Q3 2022 Intercept Pharmaceuticals Inc Earnings Call
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Good day and thank you for standing by welcome to the Q3 2000 attended to intercept Pharmaceuticals earnings call. At this time, all participants are in a listen only mode.
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I would now like to hand, the conference over to your Speaker today <unk> Executive director of Investor Relations. Please go ahead.
Thank you good morning, and thank you for joining us on today's call.
This morning, we issued a press release announcing our third quarter 2022 results and business update which is available on our website at intercept pharma dot com.
Before we begin our discussion I'd like to note that during our call we will be making forward looking statements, including statements regarding our approved product and clinical development program certain regulatory matters, and our strategy prospects financial guidance and future commercial and financial performance.
Listeners are cautioned not to place undue reliance on these forward looking statements, which speak only as of the date of this call and we undertake no obligation to update such statements except as required by law.
These forward looking statements are based on estimates and assumptions that although believed to be reasonable are inherently uncertain and subject to a number of risks and uncertainties.
Some but not necessarily all of the risk factors that could cause our actual results to differ materially from our historical results or those anticipated or predicted by our forward looking statements are discussed in this morning's press release and our periodic.
Periodic public filings with the SEC.
Today's call will begin with prepared remarks from our president and CEO , Jerry Durso, Our Chief Commercial Officer, Linda Richardson, President of research and development and Chief Medical Officer, Dr. Michelle Berrey, and Chief Financial Officer, Andrew sake.
And open the call to take questions let.
Let me now turn the call over to our CEO Jerry Durso.
Thanks, <unk> and good morning, everyone. Thank you for joining us on our third quarter conference call.
I am pleased with our performance and the significant progress we made in our business this quarter.
Specifically, we accelerated in market demand for O'callaghan P. B C, resulting in a return to double digit net sales growth for the third quarter we.
We delivered positive phase III results from regenerate and continue to move towards our NDA resubmission of Oceania and liver fibrosis due to Nash and we strengthened our financial position, resulting in an overall improved capital structure.
Let me first start with our own caliber performance in PBC. We're pleased to have delivered a very strong quarter of double digit sales growth the $77 $6 million in U S. So caliber net sales reported this morning represents more than 16% growth over the prior year quarter.
We're encouraged by the accelerated growth we saw in Ocala, but sales this quarter as well as strong growth in new patient starts and as a result of increased Ocala, but non-GAAP adjusted net sales guidance to $340 million to $350 million for the year.
Linda will provide more detail about <unk> performance in the third quarter shortly.
Turning now to Nash, we remain on track to resubmit, our NDA for OCI and liver fibrosis due to Nash by the end of this year based on our positive phase III regenerate study.
Given the analysis, we've conducted on regenerate to date, we believe in the improved benefit risk profile of OCI and its potential role as the first therapy for liver fibrosis due to Nash.
In addition to our regulatory activities. Our team is focused on refining our commercial strategy and ensuring readiness, while taking a milestone based approach to our launch investments.
Lastly, as a result of recent strategic financial moves we've increased our total cash position to approximately $500 million lowered principal debt outstanding to $336 million and our net cash positive for the first time since 2019.
We now have a greater financial flexibility to propel our business forward focusing on growing o'callaghan PBC progressing fibrosis due to Nash program and advancing our pipeline.
In summary, we remain confident in our ability to drive growth of our caliber and increased market penetration and we maintain a positive long term outlook for our PBC business.
As the team will discuss later in the call the long term outcomes data and real world evidence, we're generating for O'callaghan PVC are compelling to both patients and prescribers and we're focused on reaching these audiences with these important data.
At the same time, we're continuing to advance OCI as a potential treatment for liver fibrosis due to Nash, where there remains a high unmet need.
Overall, we're well positioned to drive further growth and success.
I'll now turn the call over to Linda Richardson.
Linda.
Thanks, and good morning, everyone. As Jerry stated we are very pleased with our commercial performance. This quarter. We reported net sales of $77 6 million in Q3, 2022, representing a 16, 4% increase compared to the same period last year.
Now back to seeing accelerated double digit growth and believe that will tell us valued a P. C. PBC prescribers and patients will continue to generate increased demand.
Let's look at the positive dynamics driving these results new patients strong underlying demand and customer engagement and education.
In the third quarter <unk> reported that our <unk> volume was up 37% over the same period last year. This significant increase represents the highest interacts volume we've seen in a single quarter since the start of the COVID-19 pandemic in early 2020.
Demand units increased 10% this quarter versus the same period last year patient retention and high refill rates at approximately 90% are key contributors to the demand unit performance we are seeing.
Strong customer engagement and communication of the benefits of Ocala to remain a key element of our strategy. Our teams continue to reach prescribers in person and offices a dinner meetings and are re engaging at key congresses at professional meetings, including the gastroenterology in herpetology advanced practice providers meeting.
And the American College of Gastroenterology meeting last month pay.
Patients are an important focus of our business and staying connected with them as a priority. We've introduced a new patient campaign to educate and support those who are taking a caliber and we also attended the recent PV serious patient advocacy meeting in October finished.
Finishing up on our PBC business, we've just launched our new promotional campaign Pearl caliber pushback on PBC.
And testing doctors felt that at birth or the idea that there was something more that they could do right now for patients with PBC. We believe that this is just the message we need to convey to help increase market penetration and a sizeable segment of appropriate patients who could potentially benefit from the addition of ocala to their PBC regimen.
This new campaign will be on display at our booth at the liver meeting later this week.
You'll minutes, Michelle will discuss more of our activity at AAN, okay, including the positive real world evidence for hotels in PBC that her team continues to generate.
Turning briefly to Nash, we are actively developing and refining our Nash commercial strategy in anticipation of a potential launch next year, our Nash disease awareness website, focusing on the importance of addressing advanced fibrosis is up and running with the Nash tipping point campaign, which will also be using in our exhibit.
Okay recently.
Recent market research has shown that physicians treating Nash are aware of the need to address fibrosis and see the potential for <unk> to be an important option for patients with advanced fibrosis.
An exciting time to have the commercial team engaged in these efforts and we look forward to sharing additional details on future calls.
In closing we remain confident in our strategy to drive further adoption of Ocala, among appropriate PBC patients and we are excited about our potential future Nash, where the unmet need remains high I'll now turn the call over to Dr. Michelle Derrick Michelle.
Okay.
Thank you Linda and good morning, everyone. In addition, our update this morning I wanted to take a moment to note that we'll be sharing new data on regenerate PBC outcomes and int 787 at the liver meeting starting later this week.
Looking first at Nash as Jerry mentioned, our team is working diligently to prepare for Resubmission of our NDA for OCA and liver fibrosis due to Nash.
We announced over the summer the planned interim analysis at the month 18, liver biopsies read using their consensus panel methodology again showed a response rate for OCA 25 milligrams that was double that for placebo.
Strong dose response, and anti fibrotic effect and other signals of FX. Our agonism was also observed for the two OCA doses studied.
Fibrosis has been shown to be the strongest predictor of liver related morbidity and mortality.
Therefore, we believe this new analysis reaffirms that OCA can play an important role for people living with fibrosis due to Nash.
Safety considerations raised during the 2019 FDA review have been examined more deeply through analysis of their robust and mature safety database of more than 8000 patient years, the largest and longest running phase III trial to date in this space.
The hepatic cardiovascular and renal safety events. The FDA requested had been analyzed by experts in three adjudication committees.
Cardiovascular events reviewed by the committee showed a balanced number of events in each of the three treatment groups core mace and the major events associated with it we're balanced similarly, the adjudicated renal events, where rare and balanced.
Hepatic events shed a numerically higher number of adjudicated events for OCA 25 milligrams generally reflected biochemical changes that are common in patients with advanced fibrosis due to Nash and the effects of FX, our agonism and the vast majority were mild.
Importantly management of the types of patent events observed would be well within the purview of Gastroenterologists and other liver experts our target prescribers.
Ultimately, we believe that a larger and longer running database helps to address many of the questions raised in the first review.
As all observed safety findings are best monitor Bowl and manageable.
We look forward to sharing additional details on both efficacy and safety from regenerate in a late breaking oral presentation at the liver meeting with our new analysis in hand. It is our view that the benefit risk of OCA 25 milligrams in patients with fibrosis due to Nash is strong.
Following the NDA Resubmission, which is anticipated by the end of the year, We expect an advisory committee meeting in the spring as part of a six month review process.
While the reverse phase III study evaluating the safety and efficacy of OCA in patients with compensated cirrhosis due to Nash did not meet its histology primary endpoint. We were encouraged that the fiber scan data showed a reduction in liver stiffness of three killer Pascal a clinically significant result, and.
In addition, there were no new safety signals were observed in this population of patients.
Further analyses of reverse data are ongoing and we plan to share. These data at an upcoming scientific conference achieving statistical significance on histology endpoint and compensated cirrhosis due to Nash has proven to be an extremely high bar in clinical trials underscoring the urgency to intervene in page.
With advanced fibrosis before they progress to cirrhosis.
As we've noted previously our planned NDA resubmission is not impacted by the results of reverse the agency has been very clear that regenerate and reverse enrolled two different patient populations. Nevertheless should the FDA asked for any safety data from reverse we will be ready to provide it.
Turning to updates and PVC.
We remain committed to generating a wealth of real world evidence to support Ocala and P. B C.
Made significant progress on these plans this quarter.
First the leading journal Gastroenterology published data that showed improved transplant free survival observed for patients administered at Calvert in a clinical trial compared to natural history data from two large patient registries.
In this publication patients treated with Ocala that had an approximately 70% lower relative risk of death or liver transplant at anytime during follow up compared to the control patients from either a patient registry.
The consistent effect size across the two external control cohort strengthens our confidence in these observations.
This study is the first to demonstrate that Ocala. The treatment is associated with improved transplant free survival. The ultimate goal of therapy in PBC.
Starting later this week, we'll be sharing other real world and outcomes data for <unk> at the liver meeting we're pleased that the analysis of our phase four cobalt study with external control has been accepted as a late breaking poster presentation.
A strong benefit was demonstrated when comparing as treated subjects from cobalt with rigorously matched external control.
These data provide evidence that OCA decreases the risk of death liver transplant and decompensation.
Second we will be sharing the detailed results from he ran <unk> U S. Our real World study that Leverages Komodo health.
<unk> claims database to compare clinical outcomes in a predefined group of patients with PBC, who were treated with <unk> and a comparable group of PBC patients who were eligible but who were not treated.
As a reminder, topline data from this study were shared earlier this year and again showed a statistically significant improvement and event free survival in patients receiving <unk> for PBC, specifically individuals' on PBC received Ocala, the at a 63% reduction in risk.
All cause death, liver transplant or hospitalization for hepatic decompensation than the control group at anytime during the follow up.
The real world evidence, we have accumulated thus far from large data sets in the U S U K and Europe is compelling and consistent and demonstrates the long term clinical benefits of Ocala in PBC.
Obviously around transplant free survival, which we know to be the most important goal for patients.
Ultimately these data will be included in our regulatory submission to FDA in support of fulfilling our post marketing requirements for <unk> and P. B C. In addition to the real World evidence, we will be including expert adjudication of events from our phase four study cobalt.
Requested by FDA, which will bring our anticipated timing for the P. B C. S NDA submission into 2023.
We remain committed to working closely with PBC patients through our clinical trials meeting our post marketing commitments and demonstrating the clinical benefits of long term therapy with Ocala that.
Building on our long standing commitment to PBC.
Our fixed dose combination of OCA plus bezel five rate is ongoing and we continue to enroll patients in our phase III studies evaluating different doses of the two components.
We remain excited about the potential benefits that this combination can provide to individuals living with PBC and look forward to sharing updates on the dose selection and on our phase III study design next year.
Turning now to our earlier stage pipeline, our comprehensive phase one study for our next generation <unk> agonist Int 787 has progressed through its final cohort, we look forward to sharing data from our phase one studies at the liver meeting as well as our lead indication and updates on our proof of.
That study fresh next week.
At this point I will turn the call over to Andrew where a financial update Andrew.
Thank you Michelle and good morning, everyone I will be providing an update of our financial results and I ask that you. Please refer to our press release issued earlier today for a summary of our financial results for the third quarter ended September 32022.
As a reminder, the divestiture of our international business was completed on July one and as previously stated our full year results and guidance will include the divested business for only the first half of the year given the date of the deal closure.
Additionally, the sale of the international business and the repurchase of $389 million of our 2026 secured convertible notes and ended in a material gain to our P&L, which I will detail later in my remarks.
Let me start with revenue.
<unk> had a strong third quarter recording $77 6 million of net sales as compared to $66 6 million in net sales in the prior year quarter.
We reported $87 7 million and total operating expenses and $82 7 million and non-GAAP adjusted operating expenses. This compares to the third quarter ended September 32022, where we recorded $86 2 million and total operating expenses and $89 six.
non-GAAP adjusted operating expenses.
Cost of sales were <unk> 4 million and $2 million, respectively for quarters ended September 32022.
In 2021 consisted primarily consisted primarily of packaging labeling materials and other related expenses.
Selling general and administrative expenses were $43 $3 million in the third quarter of 2020.
Up from $41 $3 million in the prior year quarter. The increase was primarily driven by increased commercial activities and costs related to our patent defense.
Research and development expenses were $44 million in the third quarter of 2022 materially unchanged from $44 $7 million in the prior year quarter.
Interest expense in the quarters ended September 32022, and 2021 was $5 2 million and $14 $1 million respectively for.
For the quarter ended September 32020 to interest expenses related to the principal amounts of our outstanding convertible notes and no longer includes any accretion of debt discount upon adoption of ASU 2026.
We reported net income of $267 5 million, an increase compared to a net loss of $3 $6 million in the third quarter 2021.
The increase was driven by the significant gain resulting from the sale of our ex U S business of $371 5 million, which was partially offset by a loss on extinguishment of 2026 convertible secured notes of $91 8 million.
The third quarter of 2022 was a transformative one for intercept with regard to our capital structure.
During the quarter, we successfully repurchased $389 million of our 2026 secured convertible notes as a result of these transactions, we have reduced our debt by 54% and reduced our cash interest expense by 58% or $13 $6 million annually.
Further with approximately $500 million in cash cash equivalents restricted cash and investment debt securities available for sale and $336 million and that we are now net cash positive for the first time since 2019.
In summary, we have a strong financial position and are comfortable that our current balance sheet gives us financial flexibility to grow our existing business and PVC support our launch of Nash and progress our pipeline.
With that I'd now like to turn it over to the operator for any questions operator.
As a reminder to ask a question he will need to press star one on your telephone please standby, while we compile the Q&A roster.
And our first question comes from the line of Yasmin Rahimi with Piper Sandler Your line is now open.
Good morning team. Thank you so much for all the great updates I just wanted a clarification question did you comment on that at the upcoming liver meeting we will be seeing month 48.
By up to data from the Reed regenerate analyses and if you could just provide some commentary of whether we will be getting both like one point improvement of fibrosis as well as Nash resolution. So if you could just.
Provide that that would be helpful.
Joe maybe just start there.
Yes happy to good morning, yes.
We will not be giving any month 48 data. The submission is focused on the planned interim analysis of the month 18 data so that that will be our presentation and we'll stop at the month 18.
Again on the Resubmission, we are focused on the new analysis of the consensus methodology looking just at month 18.
Okay.
The Resubmission will only include weak.
18, not week 48, either that is that correct.
It's focused on the month 18, the Resubmission looking at the.
Central analysis, and the new consensus methodology.
Great and then team another one follow up question is in regards to the supplementary data that's being submitted for full approval in PBC. So.
What has been some of the communication that you have.
You've gotten from the FDA, how receptive are they two words reviewing this data.
And potentially allowing full approval.
Just if you could just provide some color beyond what you had in your prepared remarks, it would be very helpful and taken I'll jump back into the queue.
Thanks, Jeff maybe maybe I'll start and then Michelle can can add in.
As Michele outlined in her prepared remarks.
A comprehensive package that's being prepared.
She outlined obviously the data coming from from cobalt as well as a slew of real world.
Data sets that we think put us in a solid position overall in terms of the comprehensive nature.
Of the package that we also believe of course that that'll caliber continues to be in.
An important medicine and the only second line.
Therapy in PBC approved we're continuing to do the right work, we look forward to continuing what I think I would frame has been a productive dialogue with the agency and re engaging with them. Once we resubmit in defining the work we need to do more.
Moving forward so.
Michel anything else from your end.
Okay.
The only thing I'd add is we have had a very good interaction with the folks at FDA, including the individuals within the real world evidence part of the FDA. So we are excited about being what would be the first nine ultra rare disease to submit.
Stanfill package of real World evidence data that we've been generating on the standards for the real world evidence generation have to meet those.
A randomized prospectively enrolled clinical trial that we've been making sure. We reviewed every one of the guidance says that have been issued over the last 18 months or so by the F. D. A to make sure that we're meeting those criteria, but we are.
Excited about this opportunity given the breadth of data that we know we have given the 30000 patient years of data that exist for our calendar.
Thank you Michelle.
Thank you.
Your next question comes from the line of <unk> <unk> with Cowen. Your line is now open.
Good morning, guys. Thanks for taking the question I've got one high level question, a little granular one is a follow up.
Jerry.
Now that you've got this healthy balance sheet.
And youre looking towards.
Expenses for Nash launch and potential BD, how how are you looking to I guess balance.
The cost of both of them and if you could give us an update on what you might be thinking about that.
Pipeline.
Beyond 77, and the visa vibrate combo.
Okay, a few items there I'll try to step three read too. Thank you.
Very much for the questions I think.
We do as you said.
Field.
Good about the work we've done on the balance sheet, we think it puts us in a good position.
Position as we do all the right work now to finalize and resubmit by the end of the year Linda mentioned in her prepared remarks. The fact that the commercial efforts are flexing up primarily first I think in the areas of refining our strategy, taking a contemporary look back.
Into the customer considerations from the payer physician and payer side and I think you'll hear more.
As we get into next year about where we're evolving the commercial thinking.
We are going to I think take a prudent approach in how we ramp up towards commercial readiness and so we'll balance both sides of that we are excited about the first moves we made.
In our pipeline with with 787 and I'll highlight the fact that we'll have more information about 787, and what were some of the initial data, but also what we're thinking in terms of lead indication.
As we get into next week.
So those are the first bets from the pipeline will have more to say about the pipeline.
Over time, and again I think we feel that the moves we made on the finance side give us the means to do what we need to do both.
Moving Nash forward continuing to grow PBC and now.
Getting more constructive with the pipeline.
So no no no focus on BD right now and the near term future to build out the pipeline further out than what you. So look I think we're always we're always looking and considering how best to leverage the capabilities, we have and the capabilities both on the R&D side and on the.
The commercial side of the house.
But nothing else definitive for me to say right now on that.
Got it.
And just a quick follow up.
And Michelle for you on on the presentation.
On the I.
Yes.
Regenerate re read presentation, you mentioned there'll be more and more detail on the safety can you can you give us more I guess top line on the balance of the FC ease.
On the hepatic side you did mention there were more 25 milligram sorry events on the 25 milligram can you talk to the SAE number between the arms and the cholesteric events as well.
Yes, Thanks, Richard just before.
Before we leave the pipeline just wanted to mention that we are spending a lot of time and resources on our fixed dose combination and on 787, so really excited to be talking more about that at the liver meeting said look forward to sharing that on the presentation as a late breaker and we do look forward to share.
More data I think you'll be.
Pleased to see that the detail we've been able to include and hepatic events and specifically on those adjudicated by the committee.
Most of those that were seen in the placebo group are obviously most related to them.
The progression of disease and those that you see in OCA 10, and especially in OCA 25 are really biochemical excursions that <unk> seen I think with what we have been able to show and will be sharing in the presentation is very reassuring about the over.
Our profile and all.
All very monitor all manageable.
And reversible so again, that's really key when you start looking at some of these hepatic events that.
The detail that we'll be able to share next week.
Got it.
One last question as you think about the S N D a.
For for PBC.
Is there is there potential for the NDA process.
The other day.
Our cross as a full approvable endpoint for PBC, thereby potentially expediting the combination pathway.
That's a great question and one that we've spent a lot of time thinking about.
What is very clear about our path is a L. P is really helpful. In the early disease stage, but light aminotransferase as tends to burn out as patients have more advanced disease and what we are seeing is that total Billy is more important.
Stronger predictor of those outcomes now that we have outcomes data, we're really in a great place to be able to look at develop a.
Multiple.
Composite endpoint that really pulled in multiple different by payer measures for these patients beyond a L. P. Theres a lot more tier the disease than it was a great biomarker for us where the poise study in early disease patient population, but really.
As we look at the range the broad range of patients who are benefiting from <unk> I think we have in a bigger opportunity there to look at it now with our outcomes data and what is the best predictor of those outcomes.
But again that the outcomes data is really what's going to be critical for okay. All of that.
The only compound that has now shown improved.
Transplant free survival, that's really what's key.
Great. Thanks for taking all the questions and look forward to seeing you guys at <unk>.
Yes.
You will see a downturn.
Yeah.
Your next question comes from the line of Steven <unk> with Raymond James Your line is now open.
Good morning, Thank you.
Perhaps like the refill rate or the persistence and PVC has gone up recently I was hoping you could maybe expand on that and if it has improved of late what you attribute that to and if you expect that to persist going forward.
Thanks, Thanks, Steve we do feel good about the dynamics, we're seeing and then Linda can can go deeper there yeah. I think it's really remarkable that you see the refill rate and persistency kind of continuing to climb at this point.
In a product's life cycle and were very.
<unk> on that that element of our sustainability I think some of it comes from clearly understanding how to manage pruritus. That's one thing that we know that physicians understand how to do and there's also the building body of evidence where you see.
What we're reporting with outcomes and that is extremely meaningful when that has articulated physicians and nurse practitioners, who spend a lot of time with the patients when they are putting them on therapy and as they have become aware through the scientific landscape of what we what we've demonstrated.
I think that gives a meaningful push to stay on therapy when when some of the physicians who have seen this data presented.
And the articles have have engaged with us even as recently as ACG.
Can I just follow up on the Pruritus management are you noticing.
Okay.
Are you, referring to sort of just treatment regimens that in the real world.
Providers are optimizing or.
Just getting more experience.
Paper volume thanks.
Yeah, I think there's two elements there there is the reality that the.
Constant reminders and an overstatement in checking and did your edge to edge did you add should you have any sense of itching.
In the clinical trial results are different in that that we've seen in the real world and the majority of the pruritus that you see can start in the beginning and then ameliorate over time, there are activities and things that people can do to help with that and I think you know in the world.
World, We just don't see it as much and when there was an article on this that was published before on how you know it is not as extreme as it's made out to be so I think you couldnt stay on the therapy that you didn't tolerate right and we have found that this consistent refill rate as is evidence of patient satisfaction and ability to stay.
On the drug.
Thanks, so much.
Thanks, Steve.
Yeah.
Your next question comes from the line of Thomas Smith with SBB Securities. Your line is now open.
Hey, guys. Good morning, Thanks for taking the questions.
Alright on the OCA Resubmission in Nash.
<unk> previously talked about having an additional 518 month biopsies available from regenerate.
Are you expecting the Resubmission will include this additional data set and then.
Can we expect to see these results included in the <unk> late breaking presentation.
So can we take that very yes.
We will be including those patients too.
Underwent biopsy those are certainly going to be part of our submission and we will be including that what I can say about it is it's very consistent with what we have seen and the original.
ITG population that includes just the F. Two F series, but because we have an additional 750 years are patients who underwent month 18 biopsies, where we'll include that in our submission.
The primary focus of the FDA. They really wanted to look at those for whom we had a central read and this new consensus read to compare theirs, but we will be of course, including all of those data.
Okay understood.
Fair to say that this won't be a focus of the.
The late breaking presentation next week.
It's not a focus we are really focused on providing more more.
More granular data on the safety and Tolerability of these patients some of the data that we didn't have at the time of the top line.
Again that that'll be the focus of the presentation. It's only 10 minutes or we will be trying to to cram in as much as we can to make sure. We've answered all the questions that we know came up that we just didn't have the answers yet for the top line, but we will be including those additional patients who had month 18 by.
<unk>.
Okay, Great and then just.
A quick follow up.
If you could provide a little color, what's the latest projection on when we might see outcomes data from the regenerate study.
So.
And our current guidance about three years, sorry, Jerry or we are going to be looking at that with some new data that's been published.
So.
Are you able to give you a little more guidance there.
Later next year, our current estimate of our.
Our current estimate Thomas as 2025, although as Michelle said, we'll work to see if there is a.
There's a reason to update that once we have the right information.
Order to be able to model.
No.
Okay got it great. Thanks, guys. Appreciate you taking the questions and looking forward to the presentation.
Thank you.
Okay.
Your next question comes from the line of.
<unk> <unk> with B Riley your line is now open.
Yeah.
Good morning, Congrats on a strong Gordon thanks for taking our question. So maybe just a couple of related questions.
Alex volume increase.
Are you able to comment there.
The BBC.
PVC patient died.
Previously found that's why go.
Just wondering if it's about value per dollar of this behavior of course outcome data and good about base.
They should not be how you all cost level.
We ought to be elevated in a clinical trial setting it's a good comment on that.
So overall I think.
The trends look solid and really as a result of.
The updated plan from from Linda and the team I think we've been really encouraged over the past several quarters as we moved out of the label change that our ability to re stimulate the growth of new patients for the appropriate patients.
Within the within the existing label.
And really I think I would highlight a lot of the efforts not only with the you mentioned the herpetologist, but really with the.
Additional allied professionals that are supporting the community based gastroenterology practices I think theres been good traction there once we are able to get the.
Message out about the label change and as we kind of estimate it and forecast that at the time it would take a few quarters to work through and I think we're right now in that window.
Where we've worked through that history and you start to see.
The growth overall accelerating in terms of total demand, but in particularly this new patient starts, which I think speaks well about what we should see in the coming quarters, Yes, and I think this was in our minds are predictable.
Then to pivot point, where we would start to see the underlying growth for no longer talking about label change patients, who are dropping out and being compared to a larger.
Database, but we see folks understanding the impacts there is considerable opportunity within the on label population the new label population and as we continue to use our REIT strategy and talk to Gastroenterologists and their supporters in the community, that's where we're getting the message out and we have not really been able to other than.
Folks who have requested data from Msos were seeing the data or the press releases themselves heard that information being able to talk about the outcomes data at all our first opportunity to do anything with it you know in terms of of a sales rep is to potentially drop it once its been peer reviewed and published and there are ways that you can start to do that that.
We will obviously can.
Form two and follow but this is just word of mouth and people understanding and programs of the question. So we believe that the growth is still there and we will continue to move forward with that.
Okay.
Great and then just do.
Michel you can comment on.
The two pieces of the exotic.
Safety that Youre following.
Obviously, the hepatic events that you will have more data next week on the late breaker, but then also the liver outcomes idea following.
The efficacy analysis can you can you just clarify.
And maybe this is a silly question, but just to clarify how those two.
Have any overlap if any and then I just have a quick follow up.
So to be clear they don't have overlap, though there are many might be the same events there adjudicated through different experts. So we have a hepatic safety adjudication committee that is specifically looking at drug induced liver injury. So that's the focus of the same.
<unk> events.
To be clear in our presentation next week, we will not have any outcomes. The focus of this analysis towards a preplanned analysis in collaboration with the FDA. It was a re analysis of the original 931 patients that were read originally under a central read.
Now red under a consensus panel, we will be sharing those data plus the additional patients who will be submitted.
Together with the 931 patients.
And as Jerry said earlier, we expect that outcomes would be and then 2025 range. We have not started looking at those data with the new.
Modeling that's been available over the last couple of years, that's something that we'll be turning to after the NDA resubmission by the end of the year.
Thank you for that clarification and just finally Andy.
Andy.
About the IV setting and recently.
To ask about the application and how might you be dragging but are there.
<unk>.
If you'd add anything from you in the near term.
Yes.
Yes, no. Thanks for the question.
So really no change there.
We obviously have the Anda filers, we currently have six and the filers five of which are included in the current litigation.
We continue to maintain that we feel very strongly about our E&P and our current view is that we're going to continue to have IP protection.
Although calibre into the 2000 thirty's. So we're continuing to defend our IP, we feel very good about it and really no change steady as she goes.
Thanks for taking my question.
Thanks, Matt.
Your next question comes from the line of Brian Kearney with Baird. Your line is now open.
Hi, This is Luke Herman on for Brian Thanks for taking the question.
Just a follow up on 787 can you remind us how it's differentiated from o'shea from what <unk> seen pre clinically.
What we could see in the phase one data that could provide confidence in this differentiation.
Thanks for the question Lucas Michelle.
Yeah go ahead and Jonathan sorry.
We have two posters and abstracts are out now so one is the preclinical data that I think will be helpful. In understanding the differentiation.
787, as a more hydrophilic compounds. So that means that that FX are targeting is more likely to be got.
More got less liver and.
And that gives us some other opportunities you'll see that in the in the abstract.
And then the poster where we go into some of the preclinical data, including some animal models and then we also have our phase one data as we mentioned in the comments were in our last cohort of the multiple ascending dose study really just to make sure. We've got broad coverage there for the exposures, depending on which patient.
Relations and Theyre hepatic impairment.
To make sure we've got that safety. So we're really excited about this molecule.
Have a lot of breadth of opportunities to explore there, but excited about our lead indication and sharing those data with E vapor over the next week.
Great and could you share any color about expectations for the timeline to getting a phase II up and running.
I will be sharing those data next week.
Early next week.
Okay. Thank you.
Thanks, Thank you.
Your next question comes from the line of Michael Yee with Jefferies. Your line is now open.
Okay.
Hey, good morning.
I'm going to ask my questions like everybody, but I'm just going to keep it to two.
First question.
Michelle.
Or do you have any information on that.
Like progression Mr. Roessner for any of the components of the outcomes.
Have you looked at any of those individually.
And have you actually TSMC looked at either an interim or futility on the total outcome. That's question number one maybe that's one and a half questions. The second question. It's a it's been a few years actually since we went back and did.
The NASDAQ and all those types of things if we go back in and so there used to be a question about biopsies and how to think about that.
How has your thinking around the evolution of biopsy or what payers would use to define up Q3, and biopsies and that type of requirements evolved over the past year or two thank you.
Yeah, Mike maybe I'll jump on that one first and then we don't.
So all I can come back second on the point of.
So.
Obviously, Mike is as we talked about in the past.
That is an area the identification of the right patients in the real world will be an important dimension of a potential launch here where.
Doing the updated work on where is the market today the consideration of payers.
And specialists and I would anticipate similarly to what we did.
I guess it was about the end of 19, where we had kind of a fulsome look at those elements in advance of.
Our launch we will do that again I think thats some of the work and considerations that we're working through now with our updated dataset in hand, so more to come on.
Kind of the commercial thing I would just say and I'm sure.
We can go deeper on this point and then we will see some additional indicators also at the at the liver meeting next week.
Utilization and proliferation of noninvasive.
Means of identification of patients has only grown over the last couple of years and so there has been some positive progress made on that front that I think is going to be.
Again, an interesting element in the update that we'll come back with.
Your first question Mike was on outcomes.
And then Michele can can touch on that.
Yes, particularly Michelle as it relates to either Interims for utilities or what the PMC is also looking at thank you.
Yes.
Yeah sure happy to touch on that and as I said earlier. This submission is really focused on this.
This interim planned interim analysis and the re analysis of those 931 patients.
Because of that and because it was a planned interim and a reanalysis of the 931, we don't take any alpha hit.
That was really important in our conversations with the FDA that we are not looking at the outcomes is really critical we don't want them to use any of that alpha spend we want to maintain that.
And keep that four hour our outcomes data. So we have not started looking at that.
DMT is really focused on safety.
We are going to be as I said looking at the contribution of histology and progression to cirrhosis. That's a different committee. So not the daily expert. This is a group of Herpetologist, whose expertise is really in defining that progression Tuesday.
<unk>.
So there'll be they've been looking at that they report into the DMC there all of our committees are blinded.
The three safety committees. This progression to cirrhosis outcomes Committee also remains blinded and then they feed that into the DMC and just to be clear because of DMG is just looking at safety doesn't mean that they don't also look at efficacy and those those rates.
I've been involved with other <unk>, where you don't have any chance of showing an outcome and in that in that instance.
Everything that's on the safety front as a risk.
Therefore, there is no benefit risks so that's always part of the D. M C.
Charter and and kind of what underlies the DMC is wrong. So again, that's a different committee that's looking at <unk>, we will be looking at that and providing them with some additional data neck.
Next year and doing some additional modeling.
Wanted to touch again on the the noninvasive tests, we know that you can't validate noninvasive surrogate marker against another surrogate marker FDA has been pretty clear about that it's they can only be validated against outcomes. So we know collecting these data throughout this very long.
<unk> trial that we now have patients out at six and seven years. So we do have that opportunity coming around the corner for looking at outcomes.
And that is going to be really critical for the validation of some of these noninvasive tests.
A few years away as Jerry said, they're not something that's going to be validated prior to our.
Sure.
Potentially be a first approval, which is just.
Again based on these 18 month biopsies, certainly a hot topic, something we're continuing to pay a lot of attention to and amass a law.
A lot of data in these thousands of patients.
For the question Michael.
Okay.
And your next question comes from the line of.
Ed Arce with H C. Wainwright your line is now open.
Okay.
Alright, great. Thanks for taking my questions.
Firstly I wanted to ask in PBC.
Given the additional data.
Thank you.
Submitting towards full approval, including cobalt in the real World Real World data sets that you mentioned and in particular the data around transplant free survival.
I'm just wondering if there's any expectations.
Can you share with us in terms of label updates.
After that review either in terms of additional long term data or removal of any sort of warnings or restrictions and then I have a follow up thanks.
Michel maybe you can jump in there.
Yeah.
Yes, it we're really focused on the review of the real world evidence the importance of having these.
The FDA considered irreversible morbidities their survival certainly falls in that category and how that can play a role.
Having said that this would be the first non ultra rare condition that this will be reviewed so I don't really want to speak to our expectations or what we anticipate the FDA would make decisions on that basis I think the importance for us is really going to be getting the word out about these outcomes about.
Improved transplant free survival and how critical that is and we've really made beyond the biochemical markers.
It's not about an accelerated approval anymore. This is really about fulfilling our post marketing requirements and and spreading the word that across multiple different independent data sets. We now have data on transplant free survival, which I know how critical that is for patients to consider.
Okay. Thanks for that.
And then.
Turning to your pipeline.
I think you mentioned earlier a lot of time and resources are spent now on this fixed dose combination study as well as 77. So just wondering if beyond the data we can expect.
This weekend.
Wondering if you could update us on the status of both of those programs in particular the timing of.
For full timing of full data.
From the current study thank.
Thank you.
No.
Yep that fixed fixed.
Probably yes.
Early next year on the fixed dose combination, we look forward to sharing some of the data arm.
The interim analysis for these two phase III studies that are exploring different doses of OCA and of Bezeq I rate. We know that's a fiber it's been used at the higher doses 400 milligrams in a.
Generic form in Europe , we're looking at whether combinations of the two drugs can improve on advocacy improved tolerability. So a lot of questions that we wanted to look at it's not just on the PK PD, though I really want to look at at our overall safety Tolerability.
That that's a really important question for us as well as the design of the.
The phase three study so.
A lot of thinking going on right now while we're recruiting.
Finishing up the phase III studies, both in the U S Europe and beyond.
The phase Twos. In addition to our large phase one study you mentioned previously that we were back filling some of the data from phase one given it's been a while since then.
<unk> was developed.
Some of those studies werent to the standards that we wanted we really wanted to explore some of the drug drug interaction data as well.
There.
787, as well we will be sharing some data as early as next week and then I think you'll be hearing a lot more about that phase III study in early 2023.
So we're excited about the growing pipeline.
Great Thanks for that.
And look forward to keeping you in D C Peters.
And Youtube.
That.
Your next question comes from the line of Ali <unk> with UBS. Your line is now open.
Hi, guys. Thanks, so much for taking my question and congrats on all the progress in PBC.
Maybe just in terms of the recent strength in how youre thinking about longer term when you might sort of think some competition with some new players such as some other people cars, maybe kind of how you're thinking about hep azathioprine might compare to some of these <unk> and specifically comment on kind of the selectivity across <unk> Alpha Delta.
And also just in terms of.
What we can look for perhaps in some of the upcoming data that's from your pass a firebreak combo and thinking about comparing after some of the other sort of emerging at P. D C assets. Thanks.
Okay, maybe we start maybe Michel from from your side and then Linda if theres anything in terms of everything we're learning on the <unk>.
Competitive front in the market.
It can go both ways there.
I think for me.
PVC again, reiterating the importance of our ability to now show transplant free survival I know a lot of our competitors are focused on the earlier phase of development on the biochemical changes and.
How that might predict long term outcomes, but we've made passed that we now have those data from these large real world studies, including claims databases patient registries and I think that that's really what is the main take home there or from a competitor perspective, we.
We are looking at how we can help clinicians and patients understand what theyre biochemistries might mean now that we do have data outcomes data are look forward to that.
Not focused on a L. P. There, which we think is is really most helpful. In these earlier stage patients and not across the broad spectrum. So what be watching for more data again on the real world outcomes and some of the ways, we might help our patients and clinicians in projecting how the.
Changes that they are seeing might actually correlate with the outcomes that we've seen Linda.
Divide my comments into some categories related first to densify right. We know the best five rate has been studied for.
For use in the management of PVC and investigator initiated trials and in larger trials, particularly in Japan. So there is a familiarity with the effects of that does a firebreak pan <unk> activity that are well understood now when we combine that as Michel was saying with the known impacts that we have in there too.
Mechanisms of action when we're looking at the fine balance of what's the optimal potential for dosing to actually increase efficacy potentially improve tolerability and see.
If we can really come up with a new molecule that will be and then see with its own patent life et cetera. So we look at it from what can this I think the probability of success technical success in lowering and improving biomarkers in PBC is certainly there we've seen evidence from small studies in Europe with the.
Combination of the two showing an improvement after or so greater improvement if you add <unk> first and then there's a five rate second but an improvement regardless of order. So I think in terms of our commitment to PBC and lifecycle management, we certainly have that opportunity when we looked at the competition currently.
Coming out with different P pars who are.
Thank you know trying to position.
Themselves vis vis one another and creating delta P powers and whatever it's P. Par. So that's kind of some marketing activity and gamesmanship in terms of positioning so I understand totally is what's going on there, but bilirubin as Michel has indicated bilirubin, what we're seeing is the most.
Predictive element and we have very strong activity on bilirubin, and we've sustained bilirubin lowered and sustainability, we've been levels in our data and the <unk> open label extension data, we have that data we have data not only on bilirubin, but we also have data on stabilization of fibrosis.
<unk> and physicians when they've seen this presented.
Some additional information we have been talking about in our campaign that is not what one would expect right. This was prior to even having the results on outcomes. So I think all of this leads to the impressive data we've generated from multiple sources I mean, if this were a one off you'd be you'd be pleased but.
When you see it triangulating from different databases.
<unk> and coming up with the same kind of literally over label reads on the risk reduction that's a that's an impressive thing to be presenting so I feel like that data is beyond a L. P and is starting to hit the marketplace and moving forward. So we.
We'll see how that.
How other people answer to our ability to discuss and generate outcomes data.
Thanks, Alex.
Inc.
Okay.
Your next question comes from the line off.
Catherine Cooney with JMP Securities. Your line is now open.
Hi.
This catheter with corium coming on on behalf of John Walden.
That we had.
How.
Emerging market my acquaintance.
The decision regarding the supplemental package in PBC I know you've sort of discussed the commercial aspect of it but doesn't play any role.
Yeah.
A decision as it looks through the supplemental package. Thank you.
I'm, sorry, I didn't follow the first I Couldnt hear the first part of your question Katherine how what plays into the Fda's consideration.
The emerging markets the emerging pipeline, that's coming out in PBC.
Yes.
Michelle can comment I would say upfront.
I think the FDA is looking at our our package as.
As we said, it's a pretty robust.
Package, we are we're in a.
Position of advantage in terms of our ability to have a long term view at the questions on the table.
And so we've been I think generating the data accordingly, and approaching the conversation.
With the FDA with a focus on what we've been able to do from a longer term perspective based on all the experience as Michelle indicated.
The cobalt data set the real world as well as the post marketing data with with with.
So over 20000 patient years, I think puts our <unk>.
Data set and a unique perspective, there I think to the competitive.
The.
Competitors are not anticipated to be on the market during the timeframe, where we're being reevaluated and it's the only second line therapy approved for PBC patients.
Sure the competitive context comes into play with the immediacy of our our review next year potentially.
Thank you.
And I just had one follow up as far as timing.
Beyond just next year.
Are you able to refine the timing at all.
Now what I would say is the work is ongoing obviously in parallel to the to the heavy work that Michelle and her team are doing with the Nash resubmission.
Expected by the end of the year and if we.
<unk>.
Have a need to refine well, we will do that at the appropriate point.
Great. Thank you so much.
Thanks.
Your last question comes from the line of.
Salary and richer with Goldman Sachs. Your line is now open.
Hi, good morning, and thanks for taking the question. This is mason on for yourself in.
On Nash and the various segments of the patient population you're team has talked about.
All of the positioning for the more advanced population and a focus more on the F. Three later stage population so.
With respect to the reverse trial results.
Even though the FDA sees these as distinct indications do you think that missing the endpoint there.
Has any impact on how clinicians view ocala, the potential as an anti fibrotic and have three patients, especially for people who are sort of teetering between.
<unk> three and four.
It would just be really useful to understand how your team thinks about this thank you.
Yeah. Thanks. Thanks for the question Mason, we have indicated in the past and Thats part of the validation work that lenders team is.
Is undertaking now our focus more towards the advanced fibrotic segments I think we're still.
Going towards that direction, albeit we're refining exactly what that May mean with the current data set we have on mind is.
Michel indicated.
We've continued to say the agency is looked at these populations differently and it was a different population the more advanced.
Compensated cirrhotic in reverse is a different population with more advanced disease, and obviously 25 milligrams for the time studied was not an effective dose and contrast that to what we saw in regenerate where now multiple times at 25 milligrams, we see the strong anti fibrotic effect.
Yeah.
<unk>.
Understanding and the potential target physicians, gastroenterologists and herpetologist about the role of impacting fibrosis.
For those more advanced Fibrotic segment is something that is well understood and appreciated.
And I think that.
While we will refine exactly how we'll position things I do believe that the anti fibrotic effect for the more advanced populations like we studied and regenerate will be at the heart of our value proposition as we prepare to launch as I said earlier, we will have a lot more insight on that as we get close.
And we will have the opportunity to.
Similar to the way we did in the past present more details on the commercial plan.
And in the future.
Alright, thank you.
Yes, I think thats.
All the all the questions we had I want to thank everybody for joining us today as I said in the upfront.
We feel very good about the progress that we made this quarter. We look forward about the work ahead.
And particularly interesting sharing and in person.
Session with deliver community at the meeting next week down in Washington D. C. So thanks and look forward to providing.
More updates in the time to come thanks, and everybody have a great day.
This concludes today's conference call. Thank you for your participation you may now disconnect.
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
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