Earnings Call Transcript - GERN Q3 2023

Operator, Operator

Good morning. My name is Audrey, and I will be your conference operator today. I would like to welcome everyone to the Geron Corporation Third Quarter 2023 Earnings Conference Call. Today's conference is being recorded, and all lines have been placed on mute to prevent background noise. After the speakers' remarks, there will be a question-and-answer session. I would now like to turn the conference over to Aron Feingold, VP of Investor Relations and Corporate Communications. Please go ahead.

Aron Feingold, VP of Investor Relations and Corporate Communications

Good morning, everyone. Welcome to the Geron Corporation third quarter 2023 earnings conference call. I'm Aron Feingold, Geron's Vice President of Investor Relations and Corporate Communications. I'm joined today by several members of Geron's management team: Dr. John Scarlett, Chairman and Chief Executive Officer; Michelle Robertson, Executive Vice President and Chief Financial Officer; Dr. Faye Feller, Executive Vice President and Chief Medical Officer; Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer; and Dr. Andrew Grethlein, Executive Vice President and Chief Operating 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 imetelstat, anticipated clinical and commercial events, and related timelines, the sufficiency of Geron's financial resources, and other statements that are not historical facts. Actual events or results could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Geron's quarterly report on Form 10-Q for the quarter ended September 30, 2023, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. Geron undertakes no duty or obligation to update our forward-looking statements. With that, I will turn the call over to Chip. Chip?

John Scarlett, CEO

Thanks, Aron. Good morning, everyone. Thanks for joining us today. This quarter, we continue to make important progress and build momentum along our planned path to develop and commercialize imetelstat, our first-in-class telomerase inhibitor. This path, we believe, represents a great opportunity for both near and longer-term value creation. 2023 has been a significant year for us; the imetelstat NDA for the treatment of transfusion-dependent anemia in patients with lower-risk MDS was submitted and subsequently accepted for FDA review in August. The FDA assigned a PDUFA action date of June 16, 2024. This was followed by validation of the MAA for the same indication in September of this year. Now that our MAA is under review, we expect the earliest potential approval could occur in late 2024, with a European launch potentially in 2025. We're continuing to evaluate our strategic options, including self-commercialization or partnering, and expect to be able to provide an update later in 2024. If approved, we believe the imetelstat commercial opportunity in this indication is both differentiated and compelling for three reasons. First, imetelstat has been shown to be highly effective in several key patient subgroups, where today's available treatments do not satisfactorily address the needs of patients with this disease. These include RS negative patients, patients with high transfusion burdens, and patients with high serum equol levels. These key clinical attributes of imetelstat have been further reinforced by the ASH abstracts published this morning. New analyses using data from the Phase 3 IMerge trial in transfusion-dependent lower-risk MDS continue to show significant durability and breadth of transfusion independence across subgroups, including patients whose needs are not being met by current treatments. Second, there's a very large market opportunity for imetelstat and lower-risk MDS patients with transfusion-dependent anemia, which we estimate represents a total addressable market of approximately $3.5 billion by 2033 in the U.S., EU, and U.K. And third, this market has very low competitive intensity and relatively little innovation in the last decade. Despite the recently approved luspatercept label expansion, just last month, the National Comprehensive Cancer Network (NCCN) published a revised version of its MDS guidelines, which still points to limited treatment options available to hematologists as they manage their transfusion-dependent low-risk MDS patients. Moving beyond lower-risk MDS, another key component in Geron's path to value creation is an expected interim analysis in IMerge, which is a Phase 3 study in JAK1 relapsed and refractory MF that's currently anticipated in the first half of 2025. IMpactMF is the first and only Phase 3 trial with overall survival as a primary endpoint. If the expected interim analysis in 2025 or the final analysis expected in 2026 is positive, these data could be transformational for patients with relapsed refractory MF, which also represents an underserved, very substantial market opportunity, with an estimated $3.5 billion market opportunity by 2033. Together, our lead indications represent a potential total addressable market of $7 billion in 2033. And beyond that, we continue to investigate the potential of imetelstat in other hematologic malignancy indications and combination trials that could build additional value for the company. Given that opportunity, we have been preparing at an enterprise level for transitioning to a commercial company for several years. This has enabled us to efficiently hire and onboard our commercial and medical affairs leadership teams, scale our internal systems and operations, and build the competencies needed to succeed as a commercial company. Anil will speak further to the commercial opportunity later during this call. We also have a strong cash position of approximately $382 million at the end of the quarter, which, based on our current plans and expected available resources, we expect will enable us to fund a potential successful launch in transfusion-dependent lower-risk MDS in the U.S. and fund our planned operations through the end of the third quarter of 2025. Finally, we have outstanding individuals to lead our organization through this transformation from a development stage to a commercial company. These individuals now include Michelle Robertson, who we recently appointed as CFO following the retirement of our longtime CFO, Olivia Bloom. We're thrilled to have Michelle on board at this very important moment in our history. Michelle brings with her over 30 years of financial and commercial operations experience, most recently as CFO of Editas Medicine, and before that CFO of Momenta before its acquisition by Johnson & Johnson. She also spent over 13 years in the finance and commercial operations group at Genzyme. Her deep command of financial operations, her experience with managing the financial and organizational needs of a biotech company preparing to potentially launch its first commercial product, and her prior experience with investors, analysts, investment bankers, and her hands-on experience with commercial launches in the past will all be extremely valuable to our organization going forward. With that, I'll turn the call over to Faye for a regulatory and clinical update.

Faye Feller, Chief Medical Officer

Thanks, Chip, and good morning to everyone on the call. As Chip mentioned, we accomplished critical regulatory milestones this quarter, with the acceptance of our regulatory filings in the U.S. and EU for review of imetelstat for the treatment of transfusion-dependent anemia in patients with low-risk MDS who have failed to respond or have lost response to or are ineligible for ESAs. The FDA assigned a PDUFA action date of June 16, 2024. The FDA also informed us that they are planning to hold an advisory committee meeting. We have no further details at this time about a potential date or agenda for this meeting. As in best practice in our industry, we are working with a consultancy group that has expertise in advisory committees to complement our deep in-house regulatory experience, and we expect to be highly prepared. We believe we have an important medicine in imetelstat and we look forward to the opportunity to discuss it with experts. As Chip also mentioned, we are pleased that the ASH abstracts published this morning continue to demonstrate what we believe are the unique and differentiated qualities of imetelstat in lower-risk MDS seen in the IMerge Phase 3 study, including the breadth of effect across MDS subgroups and the unprecedented durability of transfusion independence. I will now provide a brief overview of the abstracts. Please note that we issued a press release this morning at 9 AM Eastern Time, which describes the abstracts in more detail and that all abstracts are available on the ASH website. The first abstract was accepted for an oral presentation and characterizes transfusion independence (TI) responses in the imetelstat and placebo-treated patients using various risk classification systems. This subgroup analysis demonstrated that imetelstat consistently had higher TI response rates than placebo across different risk subgroups, irrespective of risk classification system. Using the most recent and precise IPSS-M classification system, which takes into account the prognostic effect of molecular mutations, over 13% of IPSS low or intermediate one risk patients enrolled in the IMerge Phase 3 study have been upstaged to moderate high, high, or very high risk MDS. Notably, despite having an MDS that would be classified as higher risk under IPSS-M, these patients benefited from imetelstat treatment compared to placebo. For example, among the IPSS high and very high group, the eight-week RBCT rate was 40% for imetelstat and zero for placebo. This shows that TI with imetelstat treatment is achievable regardless of risk classification. The next abstract was accepted for poster presentation and examined the efficacy of imetelstat versus placebo across underlying mutations associated with MDS. Results show consistent TI responses in imetelstat-treated patients across different molecularly defined subgroups, regardless of the presence of mutations associated with poor prognosis, including ASXL-1 or TP53, or the number of mutations. For example, the eight-week TI rate for patients who had three or more mutations, a group with known poor outcomes, was 56% with imetelstat and 14% with placebo. These results further reinforce our belief in telomerase inhibition as a mechanism that can address the many different clones and causes of lower-risk MDS. The next abstract was also accepted for poster presentation and focuses on the patients who achieved continuous one-year TI with imetelstat treatment, an unprecedented clinical outcome in lower-risk MDS, which recapitulates what we saw in IMerge Phase 2. Among the nearly 20% of the imetelstat-treated patients who achieved a one-year TI, the median duration of TI was over two years, and the median increase in hemoglobin was over five grams per deciliter. Of the 18 imetelstat-treated one-year TI responders with mutation data available, nearly three-quarters achieved greater than 50% reduction in variant allele frequency, and importantly, nearly half experienced a reduction of MDS-associated mutations to an undetectable variant allele frequency. We believe these cases of long-term uninterrupted TI accompanied by robust increases in hemoglobin and the elimination of MDS-associated mutations suggest the potential of imetelstat to have disease-modifying activity. The next abstract accepted for poster presentation summarizes results of Geron's sponsored study in collaboration with the Moffitt Cancer Center. This population-level analysis was based on a large U.S. healthcare insurance claims database that included over 5000 patients with lower-risk MDS. This real-world data analysis showed durable transfusion independence after second-line treatment is associated with improved survival. The median overall survival from the start of second-line therapy was 23.4 months overall and 37.9 months versus 9.3 months among 16-week TI responders versus non-responders. This difference in OS was clinically and statistically significant, with a p-value of less than 0.001. For transfusion-dependent patients, achievement of TI with a second-line treatment is associated with improved OS. Supporting the clinical benefit of TI and underscoring the importance of TI as a clinical trial primary endpoint. We look forward to all these presentations and discussions in San Diego this December. Turning now to our Phase 3 trial of imetelstat in relapsed refractory MF. Enrollment is progressing and we anticipate completing 50% enrollment by the end of this year. We continue to expect an interim analysis in the first half of 2025, which will occur when approximately 35% of the planned enrolled patients have died. A final analysis is expected in the first half of 2026, when over 50% of the planned enrolled patients have died. We look forward to continuing to keep you updated on this important study. In addition to our Phase 3 programs, we are also evaluating imetelstat in a Phase 1 study as combination therapy with ruxolitinib in patients with frontline myelofibrosis. The study was informed by data from preclinical studies describing that the sequential treatment of ruxolitinib followed by imetelstat has a selective inhibitory effect on malignant myelofibrosis stem cells while sparing normal hematopoietic stem cells. Our main goal for improved MF is to determine the safety profile of the combination regimen of ruxolitinib and imetelstat and in addition, we plan to explore any potential activity in the frontline MF disease setting. Last month, the improved MF safety evaluation team or SET, which is comprised of study investigators, evaluated patient data from the first cohort of patients; no dose-limiting toxicities were identified and the SET made a unanimous decision to escalate to the second dose cohort. We are very pleased with this progress and look forward to providing future updates. With that, I'll turn the call over to Anil for a commercial update. Anil?

Anil Kapur, Chief Commercial Officer

Thank you, Faye, and good morning, everyone. We have made significant progress regarding our commercial efforts in this quarter. We remain on track for launch readiness in the U.S. in early 2024 and are looking forward to the opportunity to bring this important new option to patients as they fight their disease. I'll start by highlighting the recent updates to the NCCN treatment guidelines for MDS. This follows the recent FDA label expansion from this dataset in the frontline space. As you may be aware, the NCCN guidelines, along with the publication of results from randomized trials, remain among the most important factors that influence clinical and fair pathways and significantly inform prescribing behavior. This next slide includes a simplified schematic reflecting the revised NCCN guidelines, which shows that for the largest segment of the frontline RS negative patients, PSAs remain the preferred treatment for patients. There also continue to be limited treatment options for patients with serum equol levels greater than 500, and participation in clinical trials is encouraged for those patients. Given these revised guidelines, we expect that the frontline lower-risk MDS phase will evolve towards the use of both ESAs and imetelstat. It is important to remember that the majority of patients with symptomatic anemia are treated today with ESAs in the frontline setting, and most will fail treatment in approximately two years. From our perspective, these updated guidelines reflect a lack of effective new treatment options, particularly for the RS negative lower-risk MDS patients who constitute 75% of the market and for those whose serum equol levels are greater than 500. This is a need we believe imetelstat can powerfully address, and given the lack of effective treatment options, we expect imetelstat to be adopted for these patients for the treatment of lower-risk MDS by the prescriber community. We believe that the low-risk MDS market is primed for a new, innovative, and durable treatment that can be used broadly across MDS subtypes. We expect this large attractive market opportunity for imetelstat across three main patient segments across both the U.S., EU, and U.K. highlighted on the right side of the slide. These segments include frontline patients who are ESA ineligible, given their high baseline serum equol levels; ESA failed RS positive patients, where there are limited treatment options including luspatercept and HMAs; and lastly, there is also a very large segment of approximately 24,000 ESA failed RS negative patients who tend to have worse prognosis than RS positive patients and where there is a significant need for durable treatment. Together, these three market segments represent a significant commercial opportunity for imetelstat with a total addressable market of $3.5 billion by 2033 in the U.S. and these key European markets. This slide highlights the key attributes of imetelstat in the Phase 3 IMerge trial that resonated most strongly with community and academic hematologists. Our unprecedented IMerge Phase 3 data that highlights totality of clinical benefit, achievement of transfusion independence, regardless of RS subtypes, and meaningful durability of response, along with the PRO data that highlighted improvement in fatigue when treated with imetelstat, resonate highly with physicians and serve as critical differentiators that form our value proposition. We continue to work towards bringing all of these elements, along with the real-world analysis of the importance of achieving transfusion independence to our payers and prescribers through appropriate channels to highlight the imetelstat value proposition. This slide highlights key aspects of our market research with hematologists from both the U.S. and key European markets. First, imetelstat's first-in-class mechanism of action is seen as the key driver for future market adoption. Together with the durability of response, physicians view the opportunity for a new and novel mechanism as highly compelling. Second, imetelstat is projected to be part of the standard of care across both RS negative and RS positive patients' subgroups. Physicians express a clear preference to use imetelstat first for their frontline RS negative ESA ineligible patients and across all luspatercept prior treated patients. Third, in the ESA relapsed refractory patients segment, physicians note that imetelstat demonstrates significant improvements in long-term response. That is the 24-week transfusion independence over available options, especially in the RS negative patients. Fourth, for high transfusion burden patients, relapsed and refractory low-risk MDS patients, physicians believe imetelstat may be a compelling option over currently approved therapies. This next slide highlights the results from the survey we conducted post luspatercept frontline commands data release. This was done with over 50 practicing hematologists in the U.S., across both community and academic settings, to understand how they would use imetelstat if available compared to other available therapies. On the left-hand side, you can see that the responses indicate strong enthusiasm for imetelstat to be integrated across three different patient segments in the low-risk MDS treatment landscape upon potential approval. The graph on the right-hand side shows responses further segmented for RS positive and RS negative patients within the subgroups. The responses indicate that imetelstat is not only expected to be broadly adopted for the treatment of low-risk MDS, but that it is especially likely to become a new standard of care for second-line RS negative patients. As a reminder, the RS negative patient segment is approximately three times larger than the RS positive patient segment, and treatment options for RS negative patients remain sub-optimal. Holistically, we believe that the qualitative market research shown earlier and quantitative survey highlighted here are highly aligned with the updated NCCN guidelines. These results emphasize the significant unmet treatment needs across the low-risk MDS patient population. Therefore, we strongly believe that imetelstat, if approved, can play a meaningful role in the treatment paradigm of low-risk MDS moving forward. We believe that we are well positioned to execute against this tremendous potential commercial opportunity. I have described in detail in the past our robust internal planning to prepare imetelstat, the market, and Geron as an organization so that we can deliver a seamless customer experience to all stakeholders while ensuring broad reimbursement for imetelstat. With regards to U.S. launch planning, with our PDUFA date of June 16, 2024, in hand, we expect to be ready to launch upon potential FDA approval. Significant progress on multiple fronts is highlighted on this slide. We have been highly successful in attracting deeply experienced talent to Geron with significant operational and U.S. launch experience. Our non-field facing commercial organization is now fully deployed and deeply engaged in bringing imetelstat to the U.S. market. We plan to hire our field-facing teams, including our sales force in the first quarter of 2024, to ensure proper time for onboarding and training. We have already identified many talented and experienced individuals who are eager to join the team and are very much looking forward to welcoming this critical function to Geron next year. We are pleased with our progress to date and look forward to sharing updates in the future. I will now turn the call over to Michelle for a financial update.

Michelle Robertson, CFO

Thanks, Anil, and good morning, everyone. As this is my first earnings call at Geron, I wanted to start by saying how very excited I am to be part of this amazing team and how privileged I feel to lead the finance function through this pivotal time for the company. With regards to Q3 financial results, please refer to the press release we issued this morning, which is available on our website. I will now review some highlights from the quarter. At the end of Q3, our cash, cash equivalents, and marketable securities were $381.9 million. This balance includes approximately $28.3 million in proceeds from warrant exercises in the third quarter. There are approximately 2.5 million warrants outstanding, and the potential proceeds from these warrants is $3.2 million. R&D expenses for the three and nine months ended September 30 were $29.4 million and $92.1 million respectively, compared to $24.6 million and $67.3 million for the same period in 2022. Expenses have increased year-over-year primarily related to supporting our clinical trials, IMerge Phase 3, and IMpactMF. Both personnel and consulting costs increased to support regulatory submissions, and increased investment in manufacturing as we prepare for the potential commercialization and transfusion-dependent lower-risk MDS. G&A expenses were $18.4 million and $47.7 million for the three and nine months ended September 30, 2023, compared to $15.6 million and $29.8 million for the same period in 2022. The increase in G&A expense is primarily attributed to headcount and external expenses to support the commercial readiness activities. At the end of September 30, the company had a headcount of 137 employees, which we projected to grow to approximately 160 by the end of 2023. Our projected full year 2023 GAAP operating expenses are expected to be between $200 million and $210 million. Moving forward, we plan to provide only GAAP guidance for consistency with our SEC financials. Based on our current operating plans and expectations regarding the timing of potential approval of our imetelstat NDA that is currently under FDA review and subsequent potential U.S. commercial launch, we believe that our current cash runway, together with projected revenues from U.S. sales of imetelstat, proceeds from the exercise of outstanding warrants, and funding under our loan facility, will be sufficient to support our operations through the end of the third quarter of 2025. I will now turn the call back over to Chip.

John Scarlett, CEO

Thanks very much, Michelle. With our strong IMerge Phase 3 data and with our regulatory submissions based on these data currently under review by both the FDA and EMA, we believe there's a robust market opportunity in front of us in transfusion-dependent lower-risk MDS. In addition, we remain excited by our second Phase 3 readout in JAK1 relapsed and refractory MF for which we expect an interim analysis in the first half of 2025 and the final analysis in the first half of 2026. These programs represent important opportunities for the patients we serve and for our shareholders whose interests we represent. We look forward to keeping you updated on our progress and will now open the line to questions.

Operator, Operator

We will go first to Stephen Willey at Stifel.

Tuuli Tsogtbaatar, Analyst

Yes, this is Tuuli on for Steve. Thank you for taking my questions. We have three questions on our end. Firstly, can you guys give us additional color on the dose level? Basically, what those dose levels were in the ImproveMF study and maybe more color on the dose escalation scheme whether this dosing was higher or about the same dose level as low-risk MDS dosing schedules? That would be helpful. And second, can you guys talk a little bit about whether the FDA granting a broad label to luspatercept in the first-line patients impacts your perception of the risk-benefit of imetelstat. And lastly, are you guys planning on actually disclosing or announcing when the enrollment hits the 50% target in the IMpactMF study? That would be it. Thank you.

John Scarlett, CEO

Great. Thank you very much. I'm going to invite Faye to make any comments that she can about the ImproveMF dosing and how that might relate to some of our other dosing in, for example, low-risk MDS or MF, single-agent use. Faye?

Faye Feller, Chief Medical Officer

Thank you, Chip. The dosing for the ImproveMF study is primarily determined by its nature as a safety study. It begins with a lower dose and then escalates to the highest dose we previously used in MF. The dosing details can be found on clinicaltrials.gov, and in our corporate deck, the first dose level is 4.7 milligrams per kilogram of imetelstat, followed by six milligrams per kilogram for the next level. Importantly, this study's main goal is to evaluate the safety of the combination therapy in a frontline MF setting.

John Scarlett, CEO

The second question, related, is did you have any follow-up questions or shall we move on to the FDA or sorry, the broad label commentary? Okay, let's move on. So the second question, I'm going to invite Anil to address. I believe the question was: did the assignment of a broad label to the luspatercept frontline use? Does that read in any way on from our perception on the risk-benefit from imetelstat? I believe I got that right. Anil?

Anil Kapur, Chief Commercial Officer

Thank you for the question. The frontline indication in the frontline population is very different from the population that's been studied for imetelstat and IMerge. Our focus was on ESA relapsed refractory patients who are transfusion-dependent. Those two populations are very different from the frontline commands, which looked at ESA naive patient populations that got treated. So as a non-clinician, my feeling would be that it does not have a risk-benefit impact on our trial, but I would invite Faye to provide her clinical judgment as well.

Faye Feller, Chief Medical Officer

Agree, Anil. The patient population studied in the command has minimal to no overlap with any patient population within IMerge. So the impact on risk-benefit is negligible or non-existent in my opinion.

John Scarlett, CEO

And then the third question was, do we plan on disclosing when 50% enrollment is hit in the IMpactMF? The answer is, yes, we do. That's historically been our practice with all of the clinical studies we've run for the last many years. I'm not sure exactly what form that will take; it kind of depends on timing around other activities, etc. But we do plan to make that publicly available. Okay, maybe we could go to the next question.

Operator, Operator

We'll move next to Corinne Jenkins at Goldman Sachs.

Craig Miller, Analyst

Good morning. This is Craig on for Corinne. So one question from us. You previously announced the initiation of your EAP. And I guess now having some time under your belt? Can you give us some color on the types of patients that have enrolled in that and maybe some of the feedback that you've received so far on the use of imetelstat through it?

John Scarlett, CEO

That's a great question. I think the question was what kind of feedback or what are we seeing with the types of patients who are being proposed for the EAP? Maybe Faye, you could talk a little bit about that.

Faye Feller, Chief Medical Officer

Sure. Thanks for this question. Just a reminder that the EAP is similar to a clinical trial in that enrollment criteria and site initiation criteria are similar to those we use on the IMerge Phase 3 study. However, it's different from a clinical trial in that we cannot recruit for it. It is based on investigator request. So as the trial is still in progress and ongoing, we're really assessing enrollment and the types of patients and we're not providing further details at this time.

Craig Miller, Analyst

Got it. That's helpful. And one more from us. So how are you guys all preparing for the advisory committee meeting with the FDA? And what sorts of topics do you anticipate will be in focus at the event? Thank you.

John Scarlett, CEO

I'll let Faye take that and I will supplement as needed. But Faye, why don't you take first crack at that.

Faye Feller, Chief Medical Officer

Sure. Thanks, Chip. So regarding the ODAC, we've contracted. We have been, as you know, common in the industry, preparing for an ODAC ahead of time. So even before the announcement or the communication from the FDA, we have been working with a recognized vendor that specializes in ODAC preparation in order to anticipate or game plan any types of questions or issues that may be of relevance. Overall, as with most ODAC, it will boil down to a clinical question of risk versus benefit. Other than that, we don't have any further details.

John Scarlett, CEO

Yes. Thanks, Faye. I think I'd like to make a couple of other points about the ODAC. Just to remind people we were told that the FDA is planning an ODAC, but we don't know if that will actually occur. There is historical information about other products in which ODAC had been planned; they have actually been scheduled and cancelled last minute. So I think we'll just have to wait and see on that. We often get a question, Craig, about when did the most ODACs occur? I think in general, our research shows that they occur four to six weeks before the PDUFA date something like that. And I think the other comment is that we have a variety of consultants. So as well as the consultant that Faye was describing, who is a specialized ODAC and advisory committee consultant, we have other broad regulatory consultants. I think we feel like we will be very prepared through this process for whatever may come; and as we've commented in the past, and she commented today in her prepared remarks, I think we look forward to discussing the opportunities for treatment with imetelstat in the space.

Operator, Operator

We'll go next to Kalpit Patel at B. Riley.

Kalpit Patel, Analyst

Maybe first, related to an earlier question. I know we have the updated guidelines here. But I'm curious if we have a sense of how Rebloxyl is being utilized in the real world based on your engagement with KOLs. Is there a preference to use Rebloxyl only for RS positive patients in that frontline, ESA naive group, or does that utilization, at least what you're seeing so far, look consistent with the survey data that you highlighted?

John Scarlett, CEO

Anil, that's definitely for you; Rebloxyl in the real world and is it consistent with what we've seen from survey data?

Anil Kapur, Chief Commercial Officer

Thank you for the question, Kalpit. I think our survey data, which focused on the second-line space, clearly showed where things are, but when we talk to physicians and start to dig into frontline use, what we see is a mix of both PSAs and luspatercept as part of the treatment paradigm when we are speaking to physicians, both academics and community. I think you will see a preference for RS positive patients heading towards luspatercept. But there are also important nuances that need to be kept in mind, especially serum equol levels greater than 200 typically favor luspatercept, while those less than 200 PSAs are also very much in play. And then for ESA-ineligible patients, commands did not study those patients in particular with that study, but they do have a broad label, and physicians continue to sight unmet need for that patient population. From our perspective, I think we see both. I think the degree of adoption depends upon dissatisfaction or satisfaction with ESAs; thus, prescribers will witness both these drugs used. But it will not be a replacement or displacement issue for ESAs, to the best of our judgment today as we go forward. And these patients need a lot of new treatments, and imetelstat does get referred as well, as part of the future treatment paradigm when we show them all the data. So hopefully, this will answer your question, Kalpit.

Kalpit Patel, Analyst

Yes. That's helpful. Thank you. And then, Chip, you mentioned partnering earlier; I guess any more color on how you're thinking about partnering could be useful to investors; maybe is it just for ex-U.S. territories or both U.S. and ex-U.S.?

John Scarlett, CEO

Sure, Kalpit. Thanks. Yes, look, partnering is part and parcel of our business. It's an arrow that every company would hopefully have in their quiver, and it's a conversation that needs to continue to develop and mature as you move closer and closer to potential approvals and subsequent commercialization. So I think that we have always been open to partnering. What we commented on today was specifically around European commercialization. Of course, we have the goal to bring imetelstat to patients in that marketplace as efficiently and as effectively as possible. Now that the MAA is under review, and we have a better feel for timing, we pointed out that the earliest potential approval would be in quite late 2024. This means that a European launch would be potentially in 2025. So we're going to continue to evaluate our strategic options, which include not only partnering but also self-commercialization, as we go into and progress through 2024, and I would hope we would be able to give an update; we expect to give an update later in 2024 in that specific part of the world.

Kalpit Patel, Analyst

Perfect. And one last question. Do you have this abstract that shows the differences in overall survival between the responders and non-responders for transfusion independence? I guess, have you done any sort of early analysis for your own patients in the IMerge study? And whether that data is consistent with what you're showing in that claims data from the analysis study?

John Scarlett, CEO

Well, I think that claims data first and foremost; I think that claims data is what I would call very mature data. It was a large-number study, I don't remember the exact ends, but it is very large. I think the purpose of that study was to provide additional insights across various platforms and across various drugs as to the value of transfusion independence. This has been a staple of belief amongst practitioners and, for that matter, academics. But I do think that since we interact with claims databases all the time, in doing our assessments, we thought this was really valuable and interesting, and collaborated with others to help them analyze these data and make this presentation. So I think it stands on its own, honestly, as an overview of the value in the marketplace of achieving transfusion independence. Thanks.

Operator, Operator

Next, we'll move to Gil Blum at Needham & Company.

Ethan Markowski, Analyst

Hi, this is Ethan Markowski on for Gil. Thank you for taking our questions. So just two quick ones from our side. The first one, maybe a little bit of a follow-up from one of the previous questions. I did try to look quickly, but I was unable to find it. Could you give any color on the rux dosing that was used in improving that? I know you've mentioned imetelstat dosing. And then the other question I'm looking at, Slide 10 of the presentation, the ASH abstract regarding mutations, and you can definitely see a pretty clear efficacy across the various mutations. I was just wondering if there's any biologic rationale why, in particular, ASXL-1 appeared to have a little bit lower effect than the others, or if you think it's just small numbers. Thank you for taking the question.

John Scarlett, CEO

Yes, Ethan, thanks very much. Both are interesting and good questions. I will invite Faye to comment on the rux dosing first and then riff a bit on the efficacy across the different mutations and how patients with ASXL-1 appear to be particularly difficult to treat. Faye?

Faye Feller, Chief Medical Officer

Thanks. Sure, Chip. And thanks for the question, Ethan. Regarding ASXL-1 first, it appears that there’s a smaller magnitude of benefit, and that's mostly due to the low number of patients with the ASXL-1 mutation. That mutation in particular portents a very poor prognosis and a quick transformation to higher risk disease or AML. It was even a bit surprising that we had patients with these mutations in the lower-risk population. This speaks further to the relevance of the IPSS-M classification and the results that we are showcasing in the ASH regarding that abstract. So it all fits together that because of the mechanism of imetelstat that's directed at telomerase and telomerase is overexpressed in malignant cells and drives the malignant phenotype by targeting the disease itself, we have activity across the broad mutations, regardless of what prognosis they suggest for patients. To address your second question or if it was actually your first, the dosing for ruxolitinib in the study aims to assess safety in the context of real-world use. So patients enter the study on ruxolitinib at whatever dose was most beneficial and tolerable for each individual patient, meaning the ruxolitinib dose varies per patient.

Operator, Operator

We'll call next to Joel Beatty at Baird.

Joel Beatty, Analyst

In considering the market research data that shows a larger market share for imetelstat than luspatercept, do you expect that upon launch there could be some moving from luspatercept to imetelstat; some switching? Or would use upon launch mainly be for patients who are newly diagnosed or failing their previous therapy?

John Scarlett, CEO

Thanks again. I think this is Anil's area to comment on whether there’s a possibility of switching, etc., at launch. Anil?

Anil Kapur, Chief Commercial Officer

Sure, Joel, thank you for the question. I think, Joel, just one fact to keep in mind as I answer the question is that there are very few treatment options for low-risk MDS. As Chip spoke to earlier, the market is competitively less intense. In practice, physicians only have a handful of choices. So what we feel is while we may expect or want patients, I think the key need here is for patients to be best treated with whatever option the physician thinks for them until they no longer see benefit. So in the case of a patient not seeing a benefit, and there are more effective options, I think physicians will consider switching the patient over. However, if the patient is responding, the typical clinical practice is to allow that patient to fully benefit through that disease with that treatment choice, then consider other choices for that patient based on where they are. But so hopefully that answers that part of the question. The last remark I'll make here is that having a completely new novel mechanism of action with the level of durability and all the clinical effectiveness that we have shown will become a significant tool for physicians to consider to continue optimizing patient therapy. So I'll stop here.

John Scarlett, CEO

Okay. Thank you. Any further questions, Joel, or did that?

Joel Beatty, Analyst

Great. Thank you.

Operator, Operator

And there are no further questions at this time. I would like to turn the conference back over to Aron Feingold for closing remarks.

Aron Feingold, VP of Investor Relations and Corporate Communications

Thanks so much, Operator. Thank you, everyone, so much for your participation today. We look forward to keeping you updated on our progress. Thanks so much.

Operator, Operator

And this concludes today's conference call. Thank you for your participation. You may now disconnect.