Geron Corporation

Hello and welcome to the GERON first quarter 2025 earnings 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, please press star 1 on your telephone keypad. I would now like to turn the conference over to Ron Moldaver, Investor Relations. You may begin.

Good morning, everyone. Welcome to the Jaron Corporation first quarter 2025 earnings conference call. 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 related to the launch, commercial opportunity, and therapeutic potential of Ritello, anticipated clinical and commercial events, and related timelines, the sufficiency of Jerron'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 with the SEC, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statement and our future updates to those risk factors. Geron undertakes no duty or obligation to update our forward-looking statements. With that, I'll turn the call over to Dawn Burr, Interim President and Chief Executive Officer.

Good morning. Thank you, Ron, and thank you all for joining us. I'll begin on slide four. I'm joined today by several members of Geron's management team. Michelle Robertson, our Chief Financial Officer, Jim Ziegler, our Chief Commercial Officer, and Dr. Joseph Ede, our Executive Vice President of Research and Development. Let's continue on the next slide. I'll begin by stating that Ritello U.S. commercial launch success is our number one corporate priority. Ritello is a first in class novel telomerase inhibitor recently approved for the treatment of certain patients with lower risk MDS, a disease with significant unmet need. We believe that there is a large U.S. market opportunity for Rytello, and Q1 sales were not where we expect them to be. Q1 Rytello net revenues were $39.4 million, down $8 million from Q4, while demand in the 13-week period through the week ending March 28th was relatively flat at plus 1% versus the prior 13 weeks. The lower quarter-over-quarter net revenue is due to the inventory drawdown among our distributors from Q4 into Q1. Michelle will address this in greater detail in our financial update. Personally, I stepped into this role because I'm excited by the opportunity to bring this important medicine to eligible patients and the healthcare community, and together with this leadership team, execute on this commercial opportunity and drive value for all involved. Today, we'll share key factors that we believe have influenced the recent soft performance, as well as specific enhancements we've made and continue to make to support U.S. commercial success. We expect our increased commercial investments to bolster uptake across a broader group of prescribers and drive long-term demand. Since our last earnings call, we've performed an in-depth analysis of our commercial efforts with the current market, And we're focused on three key strategies to integrate sales growth. First, we are investing additional resources to increase brand awareness among the highest decile US hematologists treating the greatest number of lower risk MDS patients today. Second, we're refining our marketing and medical efforts to enhance prescribing clarity and competence with the use of Ritello. articulating how and where to use it successfully as indicated in our approved label with the goal of supporting positive HCP and patient experiences and continued use. And third, we're implementing programs to expand US KOL support and advocacy through aligned messaging, education, and through both commercial and medical affairs engagement efforts. Today, Jim and Joe will share further details of specific commercial and medical affairs actions to implement these three key strategies. This includes refined HCP target identification, expanded sales and medical field headcount, and the addition of newly created goals to highlight only a few. We're confident that by intensifying our focus on the strong execution of launch fundamentals that we'll see performance trends moving in the right direction. and are encouraged by a few recent early performance indicators that we will share with you today. Success takes an organized team effort, and we've invested with deliberate attention and urgency to reinvigorate this launch. With our recent EU approval in March, we are pursuing what we believe is a targeted, disciplined path to make Ritello available to patients beyond the United States while being fiscally responsible. Our strategy is to work with experienced third parties to help minimize the investment needed outside of the United States, allowing our teams to focus on our top priority of driving our U.S. commercial efforts. We do not plan to commercialize in Europe or any other region outside of the United States independently. We're also excited about our late-stage clinical development program that could expand in MattelSTAT for use more broadly within hematology and continue to fill unmet needs. IMPACT-MF is our phase three pivotal trial evaluating imatelstat in relapsed refractory myelofibrosis with an endpoint of overall survival. If we're successful in this trial and imatelstat is approved in this setting, we believe that the opportunity exists to meaningfully expand and potentially double the commercial potential of Ritello. Joe will provide an update on enrollment and potential near-term milestones, including the interim analysis that is anticipated in the second half of next year. Before turning the call over to Jim, I will also mention that our process to identify a permanent chief executive officer is ongoing. Our board is working with an experienced executive search firm to identify and evaluate candidates with strong commercial leadership in our industry. We expect a decision to be made and announced within the next six months. With that, I'll hand the call over to Jim to provide a U.S. commercial update.

Thanks Don and good morning everyone. Today I will provide a commercial performance update and highlight key actions we have taken and are continuing to take to drive enhanced launch performance as well as recent encouraging performance indicators that we are tracking. We believe Ritello is a highly effective novel treatment that fills a significant need in an underserved therapeutic area. We also believe that Ritello has a strong and differentiated product label, positive NCCN guidelines, and broad U.S. payer coverage. This is why we believe that we can reignite this launch with the plans that we are executing and maximize Ritello's potential in a market with considerable opportunity. On slide seven, we outlined the estimated U.S. total addressable market for Ritello at approximately 15,400 lower risk MDS patients based upon the label and NCCN guidelines. To date, most usage has been in the third line plus setting. Use in later lines often occurs until HCPs gain experience with the new therapeutic agent. There is significant opportunity for Ritella to expand use in earlier lines of treatment, including first line, ESA ineligible, and second line ESA relapse refractory patients. In Europe, we estimate that the EU4 total addressable market for Ritello is approximately 80% of the U.S. Later in this call, Jill will provide an update on our ongoing phase three relapse refractory myelofibrosis clinical trial, IMPACT-MS, with a planned interim analysis expected in the second half of 2026. Early pre-commercial planning, including market and landscape assessment, is now underway. Our preliminary estimate for the U.S. total addressable market is approximately 10,000 JAK inhibitor relapse refractory myelofibrosis patients, and the EU4 total addressable market is approximately 9,000 JAK inhibitor relapse refractory myelofibrosis patients. We will provide commercial planning updates as we approach key impact MS clinical and regulatory milestones. Our top corporate priority is the successful commercialization of Ritello in the U.S. On slide eight, I will highlight our strategy, plan of action, and thoughtful investments to support this priority. First, We are working to improve Ritello brand awareness, and we have invested in our team to better reach, inform, and educate healthcare providers, especially community-based HCPs. Our strategy is to increase our brand awareness through greater presence and share of voice within our HCP targets to treat the majority of lower-risk MDS patients. We believe that the sales team is the most effective and efficient way to reach our target HCP audience with an aligned message, and one of the most powerful communication forces we can employ to make an impact quickly. We are increasing our customer-facing teams by more than 20%, which is designed to improve our reach and message delivery, especially for higher-decile HCPs who treat the greatest number of Ritello-eligible lower-risk MDS patients. This expansion includes adding not only additional key account managers, but also oncology clinical educators and a newly created field-based regional marketing team. Recruiting and hiring is underway. We plan to have the new hires on board and in the field beginning in early Q3 and expect to see their impact later this year. In addition to the field team expansion, We are also pursuing community-based educational and outreach initiatives, such as speaker programs, webinars, and digital campaigns designed to drive broad reach and awareness, especially for lower-decile community HCPs to treat fewer lower-risk MDS patients and may not see a key account manager as often. Second, we are working to increase HCP prescribing competence through clinical experience and patient success stories. We believe there is an opportunity to reinforce Ritella's strong therapeutic profile and product differentiation, especially focusing on the second line post-ESA or ESA ineligible patients to drive earlier use aligned with our approved label. Our strategy is to increase HCP prescribing competence and clarity through education and strong messages that reinforce Ritella's product differentiation through the expanded field team, especially targeting our higher volume, lower risk MDS treaters. We are also enhancing our omni-channel initiatives, including social and digital campaigns in an effort to expand the reach of our key marketing messages, especially for our lower volume, community-based, lower risk MDS treaters, and complement the messaging efforts of our sales team. Our commercial and medical affairs teams are also addressing and educating HCPs on appropriate cytopenia management to increase HCP prescribing confidence. And Joe will highlight key considerations on cytopenia management and expectations later during his section. Third, we are working to generate stronger KOL support and advocacy across the U.S. We believe that increased KOL advocacy is essential to building broader support and use of Rytello given the limited number of U.S. clinical trial investigators and patients who participated in I-MIRN. Our strategy is to strengthen U.S. KOL advocacy through education and engagement supporting our launch success, and we have made investments to do so. To support the commercial team's engagement with KOL, We have further expanded our commercial team headcount, creating a new field-based regional marketing team. Their responsibilities are to cultivate and develop stronger KOL relationships in support of advancing patient care and lower risk MDS. The regional marketing team identifies opportunities and data needs to further support product differentiation with KOL input and validation. Based on these opportunities and needs, The clinical and medical affairs team independently prioritizes data generation opportunities to enhance Rightella's clinical share of voice with increased publications and presentations at congresses. The regional marketing team will work with top KOLs in peer-to-peer educational initiatives like speaker programs, executive engagements, and community-focused educational initiatives. We are excited about the potential of this newly created team to strengthen our relationship with the top KOL. Turning to slide 9, we have refined and continue to refine our account and HCP targeting, which we believe will allow us to reach physicians treating the majority of lower risk MDS patients. We estimate that approximately 6,300 HCPs currently treat approximately 80% of lower risk MDS patients in the United States. We further estimate that approximately 1,300 HCPs treat approximately 50% of the currently diagnosed lower risk MDS patients. These data provide good insights into where Ritello eligible patients are being treated, and these HCPs are our commercial focus for personal and non-personal promotional efforts. Our refined targeting effort is designed to help us effectively reach, engage, and educate HCPs treating the majority of currently diagnosed Ritello-eligible lower-risk MDS patients. Turning to slide 10, we believe these recently implemented and ongoing commercial actions will drive increased product demand over time. While early, we are pleased to see modest improvements in several leading commercial performance indicators. As of April 2025, approximately 900 sites of care have utilized Vitello. This is an increase of almost 300 new sites since the end of Q4. Of the accounts that previously ordered, approximately two-thirds have reordered in Q1. Demand grew approximately 10% in the current four-week period ending April 25 compared to the prior four-week period. This represents the highest month-over-month growth since October 2024. The rolling three-month market claims data as of February 2025 estimates that approximately 25% of Ritello new patient starts were in the first and second line. We expect to see an increase in second line use as HCPs gain more experience with Ritello and become more comfortable prescribing it in earlier settings. Our recent market research evaluating intention to treat suggests physicians intend to use Ritello in earlier lines of therapy. Payer access continues to strengthen with approximately 85% of U.S. covered lives now under favorable Ritello medical coverage policies that are consistent with the FDA label and or NCCN guidelines. I want to acknowledge the cross-functional team and especially the sales team who are executing the plan to deliver on these leading performance indicators and demonstrating strong patient centricity. Turning to the EU, we outlined key considerations in our launch planning on slide 11. We have assembled a small, experienced team to focus on EU4 launch preparation. We anticipate commercialization in select EU4 countries starting in 2026 pending favorable reimbursement and completion of critical launch activities. Commercial success in ex-US markets is dependent on strong reimbursement and favorable pricing. We are engaging established third-party partners across commercial, market access, medical affairs, ATOR and distribution to prepare for successful commercialization. We also expect to maintain financial discipline in investing for the EU4 launch with further expansion pending strong reimbursement. We will provide future EU launch planning updates as we progress towards commercialization. In summary, we have implemented and continue to implement actions specifically designed to enhance US sales performance. We remain confident in the long-term potential of Ritello as a differentiated therapeutic for eligible patients with lower risk MDS. We are aligned on the opportunity and responsibility in front of us, and we are all in on driving success of Ritello. I will now turn the call over to Joe Ede, who will provide a medical affairs and clinical development update.

Thank you, Jim. I'd like to start by sharing several recent accomplishments from the Medical Affairs Organization. Since our last earnings call, we've implemented steps to further support community awareness of Rykello, develop HCP confidence in how and where to prescribe, and generate KOL advocacy within the lower risk MDS HCP community. I'm happy to share that we are executing in our plan. We are growing our medical science liaison footprint to reach more accounts by aligning their territorial coverage with the anticipated expansion of our commercial field team. This effort should help us achieve more streamlined and coordinated account management. Our field team interacts with HCPs frequently and is aligned with our corporate strategy to reach and educate the lower-risk MDS prescriber community and key opinion leaders. We've expanded the team with payer-focused MSLs and bolstered leadership in both publication planning and HE1. In fact, we are in the process of doubling the size of our overall medical affairs team since our last earnings call. We have been focused on increasing executive engagement with key institutions and thought leaders to share our data, discuss research areas of interest, and collect insights to inform our strategy. We are pleased with the positive feedback we have been hearing in these meetings. Key opinion leaders are interested in Ritello's unique mechanism of action and learning more about our data that suggests the potential for disease modification. As Jim noted, we are also focused on increasing HCP awareness of Ritello, particularly in the community setting and in centers that did not participate in our Phase III pivotal trial, which enrolled the vast majority of patients outside of the United States. We are increasing our efforts to educate and inform the U.S. prescriber community and key thought leaders. We are also pleased with the positive feedback received from many physicians who have shared their positive experience with Rytello's efficacy, especially in those hard to treat lower risk MDS patients who are not served well with other approved therapies. We are also pleased to hear their feedback regarding their experience with Rytello's safety profile which has generally been that Ritello has a manageable safety profile, including the management of cytopenia, which are considered on target or unsurprising given the drug's unique mechanism of action. In addition, we have received positive feedback of patients' experiences regarding fatigue, where other approved therapies can fall short. Our clinical experience with Imetelstat aligns with what we observed in the preclinical data An exploratory analysis of the Phase III I-MERGE data showed that the exposure to imital stat correlated both qualitatively and quantitatively with reduction in mutation burden. In other words, we observed a decrease in the number and type of mutations. This exploratory analysis showed that long and durable responders tended to have a strong correlation with mutation burden reduction. We believe that these correlations illustrate the unique mechanism of action of Hematelstat. Looking ahead, we are excited about the upcoming American Society of Clinical Oncology and European Hematology Association annual meetings this June. We have a robust plan in place at these key medical conferences to engage with many of our investigators and thought leaders, and we plan on holding strategic advisory board meetings to discuss our plans and to inform our strategies. We look forward to reconnecting with many of our stakeholders in Chicago and Milan next month. Additionally, to build on the momentum from these conferences, we plan to continue actively sharing our progress at key venues and in key journals in order to further increase support from the medical and scientific communities. We continue to receive a metal staff research interest from investigators And given its unique mechanism of action, there is eagerness to evaluate imitel stat in new settings as well as new indications. As Don and Jim mentioned, our focus and top priority remains U.S. commercialization, and we intend to be disciplined in how we deploy our resources. In the EU, we are working closely with the commercial team, and we intend to stand up and access programs to provide Ritello to eligible patients with low-risk and intermediate one, MDS. I'd also like to provide an update on our IMPACT-MF phase three trial in relapsed refractory myelofibrosis and discuss why we're excited about expanding imital statin misindication. As you know, we based the IMPACT-MF phase three trial on our single-arm phase two trial in the same JAK inhibitor relapsed refractory myelofibrosis population. In that trial, We saw a strong signal regarding prolonged survival and decreased bone marrow fibrosis after treatment, suggesting the potential for disease modification. First, we observed a prolongation of survival of almost threefold when compared with the historical cohort. Second, we observed decreased bone marrow fibrosis or complete reversal after treatment with the NatelStat. These significant observations gave us confidence in pursuing the registrational study in relapsed refractory myelofibrosis. Our confidence also stems from the unique mechanism of action of the Metallostat. Telomeres are repetitive 5'-3' DNA sequences at the end of chromosomes and serve as protective caps that can help maintain the stability and integrity of each chromosome. Selomerase is an enzyme that maintains telomere length in rapidly dividing cells. Telomerase is upregulated in more than 90% of cancers, including myelodysplastic syndrome, NMF, and leads to cell dividing uncontrollably without reaching the Hayflick limit, thereby evading apoptosis. Ritello is the first and only telomerase inhibitor approved by FDA for certain lower-risk MDS patients and is being evaluated in relapsed refractory myelofibrosis in Phase III ongoing trial. We are very encouraged with the continued interest in the IMPACT MSK3 trial, which is currently approximately 85% enrolled and expected to be on track to complete enrollment. Based on current assumptions of death events, we expect the interim analysis to read out in the second half of 2026. It is important to remember that the OS primary endpoint is event driven, and the timeline for interim and final analyses are tied to the number of death events. The IMPACT-MF phase three trial is designed with a two-to-one randomization, and the number of patients on the imetelstat arm are double the number of patients on the best available therapy arm. In addition to this phase three trial, we also have the IMPROVE-MF phase one trial, which is a frontline myelofibrosis study of imetelstat in combination with JAK inhibitor. This trial completed the dose escalation stage. We were encouraged to be able to dose roxalitinib and imetalstab at the maximum intended doses of each without observed NTD. We also observed fewer cytopenias than seen in the I-MERGE trial. The second stage of the study is enrolling now, and we are seeing excitement from the investigator community for this combination and its potential for patients with MS. This is a great opportunity for patients with unmet need and for G1 continued growth. We believe that this is an important opportunity to investigate whether Imetel's test might be able to benefit additional patients with unmet need. I'll now pass the call to Michelle to review our Q1 financial results.

Thank you, Joe, and good morning, everyone. For detailed results from the quarter, please refer to the press release we issued this morning, which is available on our website. As of March 31st, 2025, we had approximately $457.5 million in cash, cash equivalents, restricted cash, and marketable securities, compared to $502.9 million as of December 31st, 2024. Total net product revenue and total net revenue for the three months ended March 31st, 2025, were $39.4 million. There were no product or net revenues in the first quarter of last year, since Raytello was approved by the FDA in June of 2024. As Dawn mentioned, Q1 Ritello net revenues were down approximately $8 million from Q4, while demand in the 13-week period through the week ending March 28th was relatively flat versus the prior 13 weeks. The lower quarter-over-quarter net revenue is due to the inventory drawdown among our distributors from Q4 into Q1. As a reminder, revenue recognition occurs when specialty pharmacies, specialty distributors, and GPOs receive Ritello. Growth to net was similar from Q4 to Q1 and did not significantly contribute to the quarter-over-quarter net revenue decline. As Jim mentioned, we are encouraged by sales trends since the end of Q1 as we had the highest month-over-month demand growth as of April 25 since last October, representing a 10% increase in the current four-week period compared to the prior four weeks. Research and development expenses for the three months ended March 31, 2025 were $15.1 million compared to $29.4 million for the same period in 2024. The decrease was primarily due to lower clinical trial costs associated with the wind down of activity in our Phase III iMERGE MDS study after FDA approval of Ritello in 2024, as well as manufacturing and quality costs that were capitalized in the current period, now that Ritello has been approved, versus being expensed in the prior year period prior to commercialization. Selling general and administrative expenses for the three months ended March 31, 2025, were $40 million compared to $27.1 million for the same period last year. The increase is primarily due to higher personnel expenses related to additional headcount to support the commercialization of Britello in the U.S. For fiscal year 2025, we still expect our total operating expenses to be in the range of approximately $270 million to $285 million. This includes expenses associated with our continued investment in our Rytello commercialization strategy, investment in commercial supply redundancies, post-marketing commitments, as well as initial preparations to launch Rytello in selected EU countries in 2026, including the HTA evaluation process. We will be able to provide additional details as we approach the planned launch next year, but the initial work associated with launch preparation in the EU is budgeted into our long-term plans. Overall, we are confident that Geron remains in a strong financial position as we continue to integrate commercial strategy refinements outlined by Dawn and Jim, as well as monitor our sales trajectory, we will evaluate our timeline for achieving profitability. As a reminder, we have access to additional funding under our debt agreement with Pharmacon if needed. With that, I'll turn it back to Dawn.

Thank you, Michelle, and thank you all again for joining us today. We believe Ritello is a differentiated product for the treatment of certain patients with lower risk MDS, a disease with high need. The first quarter sales were modest by our expectations, and we don't believe this reflects the product's true commercial potential. I want to reiterate, our top priority remains U.S. commercialization in making Ritello part of the standard of care for eligible lower risk MDS patients. The Geron team is energized by this responsibility, and we believe that we've made and continue to make the appropriate investments to support the success of our U.S. commercial business. While it's still early, we're beginning to see a few promising performance indicators and are ready to make diligent and swift adjustments as needed to further improve upon our commercial execution. EU commercialization and access to Immatelstat are significant Geron priorities. We are carefully balancing our desire to make this important medicine available to lower risk MDS patients in the EU with thoughtful and disciplined resourcing, allowing our team to focus on Rytello's success here in the United States. And lastly, we're excited as we look towards the future. Our pivotal phase three trial evaluating imitelstat in relapsed refractory MS patients with an overall survival endpoint If successful and approved in this setting, could potentially double the commercial opportunity of Rytello. We expect that the interim data analysis could occur as soon as the second half of 2026. We look forward to keeping you informed of our progress across all of these priorities and will now open the line for questions. Operator.

Thank you. If you would like to ask a question, please press star one on your telephone keypad. If you would like to withdraw your question, simply press star one 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 Tara Bancroft with TD Cowan. Your line is open.

Hi, good morning. So I'm hoping, you know, just with the inventory impacts essentially behind you, demand is improving in recent weeks and And the increased number of commercial reps that you have out in the field and growing through Q3, can you help us understand how you're thinking about Q2 expectations and just the expected cadence for the year as to when these efforts can potentially lead to inflection in your view? Thanks.

Hi, Kara. It's Dawn Burr. Thank you so much for your question. Yes, we're excited about the future and the plans that we've put in place. So I'll allow Jim to address your question here.

Great. Hi, Tara. Good morning. In terms of Q1, thanks for acknowledging that inventory played a factor and explains the difference between revenues and underlying demand, which grew at about 1% Q1 over Q4. A lot of the changes that we are making and will make will start to have an impact now and going forward. Your specific question around the reps. We're adding the reps. We anticipate they will be in the field beginning in Q3, so we'll see their impact later this year. But a couple of the promising data points that we acknowledged on the call were the increase of approximately 300 new ordering sites Q1 over Q4, the 10% increase in growth April over March. So what we anticipate is continued momentum building into Q2 and sustaining throughout the year through 2025. Thank you.

Okay. Thanks so much.

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

Good morning. This is Teresa Vitale. I'm for Greg Harrison. Thanks for taking our question. I'm just curious if you can comment on your commercial efforts to drive the assessment of efficacy for patients on this Patercept to an earlier stage in order to help promote switching to Ritello. And maybe what are KOL citing as their reasoning behind any hesitation in switching patients from standard of care and prescribing Ritello in earlier lines of therapy? Thank you.

Terese, good morning, and thank you for your question. I think maybe to address your question, we'll start first with Jim, but I think Joe could provide a great perspective from the medical affairs point of view, so I'll let Jim kick this off.

Sure. Let's talk first about perceptions, behaviors, and results. We do something called ATU market research, awareness, trial, utilization, and it all begins with awareness. What we see in the market research is that When physicians are aware of Rytello's product profile, they view it favorably compared to those that don't understand it. And that holds for both efficacy as well as cytopenia management. In our most recent ATU, we saw a nice shift of cytopenia management, especially among those that have used Rytello being viewed as much more manageable than those that haven't used it. In terms of efficacy, One of the nice data points that we saw in the most recent market research is that the perceptions around second line RS negative has definitely shifted and increased as a source of product differentiation. The reason why I bring this up is first to acknowledge the messages delivered by the field force are resonating with the physicians. We expect to see those perceptions to translate into changes in behavior. The data point that I shared on the call, which is very positive, is that in the most recent data, we had about 20% utilization in first and second line, which is an increase over the previous results. These are all leading indicators for sustained growth. And I want to, again, acknowledge our customer-facing teams, both the CAMs as well as the oncology clinical educators. for delivering the message, because as we highlighted earlier, when the message is delivered, there is impact.

And maybe to complement Jim's answer, you specifically asked about the post-Lispatacept. Obviously, as we know, in the I-MERGE study, there was a limited number of patients who had received Lispatacept, given that it was in the early days of its approval. However, we did have subsequent trials that did include patients who have received Lusparacet. And we presented data at ASH last December that showed the activity of imitalstat, post-ESA, post-LUSPA, heavy transfusion burden, mutation burden. All these patients responded in a similar manner. There will be, obviously, more patients from the real-world data that we are collecting that will be providing additional information about that specific topic. In terms of hesitancy, as Jim has mentioned and I reemphasize, physicians who are using in the CalSTAT have experienced the positivity. benefit of this on their patients. And that is encouraging. And the efficacy is somewhat unparalleled in this space where we're seeing robust hemoglobin rises and patients' quality of life improving.

The next question comes from Peter Lawson of Barclays. Your line is open.

Great. Thank you so much. Jim, maybe you could walk through the inventory issue. Was that due to a distributor kind of stocking in 4Q? Just the dynamics there that we should be thinking about as the inventory has been burned through, and do you think that's corrected?

Thanks, Peter. First, I want to acknowledge that there are several factors that contributed to the higher inventory first. Prior to the holidays, we were on a growth trend. And so many of our SPs and SDs were using history to project the future going forward. So as the trend started to flatten, the inventory increased. Second factor, as we talked about before, was some level of seasonality that affected our product as well as other products in our category. And then the third thing is perhaps there was some anticipation of, pricing or reimbursement issues, which is not specific to Vitello, but affects all buy and build products. So while the inventory was probably at the higher end, of the range towards the end of the year, we did start to draw down that inventory. And that explains the difference between the drop in net revenues, yet the 1% increase in demand. Thanks for the question, Peter.

Great. And do you think that's kind of stabilized and kind of issues with, I guess, slow and unexpected pull through and stocking? Do you think that's in a good spot for 2Q? We do, Peter. Thanks. Yes. Great. Okay. Thank you. And then, I think you mentioned 1,300 high-priority HCPs. How many are currently covered by the field team? How frequently do they call? Where do you want that metric to be in the second half of this year?

We're not going to give the specifics, but certainly by increasing our field reps by 20%, which I previously stated that our field was 50, we increased it to 60, at least amongst the key account manager. That allows us to go deeper and with more frequency to our higher decile position. So in terms of the 1,300, they are definitely on the target list, and there are some more above and beyond that on the target list as well.

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

Good morning, everyone, and thanks for taking our questions. So maybe just one specific to treating physicians here. You mentioned the kind of feedback you've been receiving. Have there been any specific pushbacks of, you know, physicians who were less interested and have a follow-on?

Going back to the market research, what I would say is for those specifically that have not used Ritello or not necessarily educated by our key account managers, some of the often cited barriers are cytopenias or not having patients. However, that number dramatically changes when you talk about those physicians that have treated and or know about Rightello. So we believe that continued reach frequency, delivery of strong messages, especially to our targeted accounts, will start to change those dynamics. But what I would key in on is the fact that physicians that have used it and are aware of Rightello have a much more favorable view of the product profile and the utilization patterns.

Just to hone in on that, Sorry, go ahead.

If I may add, actually, we've had several engagements with physicians who have not used Ritello. And the main reason that they haven't used it, as Jim said, is they're not aware of the full potential or they have heard about the cytopenia. And in those conversations we've had with many of those type of physicians, when we do discuss the mechanism of action and that the cytopenia, are actually on target due to the mechanism of action. The whole attitude shifts and the potential for a disease modification drug for these patients does impact the physician thinking and potential utilization in their clinics.

So just to hone in on that message, would you say the main energy barrier here is just to get physicians to start treating? Is that fair?

I mean, one second, Jim. I mean, when Rebluza was launched, there was this so-called apathy among physicians converting from ESAs to Luspater sets. To this day, we see patients, in particular in the community setting, on ESAs, even with high EPO levels, over 500, or patients who have failed ESAs. That's been the pattern for 20-plus years now. in the clinics, and that's the reason for many of those barriers that we are seeing initially in the Lispatter set journey, and some of that we're seeing for the Imatel set as well. Go ahead, Jim.

Nothing to add.

Thanks, Joe. Quick one for Michelle. I see OpEx guidance has not changed, even though you guys seem to be investing more. in your sales force. Is this going to continue, or should we expect maybe a shifting more towards investment in G&A? Thank you.

Yeah, thanks. We had said previously that we had some levers to pull to maintain our OPEX guidance, particularly around some of our investment in inventory and manufacturing redundancy, and so we're going to be looking at all of that, but right now we have included all of the additional investment in commercial and medical, and we do not have to change our guidance.

The next question comes from Steven Willie of Stifel. Your line is open.

Steven Willie, Stifel, Yeah, good morning. Thanks for taking the questions. I guess you talked about 900 accounts having order to date. talk to, I guess, where those accounts fit within those prescribing buckets that you talked about? Are these accounts mostly in that top decile representing 50% of diagnosed patients? And then how does that 900 split out between academic and community?

Steven, thanks for the question. The majority of those accounts represented by the 900 are, in fact, on our target list. However, there are some that are not on our target list. In terms of the general split, it's reflective of the underlying dynamics, which is approximately one-third in the academic centers and two-thirds in the community. And what we expect going forward is that with increased personal and non-personal promotions and a focus on KOLs that we actually grow both simultaneously. but our focus is both. We are focused on both the academic as well as the community. Thanks for the question, Steven.

Okay. And then, can you also just comment in terms of what you're seeing with respect to lispatercept utilization in the frontline setting, both in terms of RS positive and RS negative? And do you have any sense if these patients are subsequently stepping through an ESA as a second line option, or is it just too early into the Luce-Pattersep frontline launch to have any real clarity here?

Thanks for the question. We do have that data. We've looked at it from a claims perspective. We haven't necessarily showed it, but I think what I could say is that we are seeing growth in the first line with Luce-Pattersep based upon the commands data. And if that happens, you know, and continues to grow, we're expecting, you know, duration of treatment fairly consistent with their study. In terms of switch, we can't promote specifically post-loose powder step. You know, our labeled indication is ESA relapse refractory or ESA ineligible. However, the NCCA guidelines is a bit broader.

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

Hi, Doreen. Thanks for the questions. I'm curious for physicians who have used Rytolo and who are not reordering, which I believe you said was about one-third of them, are there any particular reasons that you've heard for why? And maybe if you can comment on this continuation to date kind of reasonings for those, and if that's kind of in line with your clinical data expectations.

Yep. Thanks, Emily. So in terms of dose interruptions, discontinuation based upon our patient chart audits and some of our market research, it appears largely that the commercial experience is reflective of the percentages seen in iMERGE in our clinical trials. And what was the other part of the question?

For the one-third of HCPs who you commented did not reorder Rytello, if you can provide any reasonings that you're hearing for that.

Nothing specific at this point. It could just be simply a dose interruption due to a cytopenia. As you know, in this buy and build market, we don't get perfect patient-level data, so what we do is market research. patient chart audits, and we triangulate those insights, and those insights seem to be consistent with iMERGE. There aren't any new surprises in any of the data in market research.

Okay. And lastly, if you can comment on the improved MS data that you're going to have at ASCO, what differences should we be expecting versus the presentation at ASH?

I mean, we have, you know, started the second cohort, which is the established doses, which are the maximum tolerated doses of both drugs, which was a good surprise, if you will. And there were less cytopenia seen in that, you know, cohort of patients. So we are expanding and we're adding, you know, additional JAK inhibitors to the combination.

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

Yes. Hey, thanks for taking the question. Maybe first on the inventory part of this, Michelle, I think you previously communicated you know, the distributors were maintaining two to four weeks of inventory in a channel. So what's the day supply today, I guess, or at the end of the first quarter? And then I have a follow-up.

Sure. Thanks, Calvert. Yeah. So at the end of Q4, as we mentioned, it was on the higher side. So it was on the higher end of the three and a half week. And as of At the end of Q1, it was on the lower end of two plus, two and a half weeks.

Okay. Okay. Makes sense. And then at this point in the launch, are your new patient starts consistently exceeding the discontinuations? Or are you starting to see some of those early patients who received in a telestat start to roll off and offset the new starts?

We don't have perfect data on this. Again, we use patient chart audits and market research. In the buy and build market, the data isn't at a patient-specific level. But I could tell you, and generally speaking, if 80% of the patients that I described in the previous quarter were third-line plus, the duration of treatment for subsequent lines of therapy tend to be shorter. than what we often quote as the median 7.8 months. So your math is correct. As they roll off, new patient starts have to fill the funnel and continue to drive. The promising data that I shared on this call is that, you know, based upon the most recent, new patient starts number 25%, approximately 25%, and we're in first and second line. So the earlier we move up in lines of therapy, We generally expect longer duration of treatment.

Okay. And then one financial question. You reported $19.8 million net loss for the quarter and had about $45 million in cash burn. Maybe walk us through what drove that incremental $25 million in outflow. Was this any capital changes or inventory build or something else?

Well, Q1 cash burn is always higher due to payouts of bonuses and some early investment, yes, on the inventory side. That was front load.

Got it. Thank you.

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

Hey, guys. Thank you for taking the question. I just want to ask about this 10% demand increase that you've seen in April. Could you comment on, you know, sort of how sustainable you see that increase to be going forward? And also, like, how reliably do you expect it to translate into, like, true revenue growth?

Thanks, Faso. It's a great question. It's one data point. It's a promising data point, April over March. What I can tell you is that From a Salesforce perspective and market research, delivering the right message to the right physicians is leading to success. We saw the changes in perceptions that I described earlier. We're seeing at least this one data point of April over March growth. The key for all of us is to sustain that growth and build the momentum going forward. Our expectation is that, as a team, that we return to growth based upon strong execution.

Got it. Thanks.

That is all the time we have for questions. This concludes today's conference call. Thank you for joining. You may now disconnect.