Q4 2022 Intercept Pharmaceuticals Inc Earnings Call

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Speaker 3: Good day, and thank you for standing by. Welcome to the Intercept Promise Utical's fourth quarter in four-year 2022 earnings conference call.

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Speaker 3: After the speech is presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message devising your hand is raised.

Speaker 3: To withdraw your question, please press star 1-1 again. Please be advised that today's conference has been recorded. I would now like to hand the conference over to your speaker today, Narek Sigerian, Executive Director and Investor Relations. Please go ahead.

Speaker 4: Thank you. Good morning and thank you for joining us on today's call. This morning we issued a press release announcing our fourth quarter and full year 2022 results, which is available on our website at interceptfarma.com.

Speaker 4: 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.

Speaker 4: 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.

Speaker 4: 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 affairs.

Speaker 4: Some, but not necessarily all, of the list factors are tith-tother actual results to different 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 firm the

Speaker 4: Today's call will begin with prepared remarks from our President and CEO Jerry Dersow, our Chief Commercial Officer Linda Richardson, President of Research and Development and Chief Medical Officer Dr. Michelle Berry, and Chief Financial Officer Andrew Sake. We will then open the call for questions.

Speaker 4: Let me now turn the call over to our CEO , Jerry Dersow. Thanks, everyone. Thank you for joining us on our fourth quarter and full-year conference call. Intercept makes significant progress across the business in 2022, and I'm proud to highlight our achievements today.

Speaker 4: Looking at our performance in PVC, we again delivered double-digit sales growth grow Calava and ended 2022 with total US net sales of $285.7 million. This was 10% growth over 2021.

Speaker 4: Importantly, in the fourth quarter of 2022, Ocalovic generated $77.2 million in US net sales, which is 13% growth over the prior year of quarter. We now look to 2023 as a year to continue driving growth, and we're more confident than ever in the longevity of our PVC business.

Speaker 4: We know there remains a significant number of people living with PVC who can benefit from adding O'Calava as the second-line therapy. We added more certainty in the runway of our life cycle with the resolution of our patent infringement case for O'Calava that was scheduled for trial in the U.S. District Court on February 27th of this year. The settlements protect O'Calava Market Expo Civility into the 2030s and reinforce the long-term opportunity we have in PVC.

Speaker 4: In addition, we continue to progress our next generation PBC therapy to fix those combination of OCA and BESA 5 rate, which is another component of our long-term strategy. We look forward to sharing data on our next generation medicine later this year and are excited about its potential.

Speaker 4: Turning now to NASH. At the end of the fourth quarter, we resummitted our NDA for OCA and pre-cerotic liver fibrosis due to NASH. Following FDA's acceptance in January , the agency assigned a pedophilic target action date of June 22nd. Reaching this point is the result of hard work and dedication from patients.

Speaker 4: position, study personnel, and our team here at Intercept, and is a major milestone for the Nash community. OCA has demonstrated a strong and confirmed and bi-biotic effect in our rigorous Nash program, but we believe it has the potential to become an impactful therapy.

Speaker 4: We're now working through the regulatory review process and are advancing our launch readiness planning while taking a measured approach to investment as we progress through the upcoming milestones. We also may stride in our pipeline program whether next generation FXR Agonist INT 787.

Speaker 4: In November , we announced a lead indication for this investigational therapy, severe alcohol associated hepatitis, and initiated our phase 2 fresh trial. The shell will elaborate on this later in the call. Notably, the progress we made last year was complemented by the transformation of our capital structure. As a result of this work, we finished the year with nearly $500 million of cash on hand.

Speaker 4: 2023 will be a pivotal year for Intercept and we're operating from a position of strength. Our balance sheet and foundational PBC business provide us with the financial flexibility and the strategic optionality to drive growth while positioning ourselves for success and match. This year I look forward to working alongside the team.

Speaker 4: as we build on the momentum of last year's performance and grow our commercial PVT business. As we work through the regulatory review of OCA while preparing for a commercial launch in Nash, and as we progress our pipeline opportunities while continuing to innovate on behalf of people living with liver diseases.

Speaker 4: I look forward to sharing updates on our progression of these priorities throughout the year ahead.

Speaker 3: With that, I'll now turn the call over to Linda. Thanks, Jerry, and good morning, everyone. I'm pleased to share a performance highlights for 2022. It was another strong year for our foundational Cal over business, underscoring the strength of a Cal over market position as the only second-line agent approved for use in PBC.

Speaker 3: We achieved double-digit growth for both the fourth quarter and the full year compared to the same timeframes last year. Our performance in PBC was driven by a strong return to growth in the second half of 2022, with a few notable contributing factors. First, our new to brand prescriptions grew nearly 30 percent

Speaker 3: during the second half of 2022, as reported by Acubia's NPA audit. We believe this would be the trend as we passed the one-year mark post-label change in June of 2022. While over 95% of our business is driven by existing patients, it's good to see solid growth in new patients receiving O'Cala.

Speaker 3: and speaks to the ongoing need for second-line therapy for many patients with PBC. Second, as a result of our ongoing efforts to reach new prescribers, we continue to see an increase in first-time localeable writers. More specifically, we saw a 42% increase in new writers in the second half of 2022 versus...

Speaker 3: pharmacy time to fill. We want to ensure that appropriate eligible patients can quickly start treatment with O'CalVA. Simplifying facilitating processes here helps sustain existing patients and initiate new ones.

Speaker 3: Strong customer engagement and communication of the benefits of O'Cala remain a focus for our commercial team in the field at major conferences and with patients. Last fall we kicked off our new HCP and patient marketing campaigns. Each with updated messaging designed to drive urgency.

Speaker 3: and demonstrate the need to go beyond ALP management in fully addressing PVC treatment. We recently began to proactively provide to HCPs the gastroenterology publication that presented in greater detail some of our strong real-world evidence regarding improved outcomes for patients taking al-Calaba. We anticipate additional publications and presentations of new real-world evidence later this year.

Speaker 3: Prescribers recognize the significance of real-world outcomes data when treating PVC. In market research studies, we have seen a significant increase in projected ol' Calvab market share once a PEPP and GI presented with results from the real-world evidence studies.

Speaker 3: Turning now to Nash, we are engaging with all key stakeholders as we prepare to execute against our go-to-market commercial strategy. We continue to meet with payers to refiner thinking as we prepare for a potential launch in Nash.

Speaker 3: We are focused on understanding their needs and concerns, which has allowed us to gain valuable insight into our pricing, reimbursement, and overall access strategy. Market research with healthcare professional shows that reversal of fibrosis, stopping further progression of fibrosis.

Speaker 3: and the prevention of cirrhosis will be the three key drivers of prescribing for NASA patients with advanced fibrosis without cirrhosis. We believe that the strong and confirmed antibiotic effects of OCA, shown in our regenerate trial, address all these areas of concern with a unique, differentiating mechanism of action.

Speaker 3: Importantly, our well-established US field presence and broad geographic footprint provide intercept with a competitive advantage. Based on our analysis, nearly three in four of the highest potential prescribers for Nash already are within our existing PBC customer base, where we've been building relationships for the past six years.

Speaker 3: This overlap will enable us to easily flex to national disease awareness messages and then oca specific ones, while also covering our current PBC targets.

Speaker 3: In the meantime, our disease awareness activities continue. Our unbranded website hosts our Nash Tipping Point campaign, educating providers on the significant risks associated with advanced fibrosis due to Nash. We will continue our presence at key congresses while also initiating disease awareness programs. In closing, we have strong PBC performance in 2022.

Speaker 3: We remain confident in our ability to increase the count of the market penetration in 2023 and maintain a positive long-term outlet for our PVC franchise. The commercial team is actively and passionately preparing for our future in Nash. I'm proud of the team's performance and look forward to sharing updates on our progress throughout the year.

Speaker 3: I'll now turn the call over to Dr. Michelle Baird.

Speaker 5: Thank you, Linda, and good morning, everyone. In 2022, we made substantial progress in our NASH development program and building out our pipeline. Looking first at NASH in January , the FDA accepted the resubmission of our new drug application.

Speaker 5: for OCA and pre-cerotic liver fibrosis due to Nash. We are thrilled to have progressed to this regulatory milestone one step closer to reaching our goal of delivering the first FDA approved therapy for this devastating disease. There's a critical need to address liver fibrosis due to Nash before patients progress to the diagnosis.

Speaker 5: A pivotal point in Nash disease progression associated with increased risk of bug liver specific and all cause mortality. Our NDA is supported by a robust body of evidence from the OCA-NASH clinical development program, including two positive 18-month interim analyses from the pivotal phase 3 regenerate study, and a large robust safety assessment

Speaker 5: that includes the 2,477 patients from Regenerate, with nearly a thousand subjects on study drug for at least four years.

Speaker 5: OCA has demonstrated a consistent of antifibrotic effect across two studies and multiple analyses of the Regenerate study that we shared over the course of 2022.

Speaker 5: Through two independent histologic methodologies, OCA demonstrated by grosses improvement of at least one stage without worsening as any of the three histologic parameters that comprise the Nafold activity score or NASS. In both methodologies, OCA 25 milligrams

Speaker 5: demonstrated double the response rate of placebo in reducing liver fibrosis stage without worsening of any of the three histologic components.

Speaker 5: It's important to note that this endpoint was defined as a result of direct interactions with the FDA prior to finalization of the Regenerates Statistical Analysis Plan.

Speaker 5: In addition to robust efficacy data, our safety database, which is the largest in the Nashville with the longest duration of patient exposure, shows a well-characterized safety and tolerability profile that supports the potential chronic administration of OCA.

Speaker 5: We know that fibrosis is the strongest predictor of clinical outcomes in patients with Nash, and we continue to believe that OCA has the potential to become the first approved therapy in this disease. FEA indicated that it considers this a class 2 resubmission and has assigned a pedupa target action date of June 22 for the NDA. We fully anticipate an advisory committee meeting as part of this process.

Speaker 5: of the regulatory submission to FDA this year in support of fulfilling post marketing requirements for a CalvA and PBC. The real world data we have generated to date demonstrates the actual long-term clinical benefits of a CalvA. Specifically, patients taking OCA have improved.

Speaker 5: transplant-free and decompensation-free survival, which we know to be the most important treatment goals both for individuals living with PBC and for their clinicians. Building on our commitment to innovating in PBC, we are making great progress with our VIXTO's combination of OCA and VESA-PIPAR agonist. One of our two phase two studies is now fully enrolled and we're accelerating recruitment of patients into a second. These phase two studies...

Speaker 5: and our Pharmacokinetic analyses will inform dose selection and study design for a Phase III trial. We anticipate selecting doses for the fixed dose combination, as well as sharing data from planned analyses of the large Phase I and Phase II studies later this year.

Speaker 5: The OCA-Vesify Great Combination has synergistic mechanisms of action with the potential to further lower key biochemical measures that predict long-term outcomes in PBC while also improving tolerability. We're excited to share the potential impact of this combination that we believe has best in place.

Speaker 5: Alcohol-related liver disease as the cause of chronic liver disease is on the rise and is currently the leading indication for liver transplant in the U.S. Despite the increasing incidence of SAH in the U.S., there are no approved therapies for people who could develop this disease.

Speaker 5: We believe there are several indications in which 787 could make a potential impact. However, SAH provides us with a great initial opportunity for this FXR Agnes with a different gut to liver ratio compared to OCA. In November ,

Speaker 5: add additional sites in the US, UK, and France.

Speaker 4: for financial updates. Thank you, Michelle, and good morning, everyone. We've had a very strong 2022, and I look forward to sharing our results and discussing our plans for the pivotal year ahead. I encourage you to please refer to our press release for a detailed summary of our financial results for the fourth quarter and year-end of December 31, 2022.

Speaker 4: For this call, I will focus on the highlights as they relate to 2022 and will also provide guidance for 2023. As I begin, I would like to remind everyone that as you review our fourth quarter and full-year financial information, please note that the divestiture of our international business was completed on July 1st and our full-year non-GAP results include the divested business for the first half of the year.

Speaker 6: In our financial statements, the divested business has been moved to discontinued operations. Turning to the highlights for the fourth quarter and full year ended December 31, 2022. We were very pleased with the growth of Ocalava in KBC in 2022. Our fourth quarter net sales growth was 13% over the prior year quarter for Ocalava in the U.S. We were very pleased with the growth of Ocalava in the U.S.

Speaker 6: For the full year, we reported worldwide of Calv. non-GAP-adjusted nut sales of $343.8 million with $285.7 million in total U.S. net sales compared to $260.8 million in total U.S. net sales in 2021.

Speaker 6: compared to $46.3 million in 2021. The period over period increase was primarily driven by investment in national launch preparation. SGNA expenses were $176.3 million in full year 2022, compared to $177.5 million in 2021.

Speaker 6: with a decrease in personal related costs offset by an increase in national launch preparation. Research and development expenses decrease to $40.7 million in the fourth quarter of 2022 from $51.1 million in the prior year quarter.

Speaker 6: The decrease was primarily driven by lower-nash-related costs and cost-sharing reimbursements. R&D expense decreased to $176.6 million in 2022, down from $182.7 million in 2021. The decrease was primarily driven by lower-nash costs.

Speaker 6: and cost-earing reimbursements, and were partially offset by the recognition of lower R&D tax credits. In 2022, approximately two-thirds of our R&D costs were related to our national program spent.

Speaker 6: 2022 was a year of financial transformation for the company. We executed a series of strategic transactions to transform our capital structure, which included the sale of our international business and several private repurchases of senior secured? análise.

Speaker 6: Regarding our convertible notes, as a result of the repurchases during 2022, the principal balance of the 2026 convertible secured notes was reduced by approximately 78% to $111 $1.1 million.

Speaker 6: Moreover, the company dramatically decreased annual cash interest. For 2023, cash interest expense will be $8 million as we anticipate our 2023 notes will be redeemed in July with cash on hand. A year in, the company had $491 million in cash and cash equipped once.

Speaker 6: and $336 million in outstanding debt. We ended 2022 with the financial flexibility to move our business forward, regardless of the FDA decision on OCA in Nash expected later this year. Turning to our financial guidance for 2023, we are guiding to $310 to $340 million of a $1 million.

Speaker 6: $25 million in non-GAP operating expenses in 2022 from our continuing business when excluding the sale of the international business.

Speaker 6: Similar to what we've seen in prior years, we anticipate slightly lower revenue and higher cash utilization in the first quarter of 2023 relative to the rest of the year.

Speaker 6: We expect that little Calibre first quarter sales will be impacted by the usual seasonality as patients are faced with insurance plan resets and Medicare coverage gaps at the beginning of the year.

Speaker 6: We also anticipate greater cas use in the first quarter due to activities from work related preparing for potential approval and launch and NASH and other annual expenses.

Speaker 6: Finally, we may choose to revise our 2023 guidance later in the year, pending potential regulatory approval for an NDA for OCA and pre-cerotic liver fibrosis due to NASH. In summary, we are pleased with our financial performance in 2022 and looking forward to a strong 2023. We are in a solid financial position and believe that our current balance sheet can cash on him.

Speaker 6: gives us the financial flexibility to continue to grow our existing Ocala the business, support a potential launch in Nash and advance our pipeline programs. With that, I now like to turn it over to the operator for any questions. Operator?

Speaker 7: Thank you. As a reminder to ask a question please press star 1-1 or your telephone and wait for your name to be announced. To withdraw your question please press star 1-1 again. Please stand by when we compile the Q&A roster.

Speaker 7: Our first question comes from the line of Ritu Baral with Cowan. Your line is open. Good morning guys. Thanks for taking the question. The shell has been FDA at any point communicated to you what the topic of the adcom could be. And for any range we should be thinking.

Speaker 5: Thanks. Good morning.

Speaker 5: So we do anticipate that the focus of the advisory committee meeting would be focused on overall benigniveness. We have had multiple conversations with them since the CRL and we know that there are some areas of focus for them. We tend to convey those. Certainly we're all addressed in our NDA.

Speaker 5: the specific areas that we have communicated at the ASLV presentation and again at NASHTag. We feel that we have addressed all the areas of concern with the confirmation of the anti-bibrodic benefit and the second analysis and a much more robust safety database.

Speaker 5: with which we can address any of their earlier concerns, specifically around the long-term safety and tolerability of the drive given that this would be anticipated to be a chronically administered drug. It's important that we have years of therapy in order to demonstrate that safety and tolerability.

Speaker 4: I guess just one more point to add in there, reach out to your question as the shall indicate in or prepared remarks. All the prep for the add comm is ongoing, but we don't yet have a confirmed date.

Speaker 4: I guess just one more point to add in there, reach out to your question as the shall indicate in or prepared remarks. All the prep for the add-com is ongoing, but we don't yet have a confirmed date. Got it. Thank you.

Speaker 8: Thank you. Our next question comes from the line of mayanked Mempani with the Eurali securities. Your line is now open. Good morning. Thanks for taking our questions and congrats on the program. I have a few. Just maybe following up on the prior question as part of your acceptance letter on the NDA filing. Was it clearly communicated to you by FDA that they're planning to hold an outcome and I just wonder you'll be able to do.

Speaker 4: will be fully prepared and of course will provide any additional information as appropriate if we get it from the agency.

Speaker 8: Okay, thank you. And then on the apparently very strong guidance you had on TBC, seems like driven by new prescribers. Could you perhaps share what the overlap you may have with these new hepatologists that you're having to describe OCAF or PBC, but also they may also care for national issues.

Speaker 4: growth in the fourth quarter. Clearly, this is a long-term area of focus for us. We have been working with many of the key prescribing physicians for several years now, and Linda can provide some details how we see a large part of that core audience also being really the first potential prescribers for Nash as we do.

Speaker 3: the deep commercial planning in advance of the Padoop on Nash. Yeah, we cover right now from our analysis, three out of four of the top potential Nash prescribers already exist within our PBC call list. So we're bringing in new PBC prescribers, but also have established relationships over the past six years as familiarity with O'Caliva in that same target audience. So we feel comfortable that the work, we have the groundwork that we've laid with PBC will translate.

Speaker 8: in this drug class. So I know it's early, but to be great to have your thoughts on the page to be done.

Speaker 8: in this drug class. So I know it's early but to be great to have your thoughts on the phase

Speaker 5: Sure, yes. The great question. We are really excited about the Fixed Space combination of OGA plus bezel vibrating as you state is we are in a unique position to have two potential therapies in PVC. I have state to give a much detail on our plans for the phase three until we have those conversations with the FDA to review all the very exciting data coming out of the phase two. Thank you.

Speaker 5: But we feel we have the potential here with the combination for potential best in class for PBC. So again, it really underscores our long-term commitment to innovation in this space.

Speaker 7: Thanks, Mark. Thank you. As a reminder, we ask that you please limit yourself to one question. Our next question comes from a line of Yasmeen Rahimi with Piper Sandler. Your line is now open. Thank you.

Speaker 3: Hi, this is Emma on Free-Az. Thanks for taking our questions. So my question is, what are your thoughts on the recent ICER pricing report and with that, are you still thinking about differential pricing in NASH for TBC? And what type of tear discussions have you had to support that if any year? Thanks Emma. Maybe I'll give some overall view on how we're thinking about pricing and then Linda can comment on ICER. So, thank you for your time.

Speaker 4: As you would imagine, we're doing all the right work as we prepare for a launch that includes some up-to-date dialogue with our key pairs and those are ongoing. We'll of course take a pricing decision once we have the full information, including a final label. But we continue to work towards all the right steps to have optionality on pricing between O'Callava and OCA and Nash. Should we choose to execute a pricing strategy that way, if we would anticipate a separate brand, separate NDC, the things that give us that...

Speaker 4: that option and all the updated work including those discussions with payers are going to be important inputs. We'll share more thinking about our strategy with the with the pair which will of course be foundational for the launch as we get closer to the Padoofa date and again I think it's been several years we've had dialogue with the pairs going back to before the uh...

Speaker 3: the first pedupa date. So we've done a lot of in-depth work. We're revising it with the current context as you would need to. And then perhaps, Alindi, you can comment on Isar. Yeah, of course. Thanks for the question. Frankly, we disagree with several of the approaches that were used within the model, which generated the draft evidence report. Specifically, when we look at the model, it does not define a standard that constitutes an acceptable data set. And it kind of applies an inconsistent approach, an exclusion of available data for different therapy. So what do I mean by that?

Speaker 3: An example is, it includes only phase three data for OCA, but put both phase three and phase two data in for Magical, and even though the phase two data do not include by process improvement without worsening of Nash as a primary endpoint. And then furthermore, it does not use the updated available information for OCA. It doesn't incorporate all data that are publicly available.

Speaker 3: notably the full and robust safety data set we have for regenerate. We presented this at AISLD in November 22. And frankly, it doesn't present the new analyses that we shared at NASHTAG in January 2023. So there's kind of a lack of consistency in approach that we're recognizing and we'll see how it goes from there, but we have some concerns with them.

Speaker 3: I'm wondering how much incremental NASHFs, GNAs included there. And if it's not fully included, how much more do you think would be necessary. And then, again, you said that 2, 3rd of 2022 R&D was for NASH. You're wondering if that's the same proportion, expect the 2023. Thanks. Thanks, John . We are continuing to manage with, I think, the right-

Speaker 6: So, probably the right way to think about it, and the reason I gave sort of our continuing costs from last year. Our last year spend was around 3.25 when you don't count the international operations that we sold in July . So the way to think about it is the increase year over year is really 100% related to national launch then. So you got about 50.

Speaker 6: down as we go. With regard to R&D, we're continuing to evolve our pipeline, as you know. So reverse is done, which means that our spend on Nash is going to be reduced this year, relative to last year. Overall, R&D spend will be slightly down but materially flat.

but you're going to see more like 50% Nash and 50% pipeline. Is that helps?

see more like 50% Nash and 50% pipeline. Is that helps? Very helpful. Thanks for the call.

No problem. Thank you. Our next question comes from the line of Joseph Stringer with the Needham & Company. If you're on the open. Hi, thanks for taking our questions. Just wanted to get your updated dots on the pre-cerotic national market segmentation. And looking ahead, if OCA has approved a NASH with your desired label, what type of NASH patients would you have just be getting on the drug proof? Yeah, thanks, Joe. Maybe I can start in Linda can ship in if she wants. I think, look, when we think about how we would...

best position OCA, we continue to be focused on the anti-fibratic effect and the more advanced patients. And so I think that theme, which you've heard from me for a while, continues to be what we're getting back as we do these updated discussions with all of the stakeholders, the deep updated market research you would anticipate. We're doing as we're in this phase of preparation. So really the advanced patient who is most likely identified through non-invasive means continues to be where we would zero in on both. The, you know, really is the patient that the physician.

The payers and the patients themselves have the most amount of urgency towards seeking treatment. From the profile of OCA, including importantly, the greater level of efficacy that we showed in some of the analysis that we reported out in the latter part of last year showing higher efficacy, for example, in that F3 subset.

goes in that in that same direction. We would also be focused in the initial phase on those patients that are already under care of the specialists of HEPSEN and GI's and as Linda said earlier in response to the one of the questions, we're seeing most of those physicians already today so we I think we have a good understanding.

the bi-broadic patients, advanced patients. We estimate that there are probably 20 million adult patients with Nash, but only a small percentage roughly about 3.8 million have been actually diagnosed. There's nothing to use to treat them. So you see an increase in diagnosis that comes following the ability to have on-label treatments in therapies and lots of discussions.

We continue to estimate that approximately 500,000 diagnosed patients, these are diagnosed, are currently under the care of a HEPA GI and have advanced fibrosis without cirrhosis. So from a launch mode, we feel that those patients reside in the offices that we'll be calling on and have the most need, and we have the best data in that set.

No problem. Thank you. Our next question comes from the line of Brian Scorney with Beard. Your line is now open.

Hey, good morning guys, thanks for taking the question. I guess on the Okalaba guidance for 2022, maybe you just frame on how to think about getting a higher end of the guidance. It's almost 20% increase year-over year, which is quite a bit of acceleration compared to where it's been trending for the last two years. So can you just...

character is what you're seeing in the morning. It might get you there. And does that high end include anything for Nash? Thanks. And there may be you. You start on that. Yeah, sure. Thanks, Brian . Look, the guidance that we gave is kind of in the, you know, nine to 19% range growth. You know, we tend to try to target the center of that growth as to where our focus is internally.

Again, we're continuing to put effort and energy into growing our top line. And we're really comfortable with our guidance overall. What I would say is that the guidance that we gave on O'Cala va is unimpacted by Nash. In my prepared remarks, you probably noticed that I mentioned that we would reserve the right to come back and reissue guidance.

beginning to publish from the real world data sets on outcomes. We know that some of those publications came late in the year and all indications that data were getting it out there appropriately in the context of the medical affairs and our commercial plan.

But that data is just starting to get into the hands of the prescribers. And we know from the research market that we're doing, it can be quite important to those prescribers as they think about potentially increasing their utilization of a calibur for the right-to-secondization. Yeah, and I think the last thing to note is coming out of the second half of the year, as we predicted, we've seen accelerated growth. We saw this bolus of new writers, demand, et cetera. And we are layering that now, as Jerry knows.

We see that awareness taking up and really reframing the way that physicians evaluate what does complete PVC management look like and they've always said that you know preventing progression Maintaining the patients those are the important things and we've got not only five years of data from our poised data on looking at

stabilization of fibrosis and biliary ribbons, but now we have outcomes and we're talking about lives not lab. These are actual patients that are benefiting from treatment with O'Cala.

and fibrosis and billy-rooven, but now we have outcomes, and we're talking about lives, not labs. These are actual patients that are benefiting from treatment with Ocalaba. Great. Thank you. Thanks, Brian .

Thank you. Our next question comes from the line of Comis Smith with SVV Securities. Your line is open. Hi, everyone. This is Mike on Fertile. Thanks for taking our question. Can you provide some additional color on where you are with the PVC Regulus Award discussion and what if any are the remaining Katie factors for submission? And then just as a quick follow up, when in 2023 specifically are you targeting for submission? Yes.

comes from the line of Comis Smith with SVV Securities. Your line is open. Hi, everyone. This is Mike on Fertabh. Thanks for taking our question. Can you provide some additional color on where you are with the PVC regulatory discussion and what, if any, are the remaining gated factors for submission? And then just as a quick follow-up, when in 2023, specifically, are you targeting for submission?

Michelle, can you take that please? Yes, happy to. Thanks for the question. So we have been in discussion with the agency about the content of our planned supplemental NDA, which as we've discussed would include the cobalt results, which we top lines last year, as well as an external control, so comparing those patients. Thank you. Mr. Lao. midda.

from within the Cobalt study who were on OCA to a group of patients from external databases. We've looked at the commuter databases we've released as well as two different patient registries in the UK and...

in global PVC databases. So we've been in discussions with the agency about inclusion there. We will also be planning to publish these data as we did with the gastrocover last December in releasing the real world evidence.

The most striking thing about these data sets is the consistency. And completely independent data sets, we're seeing a 50 to 70% reduction in deaths and decompensation leading to intertransferred death. So we are really excited about those data sets.

This would be the first non-altrow-rare condition that would include real-world evidence in a significant submission. So we know there's a lot of interest here that is our plan for the submission. We haven't yet given guidance on the exact timing of that as you might understand with a small group. We are.

working in two parallel paths, so on the Nash preparations and for the PVC S-NDA. So we'll give more guidance as that date grows closer. Thanks for the question.

Understood. Thanks very much. Thank you. Thank you. Our next question comes from the line of Brian Abrams with the RBC Capital Market. She line is now open. Hey, good morning. Thanks for taking my question. A question on IP. Can you talk about your level of confidence in OCA's exclusivity extending to 2031, just given all the recent settlements that you've been able to do, but still?

not going to litigation on the IP was a great outcome for the company and getting you know 70% of the value of those 2033 patents is a real win for the company. Look we can't speak to any you know the current additional filer out there which is the Zanera Farma.

That's a separate trial. It's the same jurisdiction, the same judge, same fact set. It would, you know, but it's out there in 2024. The good news for the company is that we're completely ready for trial, right? Because we did all the work, we did all the prep. The narrow would have to start over from scratch. We were never going to predict an outcome, but it's the same fact set and we're ready to enforce our IP vigorously.

same level of comfort that we have with Okalava as we have with Nash. I don't know Jerry if you want to add to that. Oh, thank you got it.

comfort that we have with Okalva as we have with Mash. I don't know Jerry if you want to add to that. Oh, thank you got it. Thanks, Brian .

Thank you. Our next question comes from the line of Michael Yee with Jeffries. Your line is open. Thanks for updating the questions that you see on for Mike. One question from us today. So some competitors have faced three data coming up over the span of the next year.

Could you comment to us a little bit of your view on how the competitive landscape is involved is evolving and how all kind of those positions and the mandate.

So I assume you're talking about competitive landscape on PVC just just so that I'm clear. Yeah, PVC. Yeah, maybe a couple comments from me and then Linda can can get in a little deeper. I think importantly, we continue to position ourselves for a long-term effort in PVC. We have leadership there. Our goal is to maintain that leadership. And I think as Andrew just indicated.

The patent settlements give us more runway and certainty on O'Callava. And then importantly, we have the opportunity with the next generation and the FDC coming to not only potentially provide a better therapeutic solution but also more runway because there's incremental exclusivity and IP potential on the combination. So this is a long-term play for us now and as we get ready.

potentially some phase three data to comment and new entrance in the second line therapy. I think we feel good about our position and the work to do ahead. Maybe Linda, you can comment on how we see that evolving. Yeah, I mean, obviously, we're the incumbent. We are still growing. We have new data that's changing the way for subscribers. Think about the goals. We have probably two more publications to come this year reinforcing our rearward evidence.

And what we're really trying to do is say it goes beyond ALP and just normalizing or lowering scores, it really is about what is the long-term impact on the patient. And we are the only people right now in the new second line, not discounting or so, but in the second line market, we are the only ones with that data. And it is important, and we are repeating the data.

in multiple studies, and that gives credibility and credence to what we are able to communicate and generate. And in that commitment to this space, we will continue to move the goalpost. Again, impacts lives, not labs. We have the ability to still call on these folks if we have our future national launch.

We're in their day in and day out, and we're also strongly engaged with patient organizations with the groups that are making guidelines, etc. So we feel we have a lot of game and growth as evidence fire accelerating growth in the second half. Our plan is to carry that forward into the year.

and day out and we're also strongly engaged with patient organizations with the groups that are making guidelines, etc. So we feel we have a lot of game and growth as is evidence fire accelerating growth in the second half. Our plan is to carry that forward into the year. Great thank you.

Thank you. Our next question comes from the line of J. Olson with the Oppenheimer. You'll let us know if it. Oh, hey, congrats on the progress. Thank you for taking the question. I'm curious about the fresh trial for INT787. It says on clinicaltrials.gov that patients must participate in an alcohol use disorder program. So will patients be allowed to consume alcohol during this time?

is that it's really critical for outcomes for these patients to commit to being in an outpatient program immediately after their release from the hospital. So the trial is focused on hospitalized patients of course.

but then they would continue for their follow-up in this outpatient program. We do find that patients in general don't consume alcohol within the first couple of months after release from the hospital. It's a special period in that recovery. Certainly after that, we do see recidivism.

But we are working again closely with these centers who have expertise in treating these patients and in maximizing their retention in the trial and making sure that they're able to to go off to follow up patients because of recidivism early.

Sounds great. Thank you. Thanks, Jake. Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. She'll line itself in. Hi, this is Shrenautro and Salveen. Thank you for taking my question. You referred to this briefly in the buzz. So how are you thinking about the product market switch for...

got the question correctly, I understand the question kind of positioning given our stronger efficacy and f3s in the context of other data being out there. I mean, I think look, we continue to do all the deep work in market and continue to confirm the understanding that.

This incremental efficacy that we see in the advanced population is an important part of the overall value proposition. We also know that, look, there are different mechanisms of action at play here between OCA where you have clearly consistent antibiotic effect and other drugs that might be working.

differently. So again, I think everything we learn in an updated context, including consideration of other potential profiles that are out there, confirm that the unmet need is high overall the unmet need is most.

pronounced in these more advanced populations and that the well-known profile of OCA plays to that more advanced population. Of course, there is an asymmetry of information available. So we know a lot about OCA in the context of all the safety and efficacy we've put out, the profile of other emerging therapies as you would expect.

is that longer term safety experience where we believe, we have the opportunity both in the regulatory dialogue and ultimately hopefully in market to talk about appropriate chronic therapy, the right guidance around what to measure and monitor over time.

And again, I think it speaks well to that more advanced population. So, but the unmet need in Nash is high. I guess just the last point I would stress is, you know, in any chronic class and clearly Nash will be over time and important chronic class of therapy, it always takes multiple drugs.

to address the different segments of patients that are out there, and we're working towards defining the right introductory approach and the right segments for success, for OCA and for the patients who have this high level of unmini.

Thank you. Thank you. Our next question comes from the line of Eleon Emerald with UBS. You'll find it's open. It's open.

I think I think so much for taking the question. Just in terms of the national commercial landscape, you mentioned there's a large number of undiagnosed patients. I guess what trends have you been seeing recently, you know, on the horizon as potential initial therapies approved? And on the topic of reimbursement and diagnosis,

I guess as you do your pre-commercial conversations with payers, what feedback are you getting in terms of what they will view as a national diagnosis and any type of potential restrictions or step-throughs from the payer conversations just given the potential for this to be a Energy Law embryo through a safety glasses to fully identify these one-laughter

say potential biopsies or any other types of factors that might be needed or suggested by pairs. Thanks. Now maybe a couple of dynamics to have in mind, Ellie, and thank you for the question. As I indicated earlier, obviously we're doing all of the in-depth work and look, our plan would be to come back with more details on the commercial plan in a formal way when we get closer to the pedo. Nonetheless, I think there are a couple of key themes which continue to play out. One is that we continue to see the utilization of non-invasive overall move in the right direction, right? There is.

But themes which has been really important and productive for us is that we're talking in the early discussions with the pairs about a subset of our potential indication. We're talking about the more advanced population. We're talking about working together to find a way to find the right patients. And one of the big, higher concerns is always...

utilization beyond your indication. So it's a great starting point that we're talking about the more advanced population and actually identification of a subset of our indication. And I think that gives us a good productive discussion. Of course, as I said, this will be an ongoing dialogue with the pairs and we'll come back with more details as we get closer to finalization and the strategy. And just the last point, of course, our final decision on price et cetera will be taken with approval and we would communicate that as one of the last pieces in the equation.

The only thing I might add to that, Ellie, is at this point, unlike four or five years ago when we were talking about initial payer discussions, the idea and the acceptance of NITs is also broader. So that plays into people trying to get to an easier path and the expense and the time and frankly the paying for patients of biopsy. So I really feel like that is...

an advancement from where we were before and should help with different, you know, the expansion of NITs being available and access to different ways to find appropriate advanced patients really has moved significantly from our earlier work.

advancement from where we were before and should help with different, you know, the expansion of NITs being available and access to different ways to find appropriate advanced patients really has moved significantly from our earlier work. Great. Thanks for the collar.

Thanks, Alex. Thank you. Our next question comes from the line of Jeff Mietzum with Think of America. Your line is open. Hi, good morning. This is Susan on for Jeff. Given the company's stronger cash position, are there any interesting external business development opportunities? And if external business development isn't on the books this year, which internal programs do you expect to accelerate instead? Yeah, so as you can imagine, we're always looking for externally for good opportunities, but...

We're also making sure that we're managing the cash we have on hand appropriately, giving the work that we're trying to do. And funding, you know, the important internal programs that we discussed some this morning, INC 787 with the lead indication ongoing. And importantly, the long-term next-generation in PBC for the fixed-dose combination, will be our primary focus. We're also looking for additional indications for both of those internal assets. Should it make sense? So we'll continue to evolve the pipeline in the right way while we also make sure that we're focusing.

our cash and our investment on the growth drivers. Thank you. Thank you. Our next question is the follow-up from my ink, Mim Pani, with B. Raleigh's security. She'll let us know. Open.

Oh, thanks for squeezing me in for a follow up. So maybe just one more Nash, if I end here the view question, is there been any indication for biopsy endpoint definition changing or being mechanisms specific etc. You know anything that you said there's that agency might be looking to go beyond the scope of their 2018 draft guidance document. Michelle.

Well, as Linda was speaking to, we have seen a lot of interest and some great publications now coming out on the non-invasive tests. I think it's recognized certainly by the community and by the GI division that...

Both patients and providers would really look for an alternative to biopsy. Really, the only reason folks are getting a liver biopsy is to participate in clinical trials. Having said that, we have relied on histology for decades in viral hepatitis and now in Nash. And that is our agreement with the agency that this planned interim analysis would focus on histology. We're confident that the histology results that we've seen.

our confidence and our submission and our analyses that have been submitted with the NDA. Thanks for the question. Thanks for giving my follow. Thank you. And now we'll turn the call back over to Jerry for closing remarks. Jerry. So thanks everybody for joining us today. Just to reiterate, I'm.

and I definitely look forward to sharing updates as we progress through what is an important and exciting year ahead. So thanks and everybody had a great day. This concludes today's conference call. Thank you for participating. You may now disconnect. The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1-1.

I have you.

Good day and thank you for standing by. Welcome to the Intercept Promise Utical's fourth quarter in four year 2022 earnings conference call.

At this time, all participants are in a listening mode. After the speech is presentation, there will be a questioning answer session. To ask a question during the session, you will need to press star 111 on your telephone.

You will then hear an automated message of icing your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to you to speak today. Narek Sigerian, Executive Director of 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 fourth quarter and full year 2022 results, which is available on our website at interceptfarma.com. Before we begin our discussion, I'd like to note that during our call, we'll be making forward-looking statements, including statements regarding our approved product and clinical development program, certain regulatory matters, and our strategy, prospects, financial guidance, 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 took power to 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 fireings with the FEC. Today's call will begin with prepared remarks from our President and CEO Jerry Dersow, Archie commercial officer Linda Richardson, President of Research and Development and Chief Medical Officer Dr. Michelle Berry, and Chief Financial Officer Andrew Saik.

participated or predicted by our forward-looking statements are discussed in this morning's press release and in our periodic public finals with the FEC. Today's call will begin with prepared remarks from our President and CEO Jerry Dersow, our Chief Commercial Officer Linda Richardson, President of Research and Development and Chief Medical Officer Dr. Michelle Berry, and Chief Financial Officer Andrew Sake. We will then open the call for questions.

Let me now turn the call over to our CEO , Jerry Dersow. Thanks, everyone. Thank you for joining us on our fourth quarter and full-year conference call. Intercept makes significant progress across the business in 2022, and I'm proud to highlight our achievements today. Looking at our performance in PBC, we again deliver double-digit sales growth grow Calava and ended 2022 with total US net sales of $285.7 million. This was 10% growth over 2021.

Importantly, in the fourth quarter of 2022, Ocalava generated $77.2 million in US net sales, which is 13% growth over the prior year of quarter. We now looked at 2023 as a year to continue driving growth, and we're more confident than ever in the longevity of our PVC business. We know that remains a significant number of people living with PVC who can benefit from adding Ocalava as the second-line therapy. We added more certainty in the runway of our life cycle with the resolution of our patent infringement case for Ocalava that was scheduled for trial in the US District Court on February 27 of this year. The settlements protect Ocalava Market Explicitivity into the 2030s.

and reinforce the long-term opportunity we have in PDC. In addition, we continue to progress our next generation PDC therapy to fix those combination of OCA and BESA Fibrate, which is another component of our long-term strategy.

We look forward to sharing data on our next generation medicine later this year and are excited about its potential. Turning now to Nash. At the end of the fourth quarter, we resummeted our NDA for OCA in pre-cerotic liver fibrosis due to Nash. Following FDA's acceptance in January , the agency assigned a pedophilic target action date of June 22nd. Reaching this point is the result of hard work and dedication from patients.

positions, study personnel, and our team here at Intercept, and is a major milestone for the NASH community. OCA has demonstrated a strong and confirmed amphibotic effect in our rigorous NASH program, but we believe it has the potential to become an impactful therapy. We're now working through the regulatory review process and are advancing our launch readiness planning, while taking a measured approach to investment as we progress through the upcoming milestones.

We also make strides in our pipeline program with our next generation FXR Agonist, INT-787. In November , we announced a lead indication for this investigational therapy, severe alcohol associated hepatitis, and initiated our face-to-fresh trial. The shell will elaborate on this later in the call.

Notably, the progress we made last year was complemented by the transformation of our capital structure. As a result of this work, we finished the year with nearly $500 million of cash on hand. Twice twenty-three will be a pivotal year for intercepts that were operating from a position of strength. Our balance sheet and foundational PVC business provide us with the financial flexibility and the strategic optionality to drive growth while positioning ourselves for success and match. This year I look forward to working alongside the team as we build on the momentum of last year's performance.

and grow our commercial PVT business. As we work through the regulatory review of OCA while preparing for a commercial launch in Nash, and as we progress our pipeline opportunities while continuing to innovate on behalf of people living with liver diseases. I look forward to sharing updates on our progression of these priorities throughout the year ahead.

With that, I'll now turn the call over to Linda. Thanks, Jerry, and good morning, everyone. I'm pleased to share performance highlights for 2022. It was another strong year for our foundational Cal over business, underscoring the strength of a Cal over market position as the only second-line agent approved for use in PBC. We achieved double-digit growth for both the fourth quarter and the full year, compared to the same time frames last year. Our performance in PBC was driven by a strong return to growth.

in the second half of 2022, with a few notable contributing factors. First, our new to brand prescriptions grew nearly 30% during the second half of 2022, as reported by IQBIA's NPA audit. We believe this would be the trend as we passed the one-year mark post-label change in June of 2022. While over 95% of our business is driven by existing patients, it's good to see solid growth in new patients receiving O'Calva, and speaks to the ongoing need for second-line therapy for many patients with PBC. Second, as a result of our ongoing efforts to reach new prescribers, we continue to see an increase in first-time O'Calva writers.

More specifically, we saw a 42% increase in new writers in the second half of 2022 versus 2021. A dynamic we see is very positive and important. Third, our continued investment in patient support services through our award-winning hub and our specialty pharmacy network has resulted in an eight-day improvement in specialty pharmacy time to fill. We want to ensure that appropriate eligible patients can quickly start treatment with O'Calva. Simplifying facilitating processes here helps sustain existing patients and initiate new ones.

Strong customer engagement and communication of the benefits of Ocala, we made a focus for our commercial team in the field at major conferences and with patients. Last fall, we kicked off our new HCP and patient marketing campaigns. Each was updated messaging designed to drive urgency and demonstrate the need to go beyond ALP management in fully addressing PVC treatment. We recently began to proactively provide to HCP's, the gastroenterology publication that presented in greater detail.

some of our strong real-world evidence regarding improved outcomes for patients taking on Calibur. We anticipate additional publications and presentations of new real-world evidence later this year. Prescribers recognize the significance of real-world outcomes data when treating PBC. In market research studies, we have seen a significant increase in projected effected of Calibur market share once a half than GI represented with results from the real-world evidence studies.

Turning now to Nash, we are engaging with all key stakeholders as we prepare to execute against our go-to-market commercial strategy. We continue to meet with payers to refiner thinking as we prepare for a potential launch in Nash. We are focused on understanding their needs and concerns, which has allowed us to gain valuable insight into our pricing, reimbursement, and overall access strategy. Market research with healthcare professional shows that we've personally fibroasted.

stopping further progression of fibrosis, and the prevention of cirrhosis will be the three key drivers of prescribing for NAS patients with advanced fibrosis without cirrhosis. We believe that the strong and confirmed antifibrotic effects of OCA, shown in our regenerate trial, address all these areas of concern with a unique, differentiating mechanism of action. Importantly, our well-established US field presence and broad geographic footprint provide intercept with a competitive advantage.

Based on our analysis, nearly three in core of the highest potential prescribers per Nash already are within our existing PVC customer base, where we've been building relationships for the past six years. This overlap will enable us to easily flex to Nash disease awareness messages and then OCA specific ones, while also covering our current PVC targets.

In the meantime, our disease awareness activities continue. Our unbranded website hosts our Nash Tipping Point campaign, educating providers on the significant risks associated with advanced fibrosis due to Nash. We will continue our presence at key congresses while also initiating disease awareness programs. In closing, we have strong PBC performance in 2022. Remain confident in our ability to increase the accountable market penetration in 2023, and maintain a positive long-term outlook for our PBC franchise. The commercial team is actively and passionately preparing for our future in Nash.

and proud of the team's performance and look forward to sharing updates on our progress throughout the year. I'll now turn the call over to Dr. Michelle Baird. Thank you, Linda, and good morning, everyone. In 2022, we made substantial progress in our national development program and building out our pipeline.

Looking first at NASH in January , the FDA accepted the resubmission of our new drug application for OCA and pre-cerotic liver fibrosis due to NASH. We are thrilled to have progressed to this regulatory milestone one step closer to reaching our goal of delivering the first FDA-approved therapy for this devastating disease. There's a critical need to address liver fibrosis due to NASH before patients progress to therosis, a pivotal point in NASH disease progression associated with increased risk of both liver specific and all-caused mortality. Our NDA is supported by a robust body of evidence from the OCA NASH.

one stage without worsening of any of the three histologic parameters that comprise the Nathold activity score or NAS. In both methodologies, OCA 25 milligrams demonstrated double the response rate of placebo in reducing liver fibrosis stage without worsening of any of the three histologic components. It's important to note that this endpoint was defined as a original Psalmist equilibrium. chce ???phas rad theorem is not certain if it was done otherwise, but

the potential chronic administration of OCA. We know that fibrosis is the strongest predictor of clinical outcomes in patients with Nash. And we continue to believe that OCA has the potential to become the first approved therapy in this disease. FEA indicated that it considers this a class to resubmission and has assigned a pedupa target action date of June 22nd for the NDA. We fully anticipate an advisory committee meeting as part of this process.

but we do not yet have a confirmed date. We'll share additional updates as appropriate as we advance through this review process. Turning to PBC, we continue to prepare data from our post-marketing study cobalt and supplementary real-world evidence from large data sets in the US, UK, and Europe .

These data will be included in a regulatory submission to FDA this year in support of fulfilling post-marketing requirements for CalvA and PVC. The real world data we have generated to date demonstrates the actual long-term clinical benefits of CalvA. Specifically, patients taking OGAF had improved, transplant-free, and decompensation-free survival, which we know to be the most important treatment goals both for individuals living with PVC and

trial. We anticipate selecting doses for the fixed-disk combination as well as sharing data from planned analyses of the large phase 1 and phase 2 studies later this year.

The OCA-Vesify Break combination has synergistic mechanisms of action with the potential to further lower key biochemical measures that predict long-term outcomes in PBC while also improving tolerability. We're excited to share the potential impact of this combination that we believe has best in-class potential. Finally, I'm happy to provide updates on our next generation FXR Agonist.

there are no approved therapies for people who could develop this disease. We believe there are several indications in which 787 could make a potential impact. However, SAH provides us with a great initial opportunity for this FXR Agnes with a different gut-to-liber ratio compared to OK. In November , we announced initiation of our proof of concept phase 2A study called fresh.

evaluating the safety, tolerability, efficacy, and pharmacokinetics of INT-787 in patients with SAH. Our first fresh site was activated in December 2022, and we're continuing to add additional sites in the US, UK, and France. As of February 2023, we have completed recruitment for our Phase I study. We look forward to sharing additional updates as this program advances.

At this point, I'll turn the call over to Andrew for financial updates. Thank you, Michelle, and good morning, everyone. We've had a very strong 2022, and I look forward to sharing our results and discussing our plans for the pivotal year ahead. I encourage you to please refer to our press release for a detailed summary of our financial results for the fourth quarter and year ended December 31, 2022. For this call, I will focus on the highlights as they relate to 2022 and will also provide guidance for 2023. As I begin, I would like to remind everyone that as you review our fourth quarter and full-year financial information, please note that the divestiture of our international business was completed on July 1, and our full-year non-GAP results include the divested business for the first half of the year. In our financial statements, the divested business has been moved to discontinued operations. Turning to the highlights for the fourth quarter and full-year ended December 31, 2022.

$176.3 million in full year 2022 compared to $177.5 million in 2021, with a decrease in personal related costs offset by an increase in national launch preparation.

Research and development expenses decreased to $40.7 million in the fourth quarter of 2022 from $51.1 million in the prior year of quarter. The decrease was primarily driven by lower-nash-related costs and cost-sharing reimbursements. R&D expense decreased to $176.6 million in 2022 down from $182.7 million in 2021.

The decrease was primarily driven by lower NASH costs and cost-earing reimbursements, and were partially offset by the recognition of lower R&D tax credits. In 2022, approximately two-thirds of our R&D costs were related to our NASH program spent. 2022 was a year of financial transformation for the company. We executed a series of strategic transactions to transform our capital structure, which included the sale of our international business and several private repurchases of senior secured convertibles. Regarding our convertible notes, as a result of the repurchases during 2022,

The principal balance of the 2026 convertible secured notes was reduced by approximately 78 percent to $111.1 million. Moreover, the company dramatically decreased annual cash interest. For 2023, cash interest expense will be $8 million as we anticipate our 2023 notes will be redeemed in July with cash on hand. A year and the company had $491 million in cash and cash equivalent and $336 million in outstanding debt. We ended 2022 with the financial flexibility to move our business forward regardless of the FDA decision.

on OCA in Nash, expected later this year. Turning to our financial guidance for 2023, we are guiding to $310 to $340 million of Ocalava Net Sales, which compares to $285.7 million in 2022. For 2023 non-GAP-adjusted operating expenses, we are guiding to $360 million to $390 million, which compares to approximately $325 million in non-GAP operating expenses in 2022 from our continuing business when excluding the sale of the international business.

Similar to what we've seen in prior years, we anticipate slightly lower revenue and higher cash utilization in the first quarter of 2023 relative to the rest of the year. We expect that little Calibre first quarter sales will be impacted by the usual seasonality as patients are faced with insurance plan recess and Medicare coverage gaps at the beginning of the year. We also anticipate greater cash use in the first quarter due to activities from work related preparing for potential approval and launch and NAS.

and other annual expenses. Finally, we may choose to revise our 2023 guidance later in the year, pending potential regulatory approval for our NDA, for OCA, and pre-cerotic liver fibrosis due to NASH. In summary, we are pleased with our financial performance in 2022, and looking forward to a strong 2023. We are in a solid financial position, and believe that our current balance sheet in cash on him gives us the financial flexibility to continue to grow our existing occalib-

Our first question comes from the line of Ritu Baral with Kowin. Your line is open.

Good morning guys, thanks for taking the question. Michelle has the SBA at any point communicated to you what the topic of the adcom could be. And for any range we should be thinking of for the state of the adcom. I guess we're all sort of coming at it wondering, given this is a resubmission, are you going to have something like a mid-cycle review meeting where they're going to tell you these things?

You know, are you flying blind by class time? Thanks. Good morning. Retieu. So we do anticipate that the focus of the advisory committee meeting would be focused on overall benchedness. We have had multiple conversations with them since the CRL and we know that there are some areas of focus for them. We intend to convey those. Certainly we're all addressed in our NDA.

the specific areas that we have communicated at the ASLZ presentation and again at NASHTag. We feel that we have addressed all the areas of concern with the confirmation of the anti-bibrodic benefit and the second analysis and a much more robust safety database with which we can address any of their earlier concerns, specifically around the long term safety and tolerability as to drive given that this would be.

anticipated to be a chronically administered drug. It's important that we have years of therapy in order to demonstrate that safety and tolerability. I guess just one more point to add in there, Richard, to your question as the shell indicated and or prepared remarks. All the prep for the outcome is ongoing, but we don't yet have a confirmed date. Thank you. Our next question comes from the line of Mayank Mimpani.

with the Raleigh Securities. Juman is now open. Good morning. Thanks for taking our questions and congrats on the progress. I have a few. Just maybe following up on the prior question, as part of your acceptance letter on the NDA filing, was it clearly communicated to you by a TA that they're planning to hold an outcome? And I just wonder, the agency does is increasingly requiring in-person formats. So how confident you feel we get an answer by the June 22nd to do for it. And then I have a couple of follow-ups.

Yeah, I guess on the adcom itself, we have every indication that we'll have an adcom, we can't speak to a date as there's a non-confirmed yet, but we are working in the context of the existing pedophadate. And typically, you know, those come a handful of weeks prior to the pedophadate. So we're moving forward, we'll be fully prepared. And of course, we'll provide any additional information as appropriate if we get it from the agency.

Okay, thank you. And then on the apparently very strong guidance you had on PVC seems like driven by new prescribers. Could you perhaps share what the overlap you may have with these new hepatologists that you're having to describe. Or for PVC, but also they may also care for mass patients. Do you have that data card? Yeah, so so man, we do as you said, feel good about the performance on PVC both for the quarter and the year where we saw an acceleration in the second half of the year.

in the growth versus the first half and with a strong 13% growth in fourth quarter. Clearly, this is a long-term area of focus for us. We have been working with many of the key prescribing physicians for several years now, and Linda can provide some details how we see a large part of that core audience also being really the first potential prescribers for Nash as we do the deep commercial planning in advance of the Purdue Farm Nash. Yeah, we cover right now from our analysis three out of four of the top potential Nash prescribers already exist within our PBC call list.

So we're bringing in new PBC prescribers, but also have established relationships over the past six years and familiarity with O'Cala va and that same target audience. So we feel comfortable that the work we've the groundwork that we've laid with PBC will translate very nicely and efficiently into a national potential national launch. Got it. And my final question on the FAC.

I know it's early but to be greater hair your thoughts on the face you will die. Michelle you want to take a hand? well if you kill those people one with action.

Sure, yes. The great question. We are really excited about the Fixed Space combination of OGA plus Bessafybrayden as you state is we are in a unique position to have two potential therapies in PVC. I have state to give a much detail on our plans for the base three until we have those conversations with the FDA to review all the tests.

very exciting data coming out of the phase two, but we feel we have the potential here with the combination for potential best in class for PBC. So again, it really underscores our long-term commitment to innovation in this space. Thanks, Mark. Thank you.

As a reminder, we ask that you please limit yourself to one question. Our next question comes from a line of Yasmeen Rahimi with Piper Sandler. You'll let me know if you're open. Hi, this is Emma on Free As. Thanks for taking our questions. My question is, what are your thoughts on the recent ICER pricing report and with that, are you still thinking about differential pricing and NASH for a PBC and what type of tear discussions have you had to support that if any year? Thanks Emma, maybe I'll give some overall view on how we're thinking about.

Okalava and OCA in Nash. Should we choose to execute a pricing strategy that way, if we would anticipate a separate brand, separate NDC, the things that give us that option. And all the updated work, including those discussions with pairs are going to be important inputs. We'll share.

more thinking about our strategy with the pair, which will of course be foundational for the launch as we get closer to the Padoopa date. And again, I think it's been several years we've had dialogue with the pairs going back to before the first Padoopa date. So we've done a lot of in-depth work. We're revising it with the current context as you would need to.

And then perhaps, Linda, you can comment on Icer. Yeah, of course. Thanks for the question. You know, frankly, we disagree with several of the approaches that were used within the model, which generated the draft evidence report. Specifically, when we look at the model, it does not define a standard that constitutes an acceptable data set. And it kind of applies an inconsistent approach and an exclusion of available data for different therapies. So what do I mean by that? An example is, it includes only space three data for OCA.

but put both Phase 3 and Phase 2 data in for Magical. And even though the Phase 2 data do not include by process improvement without worsening of Nash as a primary endpoint. And then furthermore, it does not use the updated available information for OCA. It doesn't incorporate all data that are publicly available, notably the full and robust safety data set we have for regenerate. We presented this at AISLD in November 22. And then, frankly, it doesn't present the new analyses that we shared at Nash Day.

in January 2023. So there's kind of a lack of consistency in approach that, you know, we're recognizing and, you know, we'll see how it goes from there, but we have some concerns with the model. Thank you. Thanks so much. Thank you. Our next question comes from the line of John Wallabin with JMP Security. She'll let us know open.

Hey, good morning and thanks for taking the question. Primarily wanted to ask about OPEX guidance. Wondering how much incremental NASHF-GNA has included there, and if it's not so included, how much more do you think would be necessary? And then I think Andrew, you said that 2.3rd of 2022 R&D was for NASH, you're wondering if that's the same proportion, expect the 2023. Thanks.

Thanks, John . We are continuing to manage with, I think, the right intersection of ensuring we have the right investments as we prepare for Nash, but also paying a lot of attention to making sure that we're managing our OPEX in a responsible way. And, maybe, you can go into how we're thinking about the Nash investment and the context of the guidance that you gave earlier. Yeah, sure. Thanks for the question, John . Yeah, so probably the right way to think about it and the reason I gave sort of our continuing cost.

We're not adding a lot to infrastructure in the meantime until we get to our productive date so it's all going to be external spend that we could ratchet up or ratchet down sort of as we go. With regard to R&D, yeah, we're continuing to evolve our pipeline as you know. So reverse is done, which means that our spend on Nash is going to be reduced this year, relative to last year. Overall, R&D spend will be slightly down but materially flat, which you're going to see more like 50% Nash and 50% pipeline. If that helps.

Very helpful. Thanks for the call. No problem. Thank you. Our next question comes from the line of Joseph Stringer with the Needham and Company. Your line is now open. Hi, thanks for taking our questions. Just wanted to get your updated dots on the pre-cerotic national market segmentation. And looking ahead, if OCA has approved a national with your desired label, what type of mass patients would be interested in getting on the drug approach?

Yeah, thanks, Joe. Maybe I can start in Linda can ship in if she wants. I think, look, when we think about how we would best position OCA, we continue to be focused on the anti-fibratic effect and the more advanced patients. And so I think that theme, which you've heard from me for a while, continues to be what we're getting back as we do these updated discussions with all of the stakeholders, the deep updated market research you would anticipate. We're doing as we're in this phase of preparation. So, really the advanced patient who is most likely identified through non-invasive means.

continues to be where we would zero in on both. It really is the patients that the physicians, the payers and the patients themselves have the most amount of urgency towards seeking treatment. From the profile of OCA, including importantly, the greater level of efficacy that we showed in some of the analysis that we reported out in the latter part of last year showing higher efficacy. For example, in that F3 subset goes in that same direction. We would also be focused in the initial phase on those patients that are already under care of the specialists of HEPSEN and GI's. And as Linda said earlier in response to the one of questions, we're seeing most of those physicians already today. So we, I think we have a good understanding.

of those practices and of those individual and group subscribers. But Linda, anything you want to add on? Yeah, I think the combination of calling on these folks with the urgency that's been noted over and over again by physicians with the psychotic patients, advanced patients. We estimate that there are probably 20 million adult patients with Nash, but only a small percentage, roughly about 3.8 million, have been actually diagnosed. There's nothing to use to treat them. So you see an increase in diagnosis that comes following the ability to have on-label treatments.

Our next question comes from the line of Brian Scorney with Bear to your line of snow open. Hey, good morning guys. Thanks for taking the question. I guess on the ocalibid guidance for 2023, maybe you just frame on how to think about getting a higher end of the guidance. It's almost 20 percent, increased year-over year, which is quite a bit of acceleration compared to where it's been trending for the last two years. So can you just characterize what you're seeing in the more that might get you there? And does that high end include anything for Nash? Thanks.

Yeah, there may be you. You start on that. Yeah, sure. Thanks, Brian . Look, the guidance that we gave is kind of in the, you know, 9 to 19% range growth. You know, we tend to try to target the center of that growth as to where our focus is internally. You know, again, we're continuing to put effort and energy into growing our top line. And we're really comfortable with our guidance overall. You know, what I would say is that the guidance that we gave on O'Caliva is unimpacted by Nash. We, you know, in my prepared remarks, you probably noted that I mentioned that we would reserve the right to come back and reissue guidance. One and if we get approval.

from the FDA. And at that point, we would give more of a blended secondary guidance would include any impact from Nash on Calibur. Yeah, Brian , the only other thing that I would add, just in terms of dynamics, we talked in the second half of last year about the emerging data that we were beginning to publish from the real world data sets on outcomes. We know that some of those publications came late in the year. And look, all indications that data were getting it out there, appropriately in the context of the medical affairs and or commercial plan.

But that data is just starting to get into the hands of the prescribers. And we know from the research that we're doing, it can be quite important to those prescribers as they think about potentially increasing their utilization of a calibur for the right second-line patient. Yeah, and I think the last thing to note is coming out of the second half of the year, as we predicted, we've seen accelerated growth. We saw this bolus of new writers, demand, et cetera. And we are layering that now, as Jerry noted, with distribution of our real world evidence data.

And when we test that in market research and have people that are exposed to that data and say, all right, now projector prescribing, we see a significant increase in allocation of share to Okalaba. And as we have and we anticipate additional presentations of new real-world evidence data and frankly the publications that we will be able to disseminate, we see that awareness picking up and really reframing the way that physicians evaluate what does complete the PVC management look like and they've always said that.

you know, preventing progression, maintaining the patients. Those are the important things and we've got not only five years of data from our Poise data on looking at stabilization of fibrosis and billy-rooven, but now we have outcomes and we're talking about lives, not labs. These are actual patients that are benefiting from treatment with O'Calava. All right, thank you. Thanks, Brian . Thanks.

Thank you. Our next question comes from the line of Comis Smith with SVV Securities. Shealana is open. Hi, everyone. This is Mike on Fertile. Thanks for taking our question. Can you provide some additional color on where you are with the PVC regulatory discussion and what if any are the remaining gated factors for submission? And then just as a quick follow-up, when in 2023 specifically are you targeting for submission? Michelle, can you take that please? Yes, happy to. Thanks for the question. So we have been in discussion with the agency about the content of our planned supplemental NDA, which as we've discussed would include the cobalt results, which we top lines last year, as well as an external controls of comparing those patients from within the cobalt study who were on OCA.

to a group of patients from external databases. We've looked at the commuter databases. We've released as well as two different patient registries, the UK and global PBC databases. So we've been in discussions with the agency about inclusion there. We will also be planning to publish these data as we did with the gastro cover last December in releasing the real-world evidence. The most striking thing about these datasets is the consistency and completely independent datasets. We're seeing a 50 to 70 percent reduction in deaths and decompensation leading to intertransferienter deaths.

So we are really excited about those data sets. This would be the first non-altrow-rare condition that would include real-world evidence in a significant submission. So we know there's a lot of interest here that is our plan for the submission. We haven't yet given guidance on the exact timing that as you might understand with a small group, we are working into parallel paths, so on the Nash preparations and for the PVC SNDA. So we'll give more guidance as that date grows closer. Thanks for the question. Understood. Thanks very much. Thank you.

are really excited about those data sets. This would be the first non-altrow rare condition that would include real world evidence in a significant submission. So we know there's a lot of interest here that is our plan for the submission. We haven't yet given guidance on the exact timing that as you might understand with a small group, we are working into parallel paths, so on the Nash preparations and for the PBC SNDA. So we'll give more guidance as that date grows closer. Thanks for the question. Understood. Thanks very much. Thank you. Thank you.

Our next question comes from the line of Brian Abrams with the RBC capital market. Your line is now open. Good morning. Thanks for taking my question. A question on IP. Can you talk about your level of confidence in OCA's exclusivity extending to 2031, just given all the recent settlements that you've been able to do, but still maybe one filer remaining out there? And then how should we be thinking about that expiration potentially applying to OCA in the Nash setting versus just in the PBC setting? Thanks.

Thanks for the question, Brian . Andrew? Yeah, sure. Thanks, Brian . Yeah, so look, we're extremely happy that we were able to get such a positive settlement, not going to litigation on the IP was a great outcome for the company, and getting, you know, 70% of the value of those 2033 patents is a real win for the company. Look, we can't speak to any, you know, the current additional filer out there, which is the NARA Farma. That's a separate trial. It's the same jurisdiction, the same judge, same fax set. It would, you know, but it's out there in 2024.

The good news for the company is that we're completely ready for trial, right? Because we did all the work, we did all the prep. The narrow would have to start over from scratch. We were never going to predict an outcome, but it's the same fact set, and we're ready to enforce our IP vigorously. You know, in terms of carry on to Nash, again, you know, assuming that we get approval, that's a same fact set. It'll, you know, presumably if people file against it, it would be a completely different trial. But again, we're very comfortable with the IP. You know, we've been through it. It's the same patents. So we would have the same level of comfort that we have with Okalava as we have with Nash.

I don't know Jerry if you want to add to that. Oh, thank you got it. Thanks, Brian . Thank you. Our next question comes from the line of Michael Yee with Jeffries. Your line is open. Hey guys, thanks for stating the question that you need to see John from Mike. One question from us today. So some competitors have faced three data coming up over the span of the next year. Could you comment to us a little bit of your view on how the competitive landscape is involved is evolving and how I'll kind of as positioned in this. Thank you. So I assume you're talking about competitive landscape on PVC just just so that I'm clear. Yeah, PVC. Yeah, maybe a couple comments from me and then Linda can can get in a little deeper. I think importantly.

We continue to position ourselves for a long-term effort in PBC. We have leadership there. Our goal is to maintain that leadership. And I think as Andrew just indicated, the patent settlements give us more runway and certainty on O'Callava. And then importantly, we have the opportunity with the next generation and the FDC coming to not only potentially provide a better therapeutic solution, but also more runway because there's incremental exclusivity and IP potential on the combination. So this is a long-term play for us now. And as we get ready for potentially some phase three data to comment and new entrance in the second line therapy, I think we feel good about our position and the work to do ahead. Maybe Linda, you can comment on how we see that evolving. Yeah, I mean, obviously we're the incumbent. We are still growing.

We have new data that's changing the way for subscribers. Think about the goals. We have probably two more publications to come this year reinforcing our rearward evidence. And what we're really trying to do is say, it goes beyond ALP and just normalizing or lowering scores. It really is about what is the long-term impact on the patient. And we are the only people right now in the new second line, you know, not discounting or so, but in the second line market, we are the only ones with that data. And it is important. And we are repeating the data in multiple studies. And that gives credibility and credence to what we are able to communicate and generate. And in that commitment to the space.

We will continue to move the goalposts. Again, impacts lives, not labs. We have the ability to still call on these folks if we have our future national launch. We're in their day in and day out, and we're also strongly engaged with patient organizations with the groups that are making guidelines, et cetera. So we feel we have a lot of game and growth as is evidenced by our accelerating growth in the second half. Our plan is to carry that forward into the year. And we look further at you.

Great, thank you. Thanks. Thank you. Our next question comes from the line of J Olson with the Oppenheimer. Your light is now open. Oh, hey, congrats on the progress. And thank you for taking the question. I'm curious about the fresh trial for INT787. It says on clinicaltrials.gov that patients must participate in an alcohol use disorder program. So will patients be allowed to consume alcohol during the study? And if so, how do you plan to manage alcohol consumption and the potential impact that could have on the...

on hospitalized patients, of course, but then they would continue for their follow-up in this outpatient program. We do find that patients in general don't consume alcohol within the first couple of months after release from the hospital. That's it all. I think it.

special period in that recovery. Certainly after that, we do see recidivism, but we are working again closely with these centers who have expertise in treating these patients and in maximizing their retention in the trial and making sure that they begin to gloss to follow-up patients because of recidivism early.

special period in that recovery, certainly after that we do see recidivism, but we are working again closely with these centers who have expertise in treating these patients and in maximizing their retention in the trial, and making sure that they're getting reglucted to follow up patients because of recidivism early. Sounds great. Thank you. Thanks, Jake.

Thank you. Our next question comes from the line of Salveen Rector with Goldman Sachs, you'll find it's now open. Hi, this is Renato and for Salveen. Thank you for taking our question. You referred to this briefly in the past. So how are you thinking about the product market fit for OCAG given the data demonstrating great efficacy in app treatments compared to ectopations in Nash as well as given the data from emerging treatments like the ones from Madagrall?

Yeah, so I can start on this. I end up just make sure I got the question correctly. I understand the question kind of positioning given our stronger efficacy in F3s in the context of other data being out there. I mean, I think look, we continue to do all the deep work in market and continue to confirm the understanding that that. This incremental efficacy that we see in the advanced population is an important part of the overall value proposition. We also know that.

Look, there are different mechanisms of action at play here between OCA where you have clearly a consistent antibiotic effect and other drugs that might be working differently. So again, I think everything we learn in an updated context, including consideration of other potential profiles that are out there, confirm that the unmet need is high overall. All the unmet need is most pronounced in these more advanced populations and that the well-known profile of OCA plays to that more advanced population. Of course, there is an asymmetry of information available. So we know a lot about OCA in the context of all the safety and efficacy we've put out the profile of other emerging therapies as you would expect. There's less information. Particularly when we consider.

The longer-term experience that we now have with OCA, and importantly, when we think about the improved benefit-risk profile of OCA that we believe we have on the first submission, one of the important dimensions is that longer-term safety experience where we believe, you know, we have the opportunity both in the regulatory dialogue and ultimately hopefully in market to talk about appropriate chronic therapy, the right guidance around what to measure and monitor over time.

And again, I think it speaks well to that more advanced population. So, but the immediate and Nash is high. I guess just the last point I would stress is, you know, in any chronic class and clearly Nash will be over time and important chronic class of therapy, it always takes multiple drugs to address the different segments of patients that are out there and we're working towards defining the right introductory approach and the right segments for success, for OCA and for the patients who have this high level of unmened.

Thank you. Thank you. Our next question comes from the line of Eleon Emerald with UBS. And I think I think I think so much for taking the question. Just in terms of the national commercial landscape, you mentioned there's a large number of undiagnosed patients. I guess what trends have you been seeing recently, you know, on the horizon as potential initial therapies approved? And on the topic of reimbursement and diagnosis, I guess as you do your pre-commercial conversations with payers, what feedback are you getting in terms of what they will view as a national diagnosis and any type of potential restrictions or step through from the payer conversations, just given the potential for this to be a large class and say potential biopsies or any other types of step through.

that might be needed or adapted by payers, thanks. Now maybe a couple of dynamics to have in mind, Ellie. And thank you for the question. As I indicated earlier, obviously we're doing all of the in-depth work. And look, our plan would be to come back with more details on the commercial plan in a formal way when we get closer to Padufa. Nonetheless, I think there are a couple of key themes which continue to play out. One is that we continue to see the utilization of non-invasive overall move in the right direction. Right? There is good momentum there. There is a larger utilization of the variety of different non-invasive for identifying patients. And the payers do understand this dynamic.

and our monitoring the progress and our looking for the right ways to identify patients consistent with what the KOLs are saying and what clinical practice is, which is clearly utilizations of non-invasive. I think with the payers, one of the themes which has been really important and productive for us is that we're talking in the early discussions with the payers about a subset of our potential indication. We're talking about the more advanced population. We're talking about working together to find a way to find the right patients. And one of the big payer concerns is always...

utilization beyond your indication. So it's a great starting point that we're talking about the more advanced population and actually identification of a subset of our indication. And I think that gives us a good productive discussion. Of course, as I said, this will be an ongoing dialogue with the pairs and we'll come back with more details as we get closer to finalization and the strategy. And just the last point, of course, our final decision on price et cetera will be taken with approval and we would communicate that as one of the last pieces in the equation. The only thing I might add to that, Ellie, is at this point, unlike four or five years ago when we were talking about initial payer discussions, the idea and the acceptance of NITs is also broader. So that that plays into people trying to get to a

an easier path than the expense and the time and frankly the paying for patients of biopsy. So I really feel like that is an advancement from where we were before and should help with different, you know, the expansion of NITs being available and access to different ways to find appropriate advanced patients really has moved significantly from our earlier work. Great, thanks for the collar.

time and frankly the paying for patients of biopsy. So I really feel like that is an advancement from where we were before and should help with different, you know, the expansion of NITs being available and access to different ways to find appropriate advanced patients really has moved significantly from our earlier work. Great, thanks for the collar. Thanks, Alex.

Thank you. Our next question comes from the line of Jeff Meacham with Bank of America. Your line is open. Hi, good morning. This is Susan on for Jeff. Given the company's stronger cash position, are there any interesting external business development opportunities? And if external business development isn't on the books this year, which internal programs do you expect to accelerate? As you can imagine, we're always looking for externally for good opportunities, but we're also making sure that we're managing the cash we have on hand appropriately, giving the work that we're trying to do. And funding, you know, the important internal programs that we discussed some this morning, I and T787 with the lead indication ongoing. And importantly, the long-term next generation in PBC for the Fixed-Dose combination will be our primary focus. We're also looking for...

additional indications where bulk of both internal assets should it make sense. So we'll continue to evolve the pipeline in the right way while we also make sure that we're focusing our cash and our investment on the growth drivers. Thank you. Thank you. Our next question is the follow up from my ink Mimtoni with the Raleigh Security. She'll let us know. And oh, thanks for squeezing me in for follow up. So maybe just one more Nash. And the interview question and there been any indication for biopsy endpoint definition changing or being mechanisms with the sector. You know anything that's just the best that agency might be looking to go beyond the scope of this. So we'll be here. 2018 draft guidance document. Michelle.

Well, as Linda was speaking to, we have seen a lot of interest in some great publications now coming out on the non-invasive tests. I think it's recognized certainly by the community and by the GI division that both the patients and providers would really look for an alternative to biopsy. Really the only reason folks are getting a liver biopsy is to participate in clinical trials. I think said that we have relied on histology for decades in viral hepatitis and now in Nash and that is our agreement with the agency that this

plan interim analysis would focus on histology. We're confident that the histology results that we've seen now with two independent analyses confirm our ENC-phibotic benefit. And we're excited about that opportunity to discuss it with the agency and upcoming opportunities. So I think it does remain draft guidance as you point out though. So as more data are being reviewed, we may see some modifications to that, but we are confident in our our submission and our analyses that have been submitted with the NDA. Thanks for the question. Thanks for the Pressure-LineA column.

Thank you. And now we'll turn the call back over to Jerry for closing remarks. Jerry? So thanks everybody for joining us today. Just to reiterate, I'm really extremely proud of the performance that the Intercept team delivered both in the fourth quarter and for the year of 22. We clearly have a lot of work ahead of us, but I think the achievements that we've discussed this morning set us up to drive continued long-term growth for Intercept. And I definitely look forward to sharing updates as we progress through what is an important and exciting year ahead. So thanks and everybody had a great day. This concludes today's conference call. Thank you for participating. You may now disconnect.