EIGR (2021 - Q4)

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00:04 Good day, ladies and gentlemen, and welcome to the Eiger BioPharmaceuticals Fourth Quarter and Full-Year 2021 Financial Results and Business Update Conference Call. At this time, all participants are in listen-only mode. Later, we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this call will be recorded. 00:35 I would now like to introduce your host for today’s conference, Mr. Sri Ryali, Chief Financial Officer of Eiger. You may begin.

00:45 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 Q4 and full-year 2021 financial results, which is available on our website at eigerbio.com. 01:01 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 Investors section of our website. 01:12 Joining me on the call with prepared remarks 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. 01:29 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 should cause our actual results to different materially. 01:52 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 Investors section. All forward-looking statements are based on information currently available to Eiger, and we assume no obligation to update these statements. 02:11 I'll now turn the call over to David.

02:14 Thanks Sri. We are very excited about 2022, which we believe will be a transformational year for Eiger. Our strategy at Eiger has been to build a pipeline, designed to bring much needed medicines to patients with urgent unmet medical needs and create value for shareholders. 02:32 Today, we have a diverse late stage portfolio that includes one approved product and five FDA breakthrough therapy designated programs. The promise of our pipeline is coming into sharper focus in 2022 with two Phase 3 data readouts planned this year. First, in COVID-19 and then in Hepatitis Delta Virus. 02:56 At the core of our strategy is our HDV platform. Lonafarnib and Peginterferon Lambda, both in Phase 3 and both first-in-class therapies to treat and potentially cure HDV. HDV is our primary focus and is expected to be the indication that drives near and long-term value for Eiger. HDV is a deadly global disease impacting more than 12 million people worldwide. 03:23 Hepatitis Delta Virus is always a co-infection with HBV. However, HDV causes a much more rapid progression of liver disease than HBV alone. 15% of HDV patients are cerotic at the time of diagnosis. 03:40 Eiger is pioneering the development of treatments in this space with our HDV platform that targets critical host processes involved in viral replication, Lonafarnib and Oral Prenylation Inhibitor and Lambda and Immune modulator offer different mechanisms of action, are conveniently administered and should benefit HDV patients alone and in combinations. 04:06 Lonafarnib, the only oral treatment in development for HDV is currently dosing and delivered a landmark Phase 3 study. D-LIVR is expected to generate pivotal results that if positive, will support registration of two Lonafarnib based regimens for HDV. 04:23 D-LIVR has enrolled 407 patients across 116 clinical sites in over 22 countries, including five sites in Ukraine. We are deeply concerned for all those impacted by this conflict, including the D-LIVR patients. Investigators, site staff, and our CRO colleagues. We continue to closely monitor the evolving situation there with our CRO. 04:49 We believe D-LIVR remains more than adequately powered to demonstrate superiority of each Lonafarnib containing Arm over placebo, even if patients from Ukraine discontinue from the study. 05:01 We have also implemented a number of mitigation measures for the 11 D-LIVR sites in Russia, which should enable continued participation of these patients in the study. Ingrid will provide more details in a moment. We look forward to reporting top-line D-LIVR data by the end of 2022. 05:20 Our second therapy in development for HDV is Lambda, a well-tolerated interferon, which is now in a pivotal Phase 3 study called LIMT-2. We are also pleased to be studying Lonafarnib and Lambda in combination in the LIFT-2 study conducted at NIH. We expect the first patient to enroll in this Phase 2 study during the first half of this year. 05:44 We believe the combination of our two proprietary HDV product candidates will achieve our most robust antiviral activity. As has been the case with other viruses, we expect combination therapies will be required to conquer HDV. 06:00 Our HDV strategy is clear. First, seek regulatory approvals of Lonafarnib based regimens based on the results of the D-LIVR study. While D-LIVR includes combination with peginterferon alfa, we will quickly follow with data and regulatory submissions for the approval of lambda, a well-tolerated interferon based on the results of the LIMT-2 study. This is an efficient pathway for potential approvals of both Lonafarnib and Lambda for HDV. 06:29 In parallel, we will generate data to the LIFT-2 study that we believe will support future use of our proprietary combination for HDV. 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 patients and the physicians who care for them. 06:50 We believe that Lonafarnib and Lambda will have the potential to become foundational HDV therapies. Eiger is well-positioned to be a leader in HDV, a commercial opportunity projected to be in excess of $1 billion. 07:06 Now, turning to COVID-19. The pandemic continues to evolve with over 450 million cases and 6 million deaths around the world thus far, more treatments are urgently needed, and we expect data from the Phase 3 together study of lambda for COVID-19 this month. The study has completed enrolment of over 1,800 patients. When complete, together will be among the largest clinical trials conducted of a therapeutic for COVID-19. 07:36 If the data are positive, we intend to submit an emergency use authorization application to resistance due to variance or new strains at SARS-CoV-2 is an ongoing concern with approved vaccines, monoclonal antibody treatments, and recently approved orals. Lambda’s mechanism of action of stimulating the host immune response is agnostic to variants, and as such, we believe maybe ideally suited to treat newly diagnosed COVID-19 outpatients as a convenient one and done subcutaneous injection alone or in potential combinations. 08:13 We’re also making good progress across the rest of our rare disease pipeline. Avexitide, a novel first-in-class targeted therapy for two different orphan metabolic disorders will be Phase 3 ready this year. And with respect to Zokinvy for Progeria, our first year of commercial launch in the U.S. has been a success. 08:34 In Europe, our MAA is under review and we expect the CHMP opinion in the first half of 2022. Eldon will have more details on Zokinvy, as well as our initial plan for HBV commercialization in just a few moments. 08:49 Finally, we began 2022 with approximately 106 million in cash and total investments, which should fund planned operations through Q3 2023. 09:02 I'll now turn the call over to Ingrid to discuss our clinical development programs in more detail. Ingrid?

09:08 Thanks, David. We're making great progress across our clinical development programs and are preparing for two Phase 3 data readouts this year in COVID-19 and HDV. Our HDV platform strategy has been thoughtfully designed to generate regulatory approvals of multiple JDV treatment regimens. 09:25 We believe a win for HDV patients is approval of therapies that suppress HDV virus, which have been shown to lead to improved hepatic function, improved liver histology, and improved survival. This is also consistent with FDA industry guidance on the development of therapy for HDV. 09:44 We also believe that for chronic HDV therapy convenient administration, as well as antiviral activity are important considerations for patients and their physicians where Lonafarnib and Lambda potentially offer both. 09:57 In Phase 2, the all oral regimen of Lonafarnib boosted with Ritonavir, achieved a composite endpoint of a two-log decline in HDV RNA and normalization of liver enzyme or ALT and 29% of patients at week 24 of treatment. While Lonafarnib was combined with peginterferon alfa, the response rate more than doubled to 63%. 10:20 Importantly, the combination of Lonafarnib and peginterferon alfa was synergistic on the composite endpoint, improving both reductions 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 peginterferon alfa. 10:42 Our Phase 2 data were the basis for our D-LIVR study. D-LIVR is a global Phase 3 trial that we believe physicians Eiger to be a leader in HDV. The D-LIVR primary endpoint is a composite of a two-log decline in HDV RNA plus ALT normalization as was demonstrated in Phase 2. 11:00 The D-LIVR study design creates two opportunities for regulatory approval of Lonafarnib based therapy and all oral and a combination with peginterferon alfa. D-LIVR is a landmark study generating the single largest source of HDV patient data from a well-controlled clinical trial to better understand and characterize this devastating disease. 11:22 When we designed D-LIVR, we applied conservative assumptions in the powering of the study, modeling response rates well below what was demonstrated in Phase 2. Regarding recent events, 5 of the 116 D-LIVR sites are in Ukraine. Our priority is patient care and patient monitoring to ensure continuity in the study. 11:42 We believe the study remains more than adequately powered to demonstrate statistical significance over placebo, even if the patients from Ukraine discontinue from study. In Russia, where there are 11 D-LIVR sites, so far, there has been no interruptions to patient visits, safety monitoring, or drug supply. Eiger maintains a D-LIVR drug depot in Russia, which will have sufficient drug supply for all patients through end of treatment. 12:09 We have developed continuously plans with our CRO and central labs to ensure continuity of drug supply, and that lab samples can be stored and analyzed without compromising the integrity of end of treatment results. We implemented similar measures at the height of the COVID pandemic to successfully maintain patients in D-LIVR. 12:28 As a result of these plans, we are still tracking to deliver top-line data by end of 2022, which if positive will support regulatory filing for Lonafarnib, seeking approval of two Lonafarnib based regimens for HDV. 12:42 We’re also excited to advance our second therapy for HDV, Lambda the Phase 3 LIMT-2 study. In Phase 2, Lambda was dosed once weekly in HDV infected patients for 48 weeks with 24 weeks follow-up. 36% of who received 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 regulatory agencies and physicians as it demonstrates durability of response to a finite therapy and a potential for an HDV cure. 13:21 LIMT-2 is a randomized study to Arm study. Arm 1 is 48 weeks of 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. 13:53 We have started enrolling patients and are in process of activating 50 sites across 13 countries. These sites have been primarily selected from the best performing sites in the D-LIVR study, which should allow for efficient enrollment. A successful outcome in LIMT-2 could lead to approval of Lambda as a monotherapy for HDV and also open the door for Lambda to become the interferon of choice in HDV combination of therapies. We believe that Lambda’s tolerability profile will be preferred by physicians and patients leading to better compliance and improved outcomes. 14:27 Lonafarnib and 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 to complete suppression of HDV virus and HDV cure. 14:59 To that end, the combination of lambda and Lonafarnib ritonavir has achieved our most robust antiviral effect as demonstrated in the Phase 2 LIFT-1 study. In this study, after 24 weeks of dosing, 77% of patients achieved the primary endpoint of a two log decline in HDV RNA and 50% of patients were either HDV RNA BLQ or undetectable. After 24 weeks of follow-up, 23% of patients achieved a DDR and 55% of patients that underwent biopsies demonstrated an improvement in histology. 15:32 As David mentioned, we are excited to initiate a second Phase 2 study of the combination of Lambda and Lonafarnib / Ritonavir called LIFT-2. By dosing for 48 weeks versus 24 weeks in LIFT-1, we believe that a larger proportion of patients will demonstrate a durable response and remain below the limited in HDV RNA post treatment. LIFT-2 will generate critical data and publications to support the potential of this combination. We expect enrollment to begin this year and look forward to providing more details on this study in the future. 16:08 Turning to COVID-19 and the Phase 3 TOGETHER study, we were excited that the study is now fully enrolled with over 1,800 patients and expect data later this month. As a reminder, the primary endpoint is the reduction of hospitalization, emergency room visits, and deaths after a single dose of Lambda, a potential for our treatment for COVID-19. 16:32 Importantly, the study includes both unvaccinated and vaccinated patients, and virus will be sequenced in all patients to determine Lambda’s efficacy across variants, including Delta and Omicron. If the data are positive, we plan to submit an emergency use authorization application to FDA. 16:50 I'll now turn the call over to Eldon for a commercial update.

16:54 Thanks, Ingrid. I'm pleased to provide an update today on our initial plans for HDV commercialization and the Zokinvy launch. With D-LIVR data by end of the year, we're actively planning for HDV commercialization. The estimated prevalence for HDV in the U.S. is 100,000 patients and in Europe, 200,000. Over the past year, we've engaged in market research, speaking with physicians, KOLs, and payers. Unlike HBV and HCV, Hepatitis Delta is an orphan disease with significant unmet need. 17:26 Gilead's bulevirtide, which has conditional approval in Europe for HDV recently launched at an initial price of approximately $150,000 to $160,000 for an annual course of therapy in improved countries. Given this pricing, we would need to treat only 9,000 patients or 3% of the prevalent market to achieve over $1 billion in total sales in the U.S. and Europe. 17:50 We anticipate that D-LIVR we market in the U.S. ahead of Lonafarnib and we believe that our second to market position confirms important advantages that will allow us to leverage potential patient benefits of our products. For example, by the timing we launched Lonafarnib, we expect increased awareness and diagnosis rates of HDV made possible by greater utilization of commercial HDV PCR tests and updates to Eiger and AASLD testing guidelines. 18:18 In addition, we believe that patient preference for a convenient all oral HDV therapy will be high. In the case of combination therapy, Lonafarnib boosted Ritonavir the only therapy in development for HDV that has reported synergy with peginterferon alfa on a composite endpoint, improving both reduction in HDV viral load, as well as ALT Normalization. 18:43 We've also conducted research on HDV patients by geography. As expected, the HDV footprint overlaps well with HBV. 70% of HBV scripts are written by just approximately 3,500 prescribers or around 10% of the total prescriber base. This will allow for a focused commercial launch in the U.S. with a dedicated team, solely focused on ensuring a successful launch in HDV. 19:10 With these dynamics in mind, our plan is to prepare to launch Lonafarnib in the U.S. with a targeted and efficient commercial team. In Europe, we’re preparing future launch, but are preserving optionality for strategic collaborations. In China and rest of world, we believe that a partnership will be required to bring HDV therapies in market. We expect to deliver data by end of this year is an important for future strategic collaborations. 19:39 We have also received exceptionally positive feedback from physicians, KOLs, and payors on Lambda for HDV. Peginterferon alfa can be difficult for patients to tolerate leading to compliance issues and ultimately impacting treatment outcomes. Peginterferon lambda by contrast is a well-tolerated interferon with fewer and less severe AEs. This is demonstrated in the 2016 head-to-head study in chronic HBV patients. 20:06 Specifically, patients reported a marked difference in difficult to manage flu like symptoms and other adverse events that impact their daily lives. 20:15 Turning to Zokinvy, our initial efforts have been focused on the approximately 20 identified patients in the U.S. where we launched in January 2021. As David noted, The first year of the U.S. Zokinvy launch was very successful. 20:28 We reported 3.4 million in Zokinvy net sales in Q4 bringing our total net sales in 2021 to 12.1 million. Importantly, we've converted 8% of the identified U.S. patients to commercially reimbursed supply with 100% payor reimbursement coverage. 20:47 The patient support center we establish known as EIGER ONE CARE has facilitated an efficient U.S. launch. The primary goal of EIGER ONE CARE is unencumbered patient access to Zokinvy and this program has delivered continuous access with zero out of pocket costs for all patients. 21:03 We're actively planning for launch in Europe and anticipation of regulatory approval. We’ve established required infrastructure across the EU, including distribution and patient support services, as well as engagement with regulatory and reimbursement authorities. Last year, we received approval for our reimbursed early access program or cohort ATU from French regulatory authorities and made our first shipment under this program in Q4 of 2021. 21:30 And with that, I'll turn the call over to Sri, for a financial update.

21:37 Thanks, Eldon. In the press release we issued this afternoon included our financial update, and I'll call out a few highlights. As Eldon noted, Q4 Zokinvy net sales were $3.4 million. This compares to $3 million reported in third quarter and reflects sales recorded from the ATU shipment to France, partially offset by fewer shipments to our U.S. Specialty pharmacy related to timing and patient refills. Full-year Zokinvy net sales were $12.1 million. 22:03 Turning to our fourth quarter and full-year GAAP operating expenses, cost of goods sold was approximately $0.1 million and $0.7 million for Q4 and full-year 2021 respectively. R&D expenses were $18.2 million for the quarter and $64.4 million for full-year 2021. SG&A expenses were $6 million for the quarter and $23.9 million for full-year 2021. We did report a net loss of $21.8 million or $0.64 on a per share basis for the quarter. For full-year 2021, net loss was $33.9 million or $1 on a per share basis. 22:43 Our full-year net loss, reflects the one-time gain recorded in Q1, with the sale of Zokinvy Priority Review Voucher. Eiger retained net proceeds of approximately $46.5 million from that sale. Finally, we began 2022 with a strong cash position, with $106 million in cash, cash equivalents, and total investments, but should fund planned operations through Q3 2023. 23:07 I'll hand the call back to David for closing comments.

23:10 Thanks Sri. 2022 is a pivotal moment for Eiger. We are poised to significantly advance our HDV platform this year. Phase 3 deliver data is planned by end of year. Phase 3 LIMT-2 continues to enroll and the LIFT-2 combination study of Lonafarnib and Lambda is planned to initiate in the first half of 2022. 23:33 We also look forward to data from the Phase 3 TOGETHER study of Peginterferon Lambda for COVID-19 within the next few weeks. Lambda has the potential to be a one and done treatment for COVID-19 infection and if data from TOGETHER are positive, we plant to submit an EUA application to FDA. 23:54 Finally, our late-stage robust pipeline of orphan therapies includes multiple breakthrough therapy designated programs, and provides multiple opportunities to deliver much needed medicines to patients and value to shareholders. We look forward to providing additional updates throughout this year, including additional HDV KOL events around and AASLD. And also in R&D day that we are planning for April of 2022. 24:24 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 on our Q4 and full-year 2021 call. Operator, please provide instructions for the Q&A portion of the call.

24:39 Understood. Our first question comes from the line of Maury Raycroft from Jefferies. Your line is open.

25:14 Hi, congrats on the progress and thank you for taking my questions. I was going to ask about D-LIVR, it sounds like you have continency plans in place for D-LIVR in respect to the five sites in the Ukraine, but can you say how many Ukraine patients are actually in the Phase 3 and how many of those patients are active or have completed the Phase 3?

25:35 Hi, Maury. Thanks very much for joining the call and for your question. I’ll pass that one over to Ingrid Choong.

25:41 Hey, Maury. So, we haven’t provided guidance on patients by country. You are correct that we have five clinical trial sites in the Ukraine. We continue to closely assess the evolving situation prioritizing patient care and patient monitoring to ensure continuity of study, and we believe that delivers more than adequately powered to demonstrate superiority. The Lonafarnib containing Arms over placebo even if Ukrainian patients discontinued on the study.

26:09 Yes. So, as a result of our planning, we're still tracking to deliver top line data by end of 2022, which if positive will support filings for Lonafarnib based regimens for – actually two Lonafarnib based regimen. So, we're anxiously awaiting those results.

26:28 Got it. That's helpful. And can you talk more about next steps if the Phase 3 TOGETHER study is positive? I guess, if you had any preliminary contract or stockpiling negotiations with the U.S. or ex-U.S. countries, and can you talk about plans to scale up manufacturing, would that be done in-house or with a partner?

26:49 Yeah. So, I’ll give you an initial view and let the team time if they are interested. We have not yet seen data from the TOGETHER study, but we definitely look forward to reporting soon and will provide additional details on our plans for manufacturing, distribution, and commercialization at that time. If the data are positive, we plan to speak with regulators about submitting an emergency used authorization application. 27:19 I will add, with regard to manufacturing, we are lucky in some ways given the fact that HDV is our lead indication for peginterferon Lambda, we’ve already manufactured multiple registration lots of Lambda and so we definitely combined with the fact that COVID began now two years ago, have been thinking a lot about manufacturing in the result of positive news coming out of our Phase 3 registration enabling study. And so, we haven't guided at this point beyond that, but obviously with positive data, look forward to providing much more guidance in terms of next steps.

28:00 Got it. Okay. Thanks for taking my questions. I'll hop back in the queue.

28:03 Thank you.

28:09 Our next question comes from the line of from Yigal Nochomovitz from Citi. Your line is open.

28:15 Hi, David, and Ingrid and team. Thanks for taking the questions. I know you don't want to give country by currency guidance on enrolled patients, but I'm just wondering with respect to Russia, if those patients were to discontinue, would you still have enough power to demonstrate statistical significance?

28:33 Hey, Yigal, it’s David. Thanks so much for joining the call today and for your question. And clearly the Ukraine conflict is top of mind for everyone and we've definitely been tracking from day one. And I'll turn the question over to Ingrid address as she's daily speaking with our Ops and the CRO. Ingrid?

28:56 Hi, Yigal. Thanks for your question. As you know, D-LIVR is a landmark Phase 3 study that has enrolled 407 patients across a 116 sites in 22 countries. And so far in Russia, there hasn't been any interruption to patient visits, safely monitoring or drug supply. Eiger maintains a delivered drug as I mentioned earlier in Russia, which will have sufficient drugs supply for all patients through week 48. 29:22 The main impact in Russia is the timely export of patient samples for analysis. We've developed contingency plans with our CRO and central lab to ensure not only continuity of drug supply, but also lab samples that can be stored and analyzed without compromising the integrity of these end of treatment results. 29:41 And as you know, we’ve implemented many of these mitigation measures during the height of the COVID-19 pandemic and we're able to successfully maintain patients in D-LIVR.

29:50 Yes, I'll just add, we – to further Ingrid’s point. During the beginning of the COVID pandemic, we took charge and started managing many of these issues across the globe in 22 countries, and we're able to learn a lot, maintain all patients drug supply, remote monitoring for labs, remote monitoring for our monitors at each site, and that information and experience has definitely been instrumental in managing through this first few weeks of the Ukraine conflict that as of now, we feel very confident that this study is more than adequately powered to succeed and look forward to providing future updates on this evolving situation.

30:35 Okay, got you. That's very helpful. And then a question on HDV, more of a conceptual question. And you have several Phase 3 regimens, obviously the Lonafarnib monotherapy and the combo with peg alfa, and then, of course, at Lambda monotherapy all in Phase 3. So, that being said, I'm very curious to get a better understanding of what the decision tree would look like down the road once these are commercially available in terms of how a position will determine, which regimen to prescribe?

31:11 Yes, that's a great question, Yigal and the HDV landscape we believe will definitely evolve as therapies are formally approved. Right now, there is no approved therapy in the U.S. but the three mechanisms that are currently in Phase 3 between our own Lonafarnib oral, peginterferon Lambda as a once weekly well-tolerated subcutaneous injection or bulevirtide, which is in daily injection. 31:38 All have different mechanisms of action and investigators and key opinion leaders have already made it clear that they're interested in exploring combinations of these different mechanisms ultimately with the goal to suppress virus and hopefully keep it suppressed when drug is removed or discontinued. 31:57 And so, I think the future is going to be exciting given the fact that we have what we believe will be a patient preference and in oral therapy in Lonafarnib to be used as a monotherapy or in combination with any other agents and development. 32:11 I'll stop there, in case Eldon or Ingrid have any comments in addition to that, especially vis-à-vis the LIFT-2 study where we're actually combining Lonafarnib Lambda at the NIH. Ingrid?

32:23 Yeah. I'll just add the D-LIVR study and the LIMT-2 study, we see is the most efficient way of getting those two drugs approved and available to patients and physicians, and we've already demonstrated combinations of peginterferon Lambda Lonafarnib LIMT-2 study and LIMT-1 study at 24 weeks treatment and 24 weeks follow-up. This data was very promising. As you know, where 77% of patients had the primary endpoint. 32:50 In addition, 50% of patients were BLQ at the end of treatment and more importantly at 24-weeks post treatment, we saw a 22% . So, our next step is to – have a look to study, which will look at 48 weeks of treatment versus the 24 weeks. We believe that was longer treatment. We're going to improve that Durable Virologic Response that we saw in LIFT-1. 33:17 And as David mentioned, KOLs have already indicated that they're interested in combinations, and they're very excited about Lonafarnib and Lambda as a combination treatment given they are two complementary mechanisms of action.

33:30 Eldon?

33:30 Yeah. The only thing I would add is, as you know that all of the studies for registration are being conducted with peginterferon alfa. And as you know with our Lambda in development, which has a nice tolerability profile, I think there's going to be a transition there towards drug, but the early data that we’ve seen with Lambda certainly is promising even as a single agent. So, it would make sense for that drug to be a nice offering with its well-tolerated profile alone or in combination as well with other agents that are out there. So…

34:12 And then just one more quick one. For the LIFT-2 for NIH, I mean, what has NIH said about their interest in that regimen in terms of potentially doing a Phase 3 assuming that the smaller Phase 2 is a success?

34:31 Hey. Yigal, I'll address that as well and let the team comment. The NIH, we believe is one of the best liver centers in the United States. And so we're excited and honored that the liver section at NIH has such a strong interest in working with both Lonafarnib and peginterferon Lambda. We believe that the generation of data from LIFT-1 and LIFT-2, 24 weeks combo treatment and 48 weeks combo treatment will lend themselves well to publications and also continue listings that will support reimbursement. 35:10 Beyond that for the potential combination in registration in the future, if we have strategic options where that's an interest and easily funded will certainly be supportive. We believe the tolerability profile of Lambda is going to lend itself well to the physician and patient preference and that the NIH data will support that preference.

35:34 Great. Thank you.

35:42 Our next question comes from the line of Brian Skorney from Baird. Your line is open.

35:48 Hey, good afternoon, everyone. Thanks for taking my question. I guess, maybe I want to get some of your thoughts on just what we're seeing in terms of the European opportunity for Hepcludex, I think Gilead booked about 12 million in sales last quarter to slide over 3Q, I guess, how do you think that translates in terms of your view of the global commercial potential in HDV? And maybe you could just – aside from sort of the sub-cu versus oral opportunity for Lonafarnib, maybe talk about how we should think about once we see the D-LIVR date or what's specific efficacy advantages, disadvantages compared to Hepcludex you might be looking for?

36:30 Hey, Brian. I can start on the first part of your question. We know that the conditional approval that bulevirtide has in Europe is in a limited number of countries. So, we expect that expand that we would see additional sales reported over time and maybe I’ll let Eldon answer the question on the expectation that we have for high patient interest for an oral therapy.

36:52 Sure. I mean, we do expect that that there will be high demand for all oral treatment regimen. We believe also that convenience is always going to matter to patients very much. Patients preferred oral therapies, especially when it comes to long-term chronic dosing. So, we think that will play an important role as these therapies become available and the market evolves.

37:19 I think it's very clear from the data that we've seen thus far that all three of these mechanisms, Brian have good activity at reducing HDV RNA or HDV viral load and normalizing liver enzymes, specifically ALT, which, you know that composite is the approval endpoint. And so, we don't believe that there is any question that these three products are likely on a pathway to be approved. 37:45 We believe that that's good news for patients. It's going to provide optionality and importantly, again because these drugs work by different mechanisms, there’s high likelihood that they're going to be used in combination to determine ultimate and maximal patient benefit. And so, we view Lonafarnib Lambda as well positioned to benefit from what we believe is a growing future opportunity in HDV.

38:13 Great. Thanks. That's helpful.

38:15 Thank you, Brian.

38:21 Our next question comes from the line of Bert Hazlett from BTIG. Your line is open.

38:27 Yeah, thanks. Just one more for me on LIMT-2, just kind of thinking along the same lines is the – as you’ve articulated with regard to D-LIVR, how do you think about managing the enrollment of patients, just given what's going on with Russia and Ukraine, obviously, Ukraine is having challenges more so than Russia, but do you expect to shift your enrollment criteria, so that other countries pick up to slack and are you concerned about timing of that trial at all? Just thoughts there, thanks.

39:08 Yes. Hello Bert, good to hear you and thank you for joining the call today and for the question. I'll pass that onto Ingrid.

39:15 Hey, Bert. So as you know, LIMT-2 is ongoing and we are right now in process of enrolling patients and activating approximately 50 sites across 13 countries. While these sites have been primarily selected from the best performing sites and deliver, which we think should facilitate an efficient enrollment, we're still early enough in enrollment where we are considering other sites to include given the situation in Ukraine and Russia, and we'll be able to find more specific guidance on enrollment and data in the future.

39:44 Yes. I think that the short answer Bert is that we're lucky and that we're now just ramping up and activating sites in the LIMT-2 study for Lambda and HDV, and so we're going to have some optionality about which direction we go for enrollment. We don't anticipate any delays in our ability to enroll the Lambda trial.

40:03 Okay, great. And just, what on, so can we, when shall we expect material revenue coming from the EU or something along the lines, what was that certainly or maybe a different way? Just EU revenue in terms of materiality, can that start in the second half of 2022 or is it further out based on reimbursement?

40:28 Hey Bret, this is Sri. I can take that one. So, as we mentioned, we're expecting a CHMP opinion in the first half of this year. EU launch will vary country by country, and we'll be able to provide more information on that, once we have an approval out of the EMA. We are actively planning for the EU launch. We've built infrastructures. Eldon mentioned, that will support distribution and patient support services. 40:51 We know that we will have to apply for reimbursement country by country, and that will be the gating factor for booking revenues. We were pleased with the early access program revenues that we were able to book in Q4 in France, and we'll have more guidance in the future.

41:07 Okay, great. Thanks for taking my questions. Congratulations on the progress. Looking forward to a big 2022. Thanks.

41:13 Thank you, Bert.

41:18 Our next question comes from the line of Farhana Sakloth from Ladenburg. Your line is open.

41:34 Hi. This is Farhana here on behalf of Michael Higgins. Just want to ask two questions here. So, given the market dynamics in HDV, what are your thoughts about the pricing of Lonafarnib and how would that be impacted by the approval of Lambda?

41:53 Okay. Hey, Farhana, this is David. I'll direct that call to Eldon, and we can go from there. Eldon?

42:00 Well, yes, as I have mentioned in the script, we do have an important benchmark pricing in Europe for Hepcludex already, and of $150,000 to $160,000 and so we'll see how pricing unfolds in Europe for that product. We would, you know a fair assumptions based on our analysis of achieving 9,000 patients, which is 3% of the prevalent market would get us to 1 billion based on that pricing. 42:33 If we assume that similarly, we think we'll have a strong value proposition, as well as you've heard from Lonafarnib. So, I think that that's not an unreasonable assumption for now.

42:45 And Farhana, I'll just add to that. Lonafarnib, we anticipate should be registered through the D-LIVR study results and in immediately behind that peginterferon Lambda through the LIMT-2 results and both of these studies are designed most efficiently to get Lonafarnib Lambda approved as individual treatments for HDV. And so the results of both of these studies should lead to the physicians’ ability to prescribe these two agents either as monotherapy or in combinations. 43:21 And so, we haven't obviously received final results and guided on pricing. I think the bulevirtide benchmark is a good one in Europe. And we have two separate therapies with two separate mechanisms that we believe will be approved alone, but likely, maybe be used also in combination. And so, as obviously data become available, be able to guide more on thoughts on pricing, but we expect both Lonafarnib Lambda to be prescribed on their own and to be priced on their own. 43:54 And certainly the idea of combinations will be, I think top of mind for prescribers in patients as they try and drive this virus to negative and keep it that way.

44:06 All right. Thanks for that. I have one other question. So, congrats on the progress with Zokinvy, I was curious, so out of 3.4 million Q4 sales, how much of that is coming from France?

44:20 Yes, so approximately 800,000 of that was reflected in the shipment to France. And I think we've mentioned in the past there are two to three patients in France and that was the shipping in Q4.

44:36 Okay. Great. Thank you so much for taking my questions.

44:40 Thank you, Farhana.

44:46 I'm not showing any further questions. I would now like to turn the call back to Sri Ryali for any further remarks.

44:53 Great. Thanks everyone for joining us today. This concludes our call. If you have any additional questions feel free to contact us at info@eigerbio.com or you can reach out to a member of the management team. Thanks again.

45:08 Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.