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3/10/2022
Good day, ladies and gentlemen, and welcome to the Iger Biopharmaceuticals 4th 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. 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's conference, Mr. Sri Riali, Chief Financial Officer of Iger. You may begin.
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 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 with prepared remarks 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. 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 either's control that should cause our actual results to differ materially. A description of these risks and uncertainties is contained in Iger's 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. We are very excited about 2022, which we believe will be a transformational year for Iger. Our strategy at Iger has been to build a pipeline designed to bring much needed medicines to patients with urgent unmet medical needs and to create value for shareholders. 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 three data readouts planned this year first in COVID-19 and then in hepatitis delta virus. At the core of our strategy is our HDV platform, lonafarnib and PEG interferon lambda, both in phase three 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 IGER. HDV is a deadly global disease. impacting more than 12 million people worldwide. Hepatitis Delta virus is always a co-infection with HBV. However, HDV causes a much more rapid progression of liver disease than HBV alone. Fifty percent of HDV patients are cirrhotic at the time of diagnosis. Iger is pioneering the development of treatments in this space with our HDV platform that targets critical host processes involved in viral replication. Lonifarnib, an oral prenalation inhibitor, and Lambda, an immunomodulator, offer different mechanisms of action, are conveniently administered, and should benefit HDV patients alone and in combinations. Lonifarnib, the only oral treatment in development for HDV, is currently dosing in Deliver, a landmark Phase III study. Deliver is expected to generate pivotal results that, if positive, will support registration of two ronopharnib-based regimens for HDV. Deliver 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 Deliver patients, investigators, site staff, and our CRO colleagues. We continue to closely monitor the evolving situation there with our CRO. We believe DELIVER remains more than adequately powered to demonstrate superiority of each lonafarinib-containing arm over placebo, even if patients from Ukraine discontinue from the study. We have also implemented a number of mitigation measures for the 11 DELIVER 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 deliver data by the end of 2022. Our second therapy in development for HDV is Lambda, a well-tolerated interferon, which is now in a pivotal phase three study called Limit 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 two study during the first half of this year. 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. Our HDV strategy is clear. First, seek regulatory approvals of lonafarnib-based regimens based on the results of the DELIVER study. While DELIVER includes combination with PEG interferon alpha, we will quickly follow with data and regulatory submissions for the approval of Lambda, a well-tolerated interferon, based on the results of the LIMIT2 study. This is an efficient pathway for potential approvals of both Lona Farnes and Lambda for HDV. In parallel, we will generate data through the LIST2 study that we believe will support future use of our proprietary combination for HDV. 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 patients and the physicians who care for them. We believe that Lona Farnab and Lambda will have the potential to become foundational HDV therapies. Iger is well positioned to be a leader in HDV, a commercial opportunity projected to be in excess of $1 billion. 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 three together study of Lambda for COVID-19 this month. The study has completed enrollment of over 1800 patients. When complete, together will be among the largest clinical trials conducted of a therapeutic for COVID-19. If the data are positive, we intend to submit an emergency use authorization application to FDA. Resistance due to variants or new strains of 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 may be ideally suited to treat newly diagnosed COVID-19 outpatients as a convenient, one and done, subcutaneous injection, alone, or in potential combinations. We're also making good progress across the rest of our rare disease pipeline. Avexatide, a novel first-in-class targeted therapy for two different orphan metabolic disorders, will be phase three ready this year. And with respect to Zokenvy for Progeria, our first year of commercial launch in the US has been a success. In Europe, our MAA is under review and we expect a CHMP opinion in the first half of 2022. Elden will have more details on Zokendi as well as our initial plan for HBV commercialization in just a few moments. Finally, we began 2022 with approximately $106 million in cash and total investments, which should fund planned operations through Q3 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 and are preparing for two Phase III data readouts this year in COVID-19 and HDV. Our HDV platform strategy has been thoughtfully designed to generate regulatory approvals of multiple HDV treatment regimens. We believe a win for HDV patients is approval of therapies that suppress HDV virus, which has 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 therapies for HDV. We also believe that for chronic HDV therapies, convenient administration as well as antiviral activity are important considerations for patients and their physicians. Lonofarnib and Lambda potentially offer both. In phase two, 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 enzymes, or ALT, in 29% of patients at week 24 of treatment. When lonafarnib was combined with PEG interferon-alpha, the response rate more than doubled to 63%. Importantly, the combination of lonafarnib and PEG interferon-alpha was synergistic on the composite endpoint. improving both reduction in HDV viral load as well as ALT normalization. Lonafarna boosted with ritonavir is the only therapy in development for HDV that has reported synergy on the composite endpoint when combined with PEG interferon-alpha. Our Phase II data were the basis for the DELIVER study. DELIVER is a 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 HDB RNA plus ALT normalization, as was demonstrated in Phase II. The DELIVER study design creates two opportunities for regulatory approval of lotofarnet-based therapies, an all-oral and a combination with PEG-interferon-alpha. DELIVER is a landmark study generating the single largest source of HDB patient data from a well-controlled clinical trial to better understand and characterize this devastating disease. When we design DELIVER, we apply conservative assumptions in the powering of the study, modeling response rates well below what was demonstrated in Phase 2. Regarding recent events, five of the 116 DELIVER sites are in Ukraine. Our priority is patient care and patient monitoring to ensure continuity in the study. 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 deliver sites, so far there has been no interruptions to patient visits, safety monitoring, or drug supply. Iger maintains a delivered drug depot in Russia, which will have sufficient drug supply for all patients through end of treatment. We have developed contingency plans with our CRO and central lab 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 and deliver. 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 filings for lonofarin, seeking approval of two lonofarin-based regimens for HDV. We're also excited to advance our second therapy for HDV, Lambda, in the Phase 3 Limit 2 study. In phase two, Lambda was dosed once weekly in HDV-infected patients for 48 weeks with 24-week follow-up. 36% of patients who received Lambda achieved a durable virologic response, or a DVR, defined as HDV RNA below 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. Limit two is a randomized study, two-arm study. Arm one is 48 weeks of 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 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 DELIVER study, which should allow for efficient enrollment. A successful outcome in Limit 2 could lead to approval of Lambda as a monotherapy for HDV, and also opened the door for Lambda to become the interferon of choice in HDV combination therapies. We believe that Lambda's tolerability profile will be preferred by physicians and patients, leading to better compliance and improved outcomes. Lonafardin and 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 Lambda and lonafinavir-tonavir has achieved our most robust antiviral effect as demonstrated in the Phase 2 List 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 DVR, and 55% of patients that underwent biopsies demonstrated an improvement in histology. As David mentioned, we are excited to initiate a second Phase II study of the combination of Lambda and Lona Farna-Britonavir called LIST-2. By dosing for 48 weeks versus 24 weeks in LIST-1, we believe that a larger proportion of patients will demonstrate a durable response and remain below the limit of quantification in HDV RNA post-treatment. List 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. Turning to COVID-19 and the Phase 3 Together study, we are excited that the study is now fully enrolled with over 1,800 patients, and we expect data later this month. As a reminder, the primary endpoint is the reduction of hospitalizations, emergency room visits, and deaths after a single dose of Lambda, a potential for a one-and-done treatment for COVID-19. 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. I'll now turn the call over to Elden for a commercial update.
Thanks, Ingrid. I'm pleased to provide an update today on our initial plans for HCV commercialization and the Zakingvi launch. With delivered data by end of year, we're actively planning for HCV commercialization. The estimated prevalence for HCV 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. Gilead's Belevertide, which has conditional approval in Europe for HCV, recently launched at an initial price of approximately $150,000 to $160,000 for an annual course of therapy in approved 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. We anticipate that Belevertide will be marketed in the U.S. ahead of Lenofarnib, and we believe that our second-to-market position confers important advantages that will allow us to leverage potential patient benefits of our products. For example, by the time we launch Lenofarnib, we expect increased awareness and diagnosis rates of HDV, made possible by greater utilization of commercial HDV PCR tests and updates to EASL and AASLD testing guidelines. In addition, we believe that patient preference for a convenient all oral HDV therapy will be high. In the case of combination therapy, lanofarinib boosted with ritonavir is the only therapy in development for HDV that has reported synergy with PEG interferon alpha on the composite endpoint, improving both reduction in HDV viral load as well as ALC normalization. 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. With these dynamics in mind, our plan is to prepare to launch La Nefarta to the U.S. with a targeted and efficient commercial team. In Europe, We're preparing for future launch, but are preparing, excuse me, preserving optionality for strategic collaboration. In China and the rest of the world, we believe that a partnership will be required to bring HTV therapies to market. We expect that delivered data by end of this year is an important gating event for future strategic collaborations. We have also received exceptionally positive feedback from physicians, KOLs, and payers on Lambda for HTV. Peg interferon alpha can be difficult for patients to tolerate, leading to compliance issues and ultimately impacting treatment outcomes. Peg interferon lambda, by contrast, is a well-tolerated interferon with fewer and less severe AEs. This was demonstrated in a 2016 head-to-head study in chronic HBD patients. Specifically, patients reported a marked difference in difficult-to-manage flu-like symptoms and other adverse events that impact their daily lives. Turning to Zakimbi, 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 U.S. Zakimbi launch was very successful. We reported 3.4 million in Zakimbi net sales in Q4, bringing our total net sales in 2021 to 12.1 million. Importantly, we've converted 80% of the identified U.S. patients to commercially reimbursed supply with 100% payer reimbursement coverage. The patient support center we established, known as Iger OneCare, has facilitated an efficient U.S. launch. The primary goal of Iger OneCare is unencumbered patient access to Zikindi, and this program has delivered continuous access with zero out-of-pocket costs for all patients. We're actively planning for launch in Europe in 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 a reimbursed early access program, or cohort ATU, from French regulatory authorities and made our first shipment under this program in Q4 2021. And with that, I'll turn the call over to Sri for a financial update.
Thanks, Elden. The press release we issued this afternoon included a financial update, and I'll call out a few highlights. As Elden noted, Q4 is a convenient sales for $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 US specialty pharmacy related to timing of patient refills. Four years of convenient sales were $12.1 million. Turning to our fourth quarter and full year gap 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 64 cents, 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. Our full year net loss reflects the one-time gain recorded in Q1 of the sale of the Zochinby Priority Review voucher. IGA 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, which should fund planned operations through Q3 2023. I'll hand the call back to David for closing comments.
Thanks, Sri. 2022 is a pivotal moment for Iger. We are poised to significantly advance our HDB platform this year. Phase 3 deliver data is planned by end of year. Phase 3 limit 2 continues to enroll. and the LIFT2 combination study of lonafarnib and lambda is planned to initiate in the first half of 2022. We also look forward to data from the phase three together study of PEG interferon 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 plan to submit an EUA application to FDA. 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 HDBKOL events around EASL and AASLV, and also an R&D day that we are planning for April of 2022. 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.
Understood. Ladies and gentlemen, if you have a question at this time, please press the star, then the one key on your touchstone 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. One moment for our questions. Our first question comes from the line of Maury Raycroft from Jefferies. Your line is open.
Hi, congrats on the progress, and thank you for taking my questions. I was going to ask about deliver. It sounds like you have contingency plans in place for deliver in respect to the five sites in the Ukraine, but can you say how many Ukraine patients are actually in the Phase III and how many of those patients are active or have completed the Phase III?
Hi, Maury. Thanks very much for joining the call and for your question. I'll pass that one over to Ingrid Chone.
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 of the monopharmaceutical arms over placebo, even if Ukrainian patients discontinue from the study.
Yeah, so, you know, 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 Lona Farnett-based regimens, for actually two Lona Farnett-based regimens. So we're anxiously awaiting those results.
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?
Yeah, so I'll give you an initial view and let the team opine if they're interested in We have not yet seen data from the TOGETHER study, but we definitely look forward to reporting soon, and we'll 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 use authorization application. I will add, with regard to manufacturing, we are lucky in some ways Given the fact that HDV is our lead indication for pegylated interferon 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 three registration enabling study. 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.
Got it. Okay, thanks for taking my questions. I'll hop back in the queue.
Thank you.
Our next question comes from the line of Yigal Nakamovitz from Citi. Your line is open.
Hi, David and Ingrid and team. Thanks for taking the questions. I know you don't want to give country by country 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?
Hey, Yigal. It's David. Thanks so much for joining the call today and for your question. And, you know, 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 to address as she's daily speaking with our ops team and the CRO. Ingrid?
Hi, Yagal. Thanks for your question. As you know, DELIVER is a landmark phase three study that has enrolled 407 patients across 116 sites in 22 countries. So far in Russia, there hasn't been any interruption to patient visits, safety monitoring, or drug supply Iger maintains a delivered drug depot, as I mentioned earlier, in Russia, which will have sufficient drug supply for all patients through week 48. 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. 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 and deliver.
Yeah, I'll just add, 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. But 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.
Okay, gotcha. That's very helpful. And then a question on HDV, more of a conceptual question. I mean, you have several phase three regimens, obviously the 1,500 monotherapy, then the combo with PEG-alpha, and then, of course, PEG-lambda monotherapy, all in phase three. 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 physician will determine which regimen to prescribe?
Yeah, that's a great question, Miguel. 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 three, between our own lonafarnib oral, PEG interferon lambda as a once-weekly, well-tolerated subcutaneous injection, or Bulveratide, which is a daily injection, 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. And so I think that the future is going to be exciting given the fact that we have what we believe will be a patient preference in an oral therapy in lonafarnib to be used as a monotherapy or in combination with any other agents in development. I'll stop there in case Elden or Ingrid have any comments in addition to that, especially vis-a-vis the LIFT2 study where we're actually combining lonafarnib and lambda at the NIH. Ingrid?
Yeah, I'll just add the deliver study and the limit 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 peganifera and lambda and lonafarinib in the LIFT-1 study at 24 weeks treatment and 24 weeks follow-up. This data was very promising, as you know, where 77% of patients hit the primary endpoint. In addition, 50% of patients were BLQ at the end of treatment, And more importantly, at 24 weeks post-treatment, we saw a 23% durable urologic response. So our next step is to have the LIFT2 study, which will look at 48 weeks of treatment versus the 24 weeks. We believe that with longer treatment, we're going to be able to improve that durable urologic response that we saw in LIFT1. 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 their two complementary mechanisms of action.
Eldon? Yeah, the only thing I would add is, as you know, that all of the studies for registration are being conducted with PEG interferon alpha. And as you know, with our lambda in development, which has a nice tolerability profile, I think there's a there's going to be a transition there towards replacing that drug. But the early data that we've seen with Landis certainly is promising even as a single agent. So it would make sense for that drug to be a nice offering with its, you know, well-tolerated profile alone or in combination as well with other agents that are out there.
And then just one more quick one. For the LIFT2 for NIH, I mean, what has NIH said about their interest in that regimen in terms of, you know, potentially doing a phase three, assuming that this smaller phase two is a success?
Hey, Miguel. Yeah, I'll address that as well and let the team comment. You know, the NIH, we believe, is one of the best liver centers in the United States. We're excited and honored that the liver section at NIH has such a strong interest in working with both lonafarnib and PEG interferon lambda. We believe that the generation of data from lift one and lift two, 24 weeks combo treatment and 48 weeks combo treatment, will lend themselves well to publications and also compendia listings that will support reimbursement. Beyond that, for the potential combination in registration, in the future, if we have strategic options where that's an interest and easily funded, we'll certainly be supportive. We believe the tolerability profile of Lambda is going to lend itself well to physician and patient preference, and that the NIH data will support that preference.
Great. Thank you.
Our next question comes from the line of Brian Scorny from Baird. Your line is open.
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 Hapcludax. I think Gilead booked about $12 million in sales last quarter, which is flat 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-Q versus HDV, um oral opportunity for uh loan or foreign and maybe maybe talk about how we should think about once we see the the delivered data what uh what specific efficacy um advantages disadvantages um compared to have cludex you might be looking for hey brian it's right i can start on the first part of your your question we know that the conditional approval that bilvera type has in europe
is in a limited number of countries. So we expect as that expands 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 all oral therapy. Sure.
I mean, we do expect that, you know, that there will be high demand for an all oral treatment regimen. We believe also that convenience is always going to matter to patients, you know, very much. patients prefer oral therapies, especially when it comes to long-term chronic dosing. So we think that'll play an important role as these therapies become available and the market evolves.
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 approvable endpoint. And so we don't believe that there is any question that these three products are likely on a pathway to be approved. 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 a high likelihood that they're going to be used in combination to determine ultimate and maximal patient benefit. And so we view Lona Farnab and Lambda as well positioned to benefit from what we believe is a growing future opportunity in HDV.
Great, thanks. That's helpful.
Thank you, Brian.
Our next question comes from the line of Bert Haslett from BTIG. Your line is open.
Yeah, thanks. Just one more for me on limit two. Just kind of thinking along the same lines as you articulated with regard to deliver. 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 or enrollment so that other countries pick up the slack? And are you concerned about timing of that trial at all? Just thoughts there. Thanks.
Yep, yep. Hello, Bert. Good to hear you. And thank you for joining the call today. And for the question, I'll pass that one to Ingrid.
Hey, Bert. So as you know, Limit 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 in 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 provide more specific guidance on enrollment and data in the future.
Yeah, I think that the short answer, Bert, is that We're lucky in that we're now just ramping up and activating sites in the Limit 2 study for Lambda in HDB. 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.
Okay, great. And just a brief one on Zokinvi. When should we expect material revenue coming from the EU? I'll ask, you know... something along the lines of what was asked earlier, but maybe a different way, just the EU revenue in terms of materiality. Can that start in the second half of 22, or is it further out based on reimbursement?
Hey, Brett, 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. We'll be able to provide more information on that once we have an approval out of the EMA. We are actively planning for EU launch. We've built infrastructure, as Eldon mentioned, that will support distribution and patient support services. 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.
Okay, great. Thanks for taking my questions. Congratulations on the progress. Looking forward to a big 22. Thanks.
Us too. Thank you, Bert.
Again, if you have a question, please press star and then one key on your touchtone telephone. Our next question comes from the line of Farhana Saklot from Leidenberg. Your line is open.
Hi. This is Farhana. You're on behalf of Michael Higgins. Just want to ask two questions here. Given the market dynamics in HDV, what are your thoughts about the pricing of non of Farnib, and how would that be impacted by the approval of Lambda?
Okay. Hey, Farhana, this is David. I'll direct that call to Elden, and we can go from there. Elden?
Well, yeah, as I had mentioned in the script, we do have an important benchmark of pricing in Europe for HEP Quadex 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 assumption based on our analysis of achieving 9,000 patients, which is 3% of the prevalent market, would get us to a billion based on that pricing. If we assume that similarly, you know, we think we'll have a strong value proposition as well, as you've heard for Lana Farnett. So I think that that's not an unreasonable assumption, you know, for now.
And Farhana, I'll just add to that. Lonefarnib, we anticipate, should be registered through the DELIVER study results. And in serial, immediately behind that, pegylated interferon lambda through the LIMIT2 results. And both of these studies are designed most efficiently to get Lonefarnib and lambda approved. as individual treatments for HDB. And so, the results of both of these studies should lead to the physician's ability to prescribe these two agents either as monotherapy or in combinations. And so, we haven't obviously received, you know, final results and guided on pricing. I think the Bolveritide 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 may be used also in combination. And so as, obviously, data become available, we'll be able to guide more on thoughts on pricing. But we expect both Lorna Farnham and Lambda to be prescribed on their own and to be priced on their own. And certainly the idea of combinations will be, I think, top of mind for prescribers and patients as they try and drive this virus to negative and keep it that way.
All right. Thanks for that. I have one other question. So congrats on the progress with Zucconvi. We were just curious, so out of the 3.4 million Q4 sales, how much of that is coming from France?
Yeah, so approximately 800,000 of that was reflected in the shipment to France. Okay. I've mentioned in the past there are two to three patients in France, and that was the shipment in Q4. Okay.
Great. Thank you so much for taking my questions.
Thank you, Farhana.
I'm not showing any further questions. I would now like to turn the call back to Sri Riali for any further remarks.
Great. Thanks, everyone, for joining us today. This concludes our call. If you have any additional questions, feel free to contact us at info at iHerbio.com, or you can reach out to a member of the management team. Thanks again.
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