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spk01: Ladies and gentlemen, thank you for standing by. And welcome to the Geron Corporation fourth quarter fiscal 2021 earnings call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, please press star followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press star one. Thank you. Olivia Bloom, you may begin your conference.
spk04: Good afternoon, everyone. Welcome to the Geron Corporation fourth quarter and year-end 2021 conference call. I'm Olivia Bloom, Geron's Chief Financial Officer. I'm joined today by Dr. John Scarlett, Geron's Chairman and Chief Executive Officer, Dr. Alexander Rizzo, Geron's Executive Vice President and Chief Medical Officer, and Anil Kapoor, Geron's Executive Vice President of Corporate Strategy and Chief Commercial Officer. Before we begin, please note that during the course of this presentation and question and answer session, we will be making forward-looking statements regarding future events, performance, plans, expectations, and other projections, including those relating to the therapeutic potential and potential regulatory approval of IMITEL stats, anticipated clinical and commercial events and related timelines, the sufficiency of Geron's financial resources, and other statements that are not historical facts. actual results and events could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Jerron's annual report on Form 10-K for the year ended December 31, 2021, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. Jerron undertakes no duty or obligation to update our forward-looking statements. And now I will turn the call over to Dr. Scarlett. Chip?
spk03: Thanks, Olivia. Good afternoon, everyone. Before reviewing our significant accomplishments of 2021, and even before discussing how we plan to build on those accomplishments in 2022 and beyond, I'd like to spend a moment putting into context why we believe in the Telstat can potentially be such a transformative drug, especially in the treatment of hematologic malignancies. Next slide, please. As many of you know, telomerase is an enzyme that adds length to the ends of chromosomes, thus allowing for continued cell proliferation. This enzyme is transiently expressed in normal hematopoietic stem cells during blood cell production. In contrast, telomerase is continuously expressed in malignant hematopoietic stem and progenitor cells, leading to their uncontrolled proliferation. Imitelstat is an oligonucleotide discovered and developed by Geron. that inhibits telomerase and limits the proliferation of malignant cells where telomerase is continuously expressed. It thereby selectively induces apoptosis or killing of those malignant cells. This mechanism of action is unique and first in class, but what makes this drug so exciting and of very substantial potential value is that data from both Phase II trials in low-risk MDS and MF provide strong evidence of disease-modifying activity. Next slide, please. Here we summarize that key evidence. In both Phase II trials, Imatel-STAT's target engagement of telomerase led to reduction of telomerase activity. and depletion of malignant stem and progenitor cells in the bone marrow as evidenced by elimination of the malignant cells marked by molecular and cytogenetic abnormalities. Importantly, in our Phase II trials, the reduction in telomerase activity and depletion of malignant cells in the bone marrow is reinforced as clinically meaningful through the correlations of those biologic effects. With clinical benefits such as anemia responses in MDS, and in MF, reduction in bone marrow fibrosis, as well as, for the first time, correlation with improvement in overall survival. These data, which are of keen interest to the hematologic community, provide strong evidence of the disease modification potential of Imatelstat, which we expect will allow Imatelstat to significantly advance patient care in both lower-risk MDS and refractory MF. Now, let's talk about what happened in 2021. Next slide, please. A critical focus in 2021 involved advancing our two ongoing Phase III trials toward important readouts. These trials are designed to address high-end medical needs in lower-risk MDS and refractory MDS and are intended to be registration-enabling trials in those indications. In our eMERGE Phase III trial in lower-risk MDS, we completed patient enrollment in October of 2021. That milestone achievement enables top line results for the key efficacy and safety parameters, what we call TLR, to be announced in early January of 2023. If those phase three top line results confirm the similar safety as well as the depth, breadth, and durability of transfusion independence that was observed in our phase two trial in the same lower risk MDS patient population, Then we expect to submit an NDA for lower-risk MDS within the first half of 2023. And assuming approval, we expect Imatel stat to be commercialized as early as the first half of 2024. I can't wait to get to TLR and see those data. The next 10 months cannot come fast enough. In 2021, we also made progress in our second phase three trial, ImpactMF, with 50% of the sites being open for enrollment. We also started several new programs with high strategic value and only modest initial costs that are designed to broaden Imatelstat's potential use in additional indications and combination regimens. Alexander will provide more detail on ImpactMF and the rest of the Imatelstat clinical development programs later in the call. Finally, in 2021, we began the process of transforming Geron into a commercial stage company. We're doing this by utilizing a comprehensive milestone-driven stage-gated commercialization. We've already engaged in preparation of long lead time items for our first MBA, such as validation of commercial batches by our contract manufacturers, and are beginning to populate several key modules for the Intel Stat MBA. We also began hiring key executives in areas needed to support a commercial organization, including medical affairs, market access, and a chief business officer. Many of our internal activities are focused on keeping to aggressive timelines for submission of an NDA in the U.S. and ultimately an MAA in Europe, assuming the TLR data supports such submissions. Both the lower-risk MDS program and the refractory MF program are potentially of very significant commercial value. These two indications, assuming regulatory approval and launch in the U.S. and EU five countries, have the potential to generate annual peak revenue of greater than $3 billion in 2030. As a result, and in parallel with our continuing preparations to commercialize Imatel staff, for actively investigating potential relationships with appropriate partners. These include exploration of regional and other deal structures, possible mutual interest, which could potentially further accelerate Intel stat development and commercialization. I'd like to have the call over now to our Chief Medical Officer, Alexander Rizza. Alex will provide you with an update of our clinical efforts. Following that, our Chief Commercial Officer and Head of Corporate Strategy, Anil Kapoor, will share with you his synthesis of the expected differentiated role of Immatel stat in both lower risk MBS and refractory MF. Before I make some final comments at the end of the call about upcoming milestones, Olivia Bloom, our Chief Financial Officer, will review our fourth quarter and year-end 2021 results and provide financial guidance for 2022. Alex? Thanks, Chief.
spk04: In 2021, our clinical focus was on advancing our two Phase III trials in low-risk MDS and refractory MS. This focus will continue in 2022 as we prepare for TLR for the eMERGE Phase III trial and complete opening sites for the IMPACT MS trial. Next slide. For eMERGE Phase 3 today and for the rest of the year, the clinical team will concentrate on executing activities such as data cleaning to enable timely database logs and ensure top-line results are reportable in early January 2023. Given the number of patients and clinical sites around the world, achieving these deliverables requires significant planning, organization, and coordination amongst numerous parties with hands-on oversight by our internal team. In addition, we have implemented plans to ensure adequate resourcing for clinical operations, data management, and medical review at our CRO and internally. Our biostat team is preparing for the numerous statistical analysis and outputs that will be needed not only for a TLR, but also for future regulatory submissions. We and our investigators from the eMERGE study are eagerly looking forward to seeing the top-line results. Given current global events, I would like to make a few comments on the impact of the ongoing conflict in Ukraine and Russia on this trial. We only have two patients at one site in Ukraine. We know that this site is currently closed to patient visits, and we do not know whether these two patients will be lost for follow-up. In Russia, we have two patients at two sites, and these sites are currently open to patient visits. At this time, we do not expect an impact to the timing of the TLR due to this conflict. Like all of you, we're closely monitoring this evolving situation. Onto our second phase three trial, IMPACT-MS, which is in refractory MS patient population. I'd like to remind everyone that this is the only phase three trial in MS using overall survival, or OS, as the primary endpoint. In 2021, we opened over 50% of the planned clinical sites to patient enrollment. and we expect to open the remaining selected clinical sites by the end of 2022. For this trial, there are no Ukrainian sites participating. In Russia, we have two patients randomized and three patients in screening across four sites. However, we are uncertain of the impact this conflict will have on the opening of new sites or patient treatment and enrollment at currently open sites. Under current planning assumptions around enrollment and median OS for each treatment arm, we expect that the interim analysis for impact MS may occur in 2024. Because this analysis is event-driven, the rate at which death events occur determines the timing for the interim analysis. As a result, the number of events required to conduct the interim analysis for this study could occur before enrollment is complete, as these events will occur throughout the enrollment period. At the interim analysis, if the pre-specified statistical OS criterion is met, Then, we expect these data could support the registration of inotelstat in refractory MS, which could occur as early as 2025. If the improvement in OS that we observed in inotelstat-treated patients in our INVARC Phase II trial can be confirmed in the Phase III impact MS trial, Then, we believe imotelstat will be strongly differentiated from other treatments in MS currently approved or in development and will likely change the treatment paradigm for refractory MS patients. As you will hear from Anil shortly, physicians consider OS as a key significant measure of benefit for the treatment of their patients, especially for MS patients who no longer respond to JAK inhibitors due to their dismal prognosis and lack of desirable treatment options. Next slide. Moving on from our phase three trials to the new programs we announced last November as part of our pipeline expansion. In 2022, we look forward to the start of three new studies. First, in PRUMS, our phase one clinical study of imetalstat in combination with ruxolitinib in frontline MS remains on track to open for enrollment in the first half of 2022. Our interest here is to bring the potential of disease modification seen from Immatel-Stat to MS patients earlier in their disease. The protocol is being reviewed and approved by local investigational review boards at each clinical site. Our investigator-led studies in AML and higher-risk MDS, called IMPRESS and PILOMER, We'll evaluate Chemotelstat as a single agent and in combination with current standard of care therapy. The principal investigators for both of these studies are highly enthusiastic. AML continues to be an extraordinarily difficult heme malignancy to treat, and a new mechanism of action, like IMATELSA, that directly affects the malignant stem and progenitor cells driving the disease could provide an effective treatment option for these patients. Due to increasing requests for participation and the expansion of the studies to more sites than initially planned, we expect the start of these studies in the second half of 2022. In addition to these new studies, we have also some preclinical experiments ongoing. The preclinical work being done at MD Anderson is evaluating the TELFED potential to treat lymphoid heme malignancies. This work allows us to explore the potential use of phenotels that beyond myeloid malignancies, which is positive, could open several new indications in the future. We continue to expect preliminary data from these experiments at MD Anderson at the end of 2022. Our final new area for pipeline expansion is the next generation telomerase inhibitor discovery research program. research into the characterization of the different compounds continue, and once a lead compound is identified, we will have more details. All of these activities set up 2022 to be a busy and rewarding year, not only for Matelstad and Geron, but also for patients. Now, I will hand the call over to Anil. Anil?
spk00: Thanks, Alex, and good afternoon, everyone. I share Chip's and Alex's excitement as we get closer to the iMERGE top-line results. In my prepared remarks today, I'll first highlight Immetel Start's expected product profile in lower-risk MDS and how this will differentiate the drug in the market. After that, I'll provide insights into the fast-evolving myelofibrosis market. We believe that Imetelstat can play a meaningful role in the treatment of patients in both indications. As I'll describe, these indications represent large, addressable patient populations and significant commercial opportunities for Geron. Next slide. In lower-risk MDS, Imetelstat's product profile has been favorably received by practicing hematologists. Key attributes identified include Imatel-STAT's ability to treat a broader set of patients, which includes both ringside aeroblast positive and ringside aeroblast negative subtypes, as well as the durability of transfusion independence. In addition, Imatel-STAT's unique mechanism of action and potential for disease modification resonated well with hematologists in our market surveys. Given that Luspatacept's approval in lower-risk MDS is restricted to RS-positive patients only, we are seeing a high level of awareness among practicing hematologists for their patients' RS status. We also hear their desire for more effective treatment options for lower-risk MDS patients who are RS-negative. Thus, imital stat's ability to broadly treat patients across both RS-positive and RS-negative subtypes was seen as important by hematologists. Also, since responses to current treatment options are limited in duration, hematologists seek durable transfusion independence for their patients. As such, The 24-week and the one-year transfusion-independence data from our iMERGE Phase II trial not only provide strong evidence for the durability of transfusion-independence of hematelstat, but also were considered by hematologists to be highly clinically relevant for their patients. Next slide. Lower-risk MDS represents approximately 70% of the total MDS patient population. Chronic anemia is the predominant clinical problem in patients with lower risk MDS. Typically, erythropoietin stimulating agents or ESAs are the mainstay of treatment for the approximately 90% of lower risk MDS patients who have symptomatic anemia and do not have deletion 5q. But not all patients respond to or are eligible for ESAs. Even among responders, Responses typically last between 18 to 24 months. Treatment options remain limited for patients who have failed or are ineligible for ESAs. These patients may move on to receive hypomethylating agents or HMAs or Luspatacept if they are ringside aeroblast positive. It's important though to note that HMAs are not a preferred option given their limited benefits. They are also not broadly approved across Europe for this indication. As such, there remains a lack of effective therapies for RS-negative patients, leaving a significant unmet need for effective therapies for the remaining approximately 75% of lower-risk MDS patients and a compelling market opportunity for imital stat in this setting. Thus, given the breadth, the depth, and the durability of transfusion independence, and the potential for disease modification as evidenced by our Phase II data, we expect a highly differentiated profile for imetelstat at launch in lower-risk MDS and expect imetelstat to significantly penetrate this attractive market and become part of the standard of care in this indication. Next slide. Now, moving on to myelofibrosis. In myelofibrosis patients, improvement in overall survival remains a key unmet need that was highlighted by community hematologists in our market surveys. This is especially important given that patients who discontinue JAKI-based therapy have a dismal survival prognosis. Therapies that offer disease-modifying potential naturally carry significance in the armamentarium of treatment options offered by physicians, as these therapies have the potential to alter the course of the disease. In addition, physicians are seeking therapies for anemic or severely thrombocytopenic patients, and they also need effective second-line therapies that are non-jack-eye based. Next slide. As Alex pointed out earlier, when we asked hematologists in our surveys for the most relevant endpoint in randomized clinical trials for their JAKI-treated or JAKI-discontinued patients, the majority cited overall survival as the most relevant clinical endpoint for this population. ImpactMF, our Phase III trial intended for registration, is the first and only Phase III trial in refractory MF with OS as the primary endpoint. If IMPACT-MS can confirm the improvement in overall survival we observed in our Phase II EMBARQ trial, we expect IMITEL-STAT will transform the care of refractory myelofibrosis patients. Next slide. On to the expected myelofibrosis market evolution. The decade-old JAKA inhibitor therapy ruxolitinib has been a very successful drug in the myelofibrosis market and has established itself as the standard of care and the backbone of frontline therapy. We know that patients do not stay on this drug long-term. Real-world data suggests dismal prognosis for patients who have discontinued from ruxolitinib with median overall survival less than 12 months. As part of the natural evolution of this market, we expect to see significant expansion over the next decade as more drugs are developed to give clinicians more choices to offer tailored patient treatment options. These will include single agent or combination approaches where appropriate. We believe that the opportunity in myelofibrosis for imital strat is driven by the expectation that all JAKI inhibitor-treated patients will become unresponsive to JAKIs over time and therefore become eligible for imital strat. Like in lower-risk MDS, we expect imital strat to have a highly differentiated profile in refractory myelofibrosis and thus to potentially become part of the standard of care in back indications. Before I hand over the call to Olivia for the financial summary, just a quick update on our preparations for a metal stats commercialization, which are stage-gated across all aspects, as pointed out by Chip earlier. In 2022, the key areas of focus for the commercial organization are on activities that have long lead times, such as commercial supply chain planning and third-party logistics setups. defining our value proposition across all stakeholders, and building a deep understanding of the customer base. While we have initiated these pre-commercial activities, the bulk of our commercial investments will happen after top-line results from iMerge Phase 3. With that, I will now hand the call over to Olivia. Olivia?
spk04: Thanks, Anil. Next slide. As expected, overall operating expenses for the fourth quarter and full year 2021 were higher than the same period in 2020. Total operating expenses for the three and 12 months ended December 31, 2021 were $32 million and $115.4 million, respectively, compared to $23.3 million and $77.2 million for the same period in 2020. The increase in research and development expenses primarily reflects increased clinical development costs with our two ongoing Phase III clinical trials, higher ImatelSAT manufacturing costs for producing validation batches at contract manufacturers, and higher personnel-related costs for additional headcount. The increase in general and administrative expenses primarily reflects new costs in connection with pre-commercial activities, including modernizing our internal infrastructure to support a potential commercial launch and higher legal costs. We ended the 2021 fiscal year with $212.7 million in cash and marketable securities, which we believe is sufficient to fund current operations through the end of the first quarter of 2023. For guidance on 2022, we expect non-GAAP total operating expenses to be in the range of approximately $140 million to $150 million. This guidance reflects expenses for supporting the two ongoing Phase III clinical trials, as well as the new exploratory studies in frontline MS and AMLs. finalizing validation batches of ImatelSET at contract manufacturers to enable future production of ImatelSET for clinical and commercial purposes, initial manufacturing for commercial inventory production, preparations for top-line results in low-risk MDS and future regulatory submissions, initial commercial readiness activities, projected increases in headcounts, and larger interest payments due to higher outstanding debt. With that, I will now hand the call over to Chip to share our key upcoming corporate milestones. Chip?
spk03: Next slide, please. Thanks, Olivia. As I commented at the beginning of this call, 2021 was a year of critical execution and accomplishments for Jiraan as we drive towards significant future readouts from our phase three trials and ultimately commercialization in the Mattel stack. 2022 is equally important. Next slide, please. Our expected key upcoming milestones include ensuring delivery of top-line results for the Phase III Emerge Low-Risk MDS Trial in time for disclosure in early January of 2023. Assuming positive TOR, we are also preparing for a potential submission of the NDA in the first half of 2023, an MAA submission in the second half of 2023, and subsequent regulatory approval and commercialization in lower-risk MDS as early as the first half of 2024 in the U.S. As well, our team will continue executing on ImpactMF with opening the remaining selected sites by the end of the year. If we accomplish this, we expect that the planned interim analysis of ImpactMF may occur in 2024. Taken both separately and together, the upcoming readouts from these two Phase III registration trials have the potential to transform Geron from a late-stage development company into a commercial-stage company, and thus to realize our vision of Geron becoming a leader in the treatment of hematologic malignancies. Finally, we expect the new programs in our expanded pipeline to progress meaningfully this year and to begin the process of potential value accretion beyond our initial indications for Metelstat and possibly even beyond Imatelstat itself. Looking forward, if we accomplish each of these important value-accreting milestones successfully, we expect Imatelstat will change the treatment of lower-risk MDS and refractory MS with significant improvement for patients. Thanks very much for your interest in the company, and we'll be glad to take your questions. Operator, please open the call to questions.
spk01: At this time, I would like to remind everyone, in order to ask a question, Please press star followed by the number one on your telephone keypad. And your first question comes from Gil Bloom with Needham & Company. Your line is open.
spk02: Hi, and good afternoon, everyone. So maybe I have a quick question on myelofibrosis.
spk03: So there's a bit of a shifting of the treatment landscape with the very recent approval of pacretinib.
spk02: Do you think that it's going to extend the amount of time patients spend being refractory, i.e., living a little longer? Does that potentially increase the market for relapsed refractory?
spk03: Hi, Gil. Thanks very much. This is Chip. Can you hear me okay? Okay. Okay, great. Okay. So I think I'm going to let Anil Kapoor just take a first crack at that, and others may have a few other comments. So the question was, will the shifting, will the picritinib approval shift the landscape in any way, and in particular increase the number of patients who have a, who are jet-high refractory? I think that was the question. Go ahead, Anil.
spk00: Yep. Sure, thanks for the question, Jill. So pecritinib, as you know, was just approved for severely thrombocytopenic patients. These patients represent a small fraction of myelofibrosis patients, and it's different from the population that imital fat can serve. And we welcome the addition of all of these new JAKI therapies for MF patients. And I think to answer your question, Jill, it all depends upon the patient population actually on picretinib. So if the patient population on picretinib is less than 50,000, which is their indicated label, that population will remain distinct from the populations of biomedical stat. However, we think that this unmet need is very high, and we welcome the opportunity. But the general gist, and I think I can say that for all therapies in development, is that over time you will see this market significantly expand and, as we said, provide physicians with multiple choices across all lines, leading to a much, much larger second-line, third-line plus treatments in myelofibrosis, very similar to the dynamic as an example that we saw even in myeloma.
spk03: Thanks, Sunil. Kevin, any follow-up question on that? Maybe I sharpened that last point a little further. It was my understanding that thrombocytopenia is part of the disease progression as well as an outcome of the treatment of JAPIs over time. And basically, if patients live long enough, they will become thrombocytopenic. So it's kind of like a funnel where your patients can constantly progress to being more and more thrombocytopenic. Am I misunderstanding that? I'll let Alexandra take that since she's the clinician on the call. Go ahead, Alexandra.
spk04: Yeah, can you hear me? Yeah, sure. Yeah, again, you're correct in that saying that patients that progress over time become from a cytopenic. In addition to that, as we know, the available um or the approved jack therapy at the moment uh also doesn't serve these patients or over time this patient you know what time the patients that are treated with xoicin for example become thrombocytopenic so um i think your your your conclusion is right there and then these patients as they progress, if they do have the appropriate number of platelet counts to be treated with Imatelstat, they certainly are an option for treatment or could potentially be an option for treatment with Imatelstat.
spk03: Maybe I conclude some comments about this, Gail. I think the point as we see it is most of the patients who probably will end up on Cretinov at least early in the course would come from the front line or near front line, maybe possibly second line with low flavor counts. I think your question presupposes what will happen as patients become much more ill and ultimately patients become thrombocytopenic, neutropenic, all on their own if their bone marrow fails. While it's certainly possible that some of those patients would benefit by the availability of a drug that is not limited by platelet counts, on the other hand, most of those patients are really failing JAKI therapy in other ways, symptomatic and otherwise. So I think that... We will, I think that the dynamic will continue to evolve. And as honestly, as Anil said, we do welcome these other entrants, especially into these areas that are particularly difficult patients to treat. But how exactly it's going to play out in numbers, I put my money on the entire market expanding as more and more patients become eligible for frontline therapy. That's just my point of view. Okay. Maybe we can move on to the next question.
spk02: Yeah. Um, one additional question and then that would be for me. So, um, you guys have any timeline on potential readouts from the frontline combo study? This is a very interesting study.
spk03: Yeah, I think it's a little early to be commenting on that. We All we know is that we're feeling comfortable that we'll begin the study or we'll open the site for enrollment in the first half of this year. But we don't know exactly how long it will take to ladder up the different dosing, right? So you have to take these studies quite slowly in the interest of safety. And that's been true for every combo study I've ever done, really pretty much any indication. So the question will be, how long do we have to stick? And what do we see in the way of adverse events as we add on? So I don't think there's a good expectation at the moment. I don't know if Alexandra has any further commentary about that. Alex?
spk04: Yeah, thank you. I just wanted to make it clear that we expect to start the study in the second half of 2022. So that was something in my part of the script, just because there is a bit more I'm sorry. Chip was correct. I'm sorry. I moved to the investigator-led studies. Chip is correct. That's the company-sponsored study on time to start enrollment in the first half. As Chip said, we are first trying to safely combine the two drugs, and we are going to look for the safe dose. But with that said, it's an open-label study, so we will be able to evaluate the potential efficacy of the two drugs as we go. So that's one addition that I wanted to give to Chip.
spk03: I think that's it from me for now, and we'll continue to watch your progress. Thanks very much, Gil. Next question?
spk01: Your next question comes from the line of Stephen Lilly with Stifel. Your line is open.
spk04: Hi, this is Ellen on for Steve. Thank you for taking the question. So maybe first one on the work that's being done on the second-generation telomerase inhibitor. I'm just wondering what the ideal profile that second-gen candidate would look like, in your opinion, and, you know, what key improvements would be made compared to Imtelstat? Thanks.
spk03: Yeah, sure. I'll take that one. So our – Number one choice and what we're really going for is an orally available small molecule. That has all the usual benefits and one that would have all of the usual benefits of small molecule development, both in terms of manufacturing and also in terms of timing and, of course, the oral availability. INDICATIONS IN CERTAIN TYPES OF UTILITY. IT'S A TALL ORDER. WE STARTED OUT WITH A COUPLE OF DIFFERENT SCAFFOLDS BUT WE'RE STILL LOOKING FOR A LEAD COMPOUND IN THAT REGARD. I HAVE A LOT OF HOPE HERE BUT we're not quite ready to report any specificity around this. And we will attempt to give a little bit more specificity once we have a lead compound. And I think we've said in the past that that will likely take us the remainder of this year.
spk04: Okay, great. Thanks. And then with regards to the frontline MS study, I know, you know, the primary point is really safety and the combinability of these two drugs. but just wondering from an efficacy perspective um you know total symptom score kind of what the bar is for success here for moving the program forward uh gender you want to comment on that yeah sure yeah now i need to hear it and and i just wanted to uh you know maybe start off by saying that really the enthusiasm or enthusiasm on our side for this um for this combination is really to bring or the use-modifying data that we have seen with metallostats in the relapse and refractory setting. So while, yes, we have to really look into the endpoints that are easy to evaluate, like a TSS or an SVR, we will certainly be looking into other endpoints efficacy endpoints as well, potential TRs, PRs, improvement of fibrosis as well. So it's really going to be the topology of the data that we will be evaluating in this phase one study. So I think that's kind of how we are looking on this study. Okay, great. Thank you for taking the questions and congrats on the progress. Thank you.
spk01: As a reminder, if you would like to ask a question at this time, please press star followed by the number one on your telephone keypad. Your next question comes from the line of Joel Beattie with Baird. Your line is open.
spk02: Hi. Thanks for taking the questions. The first one is on the eMERGE phase 3 trial in MBS. Can you discuss what gives you confidence that the trial is sufficiently powered? I believe, you know, one example of something that could be successful is a 30% rate in the incalcate arm versus 7.5% in the placebo arm. Can you talk to the, I realize it's just an example, but, you know, talk to how realistic those numbers are?
spk03: Go ahead, Alex. I'll try to hear Ellie.
spk04: Yeah. I'm not sure if I heard you well in the beginning, but I think you asked whether we have discussed these with the health authorities, and that was the question. No, that wasn't at all? No. Okay. I'm sorry. I really have a hard time hearing.
spk03: You're having a little bit of trouble hearing. Let me repeat the question, and maybe I'll take a crack, and then Alex, you can fill in. So, Joel, I understood the question to be what gives us confidence in the outcome of the Emerge Phase 3 low-risk MDS study. And you cited the fact that we've commented in the past that We have fairly conservative powering assumptions, meaning that although we saw a 42% rate of eight-week TI in our phase two, we put into our powering assumptions a 30% rate, a very conservative rate. We also have noted that although in other trials the placebo rate in, for example, MDF-005, which was a competitive study in a similar patient population that had a placebo rate of around, I think it was 3% to 5% maximum. I think it was 4.5%. We've actually assumed for our statistical power infections, again, a very conservative 75%. So that we've talked about before. The other elements that make us feel really comfortable going into TLR are the similarity of the patient population. These are all patients who come from very, very similar populations. They're non-Vel5q. They all are relaxin refractory to EFAs. They have... not all are naive to HMAs and to lenalidomide. This, by the way, was a very similar patient population to the metal study for loose powder stuff, which was used for their approval. And then finally, I think that we feel I'm very comfortable that the drug is being used in exactly the same way. Starting dose is 7.5 milligrams per kilogram. We've refined, of course, for the phase three, during the course of phase two, we refined some of the dose modifications to be made during the study. But overall, I think we would say we have a very similar patient population, very similar treatment regimen and conservative statistics.
spk02: Great. Yeah, that's really helpful. Thanks for those points. Maybe moving on to a question on the impact MS trial. Are you able to discuss how the blinded event rate is comparing to the expectations going into the trial?
spk03: No, I don't think we're going to plan to do that. You're absolutely correct that the study is blinded. And at the At this point in time, we don't have any plans to discuss that event. It's a long trial, and we'll see how things progress, but right now we're focused on enrollment.
spk02: Okay, got it. Thank you.
spk01: Okay, great. Thanks. This concludes our Q&A session. I'd like to turn the call back to Dr. Starlett for closing remarks.
spk03: Okay. Well, thanks very much for those excellent questions. Thanks, everybody, for joining us today. We really appreciate you taking the time to dial in and participate. We look forward to sharing the achievements of a lot of these milestones in the coming year. Stay healthy, everyone, and stay safe. Thank you. Bye-bye.
spk01: This concludes today's conference call. You may now disconnect.
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