Eiger BioPharmaceuticals Inc (EIGR) 2021 Q3 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the Eiger Biopharmaceuticals Third Quarter 2021 Financial Results and Business Update Conference Call. At this time, all participants are in a listen-only mode. Later we will conduct a question-and-answer session, and instructions will follow at the time. (Operator Instructions). As a reminder, this call will be recorded. I would now like to introduce your host for today, Mr. Sri Ryali, Chief Financial Officer of Eiger. You may begin, sir.

Good afternoon, and thank you for joining us today. Welcome to our quarterly financial results and business update call. We issued a press release earlier this afternoon with our Q3 financial results. It's available on our website at eigerbio.com.

For today's call we will have prepared remarks from the management team followed by Q&A. We will be using slides for the webcast and will have a replay available on the investor section of our website.

Joining me on the call are David Cory, President and CEO; Eldon Mayer, our Chief Commercial Officer; and Dr. Ingrid Choong, Senior Vice President of Clinical Development. Dr. Colin Hislop, Senior Vice President of Clinical and Development Operations, will join us for the Q&A portion.

I would like to remind investors that this call will include forward-looking statements, including expectations concerning financial performance, commercial products, and potential future products in different therapeutic areas and stages of development. The forward-looking statements rely on certain assumptions and involve risks and uncertainties beyond Eiger's control, which could cause our actual results to differ materially.

A description of these risks and uncertainties is contained in Eiger's filings with the SEC, including our latest 10-K and 10-Q reports available on the Eiger website in the investor section.

All forward-looking statements are based on information currently available to Eiger, and we assume no obligation to update these statements. I'll now turn the call over to David.

Thanks, Sri. Good afternoon, and thank you for joining us today. At Eiger we're focused on the development of innovative therapies to treat and cure hepatitis delta virus infection and other serious rare diseases. We continue to make great progress across our pipeline of multiple late stage therapies. All five of our rare disease programs have FDA breakthrough therapy designation.

Lonafarnib and Peginterferon Lambda for hepatitis delta virus, Avexitide for post-bariatric hypoglycemia and congenital hyperinsulinsim, and ZOKINVY for Progeria. This demonstrates a core strength of Eiger, our proven ability to advance targeted therapies for serious rate and ultra rare disease with urgent unmet medical needs. Eiger is well positioned to advance several near-term value-creating catalysts.

Our lead clinical programs are focused on hepatitis delta virus infection, the most severe form of human viral hepatitis. Hepatitis delta virus is always a co-infection with HDV and is found in approximately 6% of HDV infected patients. However, hepatitis delta virus causes a much more rapid progression of liver disease than HDV alone.

60% of HDV patients die within 10 years after diagnosis. This is a large orphan disease in the US and Europe with an urgent unmet medical need. There is no FDA approved therapy for HDV. Eiger is pioneering the development of treatments in this space.

As we've discussed before we're often asked what would a win look like for HDV patients? HDV is a devastating, rapidly-progressing disease. The first goal of therapy is reduction in HDV viral load and reduction in liver inflammation to slow disease progression, which has been shown to lead to improved outcomes. Importantly, this is consistent with FDA guidance for the development HDV therapies.

At Eiger we are advancing an HDV platform strategy that provides multiple pathways to win for patients. We have two well characterized promising late-stage product candidates in Lonafarnib and Peginterferon Lambda. Both have different mechanisms of action, are conveniently administered, and should benefit HDV patients alone and in combinations.

Lonafarnib, the only oral treatment in development for HDV, is currently dosing in the Phase 3 D-LIVR study. With over 100 sites across 20 countries, D-LIVR is the largest Phase 3 study to be conducted in HDV. The D-LIVR study design opens the door to D-LIVR a win for HDV patients with the all oral Lonafarnib-based regimen and in combination with Peginterferon Alpha.

We were very pleased to announce earlier this week that D-LIVR is not fully enrolled with over 400 patients, exceeding our target. This is an important milestone for Eiger and for HDV patients. Complete enrollment of D-LIVR now sets up pivotal topline data release by the end of 2022.

I'd like to thank the patients and investigators and their teams for their ongoing participation in D-LIVR as well as the Eiger clinical team and their steadfast efforts to fully enroll D-LIVR. We look forward to reporting data from this landmark study.

Our second therapy in development for HDV is Peginterferon Lambda, a well tolerated interferon which is now in a pivotal Phase 3 study called LIMT-2. LIMT-2 represents an efficient pathway for Peginterferon Lambda approval in HDV, and we are no activating clinical trial sites and screening patients.

For well over a decade, Eiger has been leading the way in the clinical development of therapies for HDV. We have gained a deep understanding of the needs of HDV patients and the physicians who care for them. We believe that Lonafarnib and Peginterferon Lambda will have the potential to become foundational therapies for the treatment of HDV. Eiger is well positioned to be a leader in HDV, a commercial opportunity projected to be in excess of $1 billion.

Beyond HDV we're advancing the rest of our rare disease pipeline. Avexitide is a novel, first in class, targeted therapy for two very different orphan metabolic disorders - post-bariatric hypoglycemia and congenital hyperinsulinism. We're on track to complete regulatory activities this year and advance manufacturing necessary to support registration enabling clinical trials for both indications.

We view Avexitide as a significant commercial opportunity and we'll provide guidance in the future on how we plan to advance this program.

While we remain focused on our mission to develop innovative therapies to treat and cure HDV and other serious, rare diseases, we have opportunistically and in a capital efficient manner explored the potential of Peginterferon Lambda as a convenient outpatient treatment for COVID-19.

The placebo-controlled Phase 3 TOGETHER study is enrolling in dosing patients across multiple clinical sites in Brazil. We are - we're pleased to announce in September that the independent data safety monitoring board recommended continuation of Peginterferon Lambda, and we look forward to reporting the next interim futility analysis before the end of this year.

Peginterferon Lambda is now the only investigational agent in the TOGETHER study, and positive results from this study could support a submission for emergency use authorization.

Resistance due to variants or new strains of SARS-CoV-2 continue to be an ongoing concern with approved vaccines and monoclonal antibody treatments as well as orals that are currently in development.

Peginterferon Lambda's mechanism of action of stimulating the host immune response is agnostic to arising variants and as such we believe may be ideally suited to treat newly diagnosed COVID-10 outpatients as a convenient single-subcutaneous injection.

Now turning to ZOKINVY, we are proud at Eiger that our first approved product is for the treatment of Progeria, a devastating, universally fatal, ultra rare pediatric disease of premature aging. The US launch of ZOKINVY has progressed well.

We're in discussion with the EMA regarding our MAA and expect an opinion around the end of this year. We've also received approval of a cohort ATUY program in France. This is an important achievement and will help bring ZOKINVY to French patients with Progeria. Ingrid and Eldon will provide additional details on our progress in Europe and with the commercial launch.

ZOKINVY has demonstrated our ability to go from IND to NDA to approval and launch, and to successfully navigate complex global regulatory landscapes. We've established important infrastructure along with commercial and medical affairs functions that can scale and grow for additional commercial launches across larger orphan disease indications in the future.

Finally, we ended the quarter with $120 million in cash and investments, which should fund our planned operations into Q4 2023. I'll now turn the call over to Ingrid to discuss our clinical development programs in more detail. Ingrid?

Thanks, David. We're making great progress across our clinical development program. We've deliberately designed and are executing an HDV platform strategy with potential to generate approval for multiple HDV treatment regimens.

With the liver now fully enrolled and LIMT 2 underway Eiger is poised for important upcoming value creating milestones. We have spoken in the past at length about our HDV strategy and given the scope and breath of our program it is worth recapping.

We believe a win for HDV for patients are approved therapies that suppress HDV virus which has been shown to lead to improved hepatic function, improved liver histology, and improved survival.

We also believe that for chronic HDV therapies convenient administration as well as antiviral activity are important considerations for patients and their physicians. Lonafarnib and Peginterferon Lambda potentially offer both.

In Phase 2 the all oral regiment of lonafarnib 50 milligram BID with Retonavir achieved a composite end point of a [two log] decline in HDV RNA and normalization of liver enzyme or ALT in 29% of patients at week 24 of treatment. When lonafarnib was combined with peginterferon alpha the response rare more than doubled to 63%.

Importantly the combination of lonafarnib and peginterferon alpha was synergistic on the composite end point and proving both reduction in HDV viral load as well as ALT normalization. Lonafarnib boosted with Retonavir is the only therapy in development for HDV that has reported synergy on the composite end point with peginterferon alpha.

Our Phase 2 data was the basis for our Phase 3 D-LIVR study. D-LIVR is a foundational global Phase 3 trial that we believe positions Eiger to be a leader in HDV. The D-LIVR primary end point is a composite of a [two log] decline in HDV RNA and ALT normalization as was demonstrated in Phase 2.

The D-LIVR study design creates two opportunities for regulatory approval of lonafarnib base regimens in all oral and a combination with peginterferon alpha.

With the liver now fully enrolled we anticipate topline data by the end of 2022 which if positive will support global regulatory filings for lonafarnib seeking approval of two lonafarnib based regiments from HDV. When complete the liver will generate the single largest source of HDV patient data from a well controlled global Phase 3 study to better characterize and understanding this devastating disease.

We're also excited to advance our second therapy for HDV. Peginterferon lambda is a first in class type 3 well tolerate interferon now in the Phase 3 LIMT-2 study. In Phase 2 peginterferon lambda was dosed once weekly in HDV infected patients for 48 weeks with 24 week follow-up. Thirty-six percent of patients who received peginterferon lambda achieved a durable virologic response or DVR defined as HDV RNA below the limit of quantitation or undetectable at 24 weeks post treatment.

This post treatment DVR endpoint is most meaningful for both regulatory agencies and physicians as it demonstrates durability of response to treatment and potential for an HDV cure.

The Phase 3 LIMT-2 study is randomized two arm study. Arm one is 48 weeks of peginterferon lambda once weekly followed by 24 weeks off treatment. Arm two starts with 12 weeks of no treatment followed by 48 weeks of treatment. The primary endpoint is the proportion of patients with a durable virologic response at 24 weeks post treatment in arm one compared to 12 weeks of no treatment in arm two.

This is a very straightforward study of 150 patients where all patients will receive treatment. We have started screening patients and are in process of activating approximately 50 sites across 13 countries. These sites have been primarily selected from the best performing sites in the D-LIVR study which should allow us to unroll quickly and efficiently.

A successful outcome in LIMT-2 could lead to approval of peginterferon lambda as a monotherapy for HDV and open the door for it to become the interferon of choice in combination therapies for the treatment of HDV.

We believe that peginterferon lambda tolerability profile will be preferred by physicians and patients leading to better compliance and improved outcomes.

Lonafarnib and peginterferon lambda have distinct and complimentary mechanisms that can be used alone, in combination with each other and in combination with other HDV regimens to suppress virus, reduce liver inflammation and improve outcomes.

Ultimately our goal is complete suppression of HDV virus and HDV cure. To that end, the combination of peginterferon lambda and lonafarnib ritonavir has achieved the most robust antiviral affect after 24 weeks of therapy further demonstrating the opportunity for this combination.

Turning to COVID-19 and the Phase 3 TOGETHER Study we were pleased to report in September that the independent data safety monitoring board recommended continuing the peginterferon lambda arm without any changes to study.

The per-protocol interim futility analysis completed in mid-September was based on a sample size of 453 patients randomized one to one active treatment to placebo. As David noted, peginterferon lambda is now the only remaining investigational agent in TOGETHER.

The peginterferon lambda arm targets enrollment of up to 800 patients at high-risk for developing complications from progression of COVID-19. The primary endpoint is a clinical outcome comparing emergency setting visits and hospitalizations and peginterferon lambda treatment versus placebo. We look forward to reporting additional results in the future.

Finally, turning to our European marketing authorization application for ZOKINVY for Progeria, we've been engaged with the EMA over the past 18 months on our MAA. Discussions with EMA have been focused on additional statistical analyses of our data to support the survival benefit demonstrated across a combined analysis of two different clinical trials.

Patients treated with ZOKINVY achieved a 60% reduction in mortality and a statistically significant survival benefit of at least 2.5 years. We believe the data are robust as indicated by our FDA approval last year. Our discussions with EMA are ongoing and will likely continue through the end of the year around which time we expect a CHMP opinion. I'll now turn the call over to Eldon for a commercial update.

Thanks, Ingrid. I'm pleased to provide an update on our commercial progress and the ZOKINVY launch. Our initial efforts have been focused on the approximately 20 indentified patients in the US where we launched in January. As David noted, the US ZOKINVY launch has progressed well. We reported $3 million in ZOKINVY net sales in Q3 bringing our year-to-date net sales to $8.8 million.

Importantly, we have converted approximately 80% of the identified US patients to commercially reimburse supply. The patient support center we established known as Eiger OneCare has facilitated an efficient launch. The primary goal of Eiger OneCare is unencumbered patient access to ZOKINVY and this program has delivered continuous access with zero out-of-pocket costs for all patients.

Anticipation of an approval in Europe where there are also approximately 20 identified patients, we're actively planning for launch. We have engaged with a distributor and patient support services provided as well as local regulatory and reimbursement authorities.

We recently received approval for a cohort ATU program or temporary use authorization program from French regulatory authorities. And have just made our first shipments of ZOKINVY under this program. ATUs are reserved for products whose efficacy and safety are strongly presumed based on clinical trial data and whose therapeutic indication targets a serious, rare or disabling disease lacking appropriate treatment.

In France, pharmaceutical products not yet granted marketing authorization and not recruiting for a clinical trial can be used if the National Agency for Medicines and Health Product Safety or ANSM authorizes an ATU.

At Eiger our commitment is to provide ZOKINVY access for every child and young adult with Progeria and processing deficient Pregeroid Laminopathies. Ultimately our goal is to deliver global commercial launches across our late-stage rare disease programs.

Our execution of the ZOKINVY launch has enabled us to serve Progeria community while establishing a commercial distribution network, patient support services and [peer] engagement that will be scalable for future HDV and other larger orphan indications. With that, I'll hand the call to SRI for a financial update.

Thanks, Eldon. The press release we issued this afternoon included a financial update and I'll call out a few highlights. As Eldon noted, Q3 ZOKINVY net sales were $3 million.

This compares to $2.1 million reported in the second quarter, reflects a modest increase in inventory on-hand at our specialty pharmacy. The contribution from ZOKINVY helps offset expenses as we advance the rest of our pipeline.

Turning to our GAAP operating expenses, cost of goods sold was approximately $0.3 million in the quarter. For third quarter R&D expenses were $18.1 million and SG&A expenses totaled $6.5 million.

We did report a net loss of $22.2 million, or $.65 on a per share basis. I'm going to continued to operate with a strong cash position in the end of the quarter with $120.4 million in cash, cash equivalent, and investments. This provides us with runway into Q4 2023 and funds our ongoing phase HDV studies. I'll hand the call back to David now for closing comments.

Thanks, Sri. We're executing on our goals across all of our programs and we are well positioned to finish 2021 strong, setting up a pivotal 2022. Our HDV platform is advancing with multiple opportunities to win for patients chronically infected with hepatitis delta virus infection.

Complete enrollment of D-LIVR puts us on course for topline data by the end of 2022. The Phase 3 LIMT-2 study is screening patients and activating sites. We look forward to participating at AASLD next week and plan to host an investor key opinion leader event focused on HDV.

We are planning for Avexitide to be Phase 3 ready for post-bariatric hypoglycemia and congenital hyperinsulinism as early as 2022. We expect CHMP opinion on our MAA for ZOKINVY around the end of the year.

And finally, we look forward to additional interim futility analysis and final results from the Peginterferon Lambda COVID-19 TOGETHER study, which if positive could support an emergency use authorization application.

At this point I'd like to acknowledge the Eiger team for their relentless efforts across our programs and thank all of you for joining us today on our Q3 call. Operator, please provide instructions for the QA portion of the call.

Thank you, sir. (Operator Instructions). Our first question comes from the line of Bert Hazlett from BTIG. Your line is open. You may ask your question.

Thank you. Thank you for holding the call. Thank you for taking my question, and congratulations on all the progress you've made. Two or just one with a two component with regard to the studies upcoming in hep-D, what is your expectation fro the placebo for the Lonafarnib D-LIVR trial? And then really the same question for the Peginterferon Lambda trial, the LMIT-2 trial there. And then I have a follow up on another.

Sure. So just - and thanks, Bert. Good to hear your voice. So just to restate the question you're looking at what we've contemplated or publically communicated regarding expectations for placebo rate on both the D-LIVR Phase 3 study as well as the LMIT-2 Phase 3 study, and I'll let Ingrid take those questions.

Yes. So what I'll say, Bert, nice to speak to you again. As both D-LIVR and the LIMT-2 study are sized for approval as single pivotal trials and untreated HDV patients with no treatment are not expected to spontaneously clear virus (inaudible) and they're not anticipated to achieve the two [logs of climb at] ATL normalization. And certainly with no treatment are not expected to go BLQ or undetectable.

Yes. So I would just add to that, Bert, that our expectation although we haven't communicated any specific numbers, is that the [two log decline] in HDV RNA combined with ALT normalization, again, our primary endpoint in D-LIVR is a composite.

You don't see that very often happen without treatment, and then in LIMT-2 a very different endpoint with a DVR, a durable viralogic response, and you don't see HDV virus spontaneously clearing most key opinion leaders would tell you ever without treatment.

Terrific. Look forward to more conversation about that in a week or so. And then just one with regard to ZOKINVY. Again, nice to see the progress there in France. When do you actually think we might be able to see revenue coming from the European geographies?

Sure, sure. When we expect to see revenue coming from European geographies, and I'll let our Chief Commercial Officer handle that, Eldon Mayer.

Yes, hi. And as you probably heard on the call we had just completed our first shipment of [drug to] Europe for the French preapproval program, the cohort ATU, so that would be the beginning of that commercialization.

Beyond that we have not yet provided guidance on European revenue or reimbursement, which as you probably know is typically negotiated on a country, by country basis after regulatory approval, but we do expect EMA opinion by the end of this year, and we will be able to provide further information at that point.

OK. Very much looking forward to more information there. Thank you.

Thank you, sir. We have another question from the line of [Eigel Noshamovitz] from [SIGE]. Your line is open.

Hi, team. This is [Osha Mobart] on for [Eigel]. Thanks for taking my question. I just wanted to go back to the points on the ZOKINVY launch in Europe. What are you expecting from the CHMP that might be of interest? And I know you've mentioned that there are 23 identified patients in Europe. I'm just wondering how many are in France and maybe any of the details on some of the other country-specific numbers? Thanks.

Sure, and thanks. Good to hear from you. And we'll answer both of those questions. First, with regard to expectations on CHMP interaction I'll let Dr. Colin Hislop address that question. Colin?

Yes. Thanks, David. We're in the process of completing some sensitivity analysis that the CHMP requested of us, and as Eldon has mentioned just recently in his remarks we are expecting to complete that process and have the CHMP render their opinion by the end of this calendar year.

I think just to add to that we'll look forward to obviously providing an update when we have further guidance related to CHMP. And want to make sure that we answer your second question with regard to number of patients identified in Europe. I don't know that we've reported specific country-by-country numbers, but I'll let Eldon speak to that.

Sure. Yes. We have not - David is, of course, correct. We have not reported specific numbers by country other than what we said earlier, which is approximately two in France. And as you may know there are a number of countries where we are planning for reimbursement.

And so, the remainder of those patients are spread fairly evenly across those countries. There is some variability because of the low volume. However, like in the U.S. a good portion of those patients are on study and on our expanded access program known as MAP. And that will facilitate transition to commercial supply, and there's a similar proportion as we saw in the US.

And there are a roughly 15 to - or give or take a few handful of [HGPS] the remainder being (inaudible), but we should have more information on that. We will have at a future time, so I hope that is helpful at this point.

All right. Yes, definitely. And thanks for that. Just one other - one other quick question, which is when are you expecting that the - when will the first patient in LIMT-2 be dosed? Are you still expecting by yearend or do you expect the screening process to take a little longer?

Sure. The question is when will our first patient be dosed in the pegylated interferon lambda LIMT-2 registration trial. Ingrid?

Yes. [Start up activities for the material] are going really well with the process of activating sites across 13 countries, and we're planning for first patient to be randomized by the end of the year.

OK, great. Thank you very much.

Thank you.

Thank you. Our next question comes from the line of Maury Raycroft from Jefferies. Your line is open. You may ask your question.

Hi, everyone. Congrats on the progress and finishing enrollment with D-LIVR, and thanks for taking my questions. I was just going to ask about the timeline for LIMT-2 enrollment. You mentioned they're going to be using the best performing sites from Phase 3 D-LIVR.

And so, just wondering if I'm guessing we should expect that study to enroll faster with 150 patients based on the experience with D-LIVR, but are you seeing anything additional and how we should think about that?

Sure. That's pretty self explanatory, Maury, thank you. And good to hear from you. I'll turn that question to Ingrid.

Yes. Hi, Maury. I think you have a good handle on the study. Yes. The LIMT-2 study is less than half the size of the D-LIVR study. Given that and the fact that we are choosing the best sites from D-LIVR to LIMT-2, we do anticipate that enrollment will be much more efficient. We haven't given guidance on how long it will take enrollment to complete, but we'll provide that at a future date.

Yes, we're definitely excited, Maury, about the LIMT-2 study. We admittedly know that D-LIVR was and is a complex study to enroll. Reason we were excited to announce over 400 patients and completion of enrollment, LIMT-2 is very straight forward. It's lambda versus 12 weeks of no treatment.

And so, that in addition to the fact that we are using sites that we now have extensive experience after enrolling deliver we think will contribute to a very swift and efficient enrollment process for LIMT-2.

Got it. OK, and maybe as follow up if you could remind me how this will work commercially, if the D-LIVR combo with interferon alpha succeeds, and if the LIMT-2 study with lambda succeeds will doctors just substitute in lambda with a combo commercially or will you have to run some sort of a bridging study or will the NIH study that you guys have a report date on, would that be sufficient?

So I'll begin on that question, which is a very insightful one, Maury, and then let Ingrid comment as she sees fit.

The liver study, we are planning to have the potential of both a all-oral regimen of Lonafarnib/Ritonavir approved to treat HDV as well as the combination of Lonafarnib/Ritonavir with Pegylated Interferon Alpha, where we have seen synergy in Phase 2. And our expectations are similarly directed in the D-LIVR Phase 3 program, and we're excited about that opportunity.

Pegylated Interferon Lambda is a well-tolerated interferon. And to your point, we do believe that physicians will desire, and patients will desire, a well-tolerated interferon to be used in the treatment of HDV.

And so, our expectation is that while Pegylated Interferon Lambda will initially be approved as a monotherapy post the LIMT 2 study completion, there will be opportunities where physicians will seek to prescribe Pegylated Interferon Lambda Lonafarnib/Ritonavir.

And maybe I'll turn it over to Ingrid to comment a little bit further and also add color around what's been done at the NIH, as you mentioned, Maury, and what we are looking forward to from the NIH. Ingrid?

Sure. So hi, Maury. So as you're aware, NIH reported out at AASLD last year the completed Phase 2 LIFT 1 study. And that's the combination of Peginterferon Lambda with Lonafarnib/Ritonavir. And that indeed did show the most robust antiviral effect to date, further demonstrating the opportunity for this combination of our proprietary compounds.

Based on the promising gerbil virologic response of LIFT 1, which was a 24-week treatment study, we're planning a follow-on study with the NIH called LIFT 2. And this is a 48-week dosing of the combination of Peginterferon Lambda with Lonafarnib/Ritonavir with a 24-week follow-up.

And so hopefully, the thought is that by dosing longer you will allow for consolidation of antiviral response and result in higher durable virologic response rates. And we look forward to reporting that out in the future.

Great, okay. Thanks for taking my questions.

Thank you, Maury.

Thank you. Our next question comes from the line of Brian Skorney from Baird. Your line is open. You may ask your question.

[Thank you]. Good afternoon, everyone. Thanks for -- thanks for taking my question. I'm just wondering, on the D-LIVR study, if there's a hierarchical analysis to the statistical plan for intergroup comparisons?

And can you discuss any powering assumptions for those comparisons on a superiority basis? And also, can you just the -- any differences in the patient population between D-LIVR and LIMT 2 and why study allows cessation of all therapy without new background therapy while the others follow-up requires new background therapy?

Sure. So your first question -- Brian, thank you very much for your questions. And good to hear from you.

First question relates to the D-LIVR study and the statistical plan with regard to whether or not there's hierarchical analysis and other assumptions, and maybe we'll start there. And I'll let Ingrid address that.

So the D-LIVR study, as you know, Brian, it was looking at a primary endpoint at week 48 of a 2 log decline in HDV RNA and ALT normalization. [To when], we just have to show statistical significance of either of the Lonafarnib-based regimens over a placebo.

And so the D-LIVR study is -- it's been designed as a single pivotal study, so it's a large study that is powered to show statistical significance between each of those Lonafarnib-based arms over a placebo. We haven't given specifics as to the powering except to say that it is powered to show that statistical significance.

And as I had mentioned in an early -- to an earlier question for placebo, for patients who are not treated, they are not expected to achieve that 2 log decline in HDV -- in HDV RNA and ALT normalization. So the responders in the placebo arm should be very low.

We feel very good, in short, about the design of the Phase 3 D-LIVR study based on our Phase 2 data generated with Lonafarnib and Ritonavir and then Lonafarnib/Ritonavir in combination with Pegylated Interferon Alpha, and definitely look forward to reporting further information as it becomes available.

And Brian, I want to make sure that we address the second question related to patient populations, I think, in the D-LIVR study and the LIMT 2 study. And I believe you were asking about background therapy. Were you referring to whether or not patients were on nucleoside background therapy in both studies?

Well, yes. I guess -- I guess the question was why is D-LIVR on HBV nucleoside background therapy but LIMT 2 allows for cessation of all therapy? I don't they're on [any] therapy [in the background]...

So actually, both studies are requiring patients to be on background [nucs] and this is an FDA requirement...

[Got it].

... and FDA guidelines, yes.

Yes.

Okay, thanks.

You bet.

Thank you. (Operator Instructions). We have another question from the line of Michael Higgins from Ladenburg Thalmann. Your line is open.

Thanks, Operator. Thanks, guys, for taking the questions. Congratulations on continued progress with your developmental milestones. A lot of questions in HDV, let me switch it up a bit to Avexitide. If you could, shed some light on it for the next steps. What needs to be accomplished here? You guys have done your presentation. If you could, give us some feedback as to what's happened with Avexitide. Thanks.

Hey, Michael, good to hear your voice. And thanks for joining us and for your question.

As I think you know, Avexitide is a novel targeted therapy for two orphan indications in metabolic disorders, post-bariatric hypoglycemia and congenital hyperinsulinism. And both of these indications for Avexitide have been granted FDA breakthrough therapy designation. We believe that both indications represent significant commercial opportunities.

And again, since the congenital hyperinsulinism indication has also been granted rare pediatric disease designation, Avexitide, as you know, we believe could be PRV eligible in the event that an approval comes in congenital hyperinsulinism.

In 2021, we've been working and focused on completing manufacturing and all regulatory activities to enable Phase 3 clinical trials which could start as early as 2022. We -- I just want to reiterate -- strongly believe in the potential of Avexitide. And we are considering a range of options to take the program forward and look forward to providing additional guidance in the future.

Okay, I look forward to that. Just one other question on another program in Progeria, are you able to give us the average milligram per day of these patients that are on Zokinvy? Thanks.

Yes, I believe we've communicated that publicly. And so, I'm going to turn that over to Eldon.

Yes, it's approximately 175 milligrams a day on average. That's what we see in the US for the patients who are currently on-drug.

And just one quick follow-up if I may, how do you see the European adoption versus the pattern of adoption in the US? You've mentioned the patients are spread out quite a bit, but in terms of the timing of enrollment -- or transition, rather, how would you gage the two? Thanks.

I'll let Eldon tackle that one as well.

In the US, we had a higher percentage of patients that were on our expanded access program than we see in Europe, so it's possible that that could take a little bit more time to convert them to a commercial supply. But we are in the process of continuing to enroll them [on that]. So we will certainly have an update in the future for you on that.

And as mentioned, the ATU program allowing us to provide [drug] to patients and seek reimbursement from French authorities, and now having actually made our first shipment of Zokinvy into France, we think is definitely a great step in that direction. Given how tight the Progeria community is, we definitely are confident about our ability to execute moving forward.

Perfect. Thanks, guys.

Thank you.

Thank you. I'm not showing any further questions. I would now like to turn the call back to Mr. Sir Ryali for any further remarks. Sir?

All right, thank you. This concludes our call. If you have any additional questions, please contact us as info@eigerbio.com or you can reach out to a member of the Eiger management team. Thanks, everyone, again for joining us on our Q3 call.

Ladies and gentlemen, this concludes today's conference call. You may now disconnect. Thank you for participating. You have a good day. Goodbye.