Geron Corporation

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 Ziegler, Executive Vice President and Chief Commercial Officer. Dr. Joseph Ede, Executive Vice President, Research and Development. And Dr. Faye Fowler, Executive Vice President and Chief Medical 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 launch, commercial opportunity, and therapeutic potential of Ritello, anticipated clinical and commercial events, and related timelines, the sufficiency of Jerob'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 Jerron'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 and our future updates to those risk factors. Jerron undertakes no duty or obligation to update our forward-looking statements. With that, I'll turn the call over to Chip.

Chip? Thanks, Erin, and good morning to everyone on the call. Thanks for joining us today. 2024 was a terrific year for Jeron and for Ritello, our first-in-class phelomerase inhibitor. Ritello has a unique mechanism of action that represents a highly differentiated treatment with blockbuster potential in this high, unmet need, lower-risk MBS population. The FDA approved Ritello in June of 2024 for the treatment of certain lower-risk MBS patients including patients in the frontline who are ESA-uneligible, 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, Ritello received favorable placement in the MDS-MCCN 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 Ritello in low-risk MDS in Europe, where the CHMP adopted a positive opinion in December, recommending the approval of Ritello for the treatment of ESA-ineligible and ESA-relapsed refractory non-Delphi-Q adult patients with transfusion-dependent anemia due to low-risk MDS. The European Commission is expected to make a final decision on a Ritello 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 Imatel-STAT Phase III IMPACT-MF trial in JAKI relapsed refractory myelofibrosis. Many of you will recall this is the first myelofibrosis Phase III trial with overall survival as the primary endpoint. This study assesses the potential to alter the course of myelofibrosis with Imatel-STAT. 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, Imatelstat could transform the treatment landscape for this high-end metamine relapsed refractory myelofibrosis patient population that has such additional survival today and in doing so, to potentially double the Rytello commercial opportunity. We're proud of these robust 2024 accomplishments. Since launching in the US lower risk MDS market beginning at the end of June of 2024, we've seen positive uptake of Rytello. In the fourth quarter of 2024, our second full quarter on the market in the US, we achieved $47.5 million in Rytello 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 Ziegler, our Chief Commercial Officer, and Joe Eade, our EVP of R&D, will discuss their assessments and actions in more detail later in this call. Before I hand the call over to Jim, however, I want to reinforce our confidence in the potential commercial opportunity of Ritello, which is supported by robust clinical and scientific evidence that Ritello is a highly differentiated product. We believe that the compelling Phase III data, along with the favorable FDA label and NCCN guidelines, support Ritello's establishment as a standard of care for high-end net needs eligible lower-risk MDS patients, particularly in the second line. Most importantly, many hematologists that we speak with have the same assessment. So with that, I'll turn the call over to Jim for our commercial update. 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 Ritello in this high unmet need patient population. As described previously by Chip, we achieved $47.5 million in Ritello net product revenues in the fourth quarter 2024. This demand for Ritello is supported by strong payer access. Payers responsible for approximately 80% of U.S. covered lives have implemented medical coverage policies for Ritello that are consistent with the FDA label, clinical trials, and or NCCN guidelines. New patient starts and 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 sitting the median of approximately eight months observed in the Phase III iMERGE trial, and our market research suggests the duration of treatment in commercial Ritello 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 Ritello being utilized across RS-negative, an RS positive first line, ESA ineligible, second line ESA relapsed 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 niched to a third line treatment. We are particularly focusing on ESA relapsed refractory RS negative patients where we believe Rytella's benefits 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 uptake in earlier line patients. 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 opportunities 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 healthcare providers, or HCPs, being a key factor to changing their prescribing behaviors. We are taking steps to optimize our engagement with target HCPs. Jill will also highlight educational efforts by our medical affairs team to increase HCP awareness and education. We expect that as HCPs gain successful clinical experience with Ritello, in later lines and often difficult to treat patients. And as we work to raise awareness and increase engagement, they will choose Vitello 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 in 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 Nguyen 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. Dawn 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, strategies, 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 Ricello in lower risk MDS, which I will speak to on the next slide. As shown on slide eight in our earnings deck, we estimate that in 2025, The U.S. Ritello 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 Ritello 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 one-third of the U.S. Ritello 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 Ritello. 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 Ritello, an innovative and first-in-class drug, to as many eligible patients as possible. I joined here on 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, Rykello 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 III iMERGE investigators were ex-US. At ASH in December, new analyses from iMERGE Phase III were presented that 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 Rytello in their clinical practice. The KOL engagement at ASH was robust and encouraging, and the data presented there reinforced Rytello'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 Rytello 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 Ritello. I believe Ritello 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 myelocybrosis development programs. First, I will speak to our phase three ImpactMF clinical trial, the first with overall survival as primary endpoint. We have conviction in this first-of-its-kind trial based on significant in the clinical experience of myelocybrosis, starting with a pilot study out of Mayo Clinic, which was eventually published in the New England Journal of Medicine and was the basis for our Phase II EMBARQ study. In EMBARQ, we enrolled participants with JAK inhibitor relapsed refractory myelothibrosis to evaluate the efficacy and safety of two-dose regimens of MSL-STAT, with overall survival as a key secondary endpoint. We found that the median overall survival in the 9.4 mg per kg arm compared favorably to historical controls, 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 Mata Cancer Center's database to the 9.4 mg-mg in the Telstat arm in Embark. In this analysis, we found that median over-survival more than doubled versus those from best available therapy. This gave us the confidence to design a Phase III trial in PACT-MS with an OS primary endpoint. and two-to-one randomization, and it helps to have the best available therapy. As Chip mentioned, this trial is now 80% enrolled. Based on the enrollment rate and death rate, 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 II study, and if it reads out positively, it would be a paradigm shift and transformational for patients with JAK inhibitor relapsed refractory myelothibrosis who have limited treatment options and dismal survival. We are also sponsoring the Phase I IMPROVE-MF clinical trial, from which we presented the first results at ASH, suggesting tolerability of imetalcdat combined with rexalidib as first-line treatment in patients with myelothibrosis. We presented data from Part I of the study showing that imetalcdat was well-tolerated with no dose-limiting toxicities reported at any IntelSAT dose level within the first 28 days of Cycle 1. The PK profiles within the Telstat and roxalitinib in the study were consistent with previous monotherapy studies. Importantly, preliminary results showed variant allele frequency reductions in driver mutations associated with MS across all four dose cohorts. Additionally, patients treated with Imitalstat 9.4 mg per kg experience stable hematology values over time. Imitalstat 9.4 mg per kg 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 31st, 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, with $47.5 million and $76.5 million, respectively. There was no product revenue in the prior year periods, given that Ritello 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 31st, 2024 were $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 $783,001.3 million for the three and 12 months ended December 31st, 2024 respectively, which consisted of costs to manufacture and distribute Ritello compared to no cost of goods sold in the prior year period. Research and development expenses for the three and 12 months ended December 31st, 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 Ritello 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 Rytello. 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 periods in 2023. The increase in general 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 Rytello in the U.S. and stock-based compensation expense recognized upon FDA approval of Rytello 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 non-cash 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 Ritello, 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 secured U.S. regulatory approval for Rite Hello and Lower Risk MDS and commercially launched 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 high-end-need Lower Risk MDS population, will position us to increase our growth trajectory as these investments start translating to results. We also progressed the U.S. regulatory review process for Immacultstat and low-risk MDS, which positions us to receive EU approval in the first half of 2025 and potentially launch and select EU countries in 2026. Also in 2026, we expect key readouts from our MF clinical programs with an expected interim analysis from Phase III impact MF in the second half of 2026, as well as a primary analysis from Phase I improved MF in the same year. Lastly, we believe we're in a strong financial position thanks to the non-equity financings executed in November of 2024 and the commercial opportunity of Raytello in the US, which we believe position us to reach profitability without additional financing assuming we meet our operating expense and revenue expectations. While it is clear that we still have work to do to present Ritello as a strong treatment option in the patient populations where the needs are 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 Ritello 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. If you would like to ask a question, please press star 1 on your telephone keypad. If you would like to withdraw your question, simply press star 1 again. Please ensure you are not on speakerphone and that your phone is not on mute when called upon. Thank you. Your first question comes from Peter Lawson of Barclays. Your line is open.

Great. Thanks. Thanks for the update. Maybe the 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, and it 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. So Jim will take this question. which obviously relate to both prior revenues and also for, you know, 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 week 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 if you can stay around to kind of costs or even revenues for 2025? Michelle?

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

Yeah, 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. Yeah. I mean, we have said that we're not providing guidance on the revenue just yet. You know, we have always said that we wanted three or four quarters under our belt. And I think that, you know, 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 to 285. We've got levers that we can pull. as well as stage gating expenses. So we'll manage that as the, you know, as the quarters go on. And right now, we have no changes to our forecasts, our internal forecasts around profitability.

Gotcha. Okay. Thank you so much. Thanks, Peter.

The next question comes from Tara Bancroft with TD Cowan. 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 Rytello, but it appears to be impacting MDS as a whole with those patterns up too. 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. Good morning. Sorry, Chip. No, go ahead. Detail on the seasonality.

Great. So we have started or 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 I agree with you that as we've 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 Rightelo. It 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? 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 characterize 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 affairs, increase the education and awareness, we hope to see, you know, 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 Persis with LeRinc Partners. Your line is open.

Hey, guys. On the trends that you've been seeing lately, could you comment on how much of that was an impact on new patient starts as opposed to discontinuations or dose modifications in holidays? I guess the reason for the question is But even if you're starting mostly in third line patients, right, like shouldn't 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, you know, 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, Foster. Good morning. You know, 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 and that we're only approaching the median duration of treatment in iMERGE about right now, that does not appear to be an issue based upon our own market research in 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 and iMERGE. And so we have seen some softness, and it's related to new patient starts. I think the way to characterize it is, you know, we saw uptake and unmet need, and the treatment was really with some of these early adopters who believed, who understood and believed in the product. And it's our obligation to really increase the reaching frequency, the share of voice amongst the majority of physicians who have yet to treat patients with Ritella.

Got it. Thank you. And then in terms of like the inflection or potential inflection this year, like you guys have visibility that you should be kind of like at a bottom on new patient growth now. And then, you know, like how confident are you that like the new sales strategy will cause an inflection and what kind of, timing 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 peer execution in order to increase market share and to 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 Ritello as much in earlier lines of therapy and 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 abused Ritello very simply can be summarized as Ritello 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 reach and frequency, our education and awareness, and share a voice, especially, as you point out, with the community. I'll just give you a very simple, you know, 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 US. 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 Wiley of Stiefel. Your line is open.

Yeah, 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? 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 Rytela is primarily being sequenced post-HMAs? Jim, do you want to take that?

Yeah, 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 end that 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. 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 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 Jay.

Can you repeat the question, please?

Yeah, just wondering what data you're now contemplating generating to build on the value proposition of RTELA.

Yeah, I mean, so, you know, the first thing, we have to look at the existing data from the phase three program, the I-MERGE, and, you know, 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 three program where we're treating patients who are in the relapse 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 vitality development.

Okay. Then maybe just last question. I guess, is what is happening in the U.S., just given the flatness in the trajectory of new patient starts, and I know you're not 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 of the United States?

Thanks. Yeah, 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 one, two, and three focus is on the U.S., the U.S., getting the U.S., on track, the 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 pre-work 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. All right. Thanks, Steve.

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

Hi. Good morning. Thanks for taking the questions. I guess I'll answer the first one. In terms of new patient starts, are you mainly seeing prescribers who have already used Ritello kind of re-prescribe it to new patients, or is it mostly coming from new prescribers and new centers? And then maybe if you 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 the enrollment.

Great. Thank you. 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. 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 Ritella.

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

Sure. Thanks, Emily. We're talking about the enrollment in MYF 3001 in the phase three, right? MS study. Yeah. Okay. Just to be sure. So, the enrollment in the phase three study is proceeding along well and has been, you know, steadily and as expected.

Is there any timeline 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. Over. Thank you.

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

Yeah. Hey, good morning and thanks for taking the question. 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, Cal, Peter. Jim here. I would say based upon the rolling four and 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 anchor more to the four and the 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. You know, 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. You know, I think we've had that slide in your deck saying that, you know, there are 15,000 plus patients eligible, you know, 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 Ritello and based upon our KOL feedback as well as market research, Ritello works. It's that simple. It's our obligation and opportunity to help educate and increase the 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 to 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 reinforced success and broader use. It'll just take a little bit of time.

Okay, got it. Thank you very much for taking the questions. Thanks, Kyle. 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 optics guidance remains unchanged. Maybe just as a strategic question, you know, 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, Jim here. Potentially, right? If we kept the spend exactly the same and increased our non-personal spend, it would, but the way we've managed our budget is to reallocate based upon opportunities and, you know, directed our spend by shifting funds within.

All right. And maybe . Sorry. I just want to make sure. I'm sorry. I didn't. Go ahead with your second. Yeah. 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.

Yeah, I mean, Gil, 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 Ritello seem to stay on Ritello, at least up until what we would have expected from the eMERGE phase three. So it's just convincing physicians that they should give it a try, is where the problem is. Thanks.

Yes, I'd actually expand upon that. You know, we have a lot of early adopters that we've seen. prescribe it and gain that success. There's a lot more patients and physicians that have not used Vitello. 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 Erin Feingold for closing remarks.

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

This concludes today's conference call. Thank you for joining. You may now disconnect.