomes assessments. So we are both in regenerate and reverse and including AI and a couple of different companies that we've been working with on that front. I think your other question was about COBOL and the new expanded primary endpoint that includes some of the earlier events. Because I think the, all the regulators have recognized how difficult it is to ask patients to remain on a blinded placebo-controlled study when they have a progressive disease, and they can frankly look at their own biochemistry. and see whether or not they're on placebo or active drug. It's difficult to ask them to stay on what is probably a placebo arm of a long-term study. So, we are grateful that we have been able to work with the regulators to expand that primary endpoint to have a broader composite. that we believe increases the sensitivity for detecting the clinical benefit of Ocalva in these patients at an earlier phase before they progress to liver transplant hospitalization for liver events or death.

Thank you. Ladies and gentlemen, I'm sure no further questions. I'd like to turn the call back over to Jerry Dorso for any closing remarks.

So thanks everyone for joining us today. In closing, I definitely believe that the work that Intercept teams accomplished in the first quarter, in addition to all the work since then, specifically the recent agreement with Advanced Pharma puts us in a strong position to manage what we know is an extremely important time for Intercept as we build for the future. I definitely look forward to the work ahead and to sharing more updates as things progress. Last and certainly not least, as we head into this weekend, my best to all the mothers out there. Thanks, and we'll talk soon. Take care.

Thank you. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating, and have a great day. You may now disconnect.