Q1 2024 Geron Corp Earnings Call

Participants

Aron Feingold; Vice President of Investor Relations and Corporate Communications; Geron Corp

John Scarlett; Chairman of the Board, President, Chief Executive Officer; Geron Corp

Anil Kapur; Executive Vice President, Corporate Strategy and Chief Commercial Officer; Geron Corp

Faye Feller; Executive Vice President, Chief Medical Officer; Geron Corp

Michelle Robertson; Chief Financial Officer, Executive Vice President, Treasurer; Geron Corp

Tara Bancroft; Analyst; TD Cowen

Gil Blum; Analyst; Needham & Company Inc.

Stephen Willey; Analyst; Stifel Nicolaus and Company, Incorporated

Joel Beatty; Analyst; Robert W. Baird & Co., Inc.

Kalpit Patel; Analyst; B. Riley Securities

Presentation

Operator

Thank you for standing by. My name is Jill, and I will be your conference operator today. At this time, I would like to welcome everyone to the Geron Q1 2024 conference 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, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one. Again, I would now like to turn the conference over to Aron Feingold, you may begin.

Aron Feingold

Good morning, everyone. Welcome to the Geron Corporation First Quarter 2024 earnings conference call and Aron Feingold Geron's, Vice President of Investor Relations and Corporate Communications.
I'm joined today by several members of Darren's management team, Dr. John Scarlett, Chairman and Chief Executive Officer, Neil Cooper, Executive Vice President of Corporate Strategy and Chief Commercial Officer, Dr. Faiz seller, Executive Vice President and Chief Medical Officer, Michelle Robertson, Executive Vice President and Chief Financial Officer, and Dr. Andrew Crestline, 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. Jeff?

John Scarlett

Thank you, and 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 16th. 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 14th, the FDA's Oncology Drug Advisory Committee or Kodak, voted 12 to two 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 order backlog was also echoed in comments from the lower-risk MDS community. During the public forum, hematologists and patients alike spoke 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 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 31st of this year, on the heels of a highly positive Modec 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 Bourbon that Farrell on 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 Jackie relapsed and refractory MF patients. As many of you will recall, impact MF is the only Phase three MS study with overall survival as the primary endpoint last month, the Data Monitoring Committee evaluated unblinded data and recommended the clinical trial continued. In addition, the company reviewed enrollment rate and blinded death rates, which are lower than anticipated based on the initial planning assumptions. Accordingly, we're updating our guidance to extend the time lines by half a year with the interim analysis now expected in early 2026. And the final analysis expected in early 2027. We have the trial investigators remain excited about this study and the potential of a treatment that could improve survival for these patients who currently have very few treatment options and dismal survival. Dave 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 German 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 IMD. 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 it's 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 Aneel for a commercial update. And Neil.

Anil Kapur

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 Jeff 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 work 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 suggests 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 expressed enthusiasm for the totality of clinical benefit seen that 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 US, as shown at the end of the slide that we are using today, we have orphan drug exclusivity through first half 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 backend, including both MDS and AML. 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 and payer pathways and significantly inform prescribing behavior. The NCCN guidelines recommend ESA's as the preferred treatment option, but the largest 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 milligrams per year 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 constitute approximately 75% of the market. This is a 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 fair priorities in the lower-risk MDS. Our findings show that these physicians know that achievement of RBCPI. and rise in hemoglobin are two key factors that drives their decision making for them. They point to the greater than 24 week TI. and patient-reported outcome data from EMERGE as essential considerations. These physicians view imetelstat as a 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 transfusion burden has 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 review publications. I've 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 long-term once potential FDA approval is secured. Our teams stand ready to engage with NCCN to begin the process of updating their guidelines. It's important to note that given the elderly patient population with transfusion-dependent, lower-risk MDS the majority of US patients are expected to be treated under the Medicare Part D setting. We are confident patients will have broad access to imetelstat. We expect to see imetelstat uptake across ESA ineligible, ESA failed RS negative and RS positive high transfusion burden patients based on our latest 2024 market research of 50 US-based practicing hematologists across both community and academic settings.
On the left-hand side of this 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 research suggests 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 within these subgroups. Our findings confirm the significant unmet need across the lower-risk MDS patient population. And we strongly believe that imetelstat is approved, can play a meaningful role in the treatment paradigm of transfusion dependent lower risk MDS.
Moving forward, we believe we are well positioned to capitalize on imetelstat opportunity in transfusion-dependent, lower-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 embrace 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 and optimize patient experience and duration of effect. This support will also help prescribers have a good first experience with imetelstat, which is another important cause 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 Fay for a medical and clinical update.

Faye Feller

Okay. Thanks, Michelle, and thanks, everyone, for joining our call today. As Tim 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 MDS. All that considered the results from our Phase three IMerge trial as well as the unmet need and 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 in the public forum provided a critical opportunity for the Autodesk to hear from members of the lower risk MDS community, including hematologists, patient advocates and patients. Throughout the testimony, there were several central themes that deeply resonates with me as a hematologist experience in treating lower risk MDS patients.
Patient events 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 were strikingly evident. These patients are chronically fatigued and struggle to keep up with their daily activities, commonly resulting in like a social and emotional burden, lower-risk MDS and the progressive disease. And by the time, the patients progress to transfusion dependence, they do not have many treatment options. In fact, hematologists at the Kodak 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 significant discussion around the deep meaningfulness of RBC transfusion independence for these patients, one of whom testified at the low deck that she believed transfusion independence would give us more time to have a better quality of life. A nurse commented in public hearing that time not spent in an infusion chair time and living for daily 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 leak Alan utilization 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 psycho social and emotional toll that transfusion dependence can take on patients, the hematology and patient communities expressed that beyond durable RBC TI., the hemoglobin increases and reduction in transfusion burden observed with Imetelstat are important indicators of clinical benefit.
Lastly, several hematologists spoke at their comfort level managing cytopenias, given their familiarity with these hematologic toxicities and the 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 hematologist patient advocates and patients express support for new treatment options in transfusion dependent, lower risk MDS, especially for treatment with the durability of our BCTI. team with 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 the medical congresses and publications awareness, not in the cost side of the hematology community has been heightened by your presence at congresses like E. half and ASH and particularly by the publication of Phase three EMERGE 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 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 three impact MF trial of imetelstat inject inhibitor relapsed refractory MF. We are proud to sponsor the first and only Phase three trial in MS that has overall survival as its primary endpoint by a total of 320 patients are planned to be enrolled into two to one randomization for the imetelstat arm versus the best available treatment arm per protocol. Interim analysis has been planned and about 35% of the planned enrolled patients have died. And the final analysis, when approximately 50% of the planned enrolled patient contacts as an overall survival study, the time line for the interim and final analysis is dependent not only on the rate of enrollment, but also on the event rate for patient death rate in the trial. The data monitoring committee evaluated unblinded data last month and recommended the study continue. In addition, we reviewed enrollment rates and blended gas rates, which are lower than anticipated in our initial planning assumptions. Accordingly, we are updating our guidance to extend the timelines by half of the 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 have 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 impact MS trial investigators and also patient advocates continue to express excitement around the potential to extend survival in this Jack inhibitor relapse refractory population by treatment of myelofibrosis is dominated by Jack inhibitors or therapies and other mechanisms of action in combination with Check inhibitors when patients become unresponsive to Jack inhibitors, which leads to treatment discontinuation for approximately 75% of patients after five 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, which helps.

Michelle Robertson

Thanks, Phil, and good morning, everyone for details 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 US. 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 the potential approval and commercial launch of imetelstat and TDLR. MDS in the US. We believe that our existing cash, cash equivalents and current and noncurrent marketable securities, together with our projected revenues from US sales of imetelstat is approved potential proceeds from the exercise of warrants and 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

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 Modec were 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 let's now open the line to questions. Operator?

Question and Answer Session

Operator

Thank you. The floor is now open for questions. If you have dialed in and would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again, if you are called upon to ask a question and are listening via loud speaker on your device, please pick up your handset to ensure that your phone is not on mute. When asking your question, your first question comes from the line of Tara Bancroft, TD Cowen. Your line is open.

Tara Bancroft

Hi, good morning and thanks so much for taking the questions. So mine is on regarding the myelofibrosis trial timelines. 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. Thanks.

John Scarlett

And I'm sorry, go ahead. I'll take that, please. They are you off mute.

Faye Feller

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

Tara Bancroft

Okay. Thank you.

John Scarlett

Thanks, Dan.

Operator

Your next question comes from the line of Karin JOHNSON of Goldman Sachs. Your line is open.

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

John Scarlett

Yes. So we've received pretty smooth, Craig. We've received comments from the FDA on our on our draft label. However, as you would imagine, the FDA hasn't yet completed its review so we certainly look forward to continuing our conversations with the agency as we approach the data. But we do not expect to publicly disclose or discuss any ongoing regulatory interactions with the division prior to private producers.

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 imetelstat?

John Scarlett

And Neil, can you take that one short pause?

Anil Kapur

So Greg, we are able to provide an official submission to NCCN upon approval, which we are ready to do. So. This obviously includes the approved prescribing information or the label. It includes the peer-reviewed publication Lancet, which exists and it includes our cover letter, highlighting the patient populations. Typically NCCN update the guidelines within two to three months for new drugs that are received for low-risk MDS within the NCCN, low-risk MDS committee. So our expectation is if we submit in June upon approval about two to three months later, we would expect to see the guidelines reflect imetelstat.

Got it. Thank you so much.

Operator

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

Gil Blum

Hi, good morning, everyone, and thanks for taking the questions. Maybe a slightly different tack on my list fibrosis. 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 and competition from commercial treatments, other studies, whatever information you could provide? Thank you.

John Scarlett

Elekta pay, take it first and I'll address it if necessary and go ahead.

Faye Feller

Thanks for the question. Got plenty of Durbin and indeed, we've had the approval of <unk> few more Jack inhibitors over the last couple of years. I do believe that has impacted the enrollment rate excuse me a couple, but it is multifactorial, including the new approvals of Jack inhibitors, the lack of Jack inhibitor treatment option in the BAT arm and even still challenges of resourcing issues at site and staffing. So all of these contribute to the lower enrollment rates that we predicted. And we then predicted, but we have not unanticipated and conditional amendment of the Bush.

Gil Blum

All right. Thanks for the color.

Operator

Okay, thanks again, if you would like to ask a question, press star then followed by the number one on your telephone keypad.
Your next question comes from the line of Stephen Willey of Stifel. Your line is open.

Stephen Willey

Hi, good morning, guys. This is Tony on for Steve. Thank you for taking my questions and congrats on the progress. And we have just two questions on our end. The first one is And regarding the launch preparation process for that coming on approval. So I mean that you definitely provided list of things that you guys have accomplished so far. So in terms of preparation, what are the major steps that need to be done and maybe like additional color on that. And the second question is related to just a follow up on the prior questions regarding MS trial. So is there. So would it be possible to provide any like number or percentage like percentage wise in terms of like our enrollment rate and John and also like what are the steps that you guys are actually taking in order to expedite enrollment? And what is your confidence level that you guys will not need to actually extend the extend the time line for interim and final analysis.

John Scarlett

Thank you. But so I'll take the first question on the launch preparations, and Neil will take that one. And then we'll I'll pivot over after that. To your follow question on the MF trial. Go ahead.

Anil Kapur

Sorry. Sure. So thanks for the question on a really important step for us is the completion of the 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 producer 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 to the populations that we interact with. We have identified the prescriber base. We are looking towards our access and affordability solutions. Everything remains on track and our expectation is a well-executed launch Quadrem. It'll start in the U.S. market upon approval.

John Scarlett

It's got to name and then, hey, why don't you take the question on the follow-up question on the MF?

Faye Feller

Yes, thanks for the question. 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 and Enrollment is continuing.
It is at a steady pace. As I mentioned before, enthusiasm has not really diminished for this study. So we continue to see movement of it. Remind me the other question.

John Scarlett

I can take it. I think that would yes. I think what she was getting at was sort of the in issue of how we would follow all of this going forward in might it be necessary to to refine further?
Look, I think you said in your prepared comments that these estimates are really variable to pardon me and pretty difficult because you have two variables, right? You have an enrollment rate which and really cannot be seen as the only contributor to the time lines here. And we're as you heard, we're doing everything we can to keep that enrollment rate up and say commented in answer to a previous question on whether there was going to ask about to commercial it launches of other competing Jack products. She mentioned the fact that the and that we don't have a Jack inhibitor in the in the BAT arm and so forth. But I think the other side is the pace at which we accrue events, right? Does it ends and that's a lot harder to predict. And I'll just simply say because we do not and have not unblinded the study, of course, important to note, all we can look at is sort of the pace of those events. And I will remind everybody that the study is a two for one randomization. So I think we and we made the comment in the prepared remarks that we will have to follow along. And if things require further updates, either we go slower and in towards the interim and final analysis or we go faster, we'll certainly need to update but we don't make a specific commitment on exactly when we would do that. So I hope we'll continue to monitor both enrollment and event rates and update guidance as required.
So I hope that answers your question. Happy to take a follow on if needed,

Faye Feller

you can absolutely there because one into the question about what we're doing to them enhanced enrollment and I'll just speak quickly about that, that we are putting a lot of effort to that meeting with investigators and each country and thought leaders, especially on a one to one level with Geron, Garen operations and clinical development staff as well as frequent virtual meetings and virtual. I guess you can call them like investigator type meetings to remind investigators about the study and to hear any feedback on enrollment. We also on with our medical affairs team have been engaging more aggressively with myelofibrosis advocacy groups, both in the US and international.

Stephen Willey

Thanks, guys.

Operator

Your next question comes from the line of Joel Beatty of Baird. Your line is open and thanks for taking the questions.

Joel Beatty

The first one is what percent of luspatercept uses currently in RS positive compared to RS negative? And would you expect a similar split for imetelstat?

John Scarlett

Yes, sure.

Aron Feingold

So we don't have syndicated data to answer this question. What we do have is public statements from the companies stating that Anadys positive. They are very well penetrated and the numbers quoted are in excess of 65% from public statements from Squibb for RS positive. Does that answer your question?

Joel Beatty

Yes, that's helpful. Thank you. And then on the last question, is there a kind of specific definition of ESA failure and that might prompt starting imetelstat now? Or is there some clinical judgment involved? So I wonder if patients go through a period of time and with serially partially responding to ESAs

Faye Feller

I asked Altix after the clinical trial, we had a specific definition and what will be on the label remains to be seen, but will be according to the investigator our sorry, physician adjustments.

John Scarlett

I think if you have any further comments, sorry, go ahead.

Anil Kapur

And yesterday and Joel, I also will point you to our deck that we are using for the call because we have recently completed on a survey of US physicians, 50 of them, both academic and community. And if you look on our debt 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. Our for imetelstat is 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. And I think these are the places where we are extremely differentiated and are serving a very high level of unmet need.

Operator

Your next question comes from the line of Kalpesh Patel of B. Riley Securities. Your line is open.

Kalpit Patel

Yes, hey, good morning. And thanks for taking the question. And I think Chip, you've previously said that you'd make the patent life cycle decision for applying the PTE. to the method of use patent around the time of FDA approval. So the question is, is that guidance unchanged today? Or does the delay in the MS trial readout sort of impact the thinking behind the patent strategy.

John Scarlett

Great question. Thanks, Kyle. But I think the 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 on after you have your first approval, you can consider whether you have had a clear strategic idea of where you would like to apply PPD. And right now, all of that is pointing towards the method-of-use patents. The reason for that is fairly straightforward as many people in the investment community have pointed out many and you have pointed out in your coverage and we're covered quite well with the with the orphan drug exclusivity and you can apply in PTE. to the compact and wouldn't really trumps that. And so there's every reason to imagine putting the PTD. onto the MOU. We've done a lot of consideration and working on this and at the end of the day, we have to indicate to FDA when you plan at some point after approval, what we wanted 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 assuming all goes well, they're out. I think it's important to say that the X, we believe from our analysis of this in our outside terms analysis of this, that exclusivity would be extended to 2037, and it would very importantly for a method-of-use patent would apply. The PTE. would apply to all uses covered by the patent, including both MDS and AML. So a lot of incentives to to apply it to the methods of use claim, 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 our current expectation.

Kalpit Patel

Okay. Thank you. 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. Okay. And then I have a follow-up.

John Scarlett

Yes, I I think we're not going to provide specific numbers. I'll follow up there, but I think that we are comfortable and as things have proceeded to date, where still looking forward to, I could do for a date with an approval. And that's the best I can really say. We all know there. There's always some degree of uncertainty. But other than that, I don't think we're making specific comments about the piece by piece of march towards could do for you on any of the different fronts, including manufacturing inspections.

Kalpit Patel

Okay. Okay. And then last one, we've been getting questions on we should be modeling the US launch and the initial ramp. I guess maybe one for Aneel. Are there good examples or analogs that the investor community can use to kind of project this at least for the initial ramp for the 1st year or two and regular Zelle 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

Yes. So on, I think the best guidance I would give is to focus on 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% and 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 on those are three patient populations where physicians will use a drug such as ours. We also know that as you yourself said, luspatercept has been in this marketplace for the last two to three years we would expect to see patients who have been treated with luspatercept and physicians are looking for more options are both our Phase two study and our Phase three part of the study covered the luspatercept pretreated patients. And given our 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 and alone 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 we adopted within the armamentarium of the physicians as they treat their risk MDS patients.

Kalpit Patel

Okay. Thank you very much for taking the questions.

John Scarlett

Thanks, Kelvin.

Operator

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

Aron Feingold

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.

Operator

However, that when everyone This concludes today's conference call, you may now disconnect.