Q4 2020 Intercept Pharmaceuticals Inc Earnings Call
Ladies and gentlemen, thank you for standing by and welcome to the fourth quarter 2020, intercept pharmaceuticals earnings call.
At this time all participant lines are in listen only mode. So if you require operator assistance. Please press Star then zero.
After the presentation, there will be a question and answer session to ask the question. During the session you will need the press Star then one.
Please be advised the today's conference maybe recorded.
And I'm going to hand, the conference over to your host today and as Lisa Defrancesco Senior Vice President Investor Relations and corporate Affairs. 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 2020 results and financial position, which is available on our website at www dot and ours.
From a dot com.
Before we begin our discussion I'd like to note that during the call we buy 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 the.
The 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 and our and this morning's press.
And and our periodic public filings with the SEC.
Today's call will begin my prepared remarks from our president and CEO, Jerry for ourselves and our Chief Financial Officer, and deep cut patio, well then open the call up to take your questions.
Also available for questions. Some of my leadership team will be Gail Cockwell Senior Vice President medical affair of safety and Pharmacovigilance and acting Chief Medical Officer. Please limit yourself to one question and order allowed time for all questions to be of dry.
And we now turn the call over to our CEO Jerry the ourself.
Thanks, Lisa and good morning, everyone. Thank you for joining us on our fourth quarter 2020 earnings call. This is my first earnings call as CEO of intercept and so I want to begin by saying how excited I am to lead the company as we focus on our next chapter and.
And with any new opportunity I fully expect there to be challenges, but more importantly from where I know debt I also see many potential pathways for future growth and opportunities for success as we execute on our objectives and leverage our commercial and R&D capabilities and liver disease.
In addition to the many talented and dedicated people and intercept the recently announced a number of new important leadership appointments.
With these additions to our team I believe we've assembled a strong group of leaders with diverse backgrounds, including experience with many of the very same challenges and opportunities that are ahead of us and.
And I believe this is the right team to embark on the next phase of our journey as we execute on our key objectives in 2021.
Which includes strengthening our foundation of PBC business, furthering our Nash regulatory process and the U S and Europe executing on clinical and regulatory goals and expanding our portfolio and pipeline.
Before I provide an update on Nash, let me begin today by giving an update on our core rare disease business and PVC.
I'll then provide an update on our pipeline before turning the call over to Sandeep to discuss our financials and our 2021 guidance.
We continue to gain new ground and our PVC business since the introduction of the caliber we've achieved new milestones each year, including in 2020, where we experienced strong sales growth and the face of the global pandemic.
We've continued to evolve our customer facing patient centric organization, including specialty product distribution and strong payer coverage community education, and deep relationships and the liver community and most recently expanding use of virtual channels to reach and educate our stakeholders and I'm proud to say as an organization.
We've built core competencies and each of these areas.
'twenty and 'twenty, what's the Europe growth for all caliber. Despite the challenges that COVID-19, and brought to the health care system.
For full year, 'twenty and 'twenty, we achieved net sales of $313 million, which was 25% growth over the previous year.
Our strong performance was supported by important new long term five year data that has been resonating with the specialist community.
The global pandemic, we're facing is not over and we do anticipate of continued impact of our business, particularly as the result of lower new patient starts due to fewer patient visits overall.
As we've previously mentioned we've been expanding the number of community based gastroenterologists that we're educating auto caliber of.
This education is important considering our strategy of supporting earlier identification of appropriate ocala of of patients in the community setting.
To date since the launch of about 20% of the gastro neurologist and the U S have prescribed ocala, the and we have an opportunity to continue that educational process.
When considering our efforts and PVC the current trends and future updates, we anticipate to our label and patients with the most advanced stages of PVC, which I'll talk more about in the moment I believe our PBC business continues to represent an important long term opportunity given the considerable number of appropriate PBC patients that are.
Not yet an ocala.
As we continue to discuss our PBC business I wanted to provide you with an update today on two key post marketing activities. The evaluation of the newly identified safety signal or nurse and discussion regarding the future of our post marketing studies and PVC both of which we discussed on our last earnings call and also at our most recent Investor Conference.
First regarding the ongoing process with the nurse.
As you know from previous discussions and this was identified during routine post marketing safety monitoring from the FDA and 'twenty and 'twenty.
Classified as the potential risk for liver disorder and is.
Subset of PBC patients with cirrhosis.
We completed a comprehensive safety assessment, consisting of post marketing and pharmacovigilance data at the.
And do you mean, the logical data and information from our clinical trials, including an assessment from our data monitoring committee for DMC, which looked at our key post marketing studies on and unblinded basis.
These analyses were provided to F D. A to review and we had of beating earlier and quarter one.
This process remains ongoing however, based on our interactions with the agency to date. It will ultimately result in the labeling change regarding patients with the most advanced stages of PBC.
We're now working with the FDA to align on these changes.
We'll provide further updates when the process is concluded.
As we've previously communicated the majority of patients with PBC are not cirrhotic and this is one of the main reasons. The name of the disease was changed from primary biliary cirrhosis. The primary biliary cholangitis several years ago.
Patients with advanced PBC include those patients with cirrhosis, the most severe of which progressed the day compensated cirrhosis.
We project that patients with evidence of cirrhosis make up about 15% of the overall PBC population.
And so calibers of second line treatment of the proportion of patients with cirrhosis on Ocala of is a bit higher and we estimated in the 20% range.
The most severe patients those are the D compensated cirrhosis or smaller subset of that total population and the mid single digits percentage wise.
So to summarize where we are on the nurse and the process with the FDA remains ongoing and right now we're focused on working with FDA on updates to the caliber of label for patients with the most advanced stages of PBC.
Now, let me turn to our PBC post marketing trials as a reminder, we have two post marketing placebo controlled studies ongoing and PVC, which we have also recently discussed with regulators first cobalt, which is our confirmatory study of several hundred advanced patients with PBC.
And second of the 401 study, which is the smaller study for the most advanced PBC patients who are hepatic impaired.
As we previously communicated and the second half of 2020, our DMC reviewed unblinded data from both ongoing clinical trials.
The DMC indicated through of blinded report that there were feasibility concerns. These concerns were focused on study design and patient retention, particularly given the advanced population and the commercial availability of caliber while running a placebo controlled trial.
The concerns of day rates were not related to safety, but again on the feasibility of conducting the trial is designed.
We submitted the DMC findings to support our meeting with the FDA. This quarter, we proposed modifications the cobalt, including potential conversion to an open label study designed with an external control and we are of dialogue underway to further discuss the revisions to the study.
We're also seeking scientific advice on the proposed modifications of the cobalt and the EU.
And of course future changes to our caliber of label related to the most advanced PBC patients will influence the modifications to our study design.
And the label considerations, we think it's important to look across the spectrum of information, including recent feedback from the DMC from our ongoing studies and considered the patients who we believe are benefiting from a caliber as locale of is the only approved second line treatment for this patient population.
Now, let me turn to our Nash regulatory process for OCI and advanced fibrosis, our efforts remain ongoing as we work towards potential resubmission of our NDA and the U S by the end of 2021.
As a reminder, our ongoing phase III regenerate study remains the only positive phase III study to demonstrate anti fibrotic efficacy and patients with Nash and fibrosis.
We have a strong team comprised of internal and external expertise and we've initiated the process and what will you expect will be a series of interactions with the FDA over the coming months with the goal of gaining alignment on the number of key items prior to a potential resubmission.
The key focus areas for these interactions include a comprehensive view of Oca's safety.
Biopsy methodology and potential for any additional efficacy data that we may be able to utilize to support the overall benefit risk profile.
We have specific actions underway to support these key areas, where we're seeking alignment with FDA, including preparation of a comprehensive safety update to refresh and increase the amount of safety data that we will have to discuss with FDA.
This effort will provide us an opportunity to potentially double the safety exposure from our initial filing as we focus on providing FDA with a greater understanding of the overall safety profile of OCA and Nash fibrosis.
As we focus on this process of gaining alignment with FDA and it's important to note that we have and ongoing study with regenerate where we can continue to produce important data to support the potential resubmission.
As a reminder, we also have all of a second large phase III study reverse which is underway and patients with compensated cirrhosis due to Nash, we anticipate topline data readout by the end of this year.
The readout of reversal represent important learnings and the later stage Nash population and we're very much looking forward to the data.
In parallel to our work and the U S. OCI is on file in Europe, where we submitted the responses to the day 120 questions and the review process remains ongoing.
Furthering our pipeline and evaluating opportunities for expansion of our portfolio are key areas of focus for 'twenty and 'twenty one.
We continue to enroll our phase II trial, evaluating OCI and combination with beds of five rate outside of the U S. We're pleased with the rate of enrollment so far and once the trials fully enrolled will be able to share and estimated timeline for data.
We also filed the new ion day in January as we prepare to expand the development of the OCI beds of fibroid combination into the U S. We.
We believe theres, a significant opportunity for the combination of beds of fibroid and OCI to enhance the product profile and if approved it will be an important new therapy for patients with PBC.
Intercept remains committed to innovating for patients.
We've also made the decision to move forward with at least one of our internal candidates Int 787 of next generation <unk> agonist, which we believe has great potential for differentiation and we look forward of doing the first in human work in 2021.
So overall 2021 will be a pivotal year for intercept theres a number of priorities underway this year of which will help shape, our companys future success.
And now I'll turn the call over to our Chief Financial Officer, Sandeep <unk> for a financial update.
Sandeep.
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 and full year ended December 31 2020.
We reported strong financial results and 2020 with overall worldwide of Calvin and net sales growth of 25 per cent as well as continued progress and our efforts to reduce operating expenses going forward.
Beginning with our commercial performance and the fourth quarter, we recognized $83 3 million and worldwide Ocala up of net sales our highest quarter to date up from $73 million and the fourth quarter of 2019.
For the full year, 'twenty and 'twenty worldwide O'connell of of net sales were $312 7 million compared to $249 6 million from the prior year.
Our full year of 2020 for Calvin net sales comprised of U S. Net sales of $234 million and ex U S. Net sales of $78 seven day, representing a growth of 25% and 27% respectively.
Our GAAP operating expenses for the fourth quarter were $123 9 million.
And our non-GAAP adjusted operating expenses for $106 6 million.
For the full year 2020, GAAP operating expenses for $543 9 million and and.
Our non-GAAP adjusted operating expenses for $480 million.
As a reminder, our non-GAAP adjusted operating expenses exclude stock based compensation and depreciation.
Non-GAAP adjusted operating expenses at the 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 fourth quarter reserve of point $8 million compared to $2 5 million and the prior year quarter.
For the full year, 'twenty and 'twenty cost of sales were $5 3 million as compared to $4 2 million and the prior year.
Our cost of sales consists primarily of packaging labeling materials and related expenses.
Our selling general and administrative expenses for the fourth quarter were $70 million.
This represents a decrease of $23 7 million versus the prior year quarter and was driven by our initiatives to reduce costs as the result of the postponement of the Nash launch.
For the full year 2020, selling general and administrative expenses increased to $332 5 million.
And increase of $15 1 million from the prior year.
The period over period increase was primarily driven by expenses and the first half of the year related to our launch preparation activity associated with the potential approval and commercialization of OCI for liver fibrosis due to Nash.
Our research and development expenses decreased to $51 9 million and the fourth quarter of 'twenty and 'twenty from $64 6 million and the prior year quarter.
For the full year of 2020 research and development costs decreased $291 5 million from $242 8 million as compared to the prior year.
The decrease and research and development expenses for the year was primarily driven by U K for R&D tax credit of $22 million recognized as a reduction and expenses and lower gas development costs, including the conclusion of enrollment activity for the reverse and regenerate study.
<unk> expenses were $1 2 million and $14 6 million for the three and 12 months ended December 31 2020, respectively.
These expenses were comprised of severance costs and other termination benefits included in conjunction with the 'twenty and 'twenty workforce plan.
As of December 31, 2020, we were well positioned with cash cash equivalents restricted cash and investment debt securities available for sale of approximately $477 2 million.
And now turning for our financial guidance for the year.
We expect full year of 'twenty 'twenty, one caliber of net sales to be between $325 million and $355 million.
Key drivers and assumptions include the following.
First we believe we have contemplated the scenarios of anticipated prescriber of label changes that will occur for two.
The most advanced PBC population and potential timing of those changes and our range of guidance for the year.
We will plan to refine and update throughout the year as we have more information.
Second we have also factored in and the continued impact of lower new enrollment as a result of the COVID-19 pandemic.
And lastly, as a reminder, we would expect typical seasonality and Q1 is patients are impacted with insurance plans reset and Medicare coverage gap.
Therefore, we expect higher gross to net deductions and the first quarter.
We expect full year 2021, non-GAAP adjusted operating expenses to be between 380 for $410 million.
The guidance reflects the impact of our streamlining efforts during the back half of 2020.
As we have refocused our commercial efforts on PBC, while continuing to resource our Nash program and advancing our pipeline.
So overall I'm pleased with the strong commercial performance in 'twenty, and 'twenty and our ability to pivot and reduce operating expenses quickly, which has resulted in the strong cash position entering this year.
We will continue to invest and the growth of our caliber of business support our net regulatory process with the FDA.
Fund, our key clinical trials, including reverse and regenerate.
And focus on finding ways to leverage our strength.
So with that I'd like to turn it over to the operator for any questions.
And I ask that you limit yourself to one question and reenter the queue for any follow up and we'll get to as many people as possible.
Thank you operator.
Ladies and gentlemen, if you'd like to ask a question at this time. Please press. The Star then the number one key on your Touchtone telephone to withdraw your question press the pound key.
Our first question comes from Yasmin Rahimi with Piper Sandler.
Hi team. Thank you so much for taking my questions.
So I wanted to have a better understanding on.
How many patients on the right on.
And on the regenerate study has have already completed being on track for four years three years two years.
And now it's time flies by its been almost now two years since the regenerate data read out which is the 931 patients and he could provide that and this comment is in regards to the F. D. A recently, stating that they really want to see data post year or two so if you could check that and then second quick question is can you provide a little bit color on.
Seven and eight seven and how it differentiates from LCA and thank you for taking my questions.
Yeah.
Yes, I mean, it's Gerry thank you.
For the question.
As you mentioned.
You know regenerate the.
Has been ongoing we read out at the 18 months for that group of patients.
For a while ago now so there are a considerable of portions of the population who have obviously moved through the.
And the subsequent periods, including you know that 48.
The month the window at this time enrollment was completed a while ago and you know.
The the time to completion of the overall.
<unk>, which as a reminder is in the event.
Driven a study is based on the events that are accumulating so so that pieces is some years away.
You know the ability for US for example to take advantage of the larger numbers of patients that have now reached.
And at a later time period is one of the elements and the the safety update that we are preparing for a discussion I think again it's.
One of the the elements of the <unk>.
And and ongoing study that the.
Allows us to.
Look at some of that data appropriately and and and again I think the the safety update and the roughly doubling of the exposure that we expect.
We'll be a part.
Part of the the the updated safety cut is a key element as we look to align with the agency over time in terms of the.
The comprehensive safety view of of OCI.
Yeah.
And so on 787.
And I did mentioned in the prepared remarks.
We do plan to initiate a first.
And in human.
The study this year it is of bile acid select selective FX are I think there is potential from some of the preclinical models.
You know for for differentiation for greater efficacy.
Potentially based on on some of the models, we will be doing.
Doing more work and communicating more on 787 and as we move forward.
And thank you.
Our next question comes from Steve seat House with Raymond James.
Great. Thank you, it's not entirely clear to me and whether or not the mis would have implications or change anything with respect to Nash specifically the Nash cirrhosis study.
Obviously, you titrate to a higher dose even.
So can you just comment on.
And that.
And also just quickly what is the IP on 787. Thank you.
Okay.
Thanks.
The steep so.
First of all of the.
And this as we've we've talked about the.
Is based on post marketing.
And the PBC environment, the PVC is of Cholesteric.
Disease reverses the our second large phase III.
Trial.
Of compensated cirrhotic and that that trial is fully enrolled over 900.
Patients.
The.
The the study is ongoing and continues to be monitored and all the ways that the.
Our our necessary for a study like this including.
The DMC the data monitoring committee, taking a look at the.
And that the study on a regular basis and recently the DMC has reviewed.
The reverse and come back and not recommended the any changes. So again, we look forward to continuing of forward on the reverse trial. It is a different condition, the PBC and Nash and our plan is to read out top line by the end of this year.
Yeah.
Okay.
Would you mind, just commenting on the the patent protection on seven minutes of them.
Yeah.
Yes, I don't believe we've commented on.
And the IP on 707, yet.
Okay. Thank you.
Okay.
Our next question comes from Alicia Young with Cantor.
Hey, Thanks for taking my question I'm, just curious if you can talk with any kind of.
This isn't about maybe what the FDA and.
What are the new and recent considerations around Nash and and and what's going on there and near and Dear.
And the confidence and.
And as you worked and worked through that with them.
I'm sorry of Lisa can you repeat the first part of your question you were a little low.
And I'm just curious about like you know and kind of of your conversations with the FDA and and considerations there having around that as you know if you can give any more granularity visibility on what's going on there and your general confidence around you know kind of being able to rip out for the year and thing.
Okay. Thanks for the question.
And we're heavily focused on on this.
And the engagement with the FDA, where the real.
Priority around alignment on some of the key areas of of potential.
Resubmission and it is a process that we have initiated and is it is ongoing.
<unk>.
Tried to highlight the key areas of Liza Alicia that are.
We think are most important and.
In terms of of that alignment.
The process, including.
The comprehensive safety of OS the a and again I think that having the right ability to have the.
And updated and refreshed discussion with the.
Safety update that we're preparing is going to be important.
The biopsy.
Approaches is one of the others and then of course, we're asking.
As we work through this and what.
What if any potential additional efficacy data might inform the right risk benefit discussion.
A discussion prior to two of Resubmission and so we're doing the work where we're generating the data.
And we're not going to be providing granular update that at each of discussion.
The discussion, but we would definitely look forward to as the.
The process continues and we haven't and ability.
The to refine and not to come back and and provide an update at that point.
And I think the other thing that's important.
As you know we continue to believe.
The that Oc a due to the fact that it's still the only phase III that has shown and the anti fibrotic effect in AR in the.
The advanced fibrotic patients that are you know we have to continue.
Continue to keep that in mind. These are a group of patients with the high unmet need.
Need and that's the part of the large motivation for our focus.
Thank you.
Thanks Alicia.
Our next question comes from Michael Yee with Jefferies.
Hi, Thanks for taking my question and this is already going on for Michael Yee.
And I, just want and time.
And trying to get your thoughts on the recent resignation of the CMO and any potential impact and will have three filing.
And second question relating to potentially a safety.
Safety and Tolerability benefits with the new App and with the second Gen FX are.
Thanks.
Yes.
Thanks for the question Ari.
We remain focused on our Nash efforts are I think I mentioned.
JP Morgan for example, the fact that you know we put the new dedicated team.
The onto the the the Nash efforts with the real focus on ensuring that we were bringing a combination of new perspectives and also with the <unk>.
Considerable are folks that have history on the program. So the team remains the ongoing.
Ongoing in and all of the efforts you did mention the fact that there have been some some changes.
To the leadership team I think eh and.
Ensuring.
We have the right team to take the next steps there has been a clear focus for me.
And in the first period I think.
During the leadership transition changes are always anticipated, but I've been really pleased the additionally, with our ability to bring in.
Some new top talent, bringing some some different experiences and perspectives and also having a chance to.
The two to reinforce some of our existing folks and and having some folks the <unk>.
Step into the new leadership positions, which I think creates a good mix of on the team with the.
And some new talent in some folks that through succession planning or having a.
And opportunity to play.
Play to their strength and also leverage our you know folks like us.
Sandeep and Gale, who have been with us on the the intercept journey for for a while so I feel good where we are and the leadership side at this point.
Sounds good and on the second Gen and FX are.
I'm sorry, what was your what was your question on it.
For the new for the new FX or any potential <unk>.
The and Tolerability benefits that you're seeing the pre clinically.
Yes, again I think there is reason to believe.
That Oh, there's differentiation.
Potentially bolt on the efficacy.
But also for a better.
And <unk> and as you said importantly, the processes is ongoing so we wanted to provide and update today based on the information.
That we have but it's difficult.
To get into the.
Certain level of of specificity given the conversations will continue.
I think.
We are working to finalize again updates for patients with the most advanced stage.
Stages of PVC we've.
We've tried to and the and the guidance give ya a range of of potential scenarios and then of course.
On the prepared remarks, what I, what I tried to do was to outline.
The the group of of patients that fall into these different these.
These different stages and how we see them.
So the process is ongoing will definitely come back as the as that is complete.
<unk> and deep do you want to give any additional context and the.
Sure sure Jerry just.
We announced the the sales guidance today of 325 for 355 million for worldwide of sales and 2021.
What I would say, we believe I think we've contemplated the scenarios of anticipated prescriber label changes.
That could occur and the more advanced PVC patients population and I would say along with the timing.
We're in the midst of the process of what I would say, we're continuing to refine.
Refined and update as.
As we learn more information, but I think the the current guidance provide the least some context around the.
Yes, and we can sorry.
Yes, and the <unk>, if I could just.
On that so so your guidance and basically I think effectively saying flat.
Our annual if you analyze the queue for it's effectively flap from share on a.
A couple of things on queue for a man maybe I just missed this apologies and deep but was there any inventory build of burn during the during the quarter.
And then should we think about sort of the trajectory here during the course of the year as demand continuing to do what it's doing until.
Potential label change comes in and.
And then of potential drop and demand or like how how did you sort of come to the guidance and I'm just trying to understand that did you think about the phasing there or was it just.
You took of conservative approach of kind of annualize and queue for.
Well I think look.
For a respect for the first question and in terms of inventory changes and queue for the there wasn't anything significant usually feel a little bit of of tick up at your and but that's that's every year, we do see that and then of course.
I also mentioned typically you'll see and the first quarter.
Just the insurance plans for each side and patience have.
The the Medicare covers GAAP, we have higher gross and net deductions and the first quarter. So the first quarter tends to be a bit of bit softer and then then growth.
They're so right now I think what I can say is at least we've.
Factored and some of our thinking in terms of the the potential for a label update and it sort of like the the range.
And we'll update to along the way I mean.
Thank you very much.
Our next question comes from Brian's Corny with bird.
Hey come on and everyone. Thanks for taking my question just trying to parts of the language here on Nash It seems like the line with the goal of increasing and the probability of of successful outcome for patients with advanced fibrosis student ashwood indicate.
<unk>, maybe targeting of potential narrowing of the addressable patient population for an approved product and I know, the RAF ones and and and the broader regenerate enrollment and there had been some idea of that you can get Ah maybe a broader label enough to of three so I'm. Just wondering if you know it was the thought to try to focus on the limit the patient population to of two or three and and M D a or or is it something narrower of them.
Like are you just targeting of <unk> or maybe some other criteria to kind of and.
And rich the day, though.
So as a reminder of the interim analysis readout and phase III the the successful.
The impact on fibrosis was in the population of that too and F. Three the the F ones that were in.
And the regenerates study, where and exploratory so that wasn't day a group that was part of that.
Interim analysis the result.
So the the assumption on the 18 months results is and F. Two F. Three population I think and parallel we've talked.
Over time, particularly in advance of of the complete response letter when we had.
The more in depth discussions about our commercial plan the the focus.
Around the advanced fibrotic population and this F.
Three like advanced that and.
Has always been our commercial focus because of the high level of unmet need I think the opportunity for us the dialogue with the F. D. A and this process that we're in now around the risk benefit overall, bringing new safety data into the picture I think we'll we'll allow us to have.
Of the right discussion around risk benefit and the context of of thinking about of potential resubmission, but again the population of the initial readout was that of two at three.
Group from from regenerate.
Okay. Thanks.
Thank you Brian.
Our next question comes from you tube or all of the Cowan.
Hi, guys. Thanks for thanks for choosing the question.
So Gary and it sounds like you're.
You're not reiterating.
Prior indication that of 2020 and submission is uhm.
It's likely and you talked to about this comprehensive safety update what do you think the odd sorry that you'd you'd have to develop some sort of the new efficacy submission or.
Interim and take a look.
For submission S. As part of any potential reversed you at this point.
So.
Reach you as I said, we remain focused on the interactions with the F D a and the our plan is.
That will progress through those and and and.
Ah line work towards the alignment for of potential resubmission by by the end of of 2021.
And so that's why we're intensively are focused on some of of these key areas.
I mentioned the safety update as as of key one.
Our focus and this work and are thinking include.
Includes the Indepth conversation around safety, along with any potential for additional efficacy based on on the you know what the FDA would be looking to consider in that context. So I guess I can't probably go much more of definitively than that except.
That the efficacy component is and additional and and core part of of you know the the topics that we intend to work through this alignment process on of course based on the the conversations we had for example, with the FDA at the end of towards the end of last year with the.
Type a meeting and the real focused on ensuring the right discussion around risk benefit and both sides of that equation.
Got it and and squeeze one follow up on just as far as converting cobaltous for one and two and open minded and extension and you have to general some natural history analysis before you can sort of flip the switch and turn the patient server or is it.
More complicated for Mark.
So.
And on cobalt as I mentioned the dialogue is ongoing we had proposed and open label and the plan around that including.
The the the the control we would we would recommend of course.
Since the the the dialogue is is ongoing I can't get get more and more definitive on that and that now I think one of the other points that that is important.
Is that there is and your dependency between a.
Potential for the you know.
The revision of design and what might be the right revised design.
And the final label and and that's the other component that's important to this.
This whole discussion.
Great Thanks for being the questions.
Thanks.
Our next question comes from Michael Moore idea of what's right and capital markets.
19, thanks for taking the questions I, just wanted to try and get a little bit more information any details and he can provide the upcoming of that safety data cuts and potentially the timing of when that may occur is there any delay on the one you expect that to happen and based on the the interactions with the F. D. A have you.
Finalize which trials will be involved and that safety debit card and do you have any plans to share of the results from that and balances.
So so maybe I'll I'll start.
So as I said the work on that safety update from regenerate is ongoing also part of what we would anticipate and any potential resubmission would be and update from.
Our other trials as well, we do look at the safety update that that we are in.
In the process of of working through as an important component again since it gives the significantly more.
Safety exposure for the patience with the fibrosis due to Nash from regenerate and again, that's a heavy emphasis on the team of course the alignment.
With the agency on the the analyses of that data and the the.
Data set means we expect will be the focus of of some of these ongoing.
Discussions again, the opportunity to approximately double the safety exposure from what was included in the initial file we think as of an important component and this overall discussion on.
On the.
On the the overall safety profile of us yet.
And it's just a quick follow up on that is a positive outcome of of this additional safety debit cuts.
A continuation of seeing the same safety profile of that you have seen with no worsening and and then the safety signals or are you looking to see improvement over time.
So of course, our ability to get of refresh view of the overall safe.
Safety is going to be important and and it's going to be important to look at that and the overall context and the discussion.
With the agency.
Okay. Thank you.
<unk>.
Our next question comes from Brian Abrahams with the capital markets.
Yeah.
Hey, Yeah. Good morning, guys. Thanks, so much for taking my question I have a question on the <unk> as of five right lifecycle extension of potential and I'm, just wondering what else needs to be done to move into U. S. Trials has the indy their cleared and how might U S studies differ from your approach would that combination outside of the U S.
Thanks.
Thanks for the the question Brian maybe on this one I'll start and then and then Gail can comment I think first.
The the opportunity for us to progress on our next medicine.
And PVC the.
And for US I think reinforces the long term interest, we have and and we're call of static diseases like like PBC.
I think that the opportunity that we have beds of fibroid and house and.
And access to it for the U S. We think it's a a competitive P. Part of there is a significant amount of data on.
On beds of five right and in PVC, albeit most of it from investigator initiated trials, but importantly also some some interesting combination data with those C. A.
It gives us an indication that the there is good potential here and as we look at the.
The the face too that's an ongoing.
As you say outside of the U S. Maybe gale you can comment a little bit on that and and some of the key elements as we think about the the work to start and the us now.
Thanks, very much so uhm as Jerry said, we have started our face to study with the C. A piece of fabric combination outside of the U S and very pleased with the enrollment despite the and.
Pandemic.
And that study and Creek.
To celebrate.
February two different cases penetration is clearly.
And important part of any fees and studying and.
As well as.
At the height milligram training to kind of milligrams at the.
The same time in the U S.
Have filed and I and.
And of preparing to stack additional clinical pharmacology work.
Later, this year and the U S.
And that will help us to understand more about dosing and I've faced and the Prince and and get us ready to start the pastry and activate time, we should have more information and for your guys' time, and economic progression and a face to study to provide and update later.
Got it thanks, again and thanks Terry.
Thanks, Brian.
Our next question comes from Joseph Stringer with Needham and company.
Hi, everyone and good morning, Thanks for taking our questions. The you mentioned some earlier matrix on PVC and uhm per cent of gastro and our Enterology for prescribing account of it just wondering if you could and.
And maybe speak to what what you think you know the.
The current market penetration for your address.
The address of all our target patient population is and and what.
What is key and sort of unlocking the next year of of of.
PVC patients. Thank you.
Thanks Joseph.
And I think when you consider the the PVC opportunity that we have it's important that there are a considerable.
Number of of patients that are appropriate for O caliber that aren't getting therapy, it's been a big part of the educational efforts that we've had over.
Over time, and I think the dimension of.
And of focused way expanding our education too more community based Gastroenterologists is that the the center of our strategy.
And will continue to to move now of those gastroenterologists tend to have a relatively few number of potential PBC patients and their practice. So it is important that we educate and also identify.
Where those.
Where those patients will be and particularly important and the community setting as as identification of the right patients early.
That are.
Are ready for second line therapy.
And might benefit. So this you know I think that the the fact that there's more of room for penetration and our core patient population and the the steady expansion of our reach with the Gastroenterologist continues to be a core part of our efforts both on the the commercial.
And medical affairs, the side and the U S.
Our next question comes from Jeff Meacham with Bank of America.
Hey, guys of passing up the job thanks for taking of our questions Uhm.
Both of them the pipeline first 77, and if you could quickly walk as to what you view of the development path there.
And how you're thinking about the of prioritization of development in terms of the different indications PVC and Nash or maybe something on that and then quickly on both of the private as well any plans to move by the into.
Oh for it as a model of therapy, either in Nashville, PVC or or do you kind of for you that this is purely a combo. Okay. Thank you.
Okay. Thanks first on on 787 and.
I think as I said, the early ill earlier I'm sorry.
And.
And we look forward to the first and human work this year.
We are we are doing some.
Thank good work also and looking at potential indications, it's too early to get definitive on that today, except to say that we were looking at the the potential and then across the group of of of of indications Bay.
Based on.
Where there might be the the.
The right scientific rationale.
Considering potential of path.
Forward in terms of of development and regulatory and and looking at that with the Ah rather open mind to point. This this asset towards the right indication.
And I'm sorry, you had the second.
Second question on on.
And does a five right yeah I just wanted to understand if if there was just kind of of how you view the asset and is more of a combo play regardless of indication or do you see any any.
Any path for of where you develop as as as the amount of therapy.
At this point of our primary focus has been on the the combination of the <unk> as of fixed dose combinations.
Okay. Thank you.
Thank you.
Our next question comes from jails and with Oppenheimer.
Oh, hi, Thank you for taking the question I had a financial question and and I'm curious about the path to profitability by geography, how much the visibility do you have and to achieving profitability and the U S alone and if Nash starts looking like a U S only opportunity for O T. A.
Given the lower PVC revenues and lower operating margins Act U S can intercept become profitable X U S and P. B C alone or would you consider becoming a U S focus business and out license your excuse for rights to <unk>. Thank you.
Yes, Hi, Jay Thanks, Thanks for the question.
And what we have commented on and the past is that R. PVC. Okay. All of a franchise is is the profitable franchise of the.
It is the federal business.
We're pleased with the the how.
The the revenues of grown over the past several years.
We've met at our expenses accordingly, and the businesses profitable boat and.
And the U S and outside the U S.
And when you consider of the director.
The marketing and selling expenses.
With respect the longterm profitability I think.
Something that at least we provided guidance to day kind of gives you a sense of where we expect our our our sales and operating expenses and.
And you can see it was it's meaningfully lower dark cash burn.
Compared to last year of based on based on the guidance that we provided.
That's as far as at least we can go with the stage, but hopefully that gives you some context.
Great. Thank you for <unk>.
Thanks Jay.
Our next question comes from Matthew and the Genie with you and they'll capital.
Hi, great. Thank you so much for for the man so actually on the the European question. So as it relates to match. The you intercept delayed 120 response to this year.
To try and get a better alignment with FTA guys and now responded but it seems like alignment with Fda's of course, all of a bit of of of work in progress. So just wondering how we should think about.
The you opportunity from here and then secondarily just quickly on and PVC as it relates to the nurse.
Just given everything that you've done with FTA. So far do you feel like.
And the discussion is and the homestretch and we should be expecting things to be resolved and the relatively near term or the.
The the pushing pulls related to the label and and any other open issue still relatively large and you're very much so and sort of the hammer and it out case. Thank you so much.
Thanks, maybe I'll take the.
Second one one first the Matthew so.
You know as as I've continued to say.
The the process is ongoing.
I think we're working to finalize the updates to the label.
Can't really be definitive on the timing.
Since the process is ongoing what I would say, though is based on on the regulations for these kind of interactions that the.
The process could be completed within the.
The coming months, but again it.
It is ongoing and and obviously, we're not in control of all facets of of the process.
The first question was on was on Europe.
The the.
<unk> on his on file and we did submit responses to.
And the day 120.
We are working and parallel on net.
That process and.
And the.
Ongoing important work for alignment and the U S. Prior to of potential resubmission by the end of of this year and as we go through those processed and parallel as you can imagine will be considering the best options to.
Take we are progressing through the process.
And Europe, and we would anticipate the constructive dialogue moving forward of course as a reminder.
<unk> is the first the Nash drug of also being reviewed on the European side, but we're working through that process and we'll assess things as of progressive.
Okay. Thank you.
Thanks.
Our final question comes from my and some tiny with the Riley.
The morning, this of Sahil on for my own and thanks for taking our questions and congrats on the progress and maybe a quick question on the PVC label change could you discuss how that's reflected in some of the sales got is provided today and perhaps in the context of the enrollment doing on and competitive programs, maybe from silver Bay and jumped the and how you think of.
That and the overall guidance and then finally is there a symbol of labor the similar label update process underway and that you you as well thank you.
So the Sunday, maybe you want to start on the the.
The the framing around the guidance sure I think the the guidance of February gave the 325 to 355 I think reflects the.
Couple of of different factors overall, one is contemplated what.
We would.
Anticipate of the prescriber label changes, obviously still and place. So it's hard to say specifically will continue to refine that.
The.
Throughout the year as we get more information and the other pieces and we've also factored in and.
Jerry talked about lower and your patient starts.
Based on the Covid pandemic, so you start to see some of that impact.
And as we go into this year and I think the best way to sort of also think about the the the guidance at the bottom and of the range and of reflects the greater restriction on the advanced BBC of population, while I would say the top and reflects the lesser impact overall, so hopefully that gives you a little context on that and maybe Jerry.
Yeah, and and I'm sorry, the second question.
Was.
Yeah, just in terms of of is there a similar label update process, all the way and the and you as well.
So so not of similar process per se as.
As as you know the the process that is ongoing right now was.
Initiated out of the nurse in the post marketing context for.
From the FDA of course, you know their their.
We will look to consider the right discussions with the regulators.
As we work through things with the with the U S.
But the process for that I speak about specific to the nest is the FDA specific process.
Great. Thanks for taking of our questions I appreciate it.
Thank you.
That concludes our question and answer session and I'd like to turn the call back to Jerry yourself for closing remarks.
So thanks for the questions and and look forward to continuing the dialogue I think is the Ah near the end of my first 60 day as as intercept new CEO definitely excited for the opportunity we have to grow our business support our patients with PVC nah.
Nash other serious liver diseases.
Our capabilities and importantly, our people and the strong evidence we generated with OCI gives us multiple pathways to achieve success and advanced our mission and I'm looking forward to our execution on the major objectives that we outlined the Sierra and spoke about today and which have the ability to transform our company. So I look forward to the continuing the.
Of conversation and thank you very much for joining us this morning.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
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