Eiger BioPharmaceuticals, Inc.

Good day, ladies and gentlemen, and welcome to the Iger 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. If anyone should require operator assistance, please press star, then zero on your telephone. As a reminder, this call will be recorded. I would now like to introduce your host for today, Mr. Sri Riali, Chief Financial Officer of Iger. 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, which is available on our website at IgerBio.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 we'll have a replay available on the investor section of our website. Joining me on the call are David Corey, President and CEO, Eldon Mayer, our Chief Commercial Officer, and Dr. Ingrid Chung, 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 IGERS control, which could cause our actual results to differ materially. A description of these risks and uncertainties is contained in IGERS filings with the SEC. including our latest 10-K and 10-Q reports available on the Iger website in the Investors section. All forward-looking statements are based on information currently available to Iger, 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 Iger, 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 PEG interferon lambda for hepatitis delta virus, Avexatide for post-bariatric hypoglycemia and congenital hyperinsulinism, and Zokindi for progeria. This demonstrates a core strength of Iger, our proven ability to advance targeted therapies for serious rare and ultra-rare diseases with urgent unmet medical needs. Iger 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 HBV and is found in approximately 6% of HBV-infected patients. However, hepatitis delta virus causes a much more rapid progression of liver disease than HBV alone. 60% of HDV patients die within 10 years after diagnosis. This is a large orphan disease in the U.S. and Europe with an urgent unmet medical need. There is no FDA-approved therapy for HDV. Iger is pioneering the development of treatments in this space. As we discussed before, we're often asked, what would a win look like for HDV patients? HDV is a devastating, rapidly progressive 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 of HDV therapies. At Iger, 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 PEG interferon 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 III DELIVER study. With over 100 sites across 20 countries, DELIVER is the largest phase 3 study to be conducted in HDV. The DELIVER study design opens the door to deliver a win for HDV patients with the all oral lonafarnib based regimen and in combination with PEG interferon alpha. We were very pleased to announce earlier this week that DELIVER is now fully enrolled with over 400 patients, exceeding our target. This is an important milestone for Iger and for HDV patients. Complete enrollment of DELIVER now sets up pivotal top-line data release by the end of 2022. I'd like to thank the patients and investigators and their teams for their ongoing participation in DELIVER, as well as the Iger clinical team and their steadfast efforts to fully enroll DELIVER. We look forward to reporting data from this landmark study. Our second therapy in development for HDV is PEG interferon lambda, a well-tolerated interferon, which is now in a pivotal phase three study called Limit 2. Limit 2 represents an efficient pathway for PEG interferon lambda approval in HDV, and we are now activating clinical trial sites and screening patients. For well over a decade, Iger 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 Lonefarnib and PEG interferon lambda will have the potential to become foundational therapies for the treatment of HDV. Iger 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. Avexatide 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 Avexatide as a significant commercial opportunity and will 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 PEG interferon lambda as a convenient outpatient treatment for COVID-19. The placebo controlled phase three together study is enrolling and dosing patients across multiple clinical sites in Brazil. We were pleased to announce in September that the Independent Data Safety Monitoring Board recommended continuation of PEG Interferon Lambda, and we look forward to reporting the next interim futility analysis before the end of this year. PEG Interferon 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 variance 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. Peg interferon lambda's mechanism of action of stimulating the host immune response is agnostic to a rising variance, and as such, we believe may be ideally suited to treat newly diagnosed COVID-19 outpatients as a convenient single subcutaneous injection. Now, turning to Zokenvi, we are proud at Iger that our first approved product is for the treatment of progeria, a devastating, universally fatal, ultra-rare pediatric disease of premature aging. The U.S. launch of Zokenvi has progressed well. We're in discussions with the EMA regarding our MAA and expect an opinion around the end of this year. We've also received approval of a cohort ATU program in France. This is an important achievement and will help bring Zokenvy to French patients with Progeria. Ingrid and Elden will provide additional details on our progress in Europe and with the commercial launch. Zokenvy 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 in the 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 programs. We've deliberately designed and are executing an HDV platform strategy with potential to generate approvals for multiple HDV treatment regimens. With DELIVER now fully enrolled and Limit 2 underway, Iger is poised for important upcoming value-creating milestones. We've spoken in the past at length about our HDV strategy, and given the scope and breadth of our program, it is worth recapping. We believe a win for HDV 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. Lonifarnib and Peginifera Lambda potentially offer both. In Phase II, the all-oral regimen of lonofarnib 50 mg BID with ritonavir achieved a composite endpoint 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 lonofarnib was combined with peganifran-alpha, the response rate more than doubled to 63%. Importantly, the combination of lonafarnib and peganifran-alpha was synergistic on the composite endpoint, improving both reduction in HDV viral load as well as ALT normalization. Lonafarnib boosted with ritonavir is the only therapy in development for HDV that has reported synergy on the composite endpoint when combined with peganifran-alpha. Our Phase II data were the basis for our Phase III DELIVER study. DELIVER is a foundational global Phase III trial that we believe positions Iger to be a leader in HDV. The DELIVER primary endpoint is a composite of a two-log decline in HDV RNA and ALT normalization, as was demonstrated in Phase II. The DELIVER study design creates two opportunities for regulatory approval of Lona Farna-based regimens, an all-oral and a combination with PEG interferon-alpha. With DELIVER now fully enrolled, we anticipate top-line data by the end of 2022, which, if positive, will support global regulatory filings for lonofarnib, seeking approval of two lonofarnib-based regimens for HDV. When complete, DELIVER will generate the single largest source of HDV patient data from a well-controlled global Phase III study to better characterize and understanding this devastating disease. We're also excited to advance our second therapy for HDV. PEG interferon lambda is a first-in-class type 3 well-tolerated interferon now in the phase 3 limit 2 study. In phase 2, PEG interferon lambda was dosed once weekly in HDV-infected patients for 48 weeks with 24-week follow-up. 36% of patients who received PEG interferon 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, Limit 2 study is a randomized two-arm study. Arm 1 is 48 weeks of pegynophenol lambda once weekly, followed by 24 weeks off treatment. Arm 2 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 1 compared to 12 weeks of no treatment in arm 2. 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 DELIVER study, which should allow us to enroll quickly and efficiently. A successful outcome in Limit 2 could lead to approval of PEG interferon 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 PEG interferon lambda's tolerability profile will be preferred by physicians and patients, leading to better compliance and improved outcomes. Lonefarnib and PEG interferon lambda have distinct and complementary 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 PEG-interferon Lambda and Lunafarnabirtonavir has achieved the most robust antiviral effect 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 PEG-interferon Lambda arm without any changes to study. The per-protocol inter-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, PEG interferon lambda is now the only remaining investigational agent in TOGETHER. The PEG interferon 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 in PEG interferon 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 Zolkinvy achieved a 60% reduction in mortality and a statistically significant survival benefit of at least two and a half 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 in the Zikinvi launch. Our initial efforts have been focused on the approximately 20 identified patients in the U.S. where we launched in January. As David noted, the U.S. Zikinvi launch has progressed well. We reported 3 million in Zikinvi net sales in Q3, bringing our year-to-date net sales to 8.8 million. Importantly, we've converted approximately 80% of the identified U.S. patients to commercially reimbursed supply. The patient support center we established, known as IGRA OneCare, has facilitated an efficient U.S. launch. The primary goal of IGRA OneCare is unencumbered patient access to Zikinvi, and this program has delivered continuous access with zero out-of-pocket costs for all patients. In 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 provider, 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 Zikindi 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 ANSN, authorizes an ATU. At Iger, our commitment is to provide Zikinvi access for every child and young adult with progeria and processing deficient progeria and laminopathies. Ultimately, our goal is to deliver global commercial launches across our late stage rare disease programs. Our execution of the Zikinvi launch has enabled us to serve the progeria community while establishing a commercial distribution network, patient support services, and payer engagement that will be scalable for future HDB, 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 concluded a financial update, and I'll call out a few highlights. As Eldon noted, Q3's OTV net sales were $3 million. This compares to $2.1 million reported in the second quarter and reflects a modest increase in inventory on hand at our specialty pharmacy. The contribution from Zokinvi 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 cents on a per share basis. Finally, we continue to operate with a strong cash position and end of the quarter with $120.4 million in cash, cash equivalents, and investments. This provides us with runway into Q4 2023, and funds are ongoing phase three 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 Deliver puts us on course for top-line data by the end of 2022. The Phase 3 Limit 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 Avexatide to be phase three 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 PEG interferon lambda COVID-19 together study, which if positive could support an emergency use authorization application. At this point, I'd like to acknowledge the IGER 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. Ladies and gentlemen, if you have a question at this time, please press star, then the number one key on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. We ask that you please limit yourself to one question and one follow-up. Our first question comes from the line of Bert Heslett 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. Just one with the two components with regard to the studies upcoming in HEP-T. What is your expectation for the placebo rate for the Lona Forna Deliver trial? And then really the same question for the Pegadiphirine Lambda trial, the Limit 2 trial there. And then I have a follow-up on another topic.

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

Yeah, so what I'll say, Bert, nice to speak to you again, is both DELIVER and the LIMIT 2 study are sized for approval as single pivotal trials. And untreated HDV patients with no treatment are not expected to spontaneously clear virus In the case of delivered, they're not anticipated to achieve the two-log decline in ALT normalization, and certainly with no treatment, are not expected to go BLQ or undetectable.

Yeah, 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 deliver is a composite. You don't see that very often happen without treatment. And then in limit two, a very different endpoint with a DVR, a durable virologic 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 Zokinvi. 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 do 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 have just completed our first shipment of drug to Europe for the French pre-approval 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.

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

Thank you, sir. We have another question from the line of Ihegal Noshomovitz from Citi. Your line is open.

Hi, Dean. This is Ashik Mubarak on for you, Val. Thanks for taking my question. I just wanted to go back to the point on the Zika 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 other 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?

Thanks, David. We're in the process of completing some sensitivity analyses 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.

So 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 I 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. Yeah, 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 U.S. And there are roughly 15 to, or give or take a few, a handful of HGPS, the remainder being progeri laminopathy. But we should have more information on that. We will have at a future time. So I hope that is helpful at this point.

Yeah, definitely, and thanks for that. Just one other quick question, which is when are you expecting that the – when will the first patient in limit two be dosed? Are you still expecting by year end, 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 limit two registration trial. Ingrid?

Yep. And startup activities are going really well. We're in the process of activating sites across 13 countries, and we're planning for first patient to be randomized by the end of the year.

Okay, great. Thank you very much. Thank you.

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

Hi, everyone. Congrats on the progress and finishing enrollment with Deliver, and thanks for taking my questions. I was just going to ask about the timeline for Limit 2 enrollment. You mentioned that you're going to be using the best performing sites from Phase 3 Deliver. And so just wondering if, I'm guessing we should expect that study to enroll faster with 150 patients based on the experience with deliverer, but are you saying anything additional on 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.

Yep. Hi, Maureen. I think you have a good handle on the study. Yes, the Limit 2 study is less than half the size of the DELIVER study. Given that and the fact that we are choosing the best sites from DELIVER for Limit 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.

Yeah, we're definitely excited, Maury, about the Limit 2 study. We admittedly know that DELIVER was and is a complex study to enroll. The reason we were excited to announce over 400 patients and completion of enrollment Limit two is very straightforward. 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, very swift and efficient enrollment process for limit two.

Got it. Okay. And maybe as follow-up, if you could remind me how this will work commercially if the DELIVER combo with interferon alpha succeeds and if the LIMIT2 study with lambda succeeds, will doctors just substitute in lambda with the combo commercially, or will you have to run some sort of a bridging study, or will the NIH study that you guys have reported data 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 an all-oral regimen of lonafarnabritonavir approved to treat HDV, as well as the combination of lonafarnabritonavir with pegylated interferon-alpha, where we have seen synergy in Phase II, and our expectations are similarly directed in the Deliver Phase III 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 palliative interferon lambda will initially be approved as a monotherapy post the limit to study completion, that there will be opportunities where physicians will seek to prescribe 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 AASOD last year the completed phase to LIFT-1 study, and that's a combination of peganifreon 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 durable virologic response of LIFT-1, which is 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 Pegadipherone Lambda with Lonefarnabratonavir 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 Scorney from Baird. Your line is open. You may ask your question.

Good afternoon, everyone. Thanks for taking my question. I'm just wondering on the DELIVER 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 address any differences in the patient population between DELIVER and LIMIT2 and why one study allows cessation of all therapy without new background therapy while the other's follow-up requires new background therapy? Thanks.

Sure. So your first question, Brian, thank you very much for your questions and good to hear from you. First question relates to the deliver 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 deliver study, as you know, Brian, it It's looking at a primary endpoint at week 48 of a too-long decline in HDV RNA and ALT normalization. To win, we just have to show statistical significance of either of the lonofarna-based regimens over a placebo. And so the DELIVER study, 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 lonofarna-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 earlier question, for placebo, for patients who are not treated, they are not expected to achieve that two-log decline 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 III DELIVER study based on our Phase II data generated with lonofarnib and ritonavir, and then lonofarnib-ritonavir in combination with pegylated interferon-alpha and definitely look forward to reporting, you know, 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 DELIVER study and the LIMIT-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, yeah, I guess the question was, yeah, You know, Y is deliver on HPV nucleoside background therapy, but limit two allows for cessation of all therapy. I don't think they're on NA therapy.

So actually both studies are requiring patients to be on background nukes, and this is an FDA requirement and FDA guidelines. Yep.

Okay, thanks.

You bet.

Thank you. Again, if you have a question, please press star, then the number one on your touchstone telephone. We have another question from the line of Michael Higgins from Leidenberg. Salman, your line is open.

Thanks, Apera. Thanks, guys, for taking the questions. Congratulations on continued progress with your development milestones. A lot of questions in HTV. Let me switch it up a bit to Evexitide. You can shed some light on us for the next steps. what needs to be accomplished here. You've got it done in your presentation. You can get some feedback as to what's happening with Avexatide. Thanks.

Hey, Michael. Good to hear your voice, and thanks for joining us and for your question. As I think you know, Avexatide is a novel targeted therapy for two orphan indications in metabolic disorders, post-bariatric hypoglycemia and congenital hyperinsulinism, and both of these indications, four of exotide 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, of Exatide, 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 III clinical trials which could start as early as 2022. We, I just want to reiterate, strongly believe in the potential of a vexatide, and we are considering a range of options to take the program forward and look forward to providing additional guidance in the future.

Okay, we'll look forward to that. Just one other question on the program of progeria. Are you able to give us the average milligram per day of these patients that are on zircanbicin? 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 U.S. for the patients who are currently on drug.

Just one quick follow-up, if I may. How do you see the European adoption versus the pattern of adoption in the U.S.? You mentioned the patients are spread out quite a bit, but in terms of the timing of enrollment or transition, rather, How would you gauge the two? Thanks.

I'll let Eldon tackle that one as well.

In the U.S., 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 commercial supply. But we are in the process of continuing to enroll them on MAPS, 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 Zokindi 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. Triyali for any further remarks, sir.

Thank you. This concludes our call. If you have any additional questions, please contact us at info at Igerbio.com, or you can reach out to a member of the Iger 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.