Albireo Pharma, Inc. (ALBO) CEO Ronald Cooper on Q1 2019 Results - Earnings Call Transcript

May 09, 2019 3:38 PM ETAlbireo Pharma, Inc. (ALBO)
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Albireo Pharma, Inc. (NASDAQ:ALBO) Q1 2019 Earnings Conference Call May 9, 2019 10:00 AM ET

Company Participants

Paul Arndt - Investor Relations

Ronald Cooper - President and Chief Executive Officer

Patrick Horn - Chief Medical Officer

Simon Harford - Chief Financial Officer

Conference Call Participants

Ritu Baral - Cowen and Company

Liana Moussatos - Wedbush Securities

Yasmeen Rahimi - ROTH Capital Partners

Kyung Yang - Jefferies LLC

Timothy Lugo - William Blair & Company LLC

Matthew Kaplan - Ladenburg Thalmann & Co.

Joseph Stringer - Needham & Company, LLC

Ed Arce - H.C. Wainwright & Co., LLC.

Operator

Good morning, ladies and gentlemen, and thank you for joining us for Albireo’s Conference Call and Business Update for the First Quarter 2019. Following management's prepared remarks, we'll open the call for question.

I would now like to turn the call over to Paul Arndt from LifeSci Advisors, representing Investor Relations for the Company. Please go ahead sir.

Paul Arndt

Thank you, operator, and good morning, everyone. Thank you for joining today's call. During which management will provide an update on Albireo's performance in the first quarter of 2019. Earlier today, Albireo issued a press release highlighting recent business accomplishments and noting its financial results for the first quarter ended March 31, 2019. This press release is accessible via the Company's website at www.albireopharma.com.

Before proceeding, let me mention that comments made today may include forward-looking statements made under the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements other than statements of historical fact regarding the plans for or progress, scope, cost, duration or results of development of Odevixibat, elobixibat, A3384 or any other Albireo product candidate or program.

Including prevalence data, target indications for development, size, design, population, location, conduct, objective, duration, endpoints, timing for initiation or completion of or for reporting the results from or regulatory feedback regarding any clinical trial, including Albireo's Phase III trial of odevixibat in patients with PFIC planned pivotal trial for odevixibat in biliary atresia, planned Phase II trial of elobixibat in NASH.

The timing for submission of approval of Odevixibat, the commercial outlook for any Albireo product candidate program or opportunity in any target indication, including potential approval, coverage, pricing or reimbursement. Any additional payment that Healthcare Royalty Partners or EA Pharma may make to Albireo. The period for which Albireo's cash resources will be sufficient to fund its operating requirements or Albireo's plans expectations or future operation, financial position, revenues, costs or expenses.

Actual results may differ materially from those expressed or implied by any forward looking statement as a result of many factors including those described under the heading forward looking statements in Albireo's press release from earlier today or under the heading risk factors in its most recent Form 10-K or in later filings with the SEC.

Albireo cautions you not to place any undue reliance on any forward-looking statements. Also, any forward-looking statement that is made speaks only as of today, Thursday, May 9, 2019, and should not be relied upon as representing Albireo's views as of any future date. Albireo disclaims any obligation to update any forward-looking statement except as required by applicable law.

With that, I'll turn the call over to Ron Cooper, Albireo's President and CEO. Ron?

Ronald Cooper

Thank you, Paul, and thank you everybody for joining us on today's conference call. With me today is Dr. Patrick Horn, Albireo's Chief Medical Officer; and Simon Harford, our Chief Financial Officer.

We're pleased to be here today to update you on our progress during our first quarter 2019 and our outlook for the year. This year we are focused on the following: Number one, advancing toward the potential approval and launch of odevixibat in its first indication in patients with progressive intrahepatic cholestasis or PFIC. Number two, developing odevixibat into a pediatric cholestasis medicine with the potential to benefit people across multiple cholestatic liver diseases. Number three, moving the NASH program into the clinical phase with elobixibat trial as a first step. And we're pleased with our progress on all three fronts.

So beginning with odevixibat in PFIC, we're delivering on our commitments to continue to move towards potential commercialization. You may notice, I'm no longer referring to A4250. When I talk about our investigational product candidate in PFIC. Odevixibat has now been published in the WHO drug information as the recommended international name for A4250.

So we continue to make progress in the PEDFIC program. Our Phase III program studying odevixibat in PFIC, the PEDFIC program consist of PEDFIC 1, a single randomized double blind placebo controlled multi-center clinical trial designed to enroll approximately 60 patients with PFIC Type 1 or Type 2.

And PEDFIC 2, an open label extension study designed to assess long-term safety and durability of response. PEDFIC 1 continues to enroll patients with 43 clinical trial site activities as of May 1. We anticipate topline results by late 2019 or early 2020 with the potential approval and launch in the first half of 2021. When the trial is fully enrolled, we plan to make an announcement and refine our guidance further.

PFIC is an ultra rare disease, and as expected the timing of the topline results is highly dependent upon when the last few patients are enrolled. We previously stated our commitment to generating additional data to build a pediatric liver franchise with odevixibat.

In the first quarter, we began efforts to expand the body of data we will have to support Odevixibat following the completion of the PEDFIC program by opening PEDFIC 2 to additional patient types. We believe odevixibat could benefit a wide range of patients with PFIC.

For PEDFIC 2, our long-term open label extension study, we submitted a protocol amendment for an additional cohort that would include PFIC patients who have elevated serum bile acids and pruritus aren't eligible for PEDFIC 1. That includes people with all types of PFIC along with patients over the age of 18, and younger than six months. We anticipate initiation of this additional cohort in the second half of the year.

We expect this expanded cohort will strengthen our inside it odevixibat potential to address unmet need across a wide range of patients. The PEDFIC program remains our highest priority and as we continue to deliver on the clinical front, we've been building our commercial foundation. Our approach has been to advance activities that could be rate limiting early on and then accelerate our buildup when we have pivotal data.

We have a strong [Audio Gap] the FDA Grants odevixibat orphan drug designation in biliary atresia. We now hold orphan designation in both the U.S. and the EU for odevixibat in biliary atresia. Encouraging feedback from the regulatory agencies have informed our approach in structuring the pivotal trial which we plan to initiate in the second half of this year. We will provide more details on the trial design when it's finalized.

We continue to present important data on odevixibat at major scientific conferences. At the European Association for the Study of Liver Annual Conference held in April in Vienna, we presented data from our Phase II trial in pediatric cholestasis that shows reductions in serum bile acids, in biliary atresia alagille syndrome patients treated with odevixibat.

We were honored to have the presentation in odevixibat in patients with alagille syndromes selected for inclusion in the best of International Liver Conference. Well based on a small number of patients in our Phase II study, these results further reinforce our belief in the potential of odevixibat to treat a wide range of cholestatic liver diseases.

Now also during the EASL Congress, the academic consortium NAPPED, which stands for the Natural Course and Prognosis of PFIC and Effect of biliary Diversion presented new data in the natural history of PFIC. NAPPED is the world's largest PFIC database with retrospective data in over 500 patients. In the natural history of PFIC, patients usually go on to the virgin surgery to divert bile acids and improve pruritus. The NAPPED group presented data on PEDFIC 2 patients that demonstrated that surgical diversion of bile acids is associated with improved native liver survival, decreases in bilirubin, liver transaminases and improvement in pruritus for mild to moderate genotypes.

Notably, the NAPPED showed that patients did not need to have their bile acid levels normalize to have an impact on native liver survival. NAPPED reported that lowering serum bile acids to 118 micromoles per liter or a reduction of 70% is associated with favorable native liver survival outcomes. This is really important information as we are developing odevixibat to provide both symptomatic relief and disease modification.

Note that in the odevixibat, PEDFIC 1 trial are responders to find as reaching a bile acid level of 70 micromoles per liter or having a reduction of 70%. Albireo is one of the sponsors of NAPPED through an unrestricted grant.

So as you can see, we made excellent progress with odevixibat, including continued enrollment of the PEDFIC 1 Phase III study, the announcement that will study a wider arrange of PFIC patients in PEDFIC 2, and that continued progress in initiating a second pivotal program in biliary atresia.

Finally, our NASH program continues to build momentum, which we believe also we will create major partnering opportunities. NASH is a common and serious, and sometimes fatal chronic disease that resembles alcoholic liver disease, but occurs in patients who drink little or no alcohol.

We estimate that NASH effect 2% to 3.5% of adult representing over 9 million people in United States and 10 million people in the European Union. There are currently no drugs approved for the treatment of NASH. Bile acid modulation has a strong rationale in NASH. Elevated bile acids levels are one of the markers in NASH patients.

Additionally, we have clinical data with elobixibat showing that improved cholesterol profiles and increased levels of GLP-1, which is going to approve it in insulin sensitivity in dyslipidemia and chronic constipation patients and preclinical data demonstrating a reduction of pro-inflammatory markers and improve it in fibrotic markers.

From a safety standpoint, elobixibat or IBAT inhibitor, which is approved in Japan to treat chronic constipation, has a safety database with more than 1,500 exposures.

Given the novel mechanism, we believe that elobixibat and our preclinical compound has the potential to find a significant place in this emerging national landscape as monotherapy or potentially combination therapy.

We plan to begin to Phase II multi-center placebo controlled trial for elobixibat in NASH this quarter and are pleased to report that we receive clearance with the FDA or IND. We've designed the study to enroll 46 patients with biopsy-confirmed NASH or a diagnosis of expected NAFLD or NASH based on Metabolic Syndrome definitions.

We will enroll patients with LDL greater than 130 makes per deciliter or greater than a 110 makes per deciliter, if they're already on lipid lowering medication. And with a greater than or equal to 10% liver fat on MRI. The study will compare elobixibat dosage five-milligram once daily over 16 weeks versus placebo.

The primary endpoint will be changed from baseline in LDLC. Secondary endpoints include liver fat by imaging ALT, AST and serum bile acid levels. Exploratory endpoints will include measures of glucose in the insulin homeostasis, biomarkers for inflammation fibrosis. The study is designed as consistent with recent guidance from the FDA on NASH studies and we will really provide valuable insights on the impact of our IBAT inhibitor elobixibat on NASH.

We continue to believe NASH is fundamentally a metabolic disease and our approach is based on showing a cumulative impact across multiple parameters versus a significant impact on one measure. We expect topline data mid-2020.

Before turning over to Simon for a financial update, I want to take the opportunity to welcome Pamela Stephenson, as our new CCO. Pamela brings an outstanding commercial pedigree to Albireo having spent around a decade at Pfizer and another decade at Vertex through a period of significant growth.

In leadership roles at Vertex, she led commercial strategy in operations and drove the successful launch of a rare disease therapy. She has held senior roles in Marketing, Sales and Patient Services and her last role at Vertex was Head of Global Access & Value, where was she was responsible for marketed and pipeline products.

Now given the increasing scrutiny on orphan drug pricing and access, Pamela's recent launch experience should be absolutely invaluable. We're delighted to have attracted Pamela to Albireo, as she will be a key driver in building the company and preparing us to launch odevixibat successfully.

So now it's my pleasure to turn the call over to Simon for a financial update. Simon?

Simon Harford

Thank you, Ron. Let me quickly highlight our financial results for the first quarter 2019 ended March 31, which we released earlier today. We closed the first quarter with a balance of $150.3 million in cash and cash equivalents compared to $163.9 million at December 31, 2018.

Our cash balance reduced by $13.6 million during the quarter primarily as a result of costs related to our PEDFIC 1 Phase III trial, as well as people related expenses. Our revenue was 570,000 for the first quarter ended March 31, 2019 compared to revenue of $11.2 million in the same period last year.

Revenue during Q1 this year was related to ongoing royalties related to elobixibat sales in Japan from our partner EA Pharma which are ultimately passed on to our royalty partner HCR. Last year in the same period we received a one-off milestone payment from EA Pharma for the approval of elobixibat for chronic constipation by the Japanese MHLW.

Our research and development expenses for the first quarter 2019 were $8.3 million compared to $6.2 million in the first quarter of 2018. R&D expenses in Q1 were primarily driven by headcount additions to support activities related to odevixibat, as well as programs spend related to our preclinical and elobixibat, NASH programs.

Our G&A expenses for the first quarter of 2019 were $5.3 million compared to $4.1 million in the prior year period. The increase in G&A expenses was principally attributable to headcount additions to support the Company's strategy.

Net loss for the first quarter ended March 31, 2019 was $16.7 million or a loss of $1.39 per share compared to a net loss of $1.6 million or a loss of $0.15 per share in the first quarter of 2018.

Based on our current operating plans, we anticipate our total operating expenses including R&D and G&A expenses for 2019 to be in the range of $75 million to $80 million consistent with what we have said previously. We anticipate our current cash balance to be sufficient to meet our operating needs into 2021.

And with that, let me turn the call back over to Ron for closing remarks.

Ronald Cooper

Great. Thank you, Simon. So to summarize, this is an exciting time for Albireo as we're getting closer to odevixibat Phase III completion and topline data. Our plan has always been to develop odevixibat into a leading product for multiple pediatric liver diseases and we're excited to begin generating data in additional PFIC types and starting a trial in one of the largest pediatric cholestatic liver diseases biliary atresia.

We're also accelerating multiple programs to help realize the even greater potential of our bile acid modulation platform beginning our Phase II study with elobixibat, Nash and accelerating our preclinical compounds. Our organization continues to grow with key hires as we prepare for commercialization.

So with that, we'll open up the call to questions. Operator?

Question-and-Answer Session

Operator

Thank you. We’ll now be conducting a question-and-answer session. [Operator Instructions] Our first question comes from the line of Ritu Baral with Cowen. Please proceed with your question.

Ritu Baral

Good morning, guys. Thanks for taking the question and thanks for the help getting into the queue. I wanted to ask about the commercialization strategy that Ron you very briefly touched on. Forgive me if I misheard. I think you said that you were targeting about 500 herpetologists that may have gotten that number wrong. Can you elaborate a little bit are those pediatric herpetologist and how do you find them. Are they in like a certain number of centers of excellence? How are you mapping the prescribing physician population? And then I have a follow-up on the NASH trial.

Ronald Cooper

Great. Good morning, Ritu and thanks very much for the question. I think in my prepared comments the first thing to note is that we're pretty serious about our commercialization strategy. We're trying to make sure that anything that is rate limiting to a good launch is being taken care of and part of that is making sure we have the right team, and as I noted we're delighted to have Pamela Stephenson joined us as our Chief Commercial Officer.

Now when we think about the actual targets, we estimate in the U.S. there are about 100 pediatric herpetologists and in Europe there an equivalent number. And the way to think about them from a geographic perspective really is sort of NFL cities, right. So they are in tertiary medical centers in the U.S. and in Europe as well. So we believe that we could access these individuals with a relatively small field force, we're estimating somewhere between 15 to 25 field deployed individuals.

Ritu Baral

Got it. And do you have those tertiary centers identified, how many there are and is there like a second tier that there is ROI in targeting after those 100? Initial thoughts to understand.

Ronald Cooper

Of course here we would have, we call our A targets and then our B targets. When you think of those tertiary centers you really almost have to think about the sites that we have for the PEDFIC 1 study. So I think that, we announced that we've achieved our target level of sites for the PEDFIC 1 study, we've activated 43 sites and that pretty much covers the majority of them. But then there will be some B targets as well. We estimate somewhere between a 1,000 to 1,500 B targets, because they're a group of individuals that are pediatric, gastro, hematology in that mix right. And we would estimate there's probably something similar in Europe as well.

Ritu Baral

Very helpful. And then in your NASH study, how are you defining the diagnosis of NAFLD. And is there any desired breakdown between enrollment of biopsy confirmed NASH patients versus those NAFLD patients by your clinical team in order to give you a robust enough signal – to get you what you need to design a Phase III?

Patrick Horn

Yes. So this is Pat. Again, so we have based the design of our NASH study on the latest FDA guidance and we're looking at in the early prove-of-concept. So we are looking at patients with NAFLD and NASH, and/or NASH. NAFLD is defined as meeting having the diagnosis of metabolic disease based on an elevated glucose or decreased glucose tolerance and hypoglycemia and its traditional characteristics or they could have biopsy confirmed NASH.

In this proof-of-concept study, we have said that our primary efficacy endpoint will be the long and LDL cholesterol that we don't have a set distribution for an NAFLD and NASH. We anticipate that the majority would find NAFLD rather than NASH themselves just not requiring a biopsy is expected to enhance enrollment. I should also say that in addition to meeting the metabolic criteria there is a specified amount of hepatic fat that is required to treat criteria.

Ritu Baral

Last question just mechanisticly based on other drugs in the class. What are your expectations around the move in LDL in this study?

Patrick Horn

So we have seen and we have looked at odevixibat previously in patients with hyperlipidemia and even in the chronic constipation and even in some healthy volunteers. We consistently see a lowering in LDL cholesterol, and that's what we anticipate here.

Ritu Baral

Got it. Thanks for taking all the questions.

Ronald Cooper

So you are welcome. I think the way that we think about the efficacy, IBAT inhibitor like elobixibat in NASH, we're not looking for an effect on one parameter at significant effect, but we're excited about the potential to have an effect on multiple parameters including LDL, including GLP-1, liver fibrosis, liver inflammation and other things. So thank you for your questions. We do appreciate it.

Operator

Thank you. Our next question comes from the line of Liana Moussatos with Wedbush Securities. Please proceed with your question.

Liana Moussatos

Thank you for taking my questions. It's perhaps to do with the design of PEDFIC 2. You're going to have rollover from PEDFIC 1 and then the second cohort it has ages – are you going to exclude PEDFIC 1 profile patients in PEDFIC 2 and the additional types of PFIC and how are they going to be treated like in PEDFIC 1 and then followed like in PEDFIC 2 or how is that going to work. And do you have a certain mix of patients overall in terms of [P6] type that in you're targeting for PEDFIC 2?

Ronald Cooper

Yes. Good morning, Liana. Thanks very much for the question. Let me start with a few comments, then I'll hand it over to Pat to kind of go through some of the details your question. I think we're pretty excited about starting this second cohort and start of the second cohort really fits with our overall belief of trying to build a pediatric liver disease franchise.

We made commitments before that we'll continue to generate data across multiple patient types and based on the feedback that we've received from our investigators and key opinion leaders are pretty excited about the potential to enroll a variety of patients and generate data.

And maybe Pat, you can speak little more specifically to Liana's question.

Patrick Horn

Yes. So if you look at the two studies, PEDFIC 1 and PEDFIC 2, PEDFIC 1 is six months and PEDFIC 2 is 18 months. But the initial six month of PEDFIC 2 are exactly like PEDFIC 1. So that patients who enroll directly in PEDFIC 2 will in fact have all of the procedures that they would have had with they enrolled in PEDFIC 1. So that answer is that. So we will be able to collect similar information across and even be able to – make something although a separate studies we will be able to draw some comparisons to the placebo group that is in PEDFIC 1.

So the study design actually allows us to really gather a lot of rich data from the people who are going to include. We opened up and the analysis will still be – they'll be separated by cohort. So the original analysis we are going to do on occasion to roll from PEDFIC 1 into Cohort 1 will be the same in the Cohort 2 is really good additional information.

And it was based on the desire for the investigators and for us to really understand, what is the potential range of odevixibat in the use in PEDFIC? So we're going to include – our hope is we can include a lot of the different types of PEDFIC predominately PEDFIC 2 that maybe even more kind of some of the even rarer disease causes the PEDFIC, but a lot of that will depend on the randomization and who is available.

Patients who are eligible, while PEDFIC 1 is still open, patients who are eligible to enroll in PEDFIC 1 will not enroll into PEDFIC 2. They'll go directly into PEDFIC 1 but then after PEDFIC 1 in closes. Some of those patients might be eligible to enroll into Cohort 2. We don't have a set cap on the number of patients. We want to kind of wait and see as we go – who is going to enroll and what the range we're going to see is.

Ronald Cooper

So, Liana we're pretty excited that they think that, you recall PEDFIC 1 studies PEDFIC 1, PFIC one and two patients, but there's also a wide range of other patients, other types of PFIC, other ages and other circumstance those patients that they wouldn't qualify for our original studies. So we're excited to generate some data in these patients.

Liana Moussatos

Thank you very much. Very helpful.

Operator

Thank you. Our next question comes from the line of Yasmeen Rahimi with ROTH. Please proceed with your question.

Yasmeen Rahimi

Hi, team congrats on continued progress. I have three questions. Maybe we can start off on team. Can you remind us again what elements of your trial design in PFIC insurers to minimize the placebo reported provided?

Patrick Horn

Yes. This is Pat. So you know in provide us with all of the most subjective measurements there is the possibility of placebo response. I think there are couple of things here in that we have a six-month study. So typically when you see a placebo response it's early in the course and the longer a patient goes. They realize it or maybe they work better. And in their private score tends to go up. And if you look at the previously reported studies you actually see that. So that's one of the big things in terms of private.

I think the other thing is that we really took large placebo in response - we took a large placebo response into consideration, when we did the power calculations for the study. So we assumed a relatively large placebo response and even a relatively smaller than we actually expected response in the active drug when we did our power calculation.

Ronald Cooper

I think that we understand that there's variability with these patients. We has been and I think as Pat has indicated, those are two key elements. You have a length of time and are powering assumptions which we've stated is over 18%. And as well, we have a tool that has been tested in these patients, in these parent rates. And so we're hopeful with that tool will as well help us to differentiate patients.

Yasmeen Rahimi

Thank you team. For moving on to the second question. I noticed in the filing that you had filed a complaint or litigation against barring international for compensatory damages of €37 million? Can you give us a little bit more color on this and maybe an update?

Ronald Cooper

Yes. Thanks for the question, Yasmeen. I think, I expect this comment enrolled and what we've said within just queue. So I would ask you to refer to the queue, but we have filed a complaint with a number of claims arising under the license agreement we had with barring €37 million. Our legal fees are on contingency at 33 in a third for any potential reward. And we'll update you with more information.

Yasmeen Rahimi

Thank you, Ron. And then maybe a last question, can you tell us a little bit more in regards to the recent discussions that you had with the EMA and FDA in regards to biliary atresia, maybe a tiny come up inclination on the update on this program and where it's headed or at least tell us is this the way the guidance is different between EMA versus the FDA and what it's similar and what could be different to the extent that you can?

Simon Harford

Yes. So this is the interesting thing. So in these rare diseases where they really haven't been registration studies there are no guidance. So each of the agencies is working through this on their own and we are having talks with both agencies. They're separate but parallel talks. And so we are trying to get the agencies to come to the same place and as you would expect really that the key discussion is hinging on endpoints and what the different agencies consider acceptable registration endpoints.

In addition we're having ongoing discussions with the KOLs and what the clinicians will consider acceptable endpoint. So we're narrowing it down, we’re focusing was getting them towards the same place. Whether we'll be able to actually get to the same place its kind of an unknown. For example in the PFIC program, the EMA has a different endpoint in the FDA, and it's entirely possible we could end up in a similar situation. There is just unknown. And we really can't comment on the ongoing discussions until we have kind of some final decision.

Ronald Cooper

Surprise to say them from a chrome perspective, the enthusiasm for the regulatory process is pretty high. The unmet need in biliary atresia is significant, data suggest is for number one cause of the transplants in the pediatric population. 80% of those patients require a liver transplant within their first couple of decades of life. So we hope to be able to make a difference with these patients and [indiscernible] discussions that we're having with our agents.

Yasmeen Rahimi

Thank you for taking my question.

Ronald Cooper

Yes. Yasmeen.

Operator

Thank you. Our next question comes from the line of Kyung Yang with Jefferies. Please proceed with your question.

Kyung Yang

Thank you. So in the PEDFIC 1 open label extension study for the patients who are rolling over from the randomized phase, what doses are being utilized for there?

Ronald Cooper

So it's PEDFIC 2 that the open label extension and patients who roll from PEDFIC 1 to PEDFIC 2 in fact all patients who enter PEDFIC 2 the open label extension will be treated with the higher dose, the 120 micrograms per kilogram per day.

Kyung Yang

I see. Can you comment on how many patients are from PEDFIC 1 has been transition to the open label extension by now?

Ronald Cooper

So we haven't talked about the ongoing status of our studies or where we're at.

Kyung Yang

Okay, all right.

Patrick Horn

We do have [indiscernible] so that the trial is up and running and working more.

Kyung Yang

Okay. And then PEDFIC 1, can you talk about what the powering assumptions are? And also based on the nature of history study, what do you expect the placebo rate to be?

Patrick Horn

Okay. So those are kind of separate questions. So from the natural history data there really is no placebo data. Because these are all patients with PEDFIC who have had really pretty much no therapeutic intervention it's just the natural history. So the placebo information we have comes from similar studies.

Again there haven't really been many studies in PEDFIC, but if you look at some of the other pediatric cholestatic liver diseases that have had therapeutic intervention you can give a sense of what the placebo response would be on that one. So that's kind of where we got our information on the magnitude of the placebo response. Like I said when we did our powering assumptions in our power our sample size calculation we assumed the larger size of the placebo response.

In terms of the powering assumptions. As you recall there are different primary endpoints in the two regions. So the U.S. its pruritus and in the EU it is bile acids. So when we did the power calculations for pruritus and we have a power as we said above 80%. Then that means that the power calculations for the endpoint of serum bile acid is actually much higher.

Ronald Cooper

So Kyung, and just to add to what Pat said from the natural history. We only have bile acid data from that and the NAPPED consortium presented an interesting data at the recent European Liver Meeting, where they demonstrated – they share data that said that if you were able to reduce your bile acids below 118 and/or you had a reduction of 70% or greater. That was associated with positive outcomes and more favorable outcomes and you might recall the responder definition in our PEDFIC 1 study for the bile acid endpoint is to reach a level of 70% or to have a reduction of 70%.

Kyung Yang

Thanks very much.

Ronald Cooper

Thank you, Kyung.

Operator

Thank you. Our next question comes from the line of Tim Lugo with William Blair. Please proceed with your question.

Timothy Lugo

Thanks for taking the question. And maybe you touched upon the Kyung question, but for the additional cohort in PEDFIC 2 are all those patients at the high dose even a neonate. And reading the tea leaves a bit that suggests you're happy with the safety you're seeing so far in PEDFIC 1 blinded data.

Patrick Horn

So all patients who enroll in PEDFIC 2 will get the higher dose. And we really – the other study is ongoing and blinded and we don't really talked about that and know much about it.

Ronald Cooper

I think for the neonates, remember this is a per kilogram dose right. So the 120 is adjusted for whatever the weight is.

Timothy Lugo

Understood and could you generally talk about site conduct in PEDFIC 1 today, obviously it's a rare disease, you have 43 sites open. Are you seeing enrollment fairly broadly around those 43 sites that's kind of one or two each or are there kind of stand out and in general the site conduct of those 43 sites?

Ronald Cooper

The one thing about PFIC versus other diseases of consanguinity right, some of the other cholestatic diseases you aren't on. So as a result there are some clusters of geographies where there are patients, where there's the practice more consanguinity. So some of the sites, there are as you would expect a larger group of patients whereas others it is a lower amount, so it's a bit uneven across the sites.

Timothy Lugo

Okay and for the expanded cohort for PEDFIC-2 is that a decision that you think will support a relatively broad label for elobixibat and in general can you just talk about the breadth of a label in the rare diseases things like labels tend to be broad whereas your liver disease they could be a little more focused on subtypes.

Ronald Cooper

Hard to say at this stage, I think that what our job is to generate as much data as possible in multiple different formats and we'll share that data with the agency once we have the results of PEDFIC 1 and then we'll have discussions with them.

Timothy Lugo

Understood. Thank you for the question.

Ronald Cooper

Thanks, Tim

Operator

Thank you. Our next question comes from the line of Matt Kaplan with Ladenburg Thalmann. Please proceed with your question.

Matthew Kaplan

Hi. Good morning guys. Thanks for taking questions. I wanted to zero in a little bit on your preparations for the NDA for elobixibat and I guess where are you with respect to manufacturing and then preclinical tox package and then I guess a question on PEDFIC-2 with respect to I guess the long-term safety data requirements that are necessary for the NDA filing.

Ronald Cooper

So why don’t you start with the second question, and then I'll take the first one, Pat.

Patrick Horn

Okay. Yes. So again we have the two studies ongoing in our discussion with the FDA. They have said that positive results from PEDFIC 1 study by itself would be sufficient to support an application. So the open label extension is really a chance to get long-term data and do that, but it's not a requirement for the initial application.

Ronald Cooper

And then in terms of readiness you as it should be the PEDFIC 1 study is the leading factor to our filing. So that's good news. So that means that some of the long talks – the long-term doc study that are needed for all drugs are already up and going. And they are on schedule from a CMC perspective we had a dialogue with the FDA late last year and agreed on a plan going forward.

The beauty of odevixibat it's the same supply chain that we've used for elobixibat and for elobixibat we've been able to go to commercial quality and commercial scale. So we're pretty confident our ability to get there. So like I said at the very beginning, the good thing and the way it should be its PEDFIC 1 data that is gating factor and we're looking forward to having that data at the end of this year early 2020.

Matthew Kaplan

Great. That's helpful. And then for the Phase II study in NASH and NAFLD for odevixibat primary endpointing chance in LDL. Can you give us a sense in terms of what you're targeting, in terms of entry criteria for LDL?

Ronald Cooper

So we haven't made, I don't think – I think it's on clinical trials that go into criteria should be on there. And to tell you the truth, I can't remember off the top of my head, but I believe its 130?

Patrick Horn

Yes. I believe its 130 – IBAT 130, and then if they have a [indiscernible] lowering agent with 110.

Matthew Kaplan

Okay. Thanks for taking the questions.

Patrick Horn

Thank you, Matt.

Operator

Thank you. Our next question comes from the line of Alan Carr with Needham and Company. Please proceed with your question.

Joseph Stringer

Hi, guys. This is Joe on for Alan. Congrats on the progress and thanks for taking our questions. What's the target number of sites for PEDFIC 1?

Ronald Cooper

We've guided Joe from – I think our guidance was 35 to 45. So we've achieved that having reached 43 sites and I think there's still a site or two that we're looking to finalize.

Joseph Stringer

Okay. Thanks. And just to clarify for PEDFIC 2, the protocol amendment to those patients to the PFIC patients have to be – will they be genotypes or is it just based on serum bile acid levels for in terms of inclusion into that. And would you be including any sort of symptomatic brick patients or anything like that?

Ronald Cooper

So the patients do have to be genotypes and we have to demonstrate that they have some type of PFIC and but it includes all of the types of PEDFIC, BRIC patients won't be included in that study. And that's because the episodic nature of their symptoms and their disease makes it very difficult to study in this current study design.

Joseph Stringer

Okay. Last question in terms of the types of docs that biliary atresia patients and in PFIC patients see. Is there a large overlap in terms of the – do they both see pediatric hepatologists and could you potentially see some side of overlap and PEDFIC 1 and 2 and the biliary atresia trial. Thanks.

Ronald Cooper

Thanks Joe. Yes I think that's one of the beauties is odevixibat and a desire to build that as a pediatric liver franchise, diseases such as Alagille syndrome, biliary atresia, PSC and PFIC and other diseases are treated by the same position that's predominantly treated by the same position in the pediatric hepatologist. So we believe we have tremendous synergy across the different indications as we call on these physicians and engage them with our company.

Thanks for your question Joe.

Operator

Thank you. Our next question comes from the line of Ed Arce with H.C. Wainwright. Please proceed with your question.

Ed Arce

Hi, Ron. Thanks for taking my questions. So I just wanted to ask slightly different question around PFIC 2 obviously than the new announcement this morning is around this second additional cohort and you mentioned that it could include adults in neonatal and perhaps beyond PFIC 1 and even beyond PFIC 2. Could other be other types of a PFIC, so I'm wondering as this was recently added as a second additional cohort, what discussions with the agency drove the decision to add this and what was the thinking behind ultimately how this impacts your label?

Ronald Cooper

Ed, good morning. Thanks very much for the question. It's actually not a prompting from the agency as much as the prompting from working with our investigators and the key opinion leaders, I think they're pretty excited about the potential of odevixibat in pediatric cholestatic liver diseases. I think that they are pleased to have a trial up and going for PFIC 1 patients, but I think they wanted to help other patients as well.

And so we're working very closely with our investigators and based on that dialogue and that feedback, we made the decision to open up a second cohort to help them with our patients because it becomes a therapeutic option where these children do not have an option right now. But also to fulfill our commitment to being a leading player in this space to build odevixibat into a pediatric liver franchise and to generate additional data to help us through the approval process and getting insights on odevixibat.

Ed Arce

Okay. That's helpful. Thanks. And then turning to your NASH program which is about to start up here in this quarter. Obviously, you’ve mentioned a couple of times the primary endpoint is LDL reductions and this is consistent with the FDA guidance recently put out for these earlier stage trials in NASH. I'm curious if you could expand upon your earlier comment that as opposed to robust or really deep effects or responses in one or two key measures that you expect elobixibat to accumulate impact in this disease across multiple measures, how do you see that differentiating elobixibat perhaps for either partnering and/or ultimately combination studies?

Ronald Cooper

Thanks, Ed. I think that's why we're really excited about our approach in NASH between elobixibat in [indiscernible] we have a two pronged approach here. We think that there is both an unmet medical need from efficacy standpoint and an unmet medical need from a convenience standpoint understanding that this is “asymptomatic disease”. So on the efficacy part of this, we think we know that patients who have NASH have elevated bile acids and have a problem with cholesterol, have a problem with glucose transport, problem with liver information and liver fibrosis.

And the beauty is that with our IBAT inhibitors, we've generated some clinical and preclinical data on all those parameters. So we believe that we can have an impact on multiple parameters unlike some of the other offerings that are out there now. So that's one aspect, but that's – the convenience aspect of it, elobixibat is once a day product, it has very little systemic effects right.

So most of these side effects are within the GI aspect itself and being that it has very little systemic exposure we believe it combines quite nicely with other cardiovascular drugs or potentially other NASH drugs because I think we believe that there may be some poly pharmacy there.

So the combination of multiple effects on multiple NASH parameters and the convenience of a once a day product that is non-systemic that could co-travel with others, I think it makes our offerings of elobixibat in potentially some of our other preclinical compounds kind of interesting in exciting in the NASH space.

Ed Arce

That's great. Thanks again. And then perhaps just one last question sort of big picture here as you progress and approach your first pivotal study PFIC and now excited to be moving forward and expanding FDA and ultimately I would expect over the next couple of years as you've stated multiple times – ultimately looking at a disease franchise based on odevixibat.

And you had mentioned at the beginning in your prepared remarks, you're very much focused on brand strategy in the commercial plan. So as you think about these potentially multiple indications, how does that inform and how does that work with your building out your strategy and plan?

Ronald Cooper

Thanks Ed, for the question. I think that's sort of the beauty of having a product that has multiple uses across multiple diseases right across cholestatic liver diseases, but also as I stated earlier that are managed by the same physician right and so we're developing stronger relationships with pediatric hepatologists and I think we're going to be excited to provide some initial data in PFIC and then additional data and other indications to build a very strong brand and a strong pediatric liver franchise with elobixibat.

Ed Arce

Great. Thanks again. Appreciate it.

Operator

Thank you. We have reached the end of our question-and-answer session. I would like to turn the call back over to Mr. Cooper for any closing remarks.

Ronald Cooper

Great. Thank you, operator. First of all, I'd like to thank everybody for tuning into our call today. You might note that we've changed the time of our call from earlier in the day till 10 o’clock based on some feedback. So we'd love to hear from you whether that works better for you or not.

And just to close by saying that it's a special time at Albireo. We continue to execute on our plan and deliver on our commitments. And we're looking forward to generating additional data to grow the company over time. Thanks very much. Have a great day.

Operator

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation and have a wonderful day.

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