Intercept Pharmaceuticals, Inc.

Hello, thank you for standing by and welcome to the second quarter Intercept Pharmaceuticals earnings call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1-1 on your telephone. Please be advised that today's conference may be recorded. I would now like to hand the conference over to your speaker today, Narek Segarian, Executive Director, Investor Relations. Please go ahead.

Thank you. Good morning and thank you for joining us on today's call. This morning, we issued a press release announcing our second 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 approved 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, of 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 statements are discussed in this morning's press release and in our periodic public filing 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 Saik. 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 Durso.

Thanks, Narag, and good morning, everyone. Thank you for joining us on our second quarter 2022 earnings conference call. As we move past the midway point of this transformational year for Intercept, I'm delighted with the milestones we've reached and the progress we've made to strengthen the foundation of our company. We've built a strong and successful Ocaliba franchise in PBC, and we continue to break new ground in showcasing what this treatment can bring to the appropriate patient populations. We're continuously generating and sharing new long-term data about Ocaliba. And looking ahead, we know there remains a substantial population of patients that could benefit from adding Ocaliba to their treatment regimen. This is evident in the performance we saw in the second quarter of the year, where we reported $71.8 million of U.S. Ocaliba net sales. representing 5% growth compared to the second quarter of 2021. Importantly, the underlying dynamics of Ocaliva indicate that we're moving past the forecasted implications of last year's label change, with prescribing and perception strengthening. We're looking forward to good momentum throughout the rest of the year and beyond. Turning to NASH, I'm thrilled with the results of the top-line readout we announced last month concerning the long-term use of OCA in patients with fibrosis due to NASH. In addition to reinforcing the efficacy of OCA as an antifibrotic, with the second analysis, we now have the benefit of a deeper understanding of safety over a longer period of time. Given the data we've gathered, we're confident in the improved benefit-risk profile of OCA and its potential role as the first therapy in NASH. We had a constructive pre-submission meeting with FDA in July, and we look forward to resubmitting our NDA by the end of this year. At the same time, we're in the process of refining the planning of our commercial strategy in NASH, now that we have data in hand. We expect to take a milestone-driven approach to our commercial preparations, and we'll speak more about that in the future. Regarding our second phase three trial reversed, which is evaluating OCA in patients with compensated cirrhosis due to NASH, we expect a top-line readout in late third quarter. Michelle will provide greater clarity on reverse and our other pipeline programs later in today's call. Finally, the recent sale of our international business has significantly strengthened our balance sheet, which positions us well for future growth and success. We're continuing to drive growth in our foundational business of O'Callaghan PDC, executing the next step in support of OCA's potential as the first therapy in NASH, including the resubmission of our NDA and advancing our key pipeline programs. With that, I'll now turn the call over to Linda. Linda,

Thanks, Jerry, and good morning, everyone. I'm pleased to share that we continue to drive sales growth in our PBC business in the second quarter of this year. We delivered worldwide Ocala non-gap adjusted net sales in PBC of $100.4 million and U.S. net sales of $71.8 million, representing 5% growth over the prior year quarter. Given the completion of the sale of our international business, I'll keep my comments focused on the U.S. performance to date and moving forward in 2022. As we have previously stated, the impact of the label update should be fully completed as we enter the second half of 2022, meaning that in Q3 and Q4, we will be evaluating comparable PPC populations for the first time since the label changed back in June of 2021. Our expectation is that we will see an acceleration of underlying growth during the next six months. As we reach the midpoint of the year, performance is where we expected it would be, and we see several positive signals in our foundational Ocaliba business. First, our unit demand was strong in the latter half of the quarter. This is partially related to an uptick in refill rates over the past few quarters, which we believe indicates patient satisfaction with Ocaliba. In fact, our most recent market research shows 85% of current Ocaliba users are extremely satisfied with OCA, compared to approximately 60% to 70% for ERSO. Also impacting the increase in units is the larger script size, which indicates that we are treating appropriate PBC patients, as the lower script sizes were indicative of the more advanced patient populations. Additionally, new patient enrollments were up markedly over June of last year, which is when we began educating healthcare professionals on the new label, We are seeing similar trends in July and believe that these are clear signals that the PPC business will begin rebounding nicely in the second half of 2022. Lastly, patient drop-offs have returned to level seen prior to the label update, suggesting that we are no longer seeing an impact carryover on existing patients. Recent market research provides additional context on some of these dynamics. The latest wave of our ongoing tracking study indicates that Believe in Ocaliba and intend to prescribe have both increased following the label change. Our peer-to-peer programs are largely in person and attendance has been strong, showing that HCPs are still interested in learning about Ocaliba. Furthermore, we'll be launching new promotional campaigns for both healthcare professionals and patients in the next few weeks, and we're preparing for a strong presence at the upcoming fall congresses, especially the liver meeting in November. We're actively preparing for a NASH launch using a measured approach. I'm pleased to share that we will be displaying our NASH disease awareness campaign at this year's AASLD meeting as part of our resumption of pre-launch NASH initiatives. We are also focused on ensuring that we have the right commercial strategy in place. This will involve assessing current market dynamics and understanding how these learnings will inform our commercial decision-making for NASH. It is truly exciting to have the commercial team engaged in these efforts again. 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. The long-term outcomes data and real-world evidence we are generating for Ocala and PBC is both compelling and important to patients and prescribers. We know that there remains a sizable market segment of patients, who potentially could improve with the addition of Ocaliba to their PBC treatment plan. And our commercial organization remains focused on reaching physicians with important data that can continue to drive growth and expansion of Ocaliba. We're also looking forward to a potential launch in NASH and bringing OCA to many patients who currently have no options. I'll now turn the call over to Dr. Michelle Berry. Michelle?

Thank you, Linda, and good morning, everyone. I'll start by providing updates on our NASH development program and outline some of the key data we've been generating to support Ocalva and PBC, and then discuss updates on our broader pipeline. Looking first at NASH, we were thrilled to announce positive results from the new interim analysis of our Phase III Regenerate study. This is now the second time OCA has met the agreed primary endpoint of improvement in liver fibrosis without worsening of NASH at 18 months. These results have now been demonstrated using two different biopsy reading methodologies, including the consensus reading in line with recent FDA guidance. Subjects randomized to OCA 25 milligrams had doubled the response of subjects on placebo, a highly statistically significant and clinically meaningful result. Over the last few years, fibrosis has been shown to be the strongest predictor of liver-related morbidity and mortality. We believe this new analysis reaffirms that OCA can play an important role for people living with fibrosis due to NASH. We were also pleased to see the safety and tolerability results from this new interim analysis, which included more than 8,000 patient years of safety data compared to 2,400 in the prior submission, and importantly, nearly 1,000 patients who have reached four years and regenerate. This new, larger safety database allows a more robust assessment of the safety and tolerability for a therapy likely to require chronic administration. Based on what we've seen thus far, we believe the safety and tolerability that support potential chronic treatment with OCA is well-defined, monitorable, and manageable. We look forward to sharing the details of the safety and efficacy data at scientific conferences this fall. The consistency across these analyses gives us confidence in the totality of data for the benefit-risk of OCA and fibrosis due to NASH. In late July, we had a productive pre-submission meeting with FDA in which we reviewed the planned content of our NDA and the timing of our submission by the end of 2022. As a Class 2 resubmission, this NDA will have a six-month review period. In addition, We anticipate an advisory committee meeting as part of this process. We're also continuing to work toward a top line data readout in late Q3 from our phase three reverse study, the only active late stage study in compensated cirrhosis due to NASH. As a reminder, this would be a separate NDA for the cirrhosis indication should the data support it. We will assess the regulatory opportunities for reverse when we have our top line data in hand. Overall, the amount of data we are generating in NASH is unprecedented. And ultimately, upon completion of these analyses, we will have accumulated the largest phase three clinical trial data set in the field. Now turning to PBC. In June, we provided top line data from our phase four cobalt study, as well as the first of our real world evidence studies. We will include these in our submission to the FDA later this year to meet our post-marketing commitments and help demonstrate the clinical benefits of long-term therapy with Ocaliba. As we shared previously, Cobalt was terminated early following conversations with regulatory authorities and guidance from the study's data monitoring committee or DMC. This trial had challenges in enrolling and maintaining patients in a placebo-controlled study in a rare disease when the study drug is commercially available. As a result of these and other factors, we agreed with FDA to close the trial and compile the data, which, as expected, did not demonstrate a difference between the placebo and OCA arms. We believe the data from patients randomized to OCA can form a significant component of our post-marketing requirements. They will need to be compared to matched external controls. Individuals with PBC who are not on Ocalibus from other databases, such as the Komodo claims database. In addition, we have initiated multiple real-world evidence studies, including the HEROES studies. These studies are providing consistent evidence of transplant-free survival in patients receiving Ocaliva for PBC, the ultimate goal of PBC treatment. This weight of the evidence submission will include results from COBALT, the HEROES studies, and data from our phase three POIS open label extension and will comprise the supplementary NDA we plan to submit later this year. We remain committed to fulfilling our post-marketing requirements. Moving on to OCA plus Bezify rate combination studies and PBC. We continue to screen patients and add clinical sites in our US-based phase two study. In addition, we continue to enroll our international phase two study that is evaluating different dosing regimens of the OCA-bezofibrate combination. Our large phase one study in the U.S. to better characterize the exposure data as well as any potential drug-drug interactions of the fixed-dose combination has now completed enrollment. Together, these three studies will inform the dose selection and study design for a phase three trial. Our pharmacokinetic or drug-level analyses are now underway. We anticipate selecting doses for the six-dose combination later this year and sharing data with you from the planned analyses of the phase one and phase two studies. Looking at our pipeline, our comprehensive phase one study for our next generation FXR agonist, INT787, has progressed to the final cohort. We look forward to sharing data from our phase one studies as well as our intended indication and development plans for INT 787 later this year. Before turning the call over to Andrew, I want to thank the Intercept team for their incredibly hard work over the past few months as we generated unprecedented amounts of data across NASH and PPC, all while continuing to advance our pipeline programs. I'm proud of the progress we've made and look forward to sharing data in the coming months. I'll now turn the call over to Andrew for financial updates. Andrew?

Thank you, Michelle, and good morning, everyone. I will be providing an update of our financial results, and I ask that you please refer to our press release issued earlier today for a summary of our financial results for the second quarter and the June 30th, 2022. As a reminder, our second quarter 2022 results are reflective of our ongoing operations, and the international business has been moved to discontinued operations in our financial statements. In our press release issued this morning and in my statements today, non-GAAP adjusted net sales and non-GAAP adjusted operating expenses include the international business. A reconciliation of our GAAP to adjusted non-GAAP numbers is provided in our earnings release issued earlier this morning. Additionally, we had previously suspended our financial guidance for the year due to the sale of our international business. We are now reissuing guidance of non-GAAP adjusted net sales of $325 to $345 million and non-GAAP adjusted operating expenses of $335 to $365 million. This guidance includes our international business for the first six months of the year and our ongoing business for the remainder of the year. In addition, our non-GAAP adjusted operating expense guidance includes expenditures related to NASH development and the pre-commercialization spend. In the second quarter, we recognized $71.8 million in U.S. net sales and $104 million in non-GAAP adjusted net sales. as compared to $68.2 million in U.S. net sales and $96.6 million in non-GAAP adjusted net sales in the prior year quarter. We've recorded $85.1 million in total operating expenses and $89.8 million in non-GAAP adjusted operating expenses. This compares to the quarter ended on June 30th, 2021, where we recorded $81.6 million in total operating expenses and $86.5 million in non-GAAP adjusted operating expenses. Our cost of sales were $.3 million for quarters ended June 30th, 2022 and 2021, and consisted primarily of packaging, labeling, materials, and other related expenses. Our selling general and administrative expenses were $40.0 million in the second quarter of 2022, down from $43.9 million in the prior year quarter. The decrease was driven by our ongoing efforts to manage our operational costs. Our research and development expenses were $44.8 million in the second quarter of 2022, up from $37.7 million in the prior year quarter. The increase was a result of a reduction in UK R&D tax credits recognized in the current period. Interest expense in the quarters ended June 30, 2022, and 2021 was $6.7 million and $12.6 million, respectively. For the quarter ended June 30, 2022, interest expenses related to the principal amounts outstanding for the convertible and secured note and no longer includes an accretion of debt discounts upon adoption of ASU 2020-06. For the quarter ended June 30th, 2021, interest expense is related to the principal amounts outstanding for the convertible notes. In the second quarter of 2022, we reported a net loss of $7.5 million, a decrease compared to a net loss of $11.1 million in the second quarter of 2021. As of June 30, 2022, we had cash, cash equivalents, restricted cash, and investment debt securities available for sale of approximately $412.3 million. With the addition of the $366.5 million in cash received from the completion of the sale of our international business, the company has cash, cash equivalents, restricted cash, and investment debt securities available for sale of well over $700 million. In summary, I am pleased with our commercial performance and the positive impact that the transformational sale of our international business has on our liquidity and financial position. On a pro forma basis, we now have cash well over $700 million, which gives us the ability to manage the company through the potential launch of OCA and NASH and gives us a great deal of freedom in how we manage our debt. We also have the financial flexibility to continue investing in the growth of Ocala and PBC and supporting our other development programs. This is an exciting time for the company, and I'm pleased that we are well positioned financially to drive our growth into the future. With that, I'd now like to turn it over to the operator for any questions. Operator?

Thank you. As a reminder, to ask a question, you'll need to press star 1-1 on your telephones. Please stand by while we compile the Q&A roster. Our first question comes from Yasmine Rahimi with Piper Sandler. You may proceed.

Good morning, team, and thank you so much for taking my questions. It would be wonderful if you could give us, to the extent you can, some color about how the pre-NDA submission went, you know, maybe the sentiment that the FDA shared with you in regards to how comprehensive the packaging of the data needs to be. Any details that could be helpful for us, and specifically as our clients are listening, how excited was the FDA on the data and the resubmission package and the depth of it? Thank you so much for taking my question. I'll jump back in the queue to allow my colleagues to ask their questions as well.

Thanks, Yasmeen. As we said in the prepared remarks, it was a constructive, good step for us. Michelle, perhaps can give some of the flavor around the important discussion that we had.

Yes. Hi. Good morning, and congrats to you, Yas. So, it was a very productive meeting, and we now have a clear path forward for a resubmission The FDA acknowledged the vast amount of data that we've been collecting, especially on the safety front over the last couple of years. We intend to submit by the end of 2022, as stated in our prepared remarks. We did get some additional clarity about some of the safety, specific safety events and how the agency would like for these data to be included in the submission. So again, it was a very productive meeting and helped us in planning for our submission later this year.

Thank you so much.

Thanks. Thank you. One moment for questions. Our next question comes from Michael Yee with Jefferies. You may proceed.

Hi, this is from Michael. I just want to ask about scenarios surrounding the timing of the report readout and the NDA submission. So I guess, like, in terms of what happens and how do you see the scenarios if the readouts are positive or negative and whether the FDA would take that into account when you're filing for the F23 NDA, you know, understanding that you said it's a separate process, but just trying to understand if, like, On the FDA side, they think there's any read-through between the data of the F4 trial and F2.3 NDA filing. Thank you.

Okay, great. Thanks for the question. Maybe I'll start and Michelle can add. As we indicated, we continue to work towards a top-line readout for reverse, which is the F4 study that you referenced late in the third quarter. We have said for a while and continues to be the case it is a separate IND. If, in fact, that study is positive and we intend to file, that would be a separate filing. And importantly, and I think this continues to be consistent with the planning that we're doing, our filing in fibrosis is going to be based on regenerate and isn't dependent on reverse. Of course, as you would expect, we're going to reassess next steps on the compensated cirrhosis indication once we have that data in hand. But all of the work on the first filing, which we're guiding towards the end of the year on fibrosis, is in process and is not dependent on that second important data set, which we'll see on the reverse side.

Got it. Thank you.

Michelle, anything further you want to add there?

Nope. Thank you. Covered it, Jerry.

Okay. Thanks.

Thank you. One moment for questions. Our next question comes from Brian Abrahams with RBC. You may proceed.

Hi, this is Steve on for Brian. Thanks for taking our question. Maybe shifting gears a little bit to the earlier programs, can you share a bit more on your thinking around how 787 might be differentiated and where you think the best opportunity is there? Thanks.

Thanks, Steve. We'll let Michelle take that one.

Hi, good morning, Steve. So we are looking forward to sharing more of the planned indication for 787, the preclinical data and our phase one data in the next few weeks. Really excited about this compound and how it is differentiated from OCA. So again, it'll be next few weeks, but we look forward to having data, clinical data that we can share with you at that time, as well as the indication and our development plans. Thanks for the question.

Great, thanks.

Thank you. One moment for questions. Our next question comes from Steve Seathouse with Raymond James. You may proceed.

Good morning. Thanks for taking the question. I wanted to ask about your just updated thoughts the market in NASH and a launch strategy. You know, years ago, you discussed prioritization of certain patients with advanced fibrosis under care of hepatologists, et cetera. And I'm just curious if that thinking has evolved at all and also just any preparation that you need to do in the next year, given this is only a six-month review cycle, hiring, et cetera, that needs to be done for a launch. Thank you.

Yeah, thanks, Steve. I'll start, and then Linda can add in. I think, you know, as we indicated, and as you would expect, we have the updated top-line readout in hand, so we're already working on – What I would call is refinement and an update of the commercial strategy. So we're taking advantage of all of those learnings, historical work that we've done that you mentioned. I think there's probably a couple of important elements that are still going to guide us, but we're open for that updated view that we will be doing in terms of the updated prescriber and payer and patient view. I think we'll continue to focus on the antifibrotic effect as the main differentiator when we think about introducing OCA. And I do think that generally, the advanced segment and the focus on the specialists and those patients that are already, and we did in the past, talk about segmentation. you know, a reasonable number of patients with advanced fibrosis due to NASH who are already identified and under treatment of the specialists. I do think that will continue to be our initial focus, but a lot of important work to do to refine that. And as you would expect, look, we'll provide updates as our work progresses. And I'm sure as we move towards, uh, you know, and resubmit. We'll have important updates on the commercial side as Linda and the team do the work. I guess the second half of your question was just on kind of general preparation overall and how we're thinking about that as we move through these next several quarters, and Linda can give you our current thinking on that.

Yeah, thanks, Jerry. I think it's really important that we look at what we hold to be truths in patient population, looking at where the label is, looking where we've demonstrated efficacy. So I think that Jerry very nicely covered off where we're focusing on a kind of patient prioritization, as well as where your audience is. What I think we need to do is look at the context of the environment. Where are we now? A lot of that work was done, frankly, three years ago. It's important that we take into consideration where is the context of where we find ourselves presently in terms of competitive set, in terms of environment and market access and pricing. And a lot of the focus will need to be on making sure that we have the right value proposition and that we're prepared to go to market strongly and supporting the brand. Currently, we already have what we believe to be very strong pre-launch materials, which I talked about. And that's focused a lot on disease education, the role and importance of fibrosis in NASH. And as I mentioned, we'll be rolling that out as soon as AISLD again. So we will take measured steps to use that which is appropriate now and also update our thinking to make sure that we launch properly and with the right kind of insights to have a successful launch in our patient target group.

Thanks, Steve. Thank you. One moment for questions. Our next question comes from Thomas Smith with SVB Securities. You may proceed.

Hey, guys. Good morning. Thanks for taking the questions. Just one on the pre-submission meeting. You previously talked about this. as more of an administrative meeting. I guess, could you just elaborate on how much discussion there was with the actual Regenerate reanalysis data set during this meeting? And did the FDA explicitly commit to holding an adcom during this meeting? Michelle?

Hi. Yep. Good morning, Thomas. As is typical for these meetings, the majority of the discussion was focused on the logistics and on the submission itself. As I said, it was a really productive meeting with some clarity on some of the specific safety events, how they wanted those presented, even very specific tables. So, again, on the how of the submission. We have been discussing with the agency the calendar, given that we have the submission coming in at the end of the year. And with a type two resubmission, there is that ability to have an advisory committee, which we have shared with the agency that we would welcome the opportunity to have an advisory committee in the first half of 2023. So I think I would anticipate that for early next year.

Okay, got it. Thanks for taking the questions.

Thank you. Thank you.

One moment for questions. Our next question comes from John Wallivan with JMP Securities. You may proceed.

Hey, good morning. I guess maybe just one follow-up on Michelle's prior comments. Can you give any more details on which specific safety events FDA, you know, wanted more clarity on in the resubmission? Thanks.

Sure. So we have previously discussed after the CRL, they wanted more specific information on hepatic cardiovascular and acute kidney injury. So we set up three independent adjudication committees, a lot of discussion with the agency about who exactly they wanted on those committees, their backgrounds, their independence, and the ability to review all of the blinded events. We also specifically went through with the agency the trigger terms, so those types of events that would be reviewed by each of the independent adjudication committees, and then what the output from those reviews was and how that was to be included in the submission. So those three specific events were ones that they had interest in either from the onset of the trial because of the higher risk of the patient population, that is enrolled in the advanced fibrosis population, increased risk of type 2 diabetes, increased obesity and other comorbidities, and why they wanted to make sure that those events were adequately characterized through the trial. So that was the specifics around those events that they wanted included in the trial, excuse me, in the submission.

Very helpful. Thanks, Michelle.

Thank you.

Thank you. And as a reminder, to ask a question, you will need to press star 1-1 on your telephone. One moment for questions. Our next question comes from Mayank Bantani with B-Riley Securities. You may proceed.

Good morning, team. Thanks for taking our question and congrats on a strong quarter. Just regarding the OpEx management, could you talk to how, you know, the SCNA came down 20% quarter over quarter when you're clearly in investment phase still with PVC and, you know, working towards two SMDA filings within this year? And then just on the constructive FDA resubmission meeting, just curious to learn Michelle, if the requested safety repackage data will be available at any of these fall conferences, and if any of the reverse safety data is at all relevant to the first SNDS resubmission. SNDS resubmission, if you could comment on that.

Okay, thanks, Mayank. We'll have Andrew start on the OPEX question, and then we can flip back to Michelle for the follow-up, the safety data.

Yeah, thanks for the question, Mayank. So with regard to OPEX, you know, and again, with moving our international business to discontinued operations, We have to be very clear on what numbers we're talking about. So our numbers that you're used to seeing, including the international business or non-GAAP operating expenses, were $90 million. Those are in line with our expectations, right? So our GAAP operating expenses were $85 million. That does not include the international operations in the second quarter. So as far as OPEX management, we're right where we expected to be. We did have a $3 million tax credit during the quarter, which also reduced our OPEX by a bit. But we, in general, from an operating expense standpoint, are right in line with where we expect it to be for the quarter.

Okay. Second question was on whether, Michelle, we should expect additional safety data to come from Regenerate later in the year. And then the second part of the question, Mike, as I understood it, was reverse safety's relevance in the context of the initial filings.

Yeah, so thanks for the question. We look forward to sharing detailed data on the safety at the fall conferences. So, again, looking at the safety on those three key adverse events of special interest that we've ran through with the top line, the kidney events, which are balanced across the arms, the cardiovascular events, which were balanced across all three arms, on the core MACE and a handful of events in the expanded MACE that were generally driven by revascularization. And then the hepatic events, as we've discussed before, were mostly mild, which means there's an elevation in transaminases or ALKFOS without jaundice. So, we will be going through all those with a smaller number of events. We can go into the specifics even in the shorter presentation. So, yes, we do look forward to sharing that data at the fall conferences and hope that would be helpful to understand why we are so enthusiastic about this new data set. With regard to reverse, the reverse safety data will be submitted as we'll have top line data which we'll share. We anticipate having those data at later in the 3rd quarter and would have both safety and efficacy at the same time. We don't anticipate submitting the safety data from reverse is such a separate and that's a separate. The FDA is pretty clear that they consider these 2 very separate populations 1, preventing the progression to services and in the reverse study. the reversal of cirrhosis, bringing those patients back from an F4 to an F3. The safety data would be submitted along with those efficacy data and not with the regenerate submission. But we did have that conversation just for clarity with the agency in the pre-submission meeting, and that remains their perspective.

Thanks very much. Appreciate the color. Thank you, Mike.

Thank you, Melissa.

Thank you. One moment for questions. Our next question comes from Ellie Merle with UBS. You may proceed.

Hey, guys. Thanks so much for taking the question. Just in terms of cost management and thinking about strategic outlook, I guess if there were to be a negative outcome from the refiling later this year, how are you thinking about the speed with which you can adjust expenses given The NASH study is ongoing into outcomes for many years and how you would approach that strategically. Thanks.

Yeah. So, I mean, obviously, we're excited to be moving towards a resubmission by the end of the year. As we've always indicated, you know, as you would expect, we do our contingency planning appropriately. If we were in a situation with a negative outcome on NASH, we have a good idea of what we would need to do. And we've always discussed kind of the fact that with large ongoing trials like Regenerate, you normally have a couple to three-quarter period where you would make that kind of move if you were in that potential scenario. I think importantly, underscoring the You know, relevance of the, we've always described our underlying Ocala business as a profitable franchise. That remains true. And, in fact, with the move and now the focus on the U.S. commercial presence only after the sale of international, you know, that we're in a strong position regarding our commercial efforts and the productivity and efficiency of those efforts on PBC in the U.S.

Got it. Thanks so much for the call.

Thanks, Ali. Thank you. One moment for questions. Our next question comes from Salveen Richter with Goldman Sachs. You may proceed.

Hey, good morning. This is Matt on for Salveen. I was hoping you could talk a little bit about expectations for the reverse readout in terms of the benefit you want to see. Is the bar lower here or how does that compare to what we've seen in Regenerate? And then could you also just discuss the relative size of these opportunities? Thank you.

Okay, thanks. So we're excited about the important data to come with reverse. Maybe Michelle can frame how we're thinking about the readout, and then I'll make some follow-up on the potential opportunity there in markets.

Sure. So, thanks for the question. As we're looking at the F4 population, and again, the only ongoing study in these advanced patients, we are really excited to see the data, again, for the latter half of the third quarter. We have not seen a difference in the ability of OCA to impact fibrosis on, as we compare F2s to F3s, for example. We continue to see that benefit in the F3, so we don't have any expectations that we would see a lower ability of the drug to act as an anti-fibrotic. Again, though we don't have any prior data from any other agent to base that on, we can look at other therapeutic areas in which you have a reduction or elimination of the injury and have seen the liver's ability to regenerate. And we are looking forward to seeing those data. I do think that this is a really critical population to understand, is there a point of no return, as has been postulated. But again, we have not seen that in our earlier data for patients who have more advanced fibrosis. We believe that an anti-fibrotic mechanism is the right approach for these more advanced patients and look forward to sharing the data with you as soon as it's available later this year.

Thanks, Matt. I'll take the second half of the question. I mean, as Michelle indicated, it's an important population. It's a high-risk population. We've described in the past the fact that we estimate there's several hundred thousand Patients with compensated cirrhosis due to NASH who are with specialists. And importantly, not only a pretty sizable number, but these tend to be patients that the understanding of the risk and the urgency to treat when a therapy comes in, available is most obvious to the treaters, right? So it's a pretty well-defined group of patients that are at there, and the payers and the physicians understand that when and if therapies come, this is a group that they would have a reasonable amount of urgency to treat. Obviously, let's see what the data looks like, and then we'll talk about what the opportunity is once we have data in hand. But we look forward to seeing that important data set. Great. Thank you very much. Thanks, man.

Thank you. And now I will turn the call back over to Jerry Durso for any closing remarks. Jerry?

So thanks, everybody, for joining us today. I'm definitely extremely proud of the progress that we've made in the first half. I believe we're in a strong position as we work through this transformative year for Intercept. We have important milestones to come that we feel we're in a good position to manage. Definitely look forward to the important updates to come as things progress. And so have a great rest of the day and enjoy the rest of your summer. Thanks.

Thank you. This concludes today's conference. Thank you for participating. You may now disconnect.