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Intercept Pharmaceuticals Inc (NASDAQ:ICPT)
Q3 2020 Earnings Call
Nov 9, 2020, 8:30 a.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Ladies and gentlemen, thank you for standing by, and welcome to the Intercept Pharmaceuticals Third Quarter 2020 Earnings Call. [Operator Instructions] After the speaker's remarks, there will be a question-and-answer session. [Operator Instructions]

I'd now like to hand the conference over to your host today, Lisa DeFrancesco, Head of Investor Relations. Please go ahead.

Lisa Defrancesco -- Head of Investor Relations

Thank you. Good morning, and thank you for joining us on today's call. This morning, we issued a press release announcing our third quarter 2020 results and financial position and also posted accompanying slides, which are available on our website at www.interceptpharma.com.

Before we begin our discussion, I'd like to note that during the call, we will be making forward-looking statements, including statements regarding our approved product and clinical development program; certain regulatory matters, including the potential approval of OCA for liver fibrosis due to NASH; and our strategy, prospects, financial guidance, and future commercial and financial performance. Listeners are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this call, and we undertake no obligation to update such statements, except as required by law. These forward-looking statements are based on estimates and assumptions that although believed to be reasonable are inherently uncertain and subject to a number of risks and uncertainties. Some, but not all of the risk factors that could cause our actual results to differ materially from our historical results or those anticipated or predicted by our forward-looking statements are discussed in this morning's press release in our periodic public filings with the SEC.

Today's call will begin with prepared remarks from our CEO, Dr. Mark Pruzanski followed by those from our Chief Operating Officer, Jerry Durso; and our Chief Financial Officer, Sandip Kapadia. We will then open the call to take your questions. Please limit yourself to one initial question in order to allow time for all questions to be addressed.

Let me now turn the call over to our CEO, Dr. Mark Pruzanski.

Mark Pruzanski -- President, Chief Executive Officer and Director

Thanks, Lisa, and good morning, everyone. Thank you for joining us on our third quarter 2020 earnings conference call. I'm pleased to report our core PBC business performed well during the quarter, which I will summarize shortly, but I want to focus first on providing a comprehensive regulatory update starting with NASH.

Last month, we had our Type A end-of-review meeting with FDA to discuss the agency's benefit-risk assessment in the CRL based on its review of the available data as well as our proposed basis for resubmitting our NDA seeking accelerated approval of OCA for NASH fibrosis. As you know, we prepared extensively for this meeting with the objective of reframing our efficacy and safety data supporting benefit-risk of OCA in NASH patients with advanced fibrosis based on the Phase 3 REGENERATE 18-month interim analysis and a refined risk management approach for appropriate patient selection and monitoring.

The end-of-review meeting was constructive and based on the final meeting minutes we recently received, FDA has provided us with helpful guidance regarding supplemental data we can provide to further characterize OCA's efficacy and safety profile, which could in fact support resubmission based on our 18-month biopsy data together with a safety update from our ongoing studies. We are advancing accordingly and plan to hold additional meetings with the agency with the goal of achieving sufficient alignment to proceed on this basis and potentially resubmit our NDA next year.

Our work generating additional efficacy and safety data is ongoing. And we remain focused on reinforcing means to identify the segment of NASH patients with advanced fibrosis who are at most risk of progression to cirrhosis and could, therefore, most benefit from OCA's anti-fibrotic effects, while achieving appropriate management of hepatic safety and other potential safety issues in treated patients. As we have stated, we believe this can be achieved based on appropriate labeling and standard non-invasive assessments used by specialist physicians to assess and monitor the functional status of their patients.

As we often pointed out, NASH patients with advanced fibrosis typically have comorbidities, take various medications and experience intercurrent illnesses that taken together render them particularly vulnerable to acute and progressive chronic injury to their liver. So we and FDA have been particularly focused on working to gain a thorough understanding of OCA's hepatic safety profile in this population and the identification of patients who may potentially be at greater risk. As we previously have shared, we conducted a comprehensive assessment of hepatic safety relatively late in the NDA review, and FDA did not have a chance to fully review it. We did have a chance to review some of the data at our end-of-review meeting. And as a first order of business, we look forward to engaging in a more focused review of the data with the agency.

A word on some of the work we are doing on the efficacy side. There is growing interest in digital pathology tools that are able to quantitatively score fibrosis and other histopathologic features of interest in biopsy specimens and provide more accurate resolution that is supportive of pathologist assessments. While these innovative tools remain exploratory, we believe there is interest on the part of FDA and that such data might bring OCA's anti-fibrotic benefit into even clearer focus.

In addition, of course, as part of any safety update from our ongoing studies, we will have the benefit of assessing the longer-term durability of OCA's treatment effect on a variety of non-invasive markers. With that, we very much look forward to continuing to engage with FDA with the hope for objective to position us for resubmission of our NDA next year, and we will of course update you on any important developments as appropriate.

A quick update now on our MAA seeking conditional approval of OCA for NASH fibrosis in Europe. As you may recall, we submitted the MAA at the end of 2019 and our application is under review. In the third quarter, we are granted an extension to respond to the Day 120 questions we received from the EMA with our responses now due this coming January. We requested the extension to help ensure consistency in our approach in both the US and Europe.

It's useful to pull back and remind you that based on recent literature, NASH is now the most rapidly increasing indication for liver transplant in the US. And there is an urgent unmet medical need for the treatment of advanced fibrosis due to NASH where there are no approved therapies. Unfortunately for patients, the NASH field has seen more than its fair share of failures in recent years and OCA is the only drug to have succeeded in a Phase 3 trial to date having reproducibly demonstrated its ability to improve fibrosis.

We remain committed to the NASH patient community with REGENERATE currently ongoing through clinical outcomes with the goal of confirming clinical benefit on a post-marketing basis. As a reminder, we are also conducting the Phase 3 REVERSE study in NASH patients with compensated cirrhosis with readout of the double-blind phase expected by the end of next year. Both REGENERATE and REVERSE are fully enrolled with patient retention continuing to track well despite the ongoing pandemic.

As a final note on our NASH program, our conviction in the potential for OCA to become the first drug approved and an important treatment for patients with advanced fibrosis is shared by many stakeholders in the liver community, including patient groups, opinion-leading physicians and others passionate about advancing medical innovation. So I'm excited to note that Mani Subramanian, the former Therapeutic Area Head of Liver Disease at Gilead, who successfully led efforts over a decade long tenure to secure a number of drug approvals, has agreed to join our effort to help steer OCA to approval.

Pivoting now to PBC, our performance during the third quarter was strong once again. We reported Worldwide Ocaliva net sales of $79.5 million, reflecting impressive growth versus the prior year quarter. We believe the growth opportunity for our PBC business remains attractive over the long term. As a reminder for those of you not familiar with the regulatory history, Ocaliva was approved in May 2016 in the US as a second-line treatment for patients with PBC under the accelerated approval pathway based on a reduction in alkaline phosphatase as a surrogate endpoint reasonably likely to predict clinical benefit. It also received conditional approval for PBC from EMA in December 2016.

Full approval of Ocaliva for PBC is contingent upon among other post-marketing requirements, the confirmation of clinical benefit in our ongoing Phase 4 outcome study COBALT. COBALT is a placebo-controlled multicenter study designed to evaluate clinical outcomes in more than 400 PBC patients given the challenge in successfully completing multi-year post-marketing placebo-controlled studies in a rare disease setting, due, for example, to patient dropouts and placebo crossover to commercial drug over time. Prior to initiating COBALT, we discussed with regulators potential conditions under which it might be converted to an open label study of OCA compared to a historic case match control from available natural history datasets.

While we've been enrolling COBALT globally in more than 30 countries, we've continued discussions with both FDA and EMA concerning the merits of potentially converting to an open label study design, and both agencies advise that we revisit this possibility, if warranted, after a pre-specified interim efficacy analysis by our Data monitoring Committee or DMC, which was recently completed. The analysis included DMC review of unblinded safety data, and no safety concerns were reported resulting in no changes recommended to study conduct. However, the DMC did conclude that it doesn't seem feasible to continue COBALT as designed. Of course, we remain blinded to data in the ongoing study and as is typical with such DMC interactions focused on maintaining data integrity, there was minimal additional detail provided as to the relative impact of confounding factors observed by the DMC, including patient discontinuations and placebo crossover to commercial Ocaliva.

We've notified both FDA and EMA of the DMC's conclusion and further respective recommendations, plan on holding a meeting with FDA early in the New Year, while seeking formal EU scientific advice. There are examples of other confirmatory outcomes open-label studies relying on historic controls for rare disease drugs approved on an accelerated basis. And we, of course, remain committed to working with the FDA and EMA to come to resolution on a potential modification of COBALT as soon as possible.

I also wanted to address the "newly identified safety signal or NISS" for Ocaliva in the PBC post marketing setting that was posted on FDA's website last month. For background, FDA has long conducted safety evaluations in the post-marketing setting and in recent years, has taken steps to increase the transparency with respect to such reviews. In our case, as we previously disclosed, the agency notified us that it had initiated in this regarding liver disorder that it classifies as a potential risk, the lowest level of risk. Per its guidance, FDA estimate upto a 12-month timeline for the evaluation of this kind of NISS as compared to a more rapid timeline for evaluating and FDA determines is either an important potential risk or an emergency.

We understand that this potential Ocaliva risk in PBC was identified in the course of FDA's routine safety monitoring activities based on a search of the FAERS database and other available external sources. And FDA has further informed us that the NISS is focused on a subset of cirrhotic or more advanced PBC patients taking Ocaliva and not the broader PBC population.

As you would expect, as part of our standard pharmacovigilance activities, we worked with FDA to reconcile our internal safety database with the FAERS database and are now conducting a comprehensive assessment of all the available data, including data from our completed clinical trials, blinded reviews from ongoing studies such as COBALT, unblinded reviews of ongoing clinical trial data by the DMC, post-marketing data and natural history data. FDA has acknowledged the limitations of post-marketing data and stated that safety data from controlled clinical studies will be of most value to inform any final assessment of a potential risk. So it is reassuring that as mentioned, our DMC recently reviewed unblinded safety data from patients enrolled in COBALT, including cirrhotic patients who comprise the majority of the study population and stated that no acute safety concerns were observed.

We are working to complete our comprehensive safety assessment, with respect to the NISS within the coming months and intend to continue to work with the FDA to complete the review. It's important to note that we have over 14,000 patient years of post-marketing exposure in PBC patients treated with Ocaliva, and our view of its benefit risk remains positive. We continue to engage the physician community and are pleased to see the continued strong interest in PBC at AASLD this year where multiple abstracts evaluating OCA for the treatment of PBC will be presented.

In particular, we look forward to the presentation of OCA's durable efficacy and safety data in PBC patients treated for up to six years. Meanwhile, we continue to be committed to fostering innovation for patients with this disease. And I'm pleased to report that we've resumed enrollment in our Phase 2 study evaluating OCA in combination with bezafibrate.

In addition to the strong net sales we reported in our PBC business in the third quarter, we also took swift steps to rightsize our organization in light of our receipt of the CRL and NASH fibrosis. This morning, we announced that we are narrowing our 2020 financial guidance, within the high end of our previously announced Ocaliva net sales range and within the lower end of our previously announced non-GAAP adjusted operating expense guidance range. This will put us in a strong position as we enter 2021 to support the continued growth and advancement of our foundational rare liver disease business and the potential resubmission of our NDA in NASH fibrosis next year.

Now, I'd like to turn the call over to Jerry, who will provide an update on our global PBC business and commercial activities. Jerry?

Jerome Durso -- Chief Operating Officer

Thanks, Mark, and good morning, everyone. I'll start by discussing our Ocaliva results for the quarter and then, provide you with an update on our commercial organization along with a summary of our current efforts in PBC.

In the third quarter, we reported $79.5 million in worldwide Ocaliva net sales, which represented growth of 29% versus the prior year quarter and is our highest quarterly sales to date. In the US, we achieved net sales of $58.6 million in the third quarter. We saw continued end-market demand growth for our Ocaliva as US total prescriptions based on IQVIA data increased by approximately 14% versus the prior year quarter. In the international region, we achieved ex-US Ocaliva net sales of $20.9 million in the third quarter. These results reflect the continued strong performance in our key international markets.

Our global Ocaliva business continues to be resilient despite the challenges resulting from the COVID-19 pandemic and we've been pleased with our ability to maintain patients on therapy. The overall slowdown in patient visits persists in the GI segment globally. And while we saw some recovery in the third quarter, trends are still below the pre-pandemic levels. We continue to experience a lower level of new patient starts during the third quarter. And although the new patient segment represents a small portion of our business, the COVID impact we've seen in 2020 is expected to have an impact on our future quarterly growth rate versus the prior year period.

As we discussed last quarter after receiving the complete response letter for NASH, we were able to take advantage of the flexibility we had built into our commercial plan to quickly prioritize our commercial activities and turn our focus back toward PBC, while postponing our NASH launch efforts and importantly, lowering our operating expenses moving forward. Subsequently, in the third quarter, we restructured our commercial and medical affairs organizations. The resulting targeted footprint in the field has been resized and is focused on maximizing the growth of our core PBC business. Through this transition, we have retained a strong team with deep experience in the hepatology and GI segments. Our teams are fully trained and now dedicated back to PBC.

As our field teams navigate their outreach given the current pandemic, we are actively leveraging technology to increase the impact of our customer interactions. Complementing the efforts of our field teams, we've seen a positive response to our digital educational programs. For example, we recently trained our speakers to deliver education that included the results from our POISE five-year open label extension study.

Overall, we have continued to experience progressive growth both in the US and internationally as we've established Ocaliva as the first new therapy for PBC in over 20 years. As our commercial efforts pivot back fully to PBC, we remain confident that there is an opportunity for continued expansion in this market over the long term.

And now, I'll turn the call over to our Chief Financial Officer, Sandip Kapadia for a financial update. Sandip?

Sandip Kapadia -- Chief Financial Officer and Treasurer

Thank you, Jerry, and good morning, everyone. Please refer to our press release issued earlier today for a full summary of our financial results for the quarter ended September 30, 2020.

We reported strong Q3 results and made solid progress in our efforts to reduce operating expenses going forward. These efforts resulted in the narrowing of our 2020 guidance toward the higher end of our Ocaliva net sales guidance range and the lower end of our non-GAAP adjusted operating expense range.

Beginning with our commercial performance, in the third quarter, we recognized $79.5 million in Ocaliva net sales. Our highest quarter to date, up from $61.5 million in the third quarter of 2019.

Our third quarter Ocaliva net sales were comprised of US net sales of $58.6 million and ex-US net sales of $20.9 million. This represents a growth of approximately 30% and 28% respectively versus the prior year quarter. As a reminder, in Q3 2019, we did experience a drawdown in trade inventories in the US. Our GAAP operating expenses for the third quarter were $134.7 million and our non-GAAP adjusted operating expenses were $118.1 million.

As a reminder, our non-GAAP adjusted operating expenses exclude stock-based compensation and depreciation. Non-GAAP adjusted operating expense is a non-GAAP financial measure under SEC regulations. Please refer to our press release issued earlier this morning for a full explanation and reconciliation of this measure.

Our cost of sales for the third quarter were $1.8 million compared to $0.5 million in the prior year quarter. Our selling, general, and administrative expenses for the third quarter were $70.6 million. This represents a decrease of $6.2 million versus the prior year quarter and was driven by our initiatives to reduce costs, including the postponement of the NASH launch.

Our research and development expenses decreased to $48.9 million in the third quarter of 2020 from $60.2 million in the prior year quarter. The decrease was primarily driven by lower NASH development costs, including the conclusion of enrollment activity for the REGENERATE and REVERSE studies prior to the third quarter of 2020 and reduced costs related to our preparation for NASH regulatory interaction. Restructuring expenses were $13.4 million for the three months ended September 30, 2020. These expenses include the costs related to the previously announced restructuring.

As of September 30, 2020, we were well positioned with cash, cash equivalents, restricted cash and investment debt securities available for sale of approximately $496.8 million.

And now turning to our updated financial guidance for the year. As I mentioned earlier, we took the necessary steps to lower our costs. The Ocaliva franchise is profitable, continues to grow and is expected to provide a strong financial foundation for our future. We are able to narrow our full-year 2020 guidance range for both net sales and non-GAAP adjusted operating expenses. We now expect Ocaliva net sales in the range of $310 million to $320 million, up from the previous range of $300 million to $320 million.

We now expect 2020 non-GAAP adjusted operating expenses in the range of $460 million to $480 million, down from the previous range of $460 million to $500 million. As we closed the year and look forward to 2021, we remain focused on top line growth and prioritization of our investments going forward.

Overall, I'm pleased with our strong commercial performance, which together with the initiatives we've taken to reduce costs, put us in a strong cash position. We are well positioned to support our NASH regulatory process with the FDA, fund our ongoing clinical trial and continue to invest in the growth of our Ocaliva business.

So with that, I'd like to turn it over to the operator for any questions. Operator?

Questions and Answers:

Operator

[Operator Instructions] Our first question comes from the line of Michael Yee with Jefferies. Your line is now open.

Michael Yee -- Jefferies -- Analyst

Hey, thanks. Good morning, and thanks for the very comprehensive update, Mark. Two questions relate to just clarifying the discussions with the agency as much as you can in terms of what specifically is required for the safety component of things and on the efficacy. To me, it sounded like a detailed discussion of hepatic safety and said that you weren't able to fully review all that. So maybe, is that kind of what is really the gating part of the safety side and the efficacy side, it sounded like a lot less stuff. So maybe just talk to those two sides again. And then on Europe, can you just clarify was there any discussions there at all. It's really focused first on FDA? Thank you.

Mark Pruzanski -- President, Chief Executive Officer and Director

Sure. Thanks, Mike. Yeah. So as I mentioned in my prepared remarks, we are happy to have the end-of-review meeting with the agency. We received the final meeting minutes and as we anticipated, this was the start reengagement with the agency with respect to potential resubmission of the NDA, and we got a lot of helpful guidance from FDA with respect to elements that we can address in support of ongoing discussion and that potential resubmission. As you mentioned, in the safety side, as we long-held, I mean liver-related safety in patients with advanced fibrosis is really important to get a handle on.

We've mentioned before that both we and the agency have really tried to understand across this population. Liver health status, there are a lot of confounding features in a population like this, as mentioned that lead to progressive disease, acute exacerbations of disease, etc. So it's a challenge. And we did conduct on this independent expert-blinded assessment of liver safety relatively late in the review cycle. So the agency didn't have a chance to really complete review of that.

So at the Type A, we did have a chance to discuss this and I do think that it is sort of the first order of business to follow up with the agency and really try to get a handle on and again part of any resubmission would be a comprehensive safety update from primarily REGENERATE and other ongoing studies. And assuming we are in a position to resubmit next year, we will essentially have the chance to virtually double the safety database with respect to duration on study just for reference when we think about the patients who comprise the month 18 interim cohort, on average, those patients are now nearing three years on study and those who were first enrolled in the study are approaching five years. So that's going to be a very rich safety update, which is invaluable in a large disease population like this.

On the efficacy side, I mentioned in my remarks, a growing interest in digital pathology tools and I personally in the context of ongoing need for liver biopsy think that these tools are going to -- also proved to have a lot of merit in addressing the well-known variability that we see with pathologist assessment of these semi-quantitative cuts, categorical features, histopathological features. So while they continue to be exploratory, I think that there is clearly a growing interest in the community and that they can bring into clearer focus the histologic benefit of a drug like OCA. So that's just one example. And then obviously, the flip side of any safety update is taking a look at the durability of response with respect to non-invasive markers of efficacy. And then -- so that's on the FDA side.

On the European side, obviously, we are earlier in review. We did get this extension to January for our day 120 responses that allows us to align our approach across both US and Europe. And we are pleased to be under way there, but premature to comment on what the issues will be.

Michael Yee -- Jefferies -- Analyst

Got it. Thank you very much.

Mark Pruzanski -- President, Chief Executive Officer and Director

Thanks, Mike.

Operator

Our next question comes from Yasmeen Rahimi with Piper Sandler. Your line is now open.

Yasmeen Rahimi -- Piper Sandler -- Analyst

Hi, team. Thank you for the color. Two quick questions. Maybe the first one is, is there really an additional meeting necessary with the FDA. I know you just had quite a lot of content from now on to prepare forward. And if you could just maybe give a little bit more granular details on terms of whether we expect NDA filing first half of '21 or second half. And then, is there a potential that you could maybe roll in the cirrhosis, the REVERSE data into the filing? And thank you again for taking my questions.

Mark Pruzanski -- President, Chief Executive Officer and Director

Thanks, Yas. So yes, we do need to have additional interactions with the agency and frankly, we welcome that. It's in our mutual interest to try to gain as much clarity and comfort with respect to this large and complex dataset prior to any resubmission. So I think that -- and we've anticipated that would be the case in it coming of the Type A meeting. And the good news is that we are constructively engaged with the review division and have a lot of guidance with respect to things that they wish to look at.

I think with respect to your -- the second part of your question on timing, it is premature right now to speculate on first half, second half we think because largely in part that we need to get our ducks in a row in terms of timing of generation of data, the interactions with FDA, which I think we can have on a timely basis, but also is a little bit of at the discussion of the agency, but they absolutely do want to continue discussion and meet with us. And again, as I mentioned assuming we get to adequate alignment, I think that could position us to resubmit next year based on the month 18 biopsy data with the safety update. With respect to REVERSE, again, we anticipate it reading out by the end of next year. It is open under separate IND, but right now it's not contemplated that we would wait for the result of REVERSE to resubmit.

Yasmeen Rahimi -- Piper Sandler -- Analyst

Thank you, Mark.

Mark Pruzanski -- President, Chief Executive Officer and Director

Thanks, Yas.

Operator

Our next question comes from Joel Beatty with Citi. Your line is now open.

Joel Beatty -- Citi -- Analyst

Hi, thanks for taking the questions. The first one is, has the next meeting with FDA already been requested?

Mark Pruzanski -- President, Chief Executive Officer and Director

Has the next meeting been. Well, look, again we don't comment on any specific meetings or timing of meetings typically, but we are right now lining up our next steps. We just came off the meeting and just received the minutes. So we are still digesting.

Joel Beatty -- Citi -- Analyst

All right. Got it. That's helpful. Then, one other question is, is there a potential that unblinded outcomes data from REGENERATE as well as COBALT would be submitted to the FDA as part of the NASH refiling?

Mark Pruzanski -- President, Chief Executive Officer and Director

Yeah, look, I mean it's a good question and that was what we are wondering after receiving the complete response letter, but what we are really pleased about coming off the Type A meeting now is that there appears to be openness on the part the agency to a potential resubmission based on the month 18 biopsy data with the safety update of course. And so, that would not necessarily include any kind of interim outcomes data from the ongoing REGENERATE study. Remember, we remain blinded to outcomes studies ongoing, as I mentioned, but as of right now, we anticipate it will take another three years or so until we get to a target number of outcomes to get to the end of the study.

Joel Beatty -- Citi -- Analyst

Got it. Thank you.

Operator

Our next question comes from Brian Abrahams with RBC Capital Markets. Your line is now open.

Brian Abrahams -- RBC Capital Markets -- Analyst

Hey, guys. Thank you so much for taking the questions. And thank you for the comprehensive update. You mentioned some of the -- I guess on the efficacy side, you talked about the potential for filing with greater clarification on the existing 18-month biopsy dataset from REGENERATE. Just wondering if you could talk a little bit more about that. You mentioned some digital assessments of histologies that -- those analyzes that you guys have already done and if not how long might those take to do?

And then secondarily, I'm wondering how much the discussion with the agency is centered around a potential narrowing of the population maybe closer to this the at-risk advanced population that you guys have always talked about is framing from a commercial standpoint versus the broader REGENERATE population? Thanks.

Operator

Brian, we may have lost Mark. Just standby while we get him back. We have Mark back on the line now.

Mark Pruzanski -- President, Chief Executive Officer and Director

Apologies. My line dropped.

Operator

Brian, can you repeat your question?

Brian Abrahams -- RBC Capital Markets -- Analyst

Yes, sure. My first question was just on the digital assessment of histology that you guys have talked about and whether you've done some of those analyzes yet and if not, how long those might take to conduct? And then secondly, just wondering the degree to which your discussions with the agency are centering around potential narrowing of the label, maybe closer to this at-risk population of advanced fibrosis patients that patients that you guys have always talked about when framing a potential commercial effort versus the broader REGENERATE population? Thanks.

Mark Pruzanski -- President, Chief Executive Officer and Director

Yeah. Thanks, Brian and sorry to drop there. So with respect to digital pathology, that work is ongoing, but I don't think it will be represent critical path with respect to getting to a potential resubmission next year and by the way, I would point out that there are a number of abstracts at this year's AASLD starting toward the end of next week to look out for just to -- if you're interested to look at the power of the technology.

With respect to second part of your question on narrowing label, I mean it's premature to speculate on labeling, but yeah, I mean, we've been very consistent with respect to our intended focus and that is on patients with advanced fibrosis who are at-most risk and that clearly represents a narrower segment than the population we studied overall.

Brian Abrahams -- RBC Capital Markets -- Analyst

Got it. Thanks.

Operator

Our next question comes from Alethia Young with Cantor Fitzgerald. Your line is now open.

Alethia Young -- Cantor Fitzgerald -- Analyst

Hey, guys. Thanks for taking my questions. The first one, can you just talk a little bit about like how you think about like macro environment, the FDA around NASH. I mean, is it like a question sort of education that you're having to provide first [Phonetic] or are people in a more jittery just because they are like -- there have been some failures in the space.

And the second question when you think about like PBC, that's crazy question asked, how do you think about potentially being more aggressive there and if you can share in light of what's going on with NASH the fact that like perhaps like hopefully that gets approved, but I think also now PBC if I think clear marketing focuses I think probably mostly deployment? Thanks.

Mark Pruzanski -- President, Chief Executive Officer and Director

Yeah, look, Alethia with respect to the first question. I mean, obviously, there is a tremendous unmet need in NASH. It's a large population as I mentioned in my remarks. It's now become the fastest growing reason for liver transplant with no approved therapies.

That said, I think it's appropriate for FDA to really scrutinize every drug that comes through. I mean, at the end of the day, we all acknowledge that these endpoints as high as the bar is our surrogate endpoints reasonably likely to predict clinical benefit. And so, you need to really rigorously assess both sides of benefit risk. I do think that on that FDA and EMA continue to be committed to NASH, to the potential for surrogate endpoint to support accelerated conditional approvals respectively.

But clearly the bar is high. And OCA is the only drug as you know to have succeeded in Phase 3 and certainly the only drug to reproducibly shown an anti-fibrotic benefit that the leading KOLs compare to the kind of anti-fibrotic effect that you see with bariatric surgery in NASH, which is the only reference standard. So we're confident in the drug, but clearly more work needs to be done in updating our safety and efficacy data and reviewing it with FDA to put us hopefully back in position for resubmission.

On the second part of your question on the PBC side, look, we clearly are very pleased with growth that we've seen in the PBC business globally. I mentioned that we're now past 14,000 years of exposure. We've got long-term safety durability -- safety and efficacy data in the population. We continue to innovate and be committed to the population maybe Jerry could ask or answer more specific question about our penetration.

Jerome Durso -- Chief Operating Officer

Yes. Hi Alethia, it's Jerry. I think clearly we believe that there is considerable potential left for us to access in PBC. I would not at all consider that we are at the late stage of the lifecycle. At this point, we should be able to continue to access more of the patients that are eligible for Ocaliva and haven't been started yet. I think when we look at the market research that we continue to do on a regular basis significant opportunities for growth remain.

I think if you look at every quarter even in the period like we are now where COVID has some disruption in the market. We're seeing new prescribers come on board for the first time, which is not always the case when you're several years into the launch. I think it just speaks to the need for us to continue to educate the market and as you said importantly now.

Our commercial and medical field teams are now refocused and dedicated and frankly, I think -- and I've been really pleased with the level of engagement on our teams as we've made the pivot over the last several months from a lot of the preparatory education for NASH back fully focused commercially to Ocaliva in PBC. So we will continue to ensure the right focus to drive the growth. But again, the key message from me is a considerable opportunity remains in PBC.

Alethia Young -- Cantor Fitzgerald -- Analyst

Thank you.

Mark Pruzanski -- President, Chief Executive Officer and Director

Thank you.

Operator

Our next question comes from Steve Seedhouse with Raymond James. Your line is now open.

Timur Ivannikov -- Raymond James -- Analyst

Yes. Hi. This is Timur Ivannikov on for Steve Seedhouse. And we have a couple of questions. So in terms of NISS, when do you expect to provide data analysis result for the FDA and then, could you remind us what portion of your PBC patients are cirrhotic? Thank you.

Mark Pruzanski -- President, Chief Executive Officer and Director

Sure. So, second part of your question, what proportion are cirrhotic. The vast majority of patients are not cirrhotic. We estimate up to 85%. So we are talking about a pretty narrow segment of the population. With respect to the work that's ongoing, I mean there's comprehensive safety assessment across post-marketing and clinical data. As I mentioned in my prepared remarks, we're working as expeditiously as we can to complete that work, which we expect to happen over the next few months and that will then facilitate discussion with FDA with respect to any resulting recommendations.

Timur Ivannikov -- Raymond James -- Analyst

Okay. Thank you for that. And then on COBALT, could you clarify what was the main reason COBALT cannot continue as a blinded study? Thank you.

Mark Pruzanski -- President, Chief Executive Officer and Director

Yeah. So you're referring to the DMC's conclusion coming off of the interim efficacy analysis. And as I mentioned, I mean we've long been aware as have the FDA and EMA the challenge of conducting these multi-year placebo-controlled outcome studies in a rare disease setting and in the post-marketing on a post-marketing basis. We've clearly done our utmost to enroll COBALT over the last few years as I mentioned in over 30 countries and also it's important context to know that it's not only that we are studying rare disease population, but this is primarily a more advanced segment in the population, right?

So, majority of the patients in COBALT are already cirrhotic when they enter the study. So it's an exceedingly tough study to enroll and takes many, many years. And the concern of course going in is that over the years, of course you're going to get patient discontinuations and you are going to get patients crossing over to commercially available drug.

So -- and this is a concern not unique to COBALT. Of course, I think it's a more generalizable challenge for anyone who follows us in PBC and frankly in other chronic rare diseases. So it is something we've had an ongoing dialog with FDA and EMA on. And as I mentioned, we will in the New Year be following up with FDA getting scientific advice in Europe to see what we can do. We remain committed of course to confirming benefit, but again need to see where the regulators would like to go with respect to modifications to the study.

Timur Ivannikov -- Raymond James -- Analyst

Okay. Thank you very much, Mark.

Mark Pruzanski -- President, Chief Executive Officer and Director

Thanks.

Operator

Our next question comes from Ritu Baral with Cowen. Your line is now open.

Ritu Baral -- Cowen -- Analyst

Hey guys, thanks for taking the question. I wanted to ask you about what you were thinking as far as your -- the strategy for your 2023 convert. Is that going to be wholly dependent on your conversations with FDA or can you sort of have a stand-alone strategy regardless on how to deal with those. And then my follow-up is on your bezafibrate study that you mentioned. One, can you talk about the data timing and potentially regulatory path beyond the current study and if you could as well, could you just walk us exactly through the rationale for the different comparator arms because it's just a little confusing on clin trials? There is a bunch of them and we're kind of at the same, but not really.

Mark Pruzanski -- President, Chief Executive Officer and Director

Sure, Ritu. Sandip, could you take the first part on converts?

Sandip Kapadia -- Chief Financial Officer and Treasurer

Sure. Hey, Ritu, thanks. Thanks for the question. I think we took a lot of the initial steps obviously to reduce our operating expenses, and we're pleased with the progress we've made so far. The first maturity on the convert is not until 2023. And so, we're always evaluating options. We're always thinking proactively and strategically ways to manage our future capital needs. I think we will certainly as we understand better the timelines for resubmission and in the coming months, we can continue to sort of evaluate and provide you an update there.

Ritu Baral -- Cowen -- Analyst

And then bezafibrate?

Mark Pruzanski -- President, Chief Executive Officer and Director

Yeah, Ritu, with respect to the combo bezafibrate, just a reminder to everybody that bezafibrate is an anti-PPAR agonist that's been on the market in a number of countries, ex-US for many, many years and there has been a lot of interest in beza in PBC specifically around the world. In fact, among many datasets at the recent European Liver Meeting, EASL, the first abstract in the general session was tenure outcomes data from Japan in PBC showing an outcomes benefit with bezafibrate treatment as compared to or so alone the first-line treatment.

There have also been several combination datasets -- clinical datasets out of Europe. There have been presented at various meetings looking at the combination of OCA with bezafibrate, which again look quite promising and support the potential for the combination as a follow-on treatment for PBC. So the Phase 2 study that is currently enrolling, I think Ritu it's premature. I mean, it was on hold during the -- a lot at the pandemic. I'm happy that we're now -- we've reinitiated enrollment, but it's a bit premature to project on timing of readout.

In terms of where -- what the regulatory path would look like, there is guidance of course for combination product development. Typically, you have to characterize component A versus component B versus component versus A plus B. Hopefully, we will be able to do a lot of that characterization in Phase 2, but ultimately Phase 3 design will be a function of our discussions with FDA and EMA at the time.

The development of the fixed-dose combination is going well from a product development standpoint, and we currently don't see any major incremental challenges there. So I'll stop there.

Ritu Baral -- Cowen -- Analyst

And so, the current study doesn't answer the factorial question that FDA will want -- that will come afterwards?

Mark Pruzanski -- President, Chief Executive Officer and Director

Well typically in Phase 3, you do -- part of the guidance, you do the factorial, you do the A versus B versus A plus B, but again there are exceptions to that. I think we will just have to see and again, I think we will want to leverage as much as possible the available data, that's why I mentioned all of the datasets that currently out there published, etc.

Ritu Baral -- Cowen -- Analyst

Got it. Thanks for taking the questions.

Mark Pruzanski -- President, Chief Executive Officer and Director

Thanks, Ritu.

Operator

Our next question comes from Jay Olson with Oppenheimer. Your line is now open.

Jay Olson -- Oppenheimer -- Analyst

Thanks for taking the questions. I had two of them, starting with the NASH CRL. I think at the time, you received the CRL, you suggested a timeline of about six months to resubmit your NDA with a six-month review and a potential NASH approval mid-2021. And I was wondering -- it just seems like today's language sounds like potentially longer timeline. So now that you've met with the FDA, what changed -- why it is the timeline seen longer now? And was there something incrementally more time consuming that you got from your FDA meeting?

And then, I had a PBC question. I'm kind of surprised Intercept would want to convert COBALT to an unblinded design since Ocaliva has repeatedly been a victim of unwarranted safety concerns, which were all based on uncontrolled safety reports. So why would you want to deliberately give up an ideal source of controlled safety data, which you could use to potentially ensure the clean safety profile of Ocaliva?

Mark Pruzanski -- President, Chief Executive Officer and Director

Sure. So with respect to the first question on timeline, right on the heels of the CR letter, I put out speculatively what a best case could look like in responding to the CR letter. Obviously, that was gated in the first instance by on timing of the first interaction the Type A end-of-review meeting, which we just had last month. So I think that we've adjusted our thinking about potential timeline accordingly.

In addition, as we contemplated at the time, we knew that this was -- the Type A meeting was an opportunity to reengage with the agency and what's helpful here is that there is a mutual desire on our part and FDA's part to get together again and have substantive interactions to try to gain further clarity and comfort with respect to first and foremost safety data, including ultimately safety update that I mentioned in my remarks and of course, additional efficacy data. But what we're pleased about is that number one, we are constructively engaged with the review division. Number two that they've expressed an openness on to potential resubmission based on the month 18 biopsy data with the safety update and that in fact was our -- was and remains our hope for objective here.

On the PBC side, look as I mentioned, we've been 100% committed to conducting COBALT globally on an ongoing basis as a placebo-controlled study. And as I mentioned also with respect to addressing the NISS that's currently being looked at, we believe that the safety data from that controlled study and again just to punctuate the point, right, majority of the patients in that study are cirrhotic patients. That will be by far the most valuable source of safety data that we will tap and we have pretty extensive safety data at this point given how long the study has been ongoing.

So with respect to, on a forward-looking basis, then the idea of converting it to open label, it's not necessarily that was our intent. It's that we have long been aware as FDA and EMA of the challenge of successfully completing a placebo-controlled confirmatory outcome study in this kind of rare disease setting, taking many years in the post-marketing setting.

So we now have a DMC conclusion based on a pre-specified interim efficacy analysis that the study doesn't seem to be feasible as currently designed. And so, that's -- that is now going to catalyze discussion with both FDA and EMA with respect to any appropriate modifications. The open label design with external control -- historic control is an option that could make sense under such circumstances.

Jay Olson -- Oppenheimer -- Analyst

Great. Thanks again for taking the question.

Mark Pruzanski -- President, Chief Executive Officer and Director

Sure.

Operator

Our next question comes from Thomas Smith with SVB Leerink. Your line is now open.

Thomas Smith -- SVB Leerink -- Analyst

Hey guys, good morning. Thanks for taking the questions. In NASH, I know you have a large number of patients who were enrolled beyond the interim analysis cohort in REGENERATE, who should be coming up to the 18-month biopsy. Can you just clarify if you're planning to analyze and submit the 18-month biopsy data from this cohort to the agency as part of the resubmission.

And then secondly, on the NASH marketing application in Europe, I understand you've asked for an extension year to try to align your responses and your approach between the two agencies, but can you comment on how closely that the Day 120 questions mirror some of the questions raised in the FDA review? Are there any notable differences in the feedback between FDA and EMA? Thanks.

Mark Pruzanski -- President, Chief Executive Officer and Director

Sure. Thanks for the questions. Yeah, the answer is, so with respect to the month 18 on biopsy data, we do have additional biopsy data. We are blinded to it right now from the cohort -- the outcomes cohort of patients. And we are considering whether it could incrementally add to the efficacy dataset that we currently have in hand. But that's going to take a little bit of time to think about.

With respect to EMA, again we are relatively speaking early in the review of the Day 120. I think that the review issues will come into better focus with Day 180, but the opportunity we have with the extension that we requested is in fact to align our approach. One thing I will say is that EMA and this is very helpful and aligned to our approach in the -- with FDA. EMA is quite focused on fibrosis and fibrosis improvement as a recognized more clinically relevant histologic feature of NASH. And so, that's very much aligned with our approach as an anti-fibrotic drug across both US and Europe.

Thomas Smith -- SVB Leerink -- Analyst

Got it. Thanks Mark for taking the questions.

Mark Pruzanski -- President, Chief Executive Officer and Director

Yes, sure.

Operator

Our next question comes from the line of Geoff Meacham with Bank of America. Your line is now open.

Aspen Mori -- Bank of America Merrill Lynch -- Analyst

Hey guys. It's Aspen on for Geoff. I appreciate you taking my question. Just a quick one on PBC understanding that it is early in the FDA investigation and that the focus population for the NISS is relatively small. Have you guys seen any impact to Ocaliva sales? Are there in their focus population or outside of it and any anecdotal feedback from patients or physicians would be greatly appreciated? Thanks.

Mark Pruzanski -- President, Chief Executive Officer and Director

Jerry. Could you take that?

Jerome Durso -- Chief Operating Officer

Yes, I would say, to date in the time since the NISS has appeared on the website. I don't see anything in the ongoing trends, which would be representative of any sort of immediate effect from that.

Operator

That concludes today's question-and-answer session. I would like to turn the call back to Mark Pruzanski for closing remarks.

Mark Pruzanski -- President, Chief Executive Officer and Director

Yeah. Thanks, Operator. Thank you everyone for listening in today. It's obviously been an eventful quarter. We are very pleased with where we are in our foundational PBC business, and we are also very pleased to have begun our reengagement with FDA with respect to next steps on getting to potentially resubmission next year assuming we, of course, get to sufficient alignment with the agency on the basis of resubmission, but it is constructive that the agency appears to be open to our risk meaning based on our month-18 biopsy data with safety update. We will continue to review the review process in Europe and we will look forward to providing you with updates across our NASH program as appropriate going forward. Thanks very much.

Operator

[Operator Closing Remarks]

Duration: 60 minutes

Call participants:

Lisa Defrancesco -- Head of Investor Relations

Mark Pruzanski -- President, Chief Executive Officer and Director

Jerome Durso -- Chief Operating Officer

Sandip Kapadia -- Chief Financial Officer and Treasurer

Michael Yee -- Jefferies -- Analyst

Yasmeen Rahimi -- Piper Sandler -- Analyst

Joel Beatty -- Citi -- Analyst

Brian Abrahams -- RBC Capital Markets -- Analyst

Alethia Young -- Cantor Fitzgerald -- Analyst

Timur Ivannikov -- Raymond James -- Analyst

Ritu Baral -- Cowen -- Analyst

Jay Olson -- Oppenheimer -- Analyst

Thomas Smith -- SVB Leerink -- Analyst

Aspen Mori -- Bank of America Merrill Lynch -- Analyst

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