Earnings Call Transcript - GERN Q1 2024

Operator, Operator

Thank you for your patience. My name is Jay, and I will be your conference operator today. I would now like to turn the conference over to Aron Feingold. Please go ahead.

Aron Feingold, Vice President of Investor Relations and Corporate Communications

Good morning, everyone. Welcome to the Geron Corporation First Quarter 2024 Earnings Conference Call. I am 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; Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer; Dr. Faye Feller, Executive Vice President and Chief Medical Officer; Michelle Robertson, Executive Vice President and Chief Financial 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 most recent periodic report filed with the SEC, 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'll turn the call over to Chip. Chip?

John Scarlett, CEO

Thanks, Aron. Good morning, everyone. Thanks for joining us. We're poised for a successful U.S. launch of imetelstat for the treatment of transfusion-dependent anemia in patients with lower-risk MDS. If approved, we're deeply excited for the opportunity to bring patients what we believe is an important and differentiated medicine. With our PDUFA date on June 16, we continue to work closely with the FDA as they complete the review of our new drug application. As part of the NDA review process, on March 14, the FDA's Oncology Drugs Advisory Committee, or ODAC, voted 12 to 2 in favor of the clinical benefit risk profile with imetelstat for its intended indication in lower-risk MDS. The resounding support for imetelstat reflected in the ODAC vote was also echoed in comments from the lower-risk MDS community during the public forum. Hematologists and patients alike spoke out about the burden of transfusion-dependent anemia in this disease and the need for new treatments, particularly for patients with difficult-to-treat subtypes such as high-transfusion burden and RS-negative patients. imetelstat is uniquely positioned to address these underserved transfusion-dependent MDS patient populations. We're in the final stages of commercial readiness execution, which has included bringing on a sales force in April 2024. We're also engaging in marketing commercial access, payer and reimbursement preparatory efforts just as we are completing the build-out of our enterprise capabilities and systems to support our transition to a commercial stage company. In short, we're building on our momentum, acting with urgency and fully confident in our readiness for a U.S. launch on potential approval. We're also financially well resourced to support the planned U.S. commercial launch with approximately $465 million on the balance sheet as of March 31 of this year. On the heels of the highly positive ODAC outcome, we raised approximately $141 million in net proceeds from an underwritten public offering of common stock and a prefunded warrant. This offering included participation from RA Capital, Fairmont, OrbiMed, Verilon, Adage, Boxer, Vivo, Deep Track and multiple large investment management firms in addition to other new and existing investors. From an EU perspective, we also have an MAA, or marketing authorization application, under review in this indication. If imetelstat is approved by the European Commission, we expect a commercial launch in Europe would occur in 2025. We're continuing to evaluate our strategic options for European commercialization, including self-commercialization or partnering and expect to provide an update later this year. I'd like to turn briefly to our ongoing clinical development efforts in JAK-I relapsed and refractory MF patients. As many of you recall, IMpactMF is the only Phase III MF study with overall survival as the primary endpoint. Last month, the data monitoring committee evaluated unblinded data and recommended the clinical trial continue. In addition, the company reviewed enrollment rates and blinded death rates, which are lower than anticipated based on the initial planning assumptions. Accordingly, we're updating our guidance to extend the timelines by half a year with the interim analysis now expected in early 2026 and the final analysis expected in early 2027. We and the trial investigators remain excited about this study and the potential of the treatment that could improve survival for these patients who currently have very few treatment options and dismal survival rates. Faye will provide more color on this trial later in the call. Before I turn the call over to the team, I'd like to take a moment to reflect on how inspired I've been by all of our Geron people. Their passion for bringing our medicine to patients is palpable and drives our culture. From our longest tenured colleagues who worked on the imetelstat IND to our sales force that joined us just a few weeks ago, there is a deeply shared sense of purpose that each one of us can meaningfully contribute to improving the lives of patients with hematologic malignancies. I believe that this unity around our mission drives our urgency and collaboration and is a critical factor in transforming our fast-growing organization into a successful commercial company. With that, I'm going to turn the call over to Anil for a commercial update. Anil?

Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer

Thanks, Chip, and good morning to everyone on the call. We believe that we are positioned very well for commercial value creation and are well prepared to execute a successful U.S. launch upon potential approval. As Chip mentioned, in April, we completed the build-out of our full commercial organization with the hiring of our sales force, which has been now integrated and trained so that they will be prepared to be deployed in the field upon potential approval. I've had the privilege of getting to know this team really well, and I'm deeply impressed by their caliber, experience and commitment. We also have commercial supply arrangements in place and have finalized our specialty distribution network and third-party logistics. From a market perspective, we have worked to identify the concentrated low-risk MDS prescriber base, and our patient access and affordability solutions are on target for implementation at launch. To support our launch preparation and commercial strategy, we have collected extensive market insights, which suggest that imetelstat is highly differentiated in this transfusion-dependent low-risk MDS market. Our research has shown that medical and payer stakeholders are dissatisfied with available options in the low-risk MDS space, which we believe creates an opportunity for imetelstat. Additionally, they express enthusiasm for the totality of clinical benefits seen with imetelstat, including durable red blood cell transfusion independence, hemoglobin increases and reduction in transfusion burden, balanced with a generally well-characterized and manageable safety profile. Lastly, from a patent and regulatory exclusivity perspective in the U.S., as shown at the end of the slide deck we are using today, we have orphan drug exclusivity through the first half of 2031 for MDS. Our method of use patent for MDS and MF expires in March 2033. But if the patent term extension is applied to this use patent, we expect exclusivity would be extended to 2037 and would apply to all uses covered by the patent, including both MDS and MF. We believe imetelstat is uniquely positioned to address unmet needs in transfusion-dependent low-risk MDS, as captured on this slide, which depicts the treatment landscape as well as a simplified schematic reflecting the current NCCN guidelines for MDS. As you may be aware, the NCCN guidelines, along with published results from the randomized trials, remain among the most important factors that influence clinical pathways and significantly inform prescribing behavior. The NCCN guidelines recommend ESAs as the preferred treatment option for the larger segment of frontline RS-negative patients. It's important to remember that many of these patients will show a loss of response to ESA treatment in the frontline setting in approximately 18 to 24 months. There also continues to be limited treatment options for patients with serum EPO levels greater than 500 mL per MU, and participation in clinical trials for ESA ineligible RS-negative patients is encouraged by NCCN guidelines. From our perspective, these guidelines reflect a lack of effective treatment options, in particular for those patients who are ESA ineligible, high-transfusion burden patients and for RS-negative, lower-risk MDS patients who constitute approximately 75% of the market. This is the need we believe imetelstat can powerfully address as a potentially durable treatment that can be used broadly across MDS subtypes. This next slide summarizes our latest market research from 2024 of 50 community and academic U.S. hematologists, when surveyed about the product profile of imetelstat and what factors may drive treatment decisions. It additionally reflects payer priorities in the low-risk MDS space. Our findings show that these physicians note that achievement of RBCTI and rise in hemoglobin are two key factors that drive their decision-making. Further, they point to the greater than 24-week TI and patient-reported outcome data from IMerge as essential considerations. These physicians view imetelstat as the likely standard of care across the relapsed/refractory RS-negative patient population, expressing enthusiasm for the significant efficacy improvement in a population with limited current treatments. These physicians also note that transfusion burden has a strong impact on treatment decisions and believe imetelstat is a compelling option for patients with high transfusion burden due to differentiated data in this patient population. The imetelstat profile also resonates with payer priorities, and they recognize the unmet need in the transfusion-dependent low-risk MDS space. They express that NCCN guideline inclusion and peer-reviewed publications are seen as important evidence for their consideration. Inclusion in the NCCN guidelines requires an FDA label as well as the publication of the pivotal data, which is already available in the line set. Once potential FDA approval is secured, our teams stand ready to engage with NCCN to begin the process of updating the guidelines. It's important to note that, given the elderly patient population with transfusion-dependent low-risk MDS, the majority of U.S. patients are expected to be treated under the Medicare Part B setting; we are confident patients will have broad access to imetelstat. We expect to see imetelstat uptake across ESA-ineligible, ESA-fail RS-negative, and RS-positive high transfusion burden patients. Based on our latest 2024 market research of 50 U.S.-based practicing hematologists across both community and academic settings. On the left-hand side of the slide, you can see that our market research suggests meaningful imetelstat use in frontline ESA-ineligible patients, especially those who are RS negative. The right-hand side of the slide shows the estimated second-line population, approximately 90% of which are expected to be ESA or luspatercept experienced. Our market leaders suggest a broad use of imetelstat across the second line, regardless of frontline therapy, particularly for RS-negative patients. As you can see on the figures on the right, which are further segmented for RS-positive and RS-negative patients with these indications. Our findings confirm the significant unmet need across the low-risk MDS patient population, and we strongly believe that if imetelstat is approved, it can play a meaningful role in the treatment paradigm of transfusion-dependent low-risk MDS moving forward. We believe we are well positioned to capitalize on the imetelstat opportunity in transfusion-dependent low-risk MDS by building on the unique product profile and executing on the launch critical success factors that are driving our commercial plan. From a prescriber perspective, we have a few important goals. That prescribers can base the totality of clinical benefit achievable with imetelstat and understand the efficacy profiles across MDS subgroups, including RS-negative and high transfusion burden patients. It's also critical that we provide education and support for physicians on the imetelstat safety profile and help them to contextualize and manage cytopenias so they can offer an optimized patient experience and duration of treatment. This support will also help prescribers have a good first experience with imetelstat, which is another important goal. From a patient access perspective, as reflected by our research, the need for new treatment options and the high unmet need populations that imetelstat can address are expected to be important considerations to drive access and reimbursement. We are honored and privileged to have the opportunity to launch a medicine that could have such significant meaning for transfusion-dependent lower-risk MDS patients and their families. And we are deeply energized to embark on this journey. With that, I'll turn the call over to Faye for a medical and clinical update. Faye?

Faye Feller, Executive Vice President and Chief Medical Officer

Thanks, Anil. And thanks to everyone for joining our call today. As Chip mentioned, on March 14, the FDA Oncologic Drugs Advisory Committee voted 12 to 2 in favor of the clinical benefit risk profile of imetelstat in transfusion-dependent, lower-risk MDS indication proposed in our NDA. ODAC considered the results from our Phase III IMerge trial as well as the unmet need of limited available treatment options for patients with this cancer. Needless to say, we are very pleased with the committee's decision to recognize the positive clinical benefit risk profile of imetelstat for the treatment of transfusion-dependent anemia in adult patients with lower-risk MDS. As Chip mentioned, the public forum provided a critical opportunity for the ODAC to hear from members of the lower-risk MDS community, including hematologists, patient advocates and patients. Throughout these testimonies, there were several central themes that deeply resonated with me as a hematologist experienced in treating lower-risk MDS patients. These sentiments also echo what we hear in our market research and at medical conferences. The profoundly negative impact of anemia and transfusion dependence on the quality of life for both patients and their families was strikingly evident. These patients are chronically fatigued and struggle to keep up with their daily activities, commonly resulting in psychosocial and emotional burdens. Lower-risk MDS is a progressive disease and by the time the patients progress to transfusion dependence, they do not have many treatment options. In fact, hematologists at the ODAC pointed out that they usually end up cycling through most or all of their options, making an additional treatment in their armamentarium potentially practice-changing. There was also a significant discussion around the deep meaningfulness of achieving transfusion independence for these patients, one of whom testified at the ODAC that she believes transfusion independence would give us more time to have a better quality of life. A nurse commented in the public hearing that time not spent in an infusion chair is time spent living, freely living. From a clinical perspective, while transfusions can provide short-term relief, they can also cause long-term consequences. Frequent red blood cell transfusions can lead to immunization and difficulty in identifying a matched donor to support the continuous transfusion need. Over time, patients can develop end-organ dysfunction due to iron overload. This is in addition to the psychosocial and emotional toll that transfusion dependence can take on patients. The hematology and patient communities expressed that beyond durable red blood cell transfusion independence, the hemoglobin increases and reduction in transfusion burden observed with imetelstat are important indicators of clinical benefit. Lastly, several hematologists spoke out about their comfort level managing cytopenias, given their familiarity with these hematologic toxicities as a side effect of many medicines regularly used in clinical practice. This reinforces our belief that with the proper context and education, these cytopenias should be able to be well managed by hematologists in a real-world setting. Overall, hematologists, patient advocates and patients expressed support for new treatment options in transfusion-dependent, lower-risk MDS, especially for treatment with the durability of red blood cell transfusion independence seen within imetelstat. Turning next to our medical affairs readiness to support our expected launch. We have a highly skilled medical affairs team in place. This team has been instrumental in conducting peer-to-peer scientific exchange of medical information, particularly via medical congresses and publications. Awareness about imetelstat in the hematology community has been heightened by Geron's presence at congresses like EHA and ASH, and particularly by the publication of Phase III IMerge data in the Lancet last year. Our medical affairs team will partner with our commercial colleagues on the important effort to have imetelstat included in the NCCN guidelines once it is approved. Lastly, our field medical colleagues are in place and are prepared to be a critical resource in helping support physicians in managing their lower-risk MDS patients. Turning now to our Phase III IMpactMF trial of imetelstat and JAK inhibitor relapsed/refractory MF. We are proud to sponsor the first and only Phase III trial in MS that has overall survival as its primary endpoint. A total of 320 patients are planned to be enrolled using the 2:1 randomization for the imetelstat arm versus the best available treatment arm. Per protocol, interim analysis has been planned since about 35% of the planned enrolled patients have died and the final analysis when approximately 50% of the planned enrolled patients have died. The Data Monitoring Committee evaluated unblinded data last month and recommended the study continue. In addition, we reviewed enrollment rates and blinded death rates, which are lower than anticipated in our initial planning assumptions. Accordingly, we are updating our guidance to extend the timeline by half a year and now expect the interim analysis in early 2026 and the final analysis in early 2027. Because the factors affecting these estimates are highly variable and difficult to predict, the actual interim and final analysis could occur sooner or later than we currently expect. As the trial continues, we'll continue to monitor enrollment and death rates and update guidance if appropriate. Of note, we have multiple ongoing work streams to increase trial enrollment. Our clinical operations team has been conducting on-site visits to clinical trial sites around the globe. Additionally, we've been increasing our engagement with patient advocacy groups in the myelofibrosis disease space. I think it's important to note that we at Geron, as well as the IMpactMF trial investigators and also patient advocates, continue to express excitement around the potential to extend survival in this JAK inhibitor relapsed/refractory population. Today, treatment of myelofibrosis is dominated by JAK inhibitors or therapies with other mechanisms of action in combination with JAK inhibitors. Once patients become unresponsive to JAK inhibitors, which leads to treatment discontinuation for approximately 75% of patients after 5 years, they face a dismal overall survival of approximately 11 to 16 months. We believe that if our trial is successful and imetelstat is approved in this indication, it could transform treatment for these patients. With that, I'll turn the call over to Michelle for a financial update. Michelle?

Michelle Robertson, Executive Vice President and Chief Financial Officer

Thanks, Faye, and good morning, everyone. For detailed Q1 2024 financials, please refer to the press release we issued this morning, which is available on our website. Now let me bring your attention to a few highlights from the quarter. As of March 31, 2024, the company had approximately $465 million in cash and marketable securities, including proceeds from an underwritten public offering of common stock and a prefunded warrant in March 2024 for net proceeds of approximately $141 million. Total operating expenses for the first quarter of 2024 were $56.4 million compared to $40.1 million for the same period in 2023. Research and development expenses for the first quarter of 2024 were $29.4 million compared to $27.2 million for the same period in 2023. The increase year-over-year primarily reflects higher CMC costs due to the timing of imetelstat commercial manufacturing batches and increased personnel-related expenses for additional headcount. G&A expenses for the first quarter of 2024 were $27.1 million compared to $12.9 million for the same period in 2023. The increase primarily reflects our investment in commercial preparatory activities and higher personnel-related expenses for additional headcount as we have been preparing to transition from a clinical to commercial stage company. As of March 31, 2024, and prior to adding our sales force in April, we had 162 full-time employees. Subject to approval of imetelstat in the U.S., we plan to grow to a total of approximately 250 to 300 employees by year-end 2024. Our projected full-year 2024 operating expenses are expected to be between $270 million and $280 million. Based on our current operating plans and our assumptions regarding the timing of a potential approval and commercial launch of imetelstat and TDLRMDS in the U.S., we believe that our existing cash, cash equivalents, and current and noncurrent marketable securities, together with our projected revenues from U.S. sales of imetelstat, if approved, potential proceeds from the exercise of our outstanding warrants and future drawdowns under our loan facility will be sufficient to support our operations into the second quarter of 2026. I will now turn the call back over to Chip.

John Scarlett, CEO

Thanks, Michelle. We believe imetelstat has the potential to offer a life-changing treatment option for patients with transfusion-dependent lower-risk MDS. Building on the momentum from the resoundingly positive ODAC, we're deeply energized and well prepared to launch imetelstat in the U.S. if approved. Driven by our experienced leaders and expected excellent execution, we feel confident in our ability to capitalize on this robust opportunity and to transform Geron into a successful commercial company. We believe this transformation will create significant value for patients and shareholders. Let's now open the line to questions. Operator?

Operator, Operator

Your first question comes from the line of Tara Bancroft of TD Cowen.

Tara Bancroft, Analyst

So mine is regarding the myelofibrosis trial timeline. Can you comment on if it was more so due to slower enrollment? Or if there was a heavier impact from having fewer events than anticipated? And if it's the latter, can you remind us of the bar here? And maybe if your expectations have changed for where OS could land for the control? Like how should we think about expectations here?

John Scarlett, CEO

Faye, go ahead and take that, please.

Faye Feller, Executive Vice President and Chief Medical Officer

I apologize for these issues. Per my comments, the enrollment and death rates are both lower than anticipated, and we are not able to provide additional detail into which one is the driving force. And as you noted, this pushes the timelines out about six months. We see continued enthusiasm for the study, and we'll continue to monitor and update as appropriate.

Operator, Operator

Your next question comes from the line of Karin Johnson of Goldman Sachs.

Unknown Analyst, Analyst

This is Craig on for Karin. So first one from us. Have you all initiated labeling discussions with the FDA of imetelstat in myelodysplastic syndrome?

John Scarlett, CEO

Yes, we have received comments from the FDA on our draft label. However, the FDA has not completed its review yet. We look forward to continuing our discussions with the agency as we approach PDUFA, but we do not plan to publicly disclose or discuss any ongoing regulatory interactions with the division before PDUFA.

Unknown Analyst, Analyst

Got it. That makes a lot of sense. And it seems like from the commercial standpoint and clinical standpoint that getting NCCN guidelines updated is a top priority. So how quickly do you think that could occur following the potential approval of the imetelstat?

John Scarlett, CEO

Anil, why don't you take that one?

Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer

Sure. We are ready to provide an official submission to NCCN upon approval, which includes the approved prescribing information of the label, the peer-reviewed publication in Lancet, and our cover letter highlighting the patient populations. Typically, NCCN updates the guidelines within 2 to 3 months for new drugs reviewed by the Low-risk MDS committee. Therefore, if we submit in June upon approval, we expect the guidelines to reflect imetelstat about 2 to 3 months later.

Operator, Operator

Your next question comes from the line of Gil Blum of Needham & Company.

Gil Blum, Analyst

Maybe a slightly different take on myelofibrosis. So were there changes to the standard of care over the last couple of years that may explain some of this slower accumulation? And secondly, can you comment on what the challenges are for enrollment? That is competition from commercial treatments, other studies? Whatever information you can provide.

John Scarlett, CEO

I'll let Faye take it first, and I'll add if needed. Go ahead, Faye.

Faye Feller, Executive Vice President and Chief Medical Officer

It's pretty observant. Indeed, we've had the approval of a few more JAK inhibitors over the last couple of years, and I believe that has impacted the enrollment rate. However, it's multifactorial, including the new approval of JAK inhibitors, the lack of JAK inhibitor treatment option in the control arm, and still facing challenges with resourcing issues at sites and staffing. All of these contribute to the lower enrollment rates, which we predicted, but this is not unanticipated and can be seen in many studies.

Gil Blum, Analyst

Alright. Thanks for the color.

Operator, Operator

Your next question comes from the line of Stephen Willey of Stifel.

Unknown Analyst, Analyst

This is Thuley speaking for Steve. Congratulations on the progress. We have two questions. The first is about the launch preparation process for the upcoming approval. You've outlined the accomplishments so far, but could you detail the major steps that still need to be taken and provide more context on that? The second question is a follow-up to the previous inquiry regarding the MF trial. Is it possible to share any numbers or percentages related to the enrollment rate? Additionally, what measures are you taking to speed up enrollment, and how confident are you that you won’t need to extend the timelines for interim and final analysis?

John Scarlett, CEO

Let's take the first question on the launch preparations and Anil will take that one, and then we'll pivot over after that to your follow-up question on the MF trial. Go ahead, Anil.

Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer

Sure. So thanks for the question. A really important step for us is the completion of our onboarding of our full commercial team. As we stated on our call, our key account managers in the field are also now fully onboarded. And we are working very hard towards our potential approval in June, given our PDUFA date. Our concentration is both on ensuring that we have full commercial supply. Our distribution network is fully finalized. We are preparing all materials to inform stakeholders, including payers, our prescribers and the populations that we interact with. We have identified the prescriber base. We are working towards our access and affordability solutions. Everything remains on track. And our expectation is a well-executed launch for imetelstat in the U.S. market upon approval.

John Scarlett, CEO

Anil, and Faye, why don't you take the question on the follow-up question on the MF?

Faye Feller, Executive Vice President and Chief Medical Officer

Olivia Bloom: I'm going to try to remember all of the components. Regarding the enrollment rate, we announced last year in November that the study was 50% enrolled, and we plan to provide updates when it's material, and enrollment is continuing at a steady pace. As I mentioned before, enthusiasm has not really diminished for the study. So we continue to see movement forward. Remind me the other questions?

John Scarlett, CEO

I appreciate the question. I believe the main concern is how we will move forward and whether further refinement will be necessary. As mentioned in the prepared comments, these estimates can vary significantly and are challenging to determine due to two main factors. First, the enrollment rate cannot solely account for the timelines we are looking at. As you've heard, we are doing everything possible to maintain that enrollment rate. Second, Faye previously addressed a question regarding the commercial launches of other competing JAK products, noting that we don't have a JAK inhibitor in the BAT arm. Additionally, the pace at which we accumulate events, specifically death events, is much harder to predict. It's important to note that we have not unblinded the study, so we can only observe the pace of these events. The study has a 2-for-1 randomization, and in our prepared remarks, we indicated that we would need to monitor the situation closely. If necessary, we may adjust our timeline for interim and final analysis. We will certainly provide updates but do not commit to specific timing. We will keep tracking both enrollment and event rates and update our guidance as needed. I hope that clarifies things, and I'm happy to answer any follow-up questions.

Faye Feller, Executive Vice President and Chief Medical Officer

I also believe there is a part of the question regarding our efforts to improve enrollment. We are dedicating significant resources to meeting with investigators and key opinion leaders on a personal level with our Geron operations and clinical development teams. Additionally, we are holding frequent virtual meetings to remind investigators about the study and gather their feedback on enrollment. Our medical affairs team has been actively engaging with myelofibrosis advocacy groups in both the U.S. and internationally.

Operator, Operator

Your next question comes from the line of Joel Beatty of Baird.

Joel Beatty, Analyst

The first one is, what percent of Luspatercept use is currently in RS positive compared to RS negative? And what do you expect a similar split for imetelstat?

John Scarlett, CEO

Anil?

Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer

Sure. So we don't have indicated data to answer this question. What we do have is public statements from the companies stating that in RS positive, they are very well penetrated and the numbers quoted are in excess of 65% from public statements from other companies regarding RS positive. Does that answer your question?

Joel Beatty, Analyst

Yes, that's helpful. And then the last question, is there a kind of specific definition of ESA failure that might prompt starting imetelstat? Or is there some clinical judgment involved? And so I wonder if patients go through a period of time in which they're like partially responding to ESAs?

Faye Feller, Executive Vice President and Chief Medical Officer

I guess I'll take that. For the clinical trial, we had a specific definition, and what will be on the label remains to be seen but will be according to physician assessment.

John Scarlett, CEO

Anil, any further comments? Sorry, go ahead.

Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer

And Joel, I also will point you to our deck that we are using for the call because we have recently completed a survey of U.S. physicians, 50 of them, both academic and community. And if you look at their expectations for imetelstat, we see ourselves being extremely well-positioned across all the patient segments that we serve, in particular what is highlighted from physicians and very favorably received by them. For imetelstat, the population, which is ESA ineligible in the frontline setting and patients who are RS negative patients irrespective of either prior treatment with Luspatercept or ESAs. I think these are the places where we are extremely differentiated and are serving a very high level of unmet need.

Operator, Operator

Your next question comes from the line of Kalpit Patel of B. Riley Securities.

Kalpit Patel, Analyst

I think, Chip, you previously said that you'd make the patent life cycle decision for applying the PTE to the method and news patent around the time of FDA approval. So the question is, is that guidance unchanged today? Or does that delay in the MS readout sort of impact the thinking behind the patent strategy?

John Scarlett, CEO

Great question. Thanks, Kalpit. I think the specifics of how application for PTE works is a little bit above my pay grade, but I'll give you my understanding of it today as best I can. After you have your first approval, you can consider whether you have a clear strategic idea of where you would like to apply PTE. And right now, all of that is pointing towards the method of use patent. The reason for that is fairly straightforward as many people in the investment community have pointed out; we're covered quite well with the orphan drug exclusivity, and applying PTE to the commercial patent wouldn't really trump that. And so there's every reason to imagine putting the PTE onto the method of use patent. We've done a lot of consideration and working on this. And at the end of the day, we have to indicate to the FDA when at some point after approval what we want to do, and they will go and provide us with estimates of the exact time frames and so forth. There's kind of a process there. Assuming all goes well, I think it's important to say that we believe, from our analysis of this and our outside firms' analysis of this, that exclusivity would be extended to 2037, and it would very importantly apply to all uses covered by the patent, including both MDS and MF. So a lot of incentives to apply it to the method of use claims and we'll take that up. Obviously, the implications come much later, but I don't know of any reason that we should not indicate that that's our current expectations.

Kalpit Patel, Analyst

Okay. And we've been getting questions on the manufacturing and CMC front, given what's happening in the industry. I guess if you can comment on the inspections and everything on that front go okay? And then I have a follow-up.

John Scarlett, CEO

Yes, we are not going to provide specific follow-up information. However, we are comfortable with how things have progressed so far and are looking forward to the PDUFA date for approval. That's about all I can say. We understand that there is always some level of uncertainty, but beyond that, I don't think we will be making specific comments on the incremental steps toward PDUFA regarding various aspects, including manufacturing and inspections.

Kalpit Patel, Analyst

Okay. And then last one. We've been getting questions on how we should be modeling the U.S. launch, the initial ramp? I guess maybe one for Anil, are there any good examples or analogs that the investor community could use to kind of project this, at least for the initial ramp for the first year or two? Reblozyl was obviously approved a few years ago, but that market wasn't built at that time. So people are curious how they should model this now.

Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer

Yes. So I think, Kalpit, the best guidance I'll give is to focus on the unmet need of this patient population. What we have heard very clearly in the low-risk MDS market, there is dissatisfaction predominantly along three segments. One is the need for better, more effective products for patients who are high transfusion burden, which remain 40% to 50% of this marketplace. Or options for RS-negative patients who today do not have effective therapies and patients, obviously, who are ineligible for ESAs because their outcomes are pretty dismal. So our expectation is that those are three patient populations where physicians will use drugs such as ours. We also know that, as you yourself said, Luspatercept has been in this marketplace for the last 2 to 3 years. So we would expect to see patients who have been treated with Luspatercept and physicians are looking for more options. Both our Phase II study and our Phase III part of the study covered with Luspatercept pretreated patients. And given the uniqueness of our mechanism, we would expect to be effective in that population as well. So I think it's a mix of these patients. It's hard to point to one effective analog because there are many characteristics which make each and every one of these launches unique. But I do think the unmet need is very high. Our data remains highly differentiated and the dissatisfaction and the need for new treatments, we should see imetelstat well positioned, and be adopted within the armamentarium of the physicians as they treat their low-risk MDS patients.

Operator, Operator

That concludes our Q&A session. I will now turn the conference back over to Aron Feingold for closing remarks.

Aron Feingold, Vice President of Investor Relations and Corporate Communications

Thanks so much to everyone for joining us today. We appreciate your interest in Geron and look forward to keeping you updated during this very exciting time for our company. Have a good one, everyone.

Operator, Operator

This concludes today's conference call. You may now disconnect.