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Albireo Pharma, Inc. (ALBO)
Q1Â 2019 Earnings Call
May. 9, 2019, 10:00 a.m. ET
Contents:
- Prepared Remarks
- Questions and Answers
- Call Participants
Prepared Remarks:
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 J. Arndt -- Investor Relations
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 31st, 2019. This press release is accessible via the Company's website at, www.albireopharma.com.
Before proceeding, let me mention that comments 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 3 trial of odevixibat in patients with PFIC, planned pivotal trial for odevixibat in biliary atresia, planned Phase 2 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 reimbursements, 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 operations, 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?
Ron Cooper -- President and Chief Executive Officer
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 disease; number three, moving the NASH program into the clinical phase with an 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 toward 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 a recommended international name for A4250.
So we continue to make progress in the PEDFIC program, our Phase 3 program studying odevixibat in PFIC. The PEDFIC program consists of: PEDFIC-1, a single randomized, double-blind, placebo controlled, multi-center clinical trial designed to enroll approximately 60 patients with PEDFIC 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 sites activities as of May 1. We anticipate top line 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 top line 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 acid levels and
pruritus but 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 insight init odevixibat's 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 build up when we have pivotal data. We have a strong foundation of commercial strategy in place including our brand strategy and commercialization plant, as well as initial planning for market access and patient support.
Our new Chief Commercial Officer and our Head of Marketing, both have extensive rare disease and launch experience. We believe there are approximately 100 key pediatric hepatologists in the US and a similar number in Europe. And we will need a relatively small field force to reach these key customers.
Moving to our program in biliary atresia, we are extremely excited to advance odevixibat as a potential treatment for a second rare pediatric liver disease with dire unmet medical need. We estimate biliary atresia to be one of the most common rare pediatric liver diseases with roughly 15,000 to 20,000 patients in the US and EU combined. Patients with biliary atresia have absent extra hepatic bile ducts and are unable to move bile from the liver to the intestine.
Virtually, all of these patients, these children are easily diagnosed in the first months of life. There stools are grey colored or not colored at all. Though after biochemical work-up and ultrasound, biliary atresia is confirmed and the child immediately undergoes a Kasai procedure. During this surgery the surgeon connects open small bile ducts to the liver directly to the small intestine. This provides a path that can restore bile flow and allow bile to drain from the liver.
A Kasai procedure is usually performed in the first 30 to 90 days of life. Despite undergoing a Kasai procedure about 80% of patients currently still require liver transplant within their first two decades of life. There is no approved pharmacologic treatment. Biliary atresia is clearly an area of high unmet need and odevixibat could potentially lower bile acids and be the first pharmacologic treatment that slows ongoing damage to the liver.
In Q1, the FDA granted odevixibat orphan drug designation for biliary atresia. We now hold orphan designations in both the US and the EU for odevixibat in biliary atresia. (inaudible) 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 2 trial in pediatric cholestasis that shows reductions in serum bile acids in biliary atresia and Alagille syndrome patients treated with odevixibat.
We were honored to have the presentation on odevixibat in patients with Alagille syndrome selected for inclusion in the best of international liver conference. While based on a small number of patients in our Phase 2 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 on 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 onto divergent surgery to divert bile acids and improve pruritus. The NAPPED group presented data on PFIC-2 patients that demonstrated that surgical diversion of bile acids is associated with improved need of liver survival, deceases in bilirubin, liver transaminase, and improvement in pruritus from mild to moderate genotypes.
Notably, the NAPPED data showed that patients did not need to have their bile acid levels normalized to have an impact on native liver survival. NAPPED reported that lowering serum bile acids to 118 micromoles per liter or a reduction of 17% is associated with favorable need of 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, a responder is defined as reaching a bile acid level of 70 micromoles per liter or having a reduction of 17%. Albireo is one of the sponsors of NAPPED through an unrestricted grant.
So, as you can see, we've made excellent progress with odevixibat, including continued enrollment of the PEDFIC-1 Phase 3 study, the announcement that we will study a wider range of PFIC patients in PEDFIC-2 and the continued progress in initiating a second pivotal program in biliary atresia.
Finally, our NASH program continues to build momentum, which we believe ultimately 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 affects 2% to 3.5% of adults, 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 acid 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 linked to improvement in insulin sensitivity in dyslipidemic and chronic constipation patients and pre-clinical data demonstrating a reduction of pro-inflammatory makers and improvement in fibrotic markers.
From a safety standpoint elobixibat, our 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 pre-clinical compounds have the potential to find a significant place in this emerging NASH landscape as monotherapy or potential combination therapy.
We planned to begin a Phase 2 multi-center placebo control trial for elobixibat in NASH this quarter and are pleased to report that we've received clearance from the FDA for our IND. We've designed the study to enroll 46 patients with biopsy confirmed NASH or a diagnosis of suspected NAFLD or NASH-based on metabolic syndrome definitions. We will enroll patients with LDL greater than a 130 mgs per deciliter or greater than 110 mgs per deciliter if they are already on lipid lowering medication, and with a greater than or equal to 10% liver fat on MRI.
The study will compare elobixibat dose at 5 milligram once daily over 16 weeks versus placebo. The primary endpoint will be changed from baseline in LDL-C, secondary endpoints include liver fat by imaging ALT, AST and serum bile acid levels. Exploratory endpoints will include measures of glucose and the insulin homeostasis biomarkers for inflammation and fibrosis. The study is design is consistent with recent guidance from the FDA on NASH studies and 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 top line data mid-2020.
Before turning it to over 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 and operations and drove the successful launch of a rare disease therapy. She has held senior roles in marketing, sales and patient services. In her last role at Vertex was Head of Global Access and Value, where 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 -- Chief Financial Officer
Thank you, Ron. Let me quickly highlight our financial results for the first quarter 2019 ended March 31st, 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 31st, 2018. Our cash balance reduced by $13.6 million during the quarter, primarily as a result of costs related to our PEDFIC-1 Phase 3 trial, as well as people related expenses.
Our revenue was $570,000 for the first quarter ended March 31st, 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 pre-clinical 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 31st, 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.
Ron Cooper -- President and Chief Executive Officer
Great. Thank you, Simon. So to summarize, this is an exciting time for Albireo as we're getting closer to odevixibat Phase 3 completion and top line 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 cholestastic liver diseases, biliary atresia.
We're also accelerating multiple programs to help realize the even greater potential of our bile acid modulation platform, beginning a Phase 2 study with elobixibat in NASH and accelerating our pre-clinical 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?
Questions and Answers:
Operator
Thank you. We will 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 -- Cowen -- Analyst
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 hepatologists. I may have gotten that number wrong. Can you elaborate a little bit, are those pediatric hepatologists? 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 draft.
Ron Cooper -- President and Chief Executive Officer
Right. 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. And 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 join us as our Chief Commercial Officer.
Now, when we think about the actual targets, we estimate, in the US, there are about 100 pediatric hepatologists and in Europe there an equivalent number. And the way to think about them from a geographic perspective really is, NFL cities right. So they are in tertiary medical centers in the US 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 -- Cowen -- Analyst
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 I understand?
Ron Cooper -- President and Chief Executive Officer
Of course, we would have what we call our A targets and our B targets. But 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 there are a group of individuals that are pediatric gastro, hepatology in that mix right. And we would estimate there's probably something similar in Europe as well.
Ritu Baral -- Cowen -- Analyst
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 3?
Patrick Horn -- Chief Medical Officer
Yes. So, this is Pat. Again, so we have based the design of our NASH study on latest FDA guidance and we're looking at in the early -- the early proof-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 look into be hyperlipidemia and 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 (Technical Difficulty) LDL cholesterol that we don't have a set distribution for an NAFLD in there. We anticipate that the majority would be NAFLD rather than NASH themselves just -- and 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 (Technical Difficulty) criteria.
Ritu Baral -- Cowen -- Analyst
The 10% you mentioned. Last question just mechanistically, based on other drugs in the class, what are your expectations around the move-in in LDL in this study?
Patrick Horn -- Chief Medical Officer
So, we have seen and we have looked at elobixibat 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 -- Cowen -- Analyst
Got it. Thanks for taking all the question.
Unidentified Speaker
So you are welcome, Ritu. I think the way that we think about the efficacy of IBAT inhibitor like elobixibat in NASH, we're not looking for an effect on one parameter or a significant effects, but we're excited about the potential to have an effect on multiple parameters including LDL, including GLP-1, including liver fibrosis, liver inflammation and other things. So, thank you for your questions, Ritu. 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 -- Wedbush Securities -- Analyst
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 has age as -- are you going to exclude the PEDFIC-1 profile patients in PEDFIC-2 and the additional types of PFIC and how are -- 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 PFIC types that you are targeting for PEDFIC-2?
Ron Cooper -- President and Chief Executive Officer
Good morning, Liana. Thanks very much first for the questions. So, let me start with a few comments, then I'll hand it over to Pat to kind of go through some of the details of your question. I think we're pretty excited about starting this second cohort and starting 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, we are pretty excited about the potential to enroll a variety of patients and generate data. Maybe, Pat, you can speak little more specifically to Liana's question.
Patrick Horn -- Chief Medical Officer
Yeah. 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 answers that. So we will be able to collect similar information across and even (Technical Difficulty) although they are 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 were going to do on the patients who rolled from PEDFIC-1 into cohort 1 will be the same and the cohort 2 is really just 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, but maybe even look into some of the even rarer diseases -- causes of 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 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 wait and see as we go, who is going to enroll and what the range we're going to see.
Ron Cooper -- President and Chief Executive Officer
So, Liana we're pretty excited about the thing that -- as you recall PEDFIC-1 studies PFIC-1 and PFIC-2 patients, but there's also a wide range of other patients, other types of PFIC, other ages and other circumstance for those patients that they wouldn't qualify for our original studies. So we're excited to generate some data in these patients.
Liana Moussatos -- Wedbush Securities -- Analyst
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 -- Roth Capital Partners, LLC -- Analyst
Hi, team. Congrats on the continued progress. I have three questions. Maybe we can start off, team, can you remind us again what elements of your trial design in PFIC ensures to minimize the placebo reported pruritus?
Patrick Horn -- Chief Medical Officer
Yeah. So again this is Pat. So in pruritus 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 that's early in the course and the longer a patient goes, they realize it or maybe they work better. And their pruritus 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 pruritus.
I think the other thing is that we really took 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 calculations.
Ron Cooper -- President and Chief Executive Officer
I think that we understand that there's variability with these patients, Yasmeen. And I think as Pat has indicated, those are two key elements, you have the length of time and our 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 parents, right. And so we're hopeful that that tool will as well help us to differentiate patients.
Yasmeen Rahimi -- Roth Capital Partners, LLC -- Analyst
Thank you, team. So, moving on to the second question, I noticed in the filing that you have filed a complaint or a litigation against Ferring International for compensatory damages of EUR37 million. Can you give us a little bit more color on this and maybe an update?
Ron Cooper -- President and Chief Executive Officer
Yeah. Thanks for the question, Yasmeen. I think, (Technical Difficulty) I can't comment more than what we've said within the Q. So I would ask you to refer to the Q, but we have filed a complaint with a number of claims arising under the license agreement we had with Ferring of EUR37 million. Our legal fees on contingent fee of 33 and third for any potential reward. And we'll update you with more information.
Yasmeen Rahimi -- Roth Capital Partners, LLC -- Analyst
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 have had with the EMA and FDA in regards to biliary atresia, maybe a tiny (inaudible) of information on the update on this program and where it's headed or at least tell us, if the way to guidance is different between EMA versus the FDA and what is similar and what could be different to the extent that you can?
Patrick Horn -- Chief Medical Officer
Yeah. So this is the interesting thing. So in these rare diseases, where there really haven't been registration studies, there are no guidances. 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 the key discussion is hinging around 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 are focusing. We are getting them toward the same place. Whether we'll be able to actually get to the same place is an unknown. For example, in the PFIC program, the EMA has a different endpoint than the FDA, and it's entirely possible we could end up in a similar situation. That is just unknown. And we really can't comment on the ongoing discussions until we have some final decisions.
Ron Cooper -- President and Chief Executive Officer
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 (inaudible) discussions that we're having with our agents.
Yasmeen Rahimi -- Roth Capital Partners, LLC -- Analyst
Thank you for taking my questions.
Ron Cooper -- President and Chief Executive Officer
Yasmeen.
Operator
Thank you. Our next question comes from the line of Kyung Yang with Jefferies. Please proceed with your question.
Eun Yang -- Jefferies LLC -- Analyst
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?
Patrick Horn -- Chief Medical Officer
So, it's PEDFIC-2 that's the open label extension and patients who roll from PEDFIC-1 to PEDFIC-2 -- in fact, all patients who enter PEDFIC-2, the opening extension will be treated with the higher dose. The 120 microgram per kilogram per day.
Eun Yang -- Jefferies LLC -- Analyst
I see. Can you comment on how many patients from PEDFIC-1 have been transitioned to the open label extension by now?
Patrick Horn -- Chief Medical Officer
So we haven't talked about the ongoing status of our studies or where we're at.
Eun Yang -- Jefferies LLC -- Analyst
Okay. All right.
Ron Cooper -- President and Chief Executive Officer
(Technical Difficulty) so that the trial is up and running and working well.
Eun Yang -- Jefferies LLC -- Analyst
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 for possible rate to be?
Patrick Horn -- Chief Medical Officer
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 a therapeutic intervention, you can get a sense of what the placebo response would be on that one. So that's where we got our information on the magnitude of the placebo response. And like I said, when we did our powering assumptions and our sample size calculation, we assumed the larger size of the placebo response.
In terms of the powering assumption, as you recalled, there are different primary endpoints in the two regions. So the US, it's 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've said above 80% then that means that the power calculations for the endpoint of serum bile acids is actually much higher.
Ron Cooper -- President and Chief Executive Officer
So, Eun, just to add to what Pat says from the natural history, we only have bile acid data from that and the NAPPED consortium presented interesting data at the recent European Liver Meeting, where they demonstrated or they shared 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 17%.
Eun Yang -- Jefferies LLC -- Analyst
Thanks very much.
Ron Cooper -- President and Chief Executive Officer
Thanks, Eun.
Operator
Thank you. Our next question comes from the line of Tim Lugo with William Blair. Please proceed with your question.
Tim Lugo -- William Blair -- Analyst
Thanks for taking my question and maybe you touched upon this in Eun's question, but for the additional cohort in PEDFIC-2, are all those patients at the high dose, even the neonates? And reading the tea leaves a bit, does that suggests you're happy with the safety you're seeing so far in PEDFIC-1 blinded data?
Patrick Horn -- Chief Medical Officer
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 -- haven't talked about that and know much about it.
Ron Cooper -- President and Chief Executive Officer
I think for the neonates, Tim, remember this is a per kilogram dose right. So the 120 is adjusted for whatever the weight is.
Tim Lugo -- William Blair -- Analyst
Understood. And could you just generally talk about site conduct in PEDFIC-1 to-date? Obviously, it's a rare disease, you have 43 sites open. Are you seeing enrollment fairly broadly around those 43 sites, so it's one or two each or are there stand outs and in general the site conduct of those 43 sites?
Unidentified Speaker
The one thing about PFIC versus other diseases is, it's a disease of consanguinity right. Some of the other cholestatic diseases aren't on. So as a result there are some clusters of geographies where there are patients where there's -- probably there is 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.
Tim Lugo -- William Blair -- Analyst
Okay. And for the extended cohort for PEDFIC-2 is that a decision that you think will support a relatively broad label for odevixibat and in general can you just talk about the breadth of a label? In the rare disease world, it seems like labels tend to be broad whereas in liver disease they could be a little more focused on subtypes?
Ron Cooper -- President and Chief Executive Officer
Hard to say at this stage, I think that what our job is to generate as much of 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.
Tim Lugo -- William Blair -- Analyst
Understood. Thank you for the question.
Ron Cooper -- President and Chief Executive Officer
Thanks, Tim
Operator
Thank you. Our next question comes from the line of Matt Kaplan with Ladenburg Thalmann. Please proceed with your question.
Matthew L. Kaplan -- Analyst
Hi. Good morning, guys. Thanks for taking the questions. I wanted to zero in a little bit on your preparations for the NDA for odevixibat? And I guess where are you with respect to manufacturing and then pre-clinical 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?
Ron Cooper -- President and Chief Executive Officer
So Why don't you start with the second question and then I'll take the first one, Pat?
Patrick Horn -- Chief Medical Officer
Okay. Yeah. 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.
Ron Cooper -- President and Chief Executive Officer
And then, in terms of readiness, 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 term talks 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 able to go to commercial quality and commercial scale. So we're pretty confident in our ability to get there. So, like I said at the very beginning, the good thing and the way it should be it's PEDFIC-1 data that is the gating factor and we're looking forward to having that data at the end of this year or early the 2020.
Matthew L. Kaplan -- Analyst
Great. That's helpful. And then for the Phase 2 study in NASH and NAFLD, for odevixibat, primary end point being change in LDL. Can you give us a sense in terms of what you're targeting, in terms of entry criteria for LDL?
Patrick Horn -- Chief Medical Officer
So we haven't made, I don't think -- I think it's on clinicaltrials.gov, the criteria should be on there. And to tell you truth, I can't remember off the top of my head, but I believe it's 130.
Ron Cooper -- President and Chief Executive Officer
I believe it's 130 individuals. And then of they have a (Technical Difficulty) lipid lowering agent is 110.
Matthew L. Kaplan -- Analyst
Okay. Thanks for taking the questions guys.
Ron Cooper -- President and Chief Executive Officer
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.
Joey Stringer -- Needham and Company -- Analyst
Hi guys. This is Joey on for Alan. Congrats on the progress and thanks for taking our questions. What's the target number of sites for PEDFIC-1?
Ron Cooper -- President and Chief Executive Officer
We've guided, Joey, 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.
Joey Stringer -- Needham and Company -- Analyst
Okay. Thanks. And just to clarify for PEDFIC-2, the amended -- the protocol amendment, do those patients -- do the PFIC patients have to be -- will they be genotyped, 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.
Ron Cooper -- President and Chief Executive Officer
No, the patients do have to be genotyped and we have to demonstrate that they have some type of PFIC but it includes all of the types of PFIC, 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.
Joey Stringer -- Needham and Company -- Analyst
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 in PEDFIC 1 and 2 and the biliary atresia trial. Thanks.
Ron Cooper -- President and Chief Executive Officer
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 -- H.C. Wainwright -- Analyst
Hi, Ron. Thanks for taking my questions.
So I just wanted to ask slightly different question around PFIC 2 obviously the new announcement this morning is around the 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?
Ron Cooper -- President and Chief Executive Officer
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 the 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 -- H.C. Wainwright -- Analyst
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?
Ron Cooper -- President and Chief Executive Officer
Thanks, Ed. I think that's why we're really excited about our approach in NASH between elobixibat in compound 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, they have a problem with cholesterol, have a problem with glucose transport, problem with liver inflammation 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 on 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 and potentially some of our other preclinical compounds kind of interesting and exciting in the NASH space.
Ed Arce -- H.C. Wainwright -- Analyst
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?
Ron Cooper -- President and Chief Executive Officer
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 in other indications to build a very strong brand and a strong pediatric liver franchise with odevixibat.
Ed Arce -- H.C. Wainwright -- Analyst
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.
Ron Cooper -- President and Chief Executive Officer
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.
Duration: 58 minutes
Call participants:
Paul J. Arndt -- Investor Relations
Ron Cooper -- President and Chief Executive Officer
Simon Harford -- Chief Financial Officer
Patrick Horn -- Chief Medical Officer
Unidentified Speaker
Matthew L. Kaplan -- Analyst
Ritu Baral -- Cowen -- Analyst
Liana Moussatos -- Wedbush Securities -- Analyst
Yasmeen Rahimi -- Roth Capital Partners, LLC -- Analyst
Eun Yang -- Jefferies LLC -- Analyst
Tim Lugo -- William Blair -- Analyst
Joey Stringer -- Needham and Company -- Analyst
Ed Arce -- H.C. Wainwright -- Analyst
