GERN - NASDAQ

Hello, and welcome to the Geron Fourth Quarter and Full Year 2024 Earnings Call. [Operator Instructions] I would now like to turn the conference over to Aron Feingold, Vice President of Investor Relations and Corporate Communications. You may begin.

Good morning, everyone. Welcome to the Geron Corporation fourth quarter and full year 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; Michelle Robertson, Executive Vice President and Chief Financial Officer; Jim

Thanks, Aron, and good morning to everyone on the call. Thanks for joining us today. 2024 was a terrific year for Geron and for RYTELO, our first-in-class telomerase inhibitor. RYTELO has a unique mechanism of action that represents a highly differentiated treatment with blockbuster potential in this high unmet need lower-risk MDS population. The FDA approved RYTELO in June of 2024 for the treatment of certain lower-risk MDS patients, including patients in the front line who are ESA ineligible, second-line ESA relapsed and refractory patients and third line plus patients regardless of RS status across lines of therapy. In addition, in August of 2024, RYTELO received favorable placement in the MDS NCCN guidelines including a Category 1 treatment recommendation in second-line RS-positive and RS-negative patients regardless of prior treatment. We've also been pleased with further validation for RYTELO in low-risk MDS in Europe, where the CHMP adopted a positive opinion in December, recommending the approval of RYTELO for the treatment of ESA ineligible and ESA relapsed/refractory del(5q) adult patients with transfusion-dependent anemia due to lower-risk MDS. The European Commission is expected to make a final decision on RYTELO marketing authorization application in the first half of 2025. Beyond lower-risk MDS, our development efforts in myelofibrosis also continued to progress in 2024. We have now achieved 80% enrollment in our pivotal imetelstat Phase 3 IMpactMF trial in JAKi relapsed/refractory myelofibrosis. Many of you will recall, this is the first myelofibrosis Phase 3 trial with overall survival as the primary endpoint. This study assesses the potential to alter the course of myelofibrosis with imetelstat. Based on our current enrollment rate and number of death rates, we expect the interim analysis may occur in the second half of 2026, while we expect the final analysis may occur in the second half of 2028. We believe that if this trial is positive, imetelstat could transform the treatment landscape for this high unmet need relapsed/refractory myelofibrosis patient population that has such additional survival today and in doing so, to potentially double the RYTELO commercial opportunity. We're proud of these robust 2024 accomplishments. Since launching in the U.S. lower-risk MDS market beginning at the end of June of 2024, we've seen positive uptake in RYTELO. In the fourth quarter of 2024, our second full quarter on the market in the U.S., we achieved $47.5 million in RYTELO net product revenue. Since product availability at the end of June 2024 and through year-end, we achieved $76.5 million in net product revenue, which exceeded our internal expectations. From a financial perspective, we ended the year with a strong cash position of approximately $503 million, which we expect will enable us to reach profitability without additional financing, if our internal sales and operating expense expectations are met. However, despite achieving this revenue in the first two quarters of launch, we have observed flat revenue trends over the last few months. As many of you will recall, beginning a few months into launch, we changed our commercial and medical affairs leadership. Jim

Thank you, Chip, and good morning, everyone. Today, I will address Q4 commercial performance and recent revenue trends, highlight our assessments and actions to focus on our key value drivers and thus help us realize the significant commercial opportunities we have with RYTELO in this high unmet need patient population. As described previously by Chip, we achieved $47.5 million in RYTELO net product revenues in the fourth quarter 2024. This demand for RYTELO was supported by strong payer access. Payers responsible for approximately 80% of the U.S. covered lives have implemented medical coverage policies for RYTELO, that are consistent with the FDA label, clinical trials and/or NCCN guidelines. New patient starts on duration of treatment are the key primary drivers of revenue. For duration of treatment, it is important to note that even the longest treated patients in the commercial setting are just hitting the median of approximately eight months observed in the Phase 3 IMerge trial and our market research suggests the duration of treatment in commercial RYTELO patients treated to date appears consistent with that observed in IMerge. However, with respect to new patient starts, we have observed flatness over the past few months. Specifically, even though we see RYTELO utilized across RS-negative and RS-positive first line ESA ineligible, second line ESA relapse refractory and third-line plus patients. The majority of new patient starts have come from the third line plus patient segment with the second line new patient starts lower than our expectations. Our priority is to drive new patient starts across the breadth of population in our FDA label so that we are not niche to a third-line treatment. We are particularly focusing on ESA relapsed/refractory RS-negative patients, where we believe RYTELO 's benefit are notably differentiated and where there is substantially unsatisfied patient population. There are other factors we are also addressing, which we believe will help accelerate uptakes in earlier line patients. First, below the national level trends, we see variability in regional territory and account level performance. Some territories and accounts are performing very well and competing and winning at the local level. Other territories and accounts have opportunity for improvement where we are refocusing our support and sales training efforts. Second, we believe the lower-risk MDS market is promotionally sensitive with time in front of the health care providers, or HCPs, being a key factor to changing their prescribing behaviors. We are taking steps to optimize our engagement with target HCPs. Joe will also highlight educational efforts by our medical affairs team to increase HCP awareness and education. We expect that as HCP's gain successful clinical experience with RYTELO in later lines and often difficult-to-treat patients, and as we work to raise awareness and increase engagement, they will choose RYTELO in earlier lines of treatment. Third, as Chip mentioned earlier, our organization changed commercial and medical affairs leadership a few months into launch. We have a balanced sense of urgency and a thoughtful approach and implementing changes to quickly drive operational excellence and minimize launch disruption. We have augmented the team with experienced senior leadership to support these efforts. Don Wynne joined in October 2024 as Senior Vice President, Commercial Strategy and Operations. Prior to joining Geron, Don was at Gilead Sciences for almost 20 years and most recently served as Vice President, Commercial Operations, where she led a team of approximately 150 people responsible for supporting the U.S. business. Don brings a deep background in commercial analytics to Geron. Jim Hassard joined in November 2024 as Senior Vice President, Sales and Marketing. He is another strong commercial leader with a 30-plus year successful track record. His prior experiences include roles as Chief Commercial Officer at two publicly traded biotech companies after spending most of his career at Amgen in senior sales and marketing leadership roles, including a country manager role. Together, Don and Jim and their teams are working to improve insights, strategy and execution. We are also assessing other possible root causes for the flat revenue trends and have implemented or are in the process of implementing several changes such as scaling up our analytics capabilities, refining our segmentation and targeting and improving our promotional and sales force effectiveness, which we believe will help us more fully capture the significant commercial opportunity for RYTELO in lower-risk MDS, which I will speak to on the next slide. As shown on Slide 8 in our earnings deck, we estimate that in 2025, the U.S. RYTELO total addressable lower-risk MDS patient population is approximately 15,400 patients and includes patients recommended in the NCCN guidelines. This includes approximately 3,400 first line ESA ineligible patients, approximately 7,600 second line and 4,400 third line plus patients with approximately 75% of patients with RS negative and 25% of patients with RS positive status. As I mentioned, our efforts are particularly focused on the eligible RS-negative population where RYTELO is the only drug approved for ESA relapsed/refractory patients. Assuming the duration of treatment observed in IMerge and based on the current net price, there is potential to achieve blockbuster status by treating approximately 1/3 of the U.S. RYTELO, total addressable patients. I want to thank our dedicated commercial team and the cross-functional teams at Geron for their hard work to ensure that treatment-eligible patients have broad and timely access to RYTELO. I will now turn the call over to Joe for a medical update. Joe?

Thank you, Jim, and good morning, everyone. As Jim mentioned, we are excited about the opportunity to bring RYTELO, an innovative and first-in-class drug to as many eligible patients as possible. I joined Geron in November and working with the medical and commercial teams, we have now identified areas for improvement. Similar to Jim's approach in the commercial organization, we are continuing to build and enhance our medical organization. As a first-in-class drug with a unique mechanism of action, RYTELO requires a steady flow of data to raise awareness and manage knowledge and data gaps at launch. To that end, we have actively prioritized our publication strategy and are targeting key medical congresses to reach the medical community to help increase awareness. Together with commercial, we are also investing in market development and KOL engagement, which is particularly important in this launch, given that 70% of the Phase 3 IMerge investigators were ex U.S. At ASH in December, new analysis from IMerge Phase 3 were presented but are a good example of our proactive approach to bring data to the medical community to increase awareness address potential knowledge gaps and educate on key data that provide insights to physicians on how they can use RYTELO in their clinical practice. The KOL engagement at ASH was robust and encouraging, and the data presented there reinforced RYTELO 's potential as a standard of care second-line treatment for lower-risk MDS patients regardless of prior therapy. In addition, the feedback we received at ASH has informed our plans to refresh our clinical development plan with the goal of generating data that will expand the application of RYTELO in MDS and other potential indications and support our scientific engagement. I expect our market development activities, data generation and publication activities to make a positive impact as they continue to roll out. Before I turn the call over to Faye, as a hematologist who has treated MDS patients for many years, I'd like to share my excitement for RYTELO. I believe RYTELO is truly an innovative drug with a unique mechanism of action that will change how MDS patients are treated and managed. I will now turn the call over to Faye for clinical update. Faye?

Thank you, Joe, and good morning, everyone. Today, I will provide an update on our ongoing myelofibrosis development programs. First, I will speak to our Phase 3 IMpactMF clinical trial. The first with overall survival is the primary endpoint. We have conviction in this first-of-its-kind trial based on significant imetelstat clinical experience in myelofibrosis. Starting with the pilot study out of Mayo Clinic, which was eventually published in the New England Journal of Medicine and was the basis for our Phase 2 IMbark study. In IMbark we enrolled participants with JAK inhibitor relapsed/refractory myelofibrosis to evaluate the efficacy and safety of 2-dose regimens of imetelstat with overall survival as a key secondary endpoint. We found that the median overall survival in the 9.4 milligram per kilogram arm compared favorably to historical control, which are around 11 to 16 months. To further validate the OS signal, we conducted a real-world data study to compare best available therapy of closely matched patients in the Moffitt Cancer Center database to the 9.4 milligram imetelstat arm in IMbark. In this analysis, we found that leading over survival more than doubled versus those on best available therapy. This gave us the confidence to design a Phase 3 trial IMpactMF with an OS primary endpoint and 2:1 randomization imetelstat to best available therapy. As Chip mentioned, this trial is now 80% enrolled. Based on the enrollment rate and death rates, we now expect the interim analysis from this study in the second half of 2026 and the final analysis in the second half of 2028. This trial was designed to confirm the strong OS signal observed in the Phase 2 study and if it read-outs positively would be a paradigm shift and transformational for patients with JAK inhibitor relapsed/refractory myelofibrosis who have limited treatment options and dismal survival. We are also sponsoring the Phase 1 IMproveMF clinical trial from which we presented the first results at ASH, suggesting tolerability of imetelstat combined with ruxolitinib treatment in patients with myelofibrosis. We presented data from Part 1 of the study showing that imetelstat was well tolerated, with no dose-limiting toxicities reported at any impulse dose level within the first 28 days of cycle 1. The PK profile with imetelstat and ruxolitinib study were consistent with previous monotherapy studies. Importantly, preliminary results showed variant allele frequency reductions in driver mutations associated with the mass across all four dose cohorts. Additionally, patients treated with imetelstat, 9.4 milligram per kilogram experienced stable hematology values over time. Imetelstat 9.4 milligrams per kilogram every four weeks was selected for dose confirmation and expansion, and we are actively enrolling patients in this Part 2 of the study. Initial results from Part 2 are expected in 2026. I look forward to continuing to keep you updated on our clinical development progress. And with that, I'll turn the call over to Michelle for a financial update. Michelle?

Thanks, Faye, and good morning, everyone. For detailed Q4 and full year 2024 financial results, please refer to the press release we issued this morning, which is available on our website. As of December 31, 2024, we had approximately $502.9 million in cash, cash equivalents, restricted cash and marketable securities. Total product revenue net for the three and 12 months ended December 31, 2024, was $47.5 million and $76.5 million, respectively. There was no product revenue in the prior year period given that RYTELO was approved by the FDA in June 2024. Total net revenue for the three and 12 months ended December 31, 2024, with $47.5 million and $77 million, respectively, compared to $23,000 and $237,000 for the same period in 2023. Total net revenue includes license fees and royalties in addition to any net product revenue. Total operating expenses for the three and 12 months ended December 31, 2024, to $67.6 million and $250.7 million, respectively, compared to $54.3 million and $194.2 million for the same period in 2023. Cost of goods sold was approximately $783,000 and $1.3 million for the three and 12 months ended December 31, 2024, respectively, which consisted of costs to manufacture and distribute RYTELO compared to no cost of goods sold in the prior year period. Research and development expenses for the three and 12 months ended December 31, 2024, were $23.4 million and $103.7 million, respectively, and $32.9 million and $125 million for the same period in 2023. The decrease is primarily due to manufacturing and quality costs that were capitalized in the current period due to FDA approval of RYTELO compared to being expensed in the prior period. The decrease is partially offset by an increase in personnel expenses related to increased headcount and incentive and stock-based compensation expense recognized for the vesting of performance-based stock options upon FDA approval of RYTELO. Selling, general and administrative expenses for the three and 12 months ended December 31, 2024, were $43.4 million and $145.7 million, respectively, and $21.4 million and $69.1 million for the same period in 2023. The increase in general and administration expenses in 2024 as compared to 2023, primarily reflects an increase in personnel expenses related to increased headcount to support the commercial launch of RYTELO in the U.S. and stock-based compensation expense recognized upon FDA approval of RYTELO due to the vesting of performance-based stock options. For fiscal year 2025, we expect total operating expenses to be in the range of approximately $270 million to $285 million, which includes noncash items such as stock-based compensation expense, amortization of debt discounts and issuance costs and depreciation and amortization. We expect to reach profitability without additional financing if our current internal sales and operating expense expectations are met. Based on our current operating plans and assumptions, we believe that our existing cash, cash equivalents and marketable securities, together with anticipated net revenues from U.S. sales of RYTELO will be sufficient to fund our projected operating requirements for the foreseeable future. I will now turn the call back over to Chip. Chip?

Thanks, Michelle. To close, we're very pleased with our accomplishments in 2024 in which we secure U.S. regulatory approval for RYTELO and lower-risk MDS and commercially launch the product in June. We're confident that the strategic and leadership changes we put in place early in the launch, combined with our differentiated product and the high unmet need, lower-risk MDS population will position us to increase our growth trajectory as these investments start translating to results. We also progressed to the U.S. regulatory review process for imetelstat in lower-risk MDS, which positions us to receive EU approval in the first half of 2025 and potentially launch in select EU countries in 2026. Also in 2026, we expect key readouts from our MF clinical programs with an expected interim analysis from Phase 3 IMpactMF in the second half of 2026 as well as the primary analysis from Phase 1 IMproveMF in the same year. Lastly, we believe we're in a strong financial position, thanks to the nonequity financing executed in November of 2024 and the commercial opportunity of RYTELO in the U.S. which we believe position us to reach profitability without additional financing, assume we meet our operating expense and revenue expectations. While it is clear that we still have work to do to present RYTELO is a strong treatment option in the patient populations where the need to greatest and the potential patient benefits are clear. I and my colleagues are confident that refining our sales strategies and execution investing further in our medical affairs functions and continuing to increase awareness and engagement with HCPs and patients will allow us to meet our goal of RYTELO, becoming a highly valued standard of care across treatment-eligible low-risk MDS patients. We will now open the line to questions. Operator?

Thank you. [Operator Instructions] Your first question comes from Peter Lawson of Barclays. Your line is open.

Great, thanks. Thanks for the update. Maybe first question would just be around how we think about revenues, your commentary around flat revenues over the last few months. Whether you're seeing any week-over-week growth. And I've seen that comment kind of captures January and February. And then the other component would just be around, how we think about 1Q revenues themselves, whether that's flat or growing versus 4Q, and then anything you can tell us around revenues and costs, as we think about 2025? Thank you so much.

Thanks, Peter. Appreciate the question. Jim will take this question, which obviously relates to both prior revenues and also for - you had some questions about potential future revenues in the first quarter. So Jim?

Good morning, Peter. So our revenues week-over-week have had some variability. But what I would say is our four and eight-week rolling averages underscore the flatness that I characterized on the call. And that flatness continued into the prior leading up to this call. So it may be a little bit too early to make a full call on Q1 revenues, but I would characterize and reinforce what we said on the earnings call that, the past couple of months have been relatively flat week-over-week in the four and eight-week averages.

And you can say around kind of cost or your revenues for 2025?

Michelle?

I'm sorry, I didn't hear the question.

Yes. Just any guidance you can provide around revenues for 2025 or indeed costs for 2025. Just kind of marrying up your comment around getting to profitability?

Right. Yes. I mean we're - we have said that we're not providing guidance on the revenue just yet. We have always said that we wanted three or four quarters under our belt. And I think that, that just remains consistent with how we're going to talk about guidance for revenue on the OpEx. We feel pretty good about our $270 million to $285 million. We've got levers that we can pull as well as stage gating expenses. So we'll manage that as the quarters go on. And right now, we have no changes to our forecast, our internal forecast around profitability.

Got you. Okay, thank you.

Thanks, Peter.

The next question comes from Tara Bancroft with TD Cowen. Your line is open.

Hi, excuse me. Good morning. And thanks for taking the question. So I was hoping you could give us maybe some more detail on the seasonality or patterns in general, not only that you're seeing with RYTELO, but it appears to be impacting MDS as a whole with luspatercept 2. So I'm curious to get your thoughts on what's happening at a higher level in this indication? And then separately, maybe, Jim, if you could tell us more about the expected cadence of growth this year that we could see, with your implemented changes that you suggested? Thanks so much.

Sure. Thank you, Tara. Good morning.

No, go ahead, sorry detail on the seasonality and…

Great. So we have started - we saw some seasonality beginning around the holidays, Thanksgiving more specifically. And there is some hesitancy in the market to start some of these products that require, in our case, some monitoring. So there was a little bit of a delay. I agree with you that as we looked at other products in this market, and ran correlations between our trends and others, there was a very high correlation. So it didn't just affect, RYTELO affected a primary product that's used in this space as well. In terms of the expected cadence, it's really driven off of our business driver, right? We characterize the most important business driver for us is new patient starts. As you know, with launch products, often start in later line, third line plus, which we characterized on this call as seeing that's, where the majority of our use was even though we saw earlier line, second line, first-line use. So - it really depends on our effectiveness in driving market share, not just in third line plus, but in earlier line, second line and first line opportunities. And our expectation is that as we increase our share of voice, our reach and frequency and together with medical fares increased education and awareness, we hope to see greater impact, and use across all lines of therapy. But it's not going to happen overnight, share of voice and increasing the prescribing behaviors will take some time.

Okay. Great. Thanks so much.

The next question comes from Faisal Khurshid with Leerink Partners. Your line is open.

Hi, guys. On the trends that you've been seeing, could you comment on like how much of that was an impact on new patient starts as opposed to like discontinuations or dose modifications and holidays? I guess the reason for the question is, even if you're starting mostly in third-line patient like you be kind of like adding patients at a consistent rate. And I guess like people are also wondering like the duration of therapy should still be longer than like the time you've been in the market in third line as well? Or is that not the way to think about it?

Jim?

Hi Faisal, good morning. No, I think the way you're thinking about it is exactly right. The primary drivers are new patient starts and duration of treatment. What I said on the call is that duration of treatment at this point, while still early in the - we're only approaching the median duration of treatment in IMerge about right now. That does not appear to be issue, based upon our own market research and KOL. As you know, there isn't perfect data that we can cite only data that, we triangulate around. But right now, at this point, we don't believe that duration of treatment is inconsistent with vaccine in IMerge. And so, we have seen some softness and it's related to new patient starts. I think the way to characterize it is we saw uptake, and unmet need and the treatment was really with some of these early adopters. Who believe - who understood and believed in the product, and it's our obligation to really increase the reach in frequency, to share of voice amongst the majority of physicians, who have yet to treat patients with RYTELO.

Got it. Thank you. And then in terms of inflection or potential inflection this year, have you guys have visibility that you should be kind of like at a bottom on new patient growth now. And then like how confident are you like the new sales strategy will cause an inflection? And what kind of timing would - should we expect on that?

That's a great question. I wouldn't characterize it as an inflection. I think others characterized it in the past as a bolus. What we're looking for is steady growth - steady growth in third line leading to earlier lines, second line and first line. So what we anticipate is that with great execution, great targeting, great messaging that as we increase our share of voice and awareness with these physicians that, we would see uptake across the board. Inflections are often associated with new indications, unique publications, things along those lines. So right now, this is pure execution in order to increase market share and begin to increase the adoption, if you will, across all lines of treatment.

Got it. Thank you.

The next question comes from Greg Harrison with Scotiabank. Your line is open.

Good morning. Thanks for taking the question. What feedback are you getting from KOLs and other providers, around why they're not using RYTELO as much in earlier lines of therapy and -- are there any differences based on setting as far as academic versus community, it sounds like from your comments just now that the bulk may be in academic?

Thanks, Greg. I think the first message that I would share with you is that our MD and our KOL feedback that have used RYTELO, very simply can be summarized as RYTELO works. And we see that in our market research and our one-on-one engagements with the KOLs. I think the biggest opportunity for us is to really increase the region frequency, our education and awareness, and share of voice especially as you point out with the community. I'll just give you a very simple mathematic equation. So if you think about the 15,400 patients that we characterize as treatment eligible, and you divide that by the number of MDS treating physicians in the U.S. It only leads to a couple of patients on average that each one of these physicians have. So it's really important for us to make sure that we get out to as many of these physicians in a cost-effective way through our sales team, our medical affairs team, and our non-personal efforts to really increase the share of voice.

Great, that's helpful. Thanks again.

Thank you, Greg

The next question comes from Stephen Willey of Stifel. Your line is open.

Yes, good morning. Thanks for taking the questions. Can you guys maybe just comment a little bit on the patient mix that you've been seeing over the last couple of months, specifically in the second-line setting, both with respect to RS status and prior therapy. And I guess, is it safe to say that given the majority of new patient starts are occurring in third-line plus patients. Does that imply that RYTELO is primarily being sequenced post HMAs?

Jim, do you want to take that?

Yes. Thanks, Stephen. So we haven't disclosed exact numbers, but what I could tell you is like most product launches, we're seeing higher use in later lines, but I would underscore that we're seeing utilization in both second line and first line, as you point out. We have an opportunity to really sharpen our product differentiation, especially in the RS negative patient population, which many physicians will acknowledge that second-line RS negative is one of the areas of high unmet need. I don't know that our messaging has been as specific as it could be, and that's one of the things that we're refining, with our segmentation targeting and messaging going forward. So we are seeing utilization across both RS positive, and especially RS negative. I think we can have a greater uptake in RS negative given that's about 75% of the underlying status.

Okay. And then can you also maybe speak to some of the data that you're now contemplating generating to build on the value proposition of the product profile?

Maybe I'll turn that to Joe and Don.

Can you repeat the question, please?

Yes. Just wondering what data you're now contemplating generating to build on the value proposition of RYTELO?

Yes. I mean -- so the first thing we have to look at the existing data from the Phase 3 program, the IMerge, and respond to questions from physicians about the full spectrum of the benefit - for patients from this drug. We are also looking at advancing within the MDS different lines of treatment, whether it's in the first line, or sequencing or combination. So those are potential ideas that we are pursuing. And we have investigators who are interested in collaborating with us. Beyond MDS, there's obviously the ongoing myelofibrosis Phase 3 program, where we're treating patients who are in the relapsed/refractory setting. But in parallel, we also have a first line in combination with the JAK inhibitor study that, is also in the second part of that development. Beyond that, there are obviously many different areas that the mechanism of action is applicable that, we are also looking at collaborating, with investigators to advance RYTELO development.

Okay. Then maybe just last question. I guess is what is happening in the U.S., just given the flatness and the trajectory of new patient starts. And I know you're now looking to commercialize in Europe until 2026, but does that now kind of change the cadence of perhaps expansion plans outside of the U.S. Do you need to get the U.S. on track and kind of growing in a new patient start direction before you embark on anything outside the United States? Thanks

Steve, it's Chip. I think that it would be very easy for us to put our hands on our hearts and say our number 1, 2 and 3 focus is on the U.S., the U.S. getting the U.S. on track. New patient starts on track appropriate - utilization throughout the areas of high unmet need. And we are absolutely taking care to look at a variety of different options, and to start some of the prework for Europe. But I think it would be very, very easy to say that, our 90-plus percent of our focus is on the U.S. right now.

All right, thanks for taking the questions.

Thanks, Steve.

The next question comes from Emily Bodnar with H.C. Wainwright. Your line is open.

Hi, good morning. Thanks for taking the questions. I guess on the first one - in terms of new patient starts, are you mainly seeing prescribers who have already used RYTELO, kind of re-prescribe it to new patients? Or is it mostly coming from new prescribers, new centers? And then maybe we could comment a bit on what factors are contributing to the slower enrollment in myelofibrosis and potential for any guidance, on when you expect to reach full enrollment? Thank you.

Okay. So Jim, why don't you comment about the new patient starts, and cadence there with various prescribers, and then we'll ask Faye to comment on enrollment?

Great. Thanks, John. On new patient starts, we're seeing repeat prescriptions amongst the early adopters largely at many of the academic medical centers. In the community, it's a little bit more diffused. So there, we're seeing more breadth than depth. But over time, as with other product launches, I expect that both breadth and depth will continue to grow, especially as physicians gain clinical experience and success with RYTELO.

Thanks Jim. And Faye, could you make a comment on sort of the cadence you see for enrollment, and how you sort of judge that today? And Emily, if you want to refine that question for Faye, please feel free to do so.

Sure. Thanks, Emily. We're talking about the enrollment in MYF3001 in the Phase 3 right. MF study. Yes. Okay. Just to be sure. So the enrollment in the Phase 3 study is proceeding along well and has been steadily and as expected. Is there...

Any like time line you can provide for when you expect to complete enrollment?

I don't think we've released that publicly, but I'll remind you also that the interim analysis, and the final analysis projected dates are not dependent necessarily on the enrollment timing, but more on the event date. So we can reach those milestones without necessarily enrollment being closed.

Okay. Thank you.

The next question comes from Kalpit Patel with B. Riley Securities. Your line is open.

Yes. Hi, good morning, and thanks for taking the questions. Maybe first on the flattening over the past few months. Can you comment on exactly which month you started, to see flattening? Was it the beginning of this year, or was it the beginning of fourth quarter last year?

Hi, Kalpit, it's Jim here. I would say based upon the rolling four an eight-week, we started to see, right, let's call it, around the holidays, Thanksgiving holiday going forward. We do see, as you know, in the weekly data, a lot of variability, which is why we incur more to four to eight-week rolling averages.

Got it. And I appreciate the color here into the more usage in the third line setting. But I'm curious to hear if there are any other specific subgroups of patients that are more heavily targeted by doctors, for example, is this mostly used in high-transfusion burden patients?

We don't have perfect data on that. So a lot of it is gathered through market research. But as you know, based upon our indication statement, we stay consistent with that. As physicians gain experience, they have the ability to use physician discretion, medical justification in areas that may go beyond the label.

Got it. Okay. And then one last one from me. I think we've had that slide in the deck saying that there are 15,000-plus patients eligible potential $1 billion plus in net revenue. Do you still stand by that $1 billion plus number?

Yes. The bottom line is for physicians that have used RYTELO and based upon our KOL feedback as well as market research, RYTELO works. It's that simple. It's our obligation and opportunity to help educate and increase awareness with a much broader group of physicians across the country, but we absolutely do believe in it. I think our opportunity is, to also drive market development and KOL development, as Joe highlighted. There's a significant opportunity for us to increase the awareness, therefore, leading to initial trial. Initial trial will lead to reinforce success and broader use. It will just take a little bit of time.

Okay. Got it. Thank you very much for taking the questions.

Thank you.

The next question comes from Gil Blum with Needham. Your line is open.

Good morning everyone, and thanks for taking our question. So we noted that the financial OpEx guidance remains unchanged. Maybe just as a strategic question, given you guys plan on investing more in outreach here, doesn't this affect your estimates, as it relates to operational expenses for 2025? Thanks.

Hi, it's Jim here. Potentially, right? If we kept the, spend exactly the same and increase our non-personal spend, it would. But the way we've managed our budget, is to reallocate based upon opportunities and directed our, spend by shifting funds within.

All right - sorry. I just want to make sure, I'm sorry, I didn't…?

Go ahead with your second. Yes. So the question was related to the OpEx unchanged, and Jim gave the commentary that we were reallocating within various portions of our budget there. I didn't know if you had any other comment on our OpEx unchanged going forward?

Yes. I mean, I guess what I can say is we had already accounted for in our budget for 2025, additional investments in medical affairs, and some other programs that we didn't get to in 2024. So we've got flexibility.

Okay. And maybe as a follow-on here. I know maybe this question was addressed previously, but just to better understand people who go on RYTELO seem to stay on rate, at least up until what we would have expected from the IMerge Phase 3. So it's just convincing physicians that they should give it a try as a sort of the problem is? Thanks.

Yes, I'd actually expand upon that. We have a lot of early adopters that we've seen prescribed and gained that success. There's a lot more patients and physicians that have not used RYTELO. So it's really us increasing the education, the awareness and driving that initial clinical experience. That's really where the opportunity, is on new patient starts. It's continuing to drive the breadth. and the breadth obviously leading to depth over time.

All right, thanks for taking our questions.

Thank you.

This concludes the question-and-answer session. I'll turn the call to Aron Feingold for closing remarks.

Thank you so much for joining us today. We appreciate your interest in Geron, and look forward to keeping you updated.