Q4 2021 Intercept Pharmaceuticals Inc Earnings Call
Hello, Thank you for standing by and welcome to the fourth quarter and full year 2021 intercept Pharmaceuticals earnings conference call. At this time all participants are in a listen only mode. After the speaker presentation there'll be a question and answer session to ask a question. During the session you will need to press star one.
On your telephone please be advised that today's conference maybe recorded if you require any further assistance. Please press star zero.
I'd now like to hand, the conference over to your speaker today.
Alright, So Gary <unk> Executive Director Investor Relations. Please go ahead.
Thank you good morning, and thank you for joining us on today's call.
This morning, we issued a press release announcing our fourth quarter and full year 2021 results and business update which is available on our website at intercept pharma dotcom.
Before we begin our discussion I'd like to note that during our call we will be making forward looking statements, including statements regarding our approved product and clinical development program certain regulatory matters, and our strategy prospects financial guidance and future commercial and financial performance.
Listeners are cautioned not to place undue reliance on these forward looking statements, which speak only as of the date of this call and we undertake no obligation to update such statements except as required by law.
These forward looking statements are based on estimates and assumptions that although believed to be reasonable are inherently uncertain and subject to a number of risks and uncertainties.
Some but not necessarily all of the risk factors that could cause our actual results to differ materially from our historical results or those anticipated or predicted by our forward looking statements are discussed in this morning's press release and in our Purion.
<unk> public filings with the SEC <unk>.
Today's call will begin with prepared remarks from our president and CEO , Jerry Durso, our Chief commercial Officer, Linda Richardson.
President of research and development and Chief Medical Officer, Dr. Michelle Berrey, Chief Financial Officer, Andrew sake. We will then open the call to take questions. Please limit yourself to one initial question in order to allow time for all questions to be addressed.
Let me now turn the call over to our CEO Jerry Durso.
Thanks, <unk> and good morning, everyone. Our performance in 2021 has put us on a solid foundation as we enter this year and embark on the next pivotal chapter for intercept in my first year as CEO , we made great strides to achieve our corporate objectives and capitalize on the opportunities to support our future growth.
Looking first at our performance in PBC, our team delivered strong double digit sales growth for our caliber and ended the year with worldwide revenue of $363 5 million. Despite the challenges associated with the pandemic and the U S label update.
We now look to 2022 as the year to continue capitalizing on this momentum as there are still a significant number of people living with PBC globally, who could benefit from adding ocala as a second line therapy to treat their disease.
We look forward to expanding our efforts to reach positions with important data that will support the continued adoption of our calibre and the appropriate PBC population.
We've also made significant progress towards generating a robust dataset that will deepen our understanding of the potential role of OCA and Nash and determine the path forward.
After an extensive dialogue last year with FDA, which focused on the regenerate study, including the consensus biopsy reading methodology and the scope of an updated safety dataset. We have been at work generating what will be the largest data package in the Nash field.
The magnitude of this work is unprecedented and we're looking forward to sharing the new data package from regenerate when our work is complete.
If the data support it we continue to target a potential pre submission meeting with FDA in the first half of this year.
Our second phase III trial reverse is evaluating <unk> in patients with compensated cirrhosis due to Nash.
Given the magnitude of the data we are generating from reverse as well as complexities associated with reading biopsies in the compensated cirrhotic population with this new method. We now expect that the delivery of these data will move into the third quarter.
I will provide more information about the status of our data generation later in the call.
As a reminder, regenerate remains the only pivotal phase III study in Nash in which an investigational compounds has demonstrated fibrosis improvement with no worsening of Nash and reverse remains the only active phase III trial in people living with compensated cirrhosis due to Nash.
Taken together regenerate and reverse represent the largest and most robust datasets in the field and include more than 3300 patients across both studies with.
We look forward to sharing these important data.
We also made meaningful advances in our pipeline in the past year as we continue to explore areas of significant medical need in liver disease. We progressed, our development program for the OCI and Beth <unk> fixed dose combination and initiated a first in human study for Int 787, our next generation.
<unk> agonist advancing these important programs will continue to be a focus in 2022 and Michelle will talk more about that later on the call.
I am pleased to note that we achieved this progress in 2021, while significantly strengthening our leadership team. We've assembled an executive leadership team with the right experience to drive intercepts next phase of growth and development.
Additionally, we successfully exchanged the majority of our near term debt to address the maturity of 2023 convertible notes.
We also remain prudent with our SG&A expenses, which decreased by more than $100 million versus the prior year, resulting in a 30% savings.
This along with our topline growth allowed us to maintain a steady cash position for a third consecutive quarter in 2021.
Our continued focus on cost management, which Andrew will elaborate on later, we're well positioned to drive another year of strong performance.
2022 is poised to be a transformational year in intercepts history.
I look forward to working alongside the dedicated intercept team as we expand and grow our commercial PBC business, where significant opportunity remains.
We deliver important data from our Nash development program that will drive decision, making for our path forward and as we progress our pipeline opportunities to continue to innovate on behalf of people living with liver diseases with significant unmet need.
In summary, I remain confident in the strong foundation, we've built and in making data driven decisions that will define the strategic path for our company's future.
I'd now like to turn the call over to Linda who will talk about our commercial performance for the fourth quarter and the full year of 2021, Michelle will then provide an update on our regulatory and R&D activities and Andrew will conclude with a review of our financial performance.
Linda.
Thanks, Jerry and good morning, everyone.
I'm happy to share some of the performance highlights of 2021 is it was another strong year for PBC commercial business. Despite the ongoing global pandemic, we drove another year of double digit sales growth underscoring the strength of a cannabis market position as the only second line agent approved for use in PBC.
The full year, we reported $363 5 million in Ocala, net sales globally, which represents 16% growth over the prior year and for the fourth quarter. We had global sales of $92 4 million, an increase of 11% versus the same period in 2020.
Let's review, how we were able to drive this growth five years post launch.
First the U S. Commercial team managed the label update in an exemplary way using multiple approaches to communicate the changes to on hcp's patients and other audiences in a focused efficient manner, we were able to fully pivot back to promotional messaging in September .
And as an organization, we've made excellent and appropriate use of the wealth of data coming from the open label long term safety extension of our poise phase three study.
Were able to successfully leverage insights from this work throughout 2021.
First we begin with highlighting the positive impact of caliber has on maintaining a L T and bilirubin levels.
Factors and monitoring PBC progression.
In the third quarter, we shared data from the same cohort of LTC patients that showed a stabilization of fibrosis something physicians have told US is an important consideration and managing PBC. This layering of key message is creating a more complete picture of how ocala that may benefit patients who need secondary.
Line therapy and that these benefits go beyond lowering alk.
The third thing I'll highlight regarding our strong performance in 2021 is the outstanding growth, we see in our international markets, where we achieved annual sales, 30% higher than the prior year.
Implementation of multichannel marketing and strong execution of commercial messaging led to an increase in underlying demand.
That new patient acquisitions in 2021 surpassed projected targets and early data in 2020 to see this trend continuing well, Italy, and Spain consistently bring strong performance. We are now seeing additional contributions coming from our other markets as well.
We know that there remain a considerable number of patients who could benefit from the addition of a second line therapy to manage their PVC.
Some estimates have shown that only about a third of eligible U S patients have ever received a second line agent.
Our focus is to continue to bring education to hcp's on the benefits of actively managing their PBC patients and to reevaluate those that could be appropriate for treatment with ocala that in 2022, we will be creating new promotional campaigns attempting major conferences in person again and.
To show the value will calibrate can bring to appropriate patients leveraging the data and insights we have from years of being on the market.
In closing I'm proud of the global commercial teams performance commitment and passion this past year and I look forward to sharing updates on our progress in 2022.
I'll now turn the call over to Dr. Michelle Berrey Michelle.
Thank you Linda and good morning, everyone I'll be providing a few updates today on our continued work to generate evidence supporting Ocala that in P. B C on our Nash development program and on our pipeline.
In 2021, we continue to add to the large evidence based supporting Ocala that N P. B C.
We now have more than 20000 patient years since Ocala, though was first approved for marketing in 2016.
We are looking into multiple real world evidence databases to better understand how to leverage these data to show the clinical benefit of continued therapy with their caliber beyond biochemical improvements.
We're now expecting to publish our data from the poise long term extension study first presented as a late breaker abstract at the liver meeting last November .
These data showed that individuals with PBC treated with Ocala that had a statistically significant greater transplant free survival.
Propensity score matched controls who were eligible but not treated with ocala that we.
We are submitting the manuscript to a global scientific journal and will disclose details as soon as we have confirmation of the publication.
In addition to the publication we expect these data to be included with other outcomes data and support for our post marketing study cobalt and a regulatory submission planned for later this year.
As we noted in the third quarter of 2021, we've been closing out our cobalt study because of the challenges with maintaining patients on a multi year placebo controlled study, which was designed to confirm benefits and clinical outcomes, but we're not therapy is commercially available.
<unk> been discussing options with regulators and we will be including the available placebo controlled data in a broader evidence package that we anticipate submitting to both FDA and EMA in the second half of 2022.
We also anticipate presenting these additional data at scientific meetings later this year and are excited about the opportunity to get back to some in person meetings with our thought leaders and physician advocates.
Turning to Nash last year, we made substantial progress on our OCA for Nash program.
After dialogue with FDA, we implemented the new consensus Reding methodology that is in line with the agency's draft guidance.
Together regenerate and reverse represent the largest phase III program ever conducted in advanced liver fibrosis, and compensated cirrhosis due to Nash and we initiated a significant amounts of data generation using this new methodology in the second half of 2021.
We are continuing to generate new data package from regenerate and as we've previously guided if the data support it we're targeting a potential pre submission meeting with FDA in the first half of this year.
We're also continuing to work towards top line data readout from our reverse study the only active late stage study in compensated cirrhosis due to Nash.
Given the magnitude of the data from reverse as well as complexities associated with reading biopsies in the cirrhotic population with multiple external parties using our new methodology more time is required to have the topline data readout. We now anticipate delivering these data in the third quarter. This year.
As a reminder, from a regulatory perspective, our efforts continue to be focused on the regenerate data set there.
Therefore, these shifts in the reverse timeline will not impact our ability to hold a potential pre submission meeting with the FDA in the first half of the year should the data from regenerate support it.
Overall, the amount of data, we're generating and Nash is unprecedented and upon completion of these analyses from regenerate and reverse we will have accumulated the largest data set in the field.
As evidence of that the regenerate safety database will now include an additional 12 months of patient data and the comprehensive assessment of the safety database will include more than three five times the drug exposure of the prior analyses and submission. In addition, this analysis will now include.
<unk> almost 1000 subjects to breached months 48 four years of data.
Once we have these new data in hand, they will provide a significantly more robust perspective on okay benefit risk profile.
Despite the substantial amount of work being done across the industry. There are unfortunately still no approved therapies to treat Nash and we're working to deliver these important data as soon as possible.
Meeting onto our pipeline.
We have several clinical trials ongoing for our OCA plus specified rate fixed dose combination M. P. B C.
In the U S. Our large phase one studies to better characterize the exposure data of the fixed dose combination is ongoing and we also are beginning to screen patients for our second phase III trial.
We are continuing to enroll patients in our international Phase III study.
These three early phase studies will inform the doses to be included in the fixed dose combination that we will study in phase III.
We believe OCA in Bezeq five rate have synergistic mechanisms of action that carry the potential to benefit individuals' with PBC and other cola static diseases when used in combination.
Both medications have been shown to help lower the key biochemical markers that predict long term outcomes in P. B C bench.
Specified rate has also been associated with improvements in pruritus potential benefit we're exploring in our phase II program.
In addition, our phase one study of our next generation ethics are agonist Int 787 is ongoing and we expect to submit an IND in the first half of this year. We're in the process of determining a target indication for 787 and look forward to sharing that information we are very excited about.
This compound and its potential applications.
I'll now turn the call over to Andrew for a financial update Andrew.
Andrew.
Thanks, Michelle and good morning, everyone I would ask that you. Please refer to our press release that was issued earlier today for a summary of our financial results for the fourth quarter and full year ended December 31 2021.
Beginning with our commercial performance in the fourth quarter, we recognized $92 $4 million in worldwide <unk> net sales up from $83 $3 million in the fourth quarter of 2020.
For the full for the full year 2021 worldwide <unk> net sales were $363 5 million compared to $312 7 million in the prior year.
Our full year 2021, <unk> net sales comprised of U S. Net sales of $260 8 million and ex U S. Net sales of $102 7 million representing growth of 11% and 30% respectively.
Our GAAP operating expenses for the fourth quarter totaled $113 3 million, which was a decrease of $10 6 million versus the fourth quarter last year.
non-GAAP adjusted operating expenses were $104 4 million in the fourth quarter, a decrease of $2 2 million versus the prior year period for.
For the full year 2021, GAAP operating expenses were $419 $1 million and our non-GAAP adjusted operating expenses were $382 3 million as a reminder, our non-GAAP adjusted operating expenses exclude stock based compensation and depreciation.
Cost of sales for the fourth quarter were $1 million compared to <unk> 8 million in the prior year period.
SG&A expenses were $66 million in the fourth quarter, a decrease of $9 4 million versus the fourth quarter of 2020.
SG&A expenses were $239 million for the full year 2021, a decrease of $101 $6 million from 2020.
Our R&D expenses in the fourth quarter were $51 7 million as compared to $51 9 million for the same period last year and were $185 3 million for the full year 2021, a decrease of $6 2 million from the full year 2020.
Approximately two thirds of our full year R&D spend was related to our Nash programs.
Cash cash equivalents restricted cash and investment debt securities available for sale at year end totaled $429 4 million.
Turning to our financial guidance for the year, we expect full year 2022, O'callaghan net sales to be between $375 million and $405 million.
This guidance contemplates a significant number of untreated PBC patients globally that could benefit from a caliber.
The strength of <unk> market position and the EU label change, which we anticipate implementing in the first half of this year.
As a reminder caliber is subject to seasonality in Q1 due to the fact that patients are faced with insurance plan resets and Medicare coverage gaps at the beginning of the year.
Therefore, similar to what we've seen in prior years, we expect lower revenue in the first quarter relative to the rest of the year.
We expect full year 2022, non-GAAP adjusted operating expenses to be between $360 million and $390 million.
This guidance range reflects our continued investment in.
Our commercial and post marketing efforts in PBC.
Our ongoing regenerate clinical trial and regulatory efforts in fibrosis due to Nash.
Our additional pipeline programs such as the <unk> combination trial and our phase one study of Int 787 or.
Our spend to support Nash data Readouts and the subsequent potential regulatory and commercial next steps in Nash as well as our normal general operating expenses.
Cash interest expense for the year is expected to be $23 $5 million based on our current capital structure.
Even though we managed to reduce SG&A expenses by over $100 million. This year relative to the prior year, we continue to find opportunities to manage expenses, while ensuring that we invest in the business to meet our company objectives.
One example of our continued focus on cost containment is our recent decision to relocate our headquarters to Morristown, New Jersey.
Our cost management efforts will continue into 2022 and beyond.
Overall I am very pleased with the progress we made in 2021 and believe that we significantly strengthened our financial foundation, we successfully derisk the balance sheet by executing in exchange for convertible notes and we have materially reduced our spend such that we have had stable cash for three consecutive quarters.
We believe that we are well positioned financially to support the company moving forward and help us achieve our strategic objectives.
Now I'll turn it back over to the operator to start the Q&A operator.
Thank you.
As a reminder to ask a question you will need to press star one on your telephone to withdraw.
Very good question, because the balance sheet.
Our first question comes from.
Alicia Young with Cantor Fitzgerald, you May proceed with your question.
Hey, guys. Thanks for taking my question.
Congrats on that.
Forward here.
I guess I was just wanted to see if you could give us more color on kind of the timeline shift reverses.
Is it kind of event driven or is there something else going on or Covid or just can you just give us any kind of color you might have on what's going on there. Thanks.
Hi, Good morning, Alicia good to hear from you, Yes, maybe Michele you can start obviously an important.
An important question for us to go into Michelle.
Yes, good morning Alicia.
First I wanted to be clear that there's a delay in our overall program or in our regulatory interactions.
We are still intending to have our pre NDA meeting in the first half of the year and you remember last year, we had discussions with the FDA on the reading methodology, and then deployed multiple panels reading the two large studies in parallel so although our major focus on the <unk>.
Dilatory interactions continues to be the regenerate study and that the delay in reverse to the third quarter is not going to impact the pre NDA meeting.
What I can say specifically about the reverse study is that it's a large study it's more complex given the advanced patient population with early cirrhosis. So we now expect those data into the third quarter.
Great. Thanks.
Thanks Lisa.
Thank you.
Thank you. Our next question comes from Yasmine <unk>.
Piper Sandler you May proceed with your question.
Good morning team and thank you for the updates just going along the same theme that elite erased.
So will you be able to share.
Sure with asked when you report out the regenerate we analyses.
Safety look into reverse I know that we may still be waiting for the histology analysis, but it is there some commentary that's going to be provided with the safety of our colleagues that looks like in the reverse population.
At the top line.
That's may be question, one and then question. Two is you know we're almost done with this quarter.
Why not why not just say the fact that youre not saying its second quarter is there any glimpse of hope that the state could come in still onto this first quarter and thank you for taking my questions.
Yes, thanks, yes.
So again on the regenerate safety database I think that's a huge question and one of the things that we really wanted to try to pull in was the additional data from regenerate. So we've now added another year. So we've added all of 2021 to our safety database.
So compared to what we had submitted with the initial interim analysis.
Back in 2019, we had.
About.
2400 patients their 24.
Sure.
Total patient years, and we're now out to eight.
Eight over 8000 in tier three and a half times the number of.
Excuse me.
The patient years, and importantly, we now have almost a thousand patients out to four years. So that was a really critical point, we wanted to pull in we will pull the safety from reverse at the same time that we did the top line for the efficacy. So it's important to lock your database.
On the same data cut off so we will have that safety data coming out around the same time, while at the same time, the topline with the efficacy from reverse and so there won't be too much of a lag between those but again our.
Our main focus with the FDA pre NDA meeting would be on the regenerate safety database and with regard to that timing.
We have our earnings call in May and May have a little more specificity at that point, but.
Speaking for them today, I think we expect it to.
They go into the third quarter. Thanks for that question.
Yeah.
Thank you.
Thank you. Our next question comes from Michael Yee with Jefferies. You May proceed with your question.
Hi, This is <unk> on for Michael Thanks for taking my question just sort of asked about the regenerate study a little more and kind of get an understanding for what are the different scenarios that we're thinking of.
Is the base case that that phase III data shows at least the same magnitude of effect in hazard ratio and your view that positive in the study.
Sorry on the safety database is now even larger and that will drive better respect for approval.
So what is there a scenario here and how are you thinking about that.
Yep.
Great question, and I think you nailed it so they're really important question from the CRA all in in 2020 was about the benefit risk and I know and much we will now have a much more robust safety database.
You know when we expect patients to be eye in Ocala, but on OCA for the rest of their lives for Nash.
And it's important that we have long term safety data so that we understand the tolerability that we make sure they're not new safety events at year three year. Four so now we have almost 1000 patients 995 patients through December 31, 2021, So that's a really important.
New set of data we back into the 2019 interim analysis.
Thank you.
Ouch months 48 year four so it's a much more robust safety database, which.
Which we felt gives us a much better assess the overall benefit risk for the drug.
Okay, great. Thank you.
Yep.
Okay.
Thank you. Our next question comes from Brian Abrahams with RBC capital markets. You May proceed with your question.
Hi, good morning, Thanks for taking my question.
With respect to reverse I was wondering if you could elaborate a little bit more on some of the key hurdles for the biopsy reads in the cirrhotic population is it just a matter of matter for <unk>.
Finding readers or variability given the severity of this deliver disease that might require any sort of special protocols are extra time and I'm. Just I guess wondering how to think about the overall reliability of the datasets that that'll be generated in this population on histology when we see the data.
Thanks for the question Bryan, we're keeping Michelle busy this morning.
Yeah.
Hi, Brian Good morning.
Sure I think.
One of the important things to understand about reading the early cirrhotic patient population is that in clinical practice, its not really critical to differentiate advanced fibrosis from an early compensated cirrhotic patient population, there's no there's nothing you're going to do differently.
<unk> two to treat that patient. Unfortunately, we still don't have any any drug available approved four for Nash. So it's never really been that critical to differentiate a high F. Three from a low S for them in a clinical trial. However, it is.
Obviously quite critical that these past the allergist are differentiating so yeah. There are some additional elements of training that we're involved we had deployed.
Parallel panels. So we had some panels may think forward for regenerate and separate panels on the reverse study there was different training for those technologies to make sure that they were paying special attention to that high three F three low ASP or differential.
Clearly that's going to be important when they progressed a reading.
A month eight genes as well.
The second element to this is the only advance trial and advanced.
Fibrosis early cirrhosis and third it's a we're deploying this new methodology. So we've learned a lot through these deploying this new methodology and are applying those learnings to the reverse trial.
Thanks, that's really helpful. I appreciate it thank.
Thank you thank you Brian .
Thank you. Our next question comes from Joseph Stringer with Needham and company. You May proceed with your question.
Hi, good morning, everyone. Thanks for taking our questions.
Couple on PVC.
2022 sales guide.
Percent of that is sort of volume growth as opposed to price increase and secondly, five years post launch in PBC.
What's your feeling on the on the.
Market penetration into the addressable PBC patient population.
At this point.
Thanks for the questions on PBC, obviously, I think as we said in the prepared remarks, we feel good about the progress we made in the growth.
In 2021, and look now to push up forward, maybe Andrew you start with the question specific to the 2022 view in how we're looking at the sales guidance that we provided yes.
Yes, sure and thanks for the question.
So with regard to PBC growth.
We are expecting continued volume growth in both the U S and international I think on the low end of our guidance. It obviously wouldn't take a great deal of volume growth to hit the low end.
But we're expecting to be obviously, we gave a range to be on the on the higher end, we would need to see continued growth internationally in the U S, which we're enjoying right now.
Yeah, I'll tack on to that is if you don't mind I think that right now.
Really a lot to be said or what we're learning about with a number of years that we've been on the market our ability as Michelle noted to generate new data, particularly when youre looking at the ultimate goal of therapy in PBC is.
As to prevent end stage liver disease transplantation or death that has we're reading out as we did in <unk>. Some of this information combined with what we're learning with our five year L. TSA data on not only lowering L P and daily, but keeping it low and then showing important.
Stability in fibrosis, we are creating a fuller package.
Data that physicians need to take into consideration when choosing to add a second line agent and this education is I think going to very much accelerate with the work that we're doing because of the data we have access to we know that in Europe . There is a stronger market for second line, it's been more established.
And he has a space that institutions more institutionally traded then perhaps community Gastro is is we have to go out and hit them across the land.
This is at a little bit easier way to penetrate than in the U S. But we did some market research that shows we have really.
Increase the confidence of physicians using <unk> to treat second line and that is really where the games being played those patients that are appropriate or being intercepted early and we're trying to manage that before you get to the point, where you are in herpetology office and very severe so we.
We intend to use new data new materials really comprehensive approach to getting out we won't have the limitations, we have seen hopefully with COVID-19 , we've overcome that and move forward with our <unk>.
With our business so that only a third of patients at all in the U S have had second line treatment. So we see the next two years as being fundamental to shifting the conversation and really increasing patients getting treated with second line therapy.
Okay.
Great. Thanks, so much for taking our questions.
Thanks, Jeff.
Thank you. Our next question comes from Thomas Smith with SVP Leerink you May proceed with your question.
Hey, guys. Good morning, Thanks for.
Taking the questions just on the reverse it sounds like the gating factor as youre pointing to around the complexity the biopsy slight interpretation.
I guess, if we turn to the safety analysis can you just remind us how much visibility you have into the ongoing safety analysis and the independent adjudication.
Safety events, there and are there.
Are there any types of events that need to be.
Adjudicated.
As being explicitly defined or have there been any changes to the types of events that are being evaluated but I guess, if you could just confirm.
If any of the delays in interpreting the data related to <unk>.
The adjudication of those events.
Yes.
Thanks, Thomas Michelle.
Hi, gentlemen, good morning.
Good question, we do have a DMC that is overseeing the Nash trials and is looking specifically at just these large patient populations just to make sure that the ongoing safety. There. There's no issues there that would require additional monitoring changes.
In this study design.
We continue to have you know can continue as designed back from our DMC with regard to patients. We have had discussions with the FDA and have specific.
And the committees look at hepatic events cardiovascular events and kidney specifically in a large number of these patients are diabetic. So that's something that they wanted to specifically look into them.
And hepatic safety events is separate so that's a more of a daily a specific review of those cases that separate them the hepatic outcomes, which will be part of the full approval analysis.
That's helpful.
Yeah, No that's helpful. Thanks Vishal.
I think you alluded to this but can you just confirm I guess do you expect to have any visibility into the reverse safety data side as you.
We engage with the FDA potentially in first half 'twenty two on on the advanced Fibrotic population.
And they should be coming in.
In the third quarter so shortly thereafter.
And wed certainly be part of our full.
Safety package that would be submitted so the.
Again, you know, we're looking through the DMC and the adjudication.
The DMT has full visibility into the adjudicated cases, so if there's any concerns they could certainly make recommendations to you asked about about altering the study or looking more specifically at any specific kinds of events, but the patient the large patient population in regenerate 20 almost 25.
500 patients and just over 900 in reverse.
Are both being reviewed by the DMC, we remain blinded.
Until the database lock purpose if those studies.
Okay got it thanks for taking the questions.
Okay.
Thank you. Our next question comes from my own plenty with B Riley Securities. You May proceed with your question.
Good morning, Congrats on the progress, notably on the financial trajectory and thanks for taking my question. So on the <unk>.
Opex guidance, maybe I'll do it seems like the Nash specific investments.
We seem to be coming down.
Anything to read into your level of conviction in the opportunity.
Can you just comment on that and then I just have a quick follow up for Michelle.
Yes sure. Thanks for the question.
Yes no.
Nash is one of our key programs and we are fully committed to funding it through the end of the studies.
You will see Nash spend as a percentage of our overall R&D spend continued to decline, but it's mainly a function of reverse finishing.
Finishing up.
So obviously our spend on Nash overall is going to reduce.
Some of our other programs are going to increase to kind of pick that up.
And that would be notably.
The combination study and the <unk> and the 787, which hopefully will get going this year. So no absolutely no lack of conviction on Nash.
Just the natural lifecycle of R&D spend.
Okay, Great and then for Michelle.
Quickly on.
On the Roche study and thinking about what you would learn from the Louisiana.
Biopsy analysis and putting in context.
<unk> Basu wanting to go there from biopsy and we've seen other studies also change the primary efficacy endpoint.
Non biopsy to evolve.
Are there more jobs.
You may elevate a secondary endpoint into the primary endpoint analysis.
And if yes what.
What might be an idea of that.
Particularly attractive to you right now.
Yeah, No. It's a great question and certainly we heard a fireside chat at Nash Tag earlier this year.
Lot of interest and the noninvasive tests, but F. D. A at this point is still considering the only validated surrogate end point is that the biopsy driven histopathology. We're certainly has a multiple noninvasive tests.
But the wet biomarkers and fiber scan and other noninvasive mechanisms to evaluate the progression.
Regression of fibrosis in these patients so we'll be pulling in all of those data as well and hope to have as much of that available at the time of our brief.
Briefing book for the agency on regenerate we have are the.
The same noninvasive assessments progressing for the reverse study.
Thanks for taking my questions. Thank.
Thank you Mike.
Thank you. Our next question comes from Steve seat House with Raymond James You May proceed with your question.
Yes, Hi, this is more of a learning curve on for Steve. So just for regenerate I wanted to clarify I'm not sure I heard correctly, but it sounds like you have an internal benchmark in order to proceed.
With submission of meeting with the FDA could you just talk about that benchmark in terms of the safety event rate and just to clarify for the 48 months safety analysis is that safety only or will you be adding any type of efficacy in terms of a.
Nash resolution and fibrosis reduction thank you.
Yeah.
The first safety and just wanted to make sure we're clear on that so in the initial interim analysis, we actually were still enrolling the study at that time back at the data cutoff, which was October 2018. So we didn't have any patients who had reached months 48 for this data cut off we are.
We will have almost a thousand patients 995 patients out to 48 months or a year four so a much much larger safety database. We went from 2400 patient years to over 8003, and a half fold almost <unk> increase in patient exposure so much more robust.
Safety database, we're not looking for this analysis I'm events. So that's not it's just not an event driven analysis. This is an interim analysis focused on an accelerated approval only so again, an interim analysis of those month 18 biopsies.
I'm not not looking at at clinical events progression et cetera that would be for the full approval. This is solely focused on an accelerated approval.
Yes, the only thing I would add is of course as Michelle indicated before the challenge of the CRM was about overall risk benefit so the opportunity to assess this total the totality of this.
Larger data set inclusive of all the safety day.
Ada that she outlined the efficacy I think it is going to put us in a good position to to assess and reengage. If the data supports us so.
Again, we look forward to getting to the end of that data generation for regenerate.
And defining the next steps.
Okay. Thank you very much.
Thank you.
Thank you. Our next question comes from Brian <unk> with Baird. You May proceed with your question.
Hi, This is Luke on for Brian . Thanks for taking the question just a quick one and apologies if you've covered this but unregenerate have you had any progression in discussions with the FDA regarding the scheduling of a pre submission meeting or is that something that youre going to do once you have data in hand.
It's a good question and not only disclosure.
They is that we continue to plan for that meeting in the first half of 2022.
Great. Thanks.
Thank you.
Thank you. Our next question comes from John Walsh with JMP Securities. You May proceed with your question.
Hey, Thanks for taking the question.
A follow up on safety for me following your withdrawal of the MAA I saw that you have made.
<unk>.
Our bridge responds mentioned also a potential concern about effect on kidney function.
Don't think I've heard discussed before so I was hoping you could provide a little more color on the potential safety signal.
Yeah, so you'll recall the MAA and the the N D. A we were not able to align on the timing of those analyses and as I just mentioned.
We are just now pulling in the data for the end of 'twenty 'twenty. One December 31, 2021, which will be the new data cut off and so obviously, we werent able to pull those data and to respond to any of the questions from the phone.
The E M E. Those data are being adjudicated is one of the requested focus areas.
And again those data had been being reviewed by the DMC, but a final adjudication will be coming in together with the with it.
The rest of that safety data package.
Unfortunately, as we've said before we just weren't able to align on the timing.
So all of those data and to respond to their questions.
Okay, and maybe a follow up if I may on the Opex with the jumps in the fourth quarter in R&D and SG&A.
How should we expect the split to move forward in 2022, given the guidance you guys gave us today.
Andrew Yes.
Yeah sure no. Thanks for the question.
When we give guidance, we typically don't break it out between R&D and SG&A and we're not expecting to at this point in time, but as I've said I mean, we're going to continue.
The pipeline as we've described.
Regenerate is going to continue on into the year reverse spend will back down a bit and then some of our other programs spend as those programs get off the ground, we will pick up.
So other than that we've given the guidance on Opex and we expect to continue to.
Look at our expenses every day and.
Manage them is as low as we can while still meeting our objectives.
Got it thanks for the color.
Sure.
Thank you. Our next question comes from Ed Arce with H C. Wainwright you May proceed with your question.
Hi, Good morning, everyone. This is Thomas Yip, asking a couple of questions for Eric.
First you touched.
Touch on it briefly.
Briefly earlier.
Regarding your discussions with the <unk> for a cleaver.
Pull forward as you underwrite so are we waiting for regenerate data to go ahead or is it a separate process from the FDA.
Yeah.
Not sure I understood. The question are we went through the MAA and so if the data supported it week or we could go forward with the Resubmission and as we are doing in the U S. So the procedures and Europe .
Russell a withdrawal in Resubmission you could answer questions for a while but unfortunately, we had used up all of the time and their procedures didn't allow us to have any other.
So it worked.
That.
And in the U S. Similarly, we are resubmitting with US now much more robust larger safety database plus the additional biopsy data that we'll have in hand this spring.
Okay. So I guess, what I meant to us was.
It may also looking for the data package that you plan to submit to the FDA. Some time first half this year.
Once we have those data in hand, we could consider a resubmission to the EMA as well it would be a similar data package yes.
Okay.
We'll assess.
Any potential next steps with with data in hand.
Okay sounds good and then perhaps one more question from me.
Can you tell us what the next milestones for the.
Okay.
Plus <unk> combination study at this year or when should we expect the first dataset.
Yeah. So we have just presented some data later this year, we are conducting as I mentioned, one large phase one studies in healthy subjects looking at our exposure data for multiple different doses in combination as well as different doses in combination.
And in a P. D C patient population with one phase two study continuing to enroll in Europe and kicking off the phase III study in the U S. So our our next big milestone for US is determining the optimal combination as we alluded to we believe that there's a potential synergistic.
Interaction between these two drugs potentially decreasing pruritus and synergistic mechanisms of action that could make for a really great combination for patients with Cola static liver disease, four P B C and beyond.
Got it. Thank you again for taking my questions.
Fourth through our progress this year.
Thank you very much.
Thank you. Our next question comes from Ellie Merle with UBS you May proceed with your question.
Hey, guys. Thanks for taking my question just on the regenerate biopsy reads again can you give us any color I guess, maybe on the proportion of biopsies you read so far and maybe the proportion remaining bolt on sort of the when you read from the initial biopsy as well as the.
New patient samples just any update in terms of where you are in that process or additional color you can get and then maybe just you know kind of like.
I'll discuss a little bit more your confidence that you'll have this data feed in time to support.
On the you know the potential.
Potential pre submission meeting with the FDA in the first half just in light of the reverse them you know update in terms of the timing and then just you know any chance that you know that's meeting potentially got moved to the second half, let's say the FDA wants to have some more of the full biopsy data from that.
The reverse.
It reads for this meeting in an episode that perhaps you know get this time frame shifted at all thanks.
Yeah. So on the regenerate study again back to the initial interim analysis with a little over 900 patient biopsies that we had a baseline and at month 18 and that was the <unk> reason, we have an additional 500 or so that we are.
Bringing and those have been being read using the same panel methodology. The reverse patient population, we have just baseline and end of study which is either right.
The majority of those are 18 months.
And those are all being read again using the same methodology as we talked about previously there there were more challenges in this patient population given the importance of differentiating the high threes.
Low asked for and we presented some of those data at the liver meeting last year talked about the large number of patients who are screened in order to identify those patients with compensated cirrhosis, both clinically and on their on their biopsies and.
So again all of those safety and efficacy data will be pulled in with the same same data cut off and will provide us with a good assessment of the benefit risk again, which we look forward to sharing a little later on this year, it's a big year for us.
Thanks for the color.
Okay. Thank you.
Thank you. Our next question comes from salary and Richter with Goldman Sachs. You May proceed with your question.
Thanks for taking the questions Andrea on herself Dean.
Wondering if you could discuss further when you do see that extended safety database, what you're looking for or what you what you'll be focused on is it primarily the cardio metabolic AE and then remind us what would be acceptable in terms of cholesterol and triglyceride.
Victor I level increases as well as very good alright, thanks, so much.
Sure Yeah. So the overall safety and if you think about it from a regulatory perspective for a therapy that we anticipate would be these patients will be requiring for the rest of their lives. It's really important to make sure that we understand the tolerability.
Things like pruritus in general looking out there they're lipid profiles given that these patients are in general in general have higher rates of obesity and type two diabetes and the general population. So just look at those general Tolerability issues also wanted to look out.
Now that we have a thousand patients out at year four it's important to make sure that there arent any new adverse events that are popping up at year, three or year. Four so those will be those specific things that we're looking at again, the DMC has been looking at and blinded data.
Throughout and and continuing to watch watch that we remain blinded now, but we'll be pulling those data in shortly.
Great. Thanks, so much.
<unk>.
Thank you and as a reminder to ask a question you will need to press star one on your telephone. Our next question comes from Geoff Meacham with Bank of America. You May proceed with your question.
Hey, guys, it's Aspen on for Jeff. Thanks for the questions I guess first off because it's clear that most of the regenerate where analysis focuses on.
A robust safety database, but maybe you can help us understand if you expect to or do you think you need to show any additional delta.
Delta versus placebo in the <unk>.
Our grocery standpoint.
And then and then to reverse maybe just remind us on after you get that data and three Q what does the regulatory pathway look like for that subset you need to generate any additional data to the.
While that was FDA or or even talk to the FDA.
And then lastly, really quickly just help us understand the gating factors versus for dosing. The first patient in the U S can negotiate vessel side. Thank you.
Mhm.
Okay. So first on the Nash program, if we look at regenerate again, it's a large study and that's our interim analysis, we do have alignment F. D. A that that would be based on a fibrosis endpoint.
For an accelerated approval and that is a focus of our discussions with the agency again at the first initial interim analysis that was also the focus and we did show statistically significant.
Reduction in fibrosis.
Patients, who have regression that at least one stage without any worsening of the Nash activity score and a worsening of inflammation or steatosis.
We now have a much much more robust safety database against which to compare that so overall, a much better opportunity to assess benefit risk there.
The reverse patient population because it is an advanced.
More advanced fibrosis early cirrhosis.
Initially the agreement was for looking at fibrosis all of the subsequent trials in this patient population. The F. D. A has stated that they wanted to look at the clinical outcomes.
We had already begun this study we are grandfathered in on that one. So this will be the final endpoint or the river study is looking at fibrosis.
Obviously, we are pulling in and as I mentioned earlier all of these noninvasive tests for both regenerate and reverse and I think they're just going to be playing obviously a much larger role as we go forward.
Hopefully the FDA are continuing to look at those data, but at this point those are considered supportive of the primary end point of reduction in fibrosis reversal.
This isn't that advanced patient population.
And comparison there.
Against the large safety database.
With regard to the fixed dose combination we do have sites open in the U S and are actively screening. So we look forward to announcing our first patient in that fixed dose combination in the U S. In our phase two study and.
And presenting some data from that later on this year.
Thanks for that question.
Thank you.
Thank you and I'm not showing any further questions. At this time I would now like to turn the call back over to Jerry Durso for any further remarks.
So thanks, everybody for joining us today.
I really believe that the work that we did and that really the team did across the business in 2021 puts us in a strong foundation.
It's clear we're embarking on what's going to be a transfer formative year for intercept and we definitely look forward to sharing more updates as things progress thanks and have a great day.
Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.
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