Hello and welcome to Geron's First Quarter 2025 Earnings Call. I will now hand over the conference to Ron Maldiver from Investor Relations. You may begin.

Good morning everyone. Welcome to the Geron 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 RYTELO, anticipated clinical and commercial events, and related timelines, the sufficiency of Geron's financial resources and other statements that are not historical facts. Actual events or results could differ materially. Therefore, I refer you to the discussion under the heading Risk Factors in Geron's most recent periodic report 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. Geron undertakes no duty or obligation to update our forward-looking statements. With that, I'll turn the call over to Dawn Bir, Interim President and Chief Executive Officer.

Good morning. Thank you, Ron, and thank you all for joining us. I'll begin on Slide 4. 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 Eid, our Executive Vice President of Research and Development. Let's continue on the next slide. I'll begin by stating that RYTELO U.S. commercial launch success is our number one corporate priority. RYTELO 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 RYTELO and Q1 sales were not where we expect them to be. Q1 RYTELO 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 +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 in 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 U.S. 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 confidence with the use of RYTELO, 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 U.S. 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 roles 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 RYTELO 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 imetelstat for use more broadly within hematology and continue to fill unmet needs. IMPACT MS is our Phase III pivotal trial evaluating imetelstat in relapsed refractory myelofibrosis with an endpoint of overall survival. If we're successful in this trial and imetelstat is approved in this setting, we believe that the opportunity exists to meaningfully expand and potentially double the commercial potential of RYTELO. 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 the 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 Dawn, 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 RYTELO is a highly effective novel treatment that fills a significant need in an underserved therapeutic area. We also believe that RYTELO 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 RYTELO’s potential in a market with considerable opportunities. On Slide 7, we outlined the estimated U.S. total addressable market for RYTELO at approximately 15,400 lower risk MDS patients based upon the label and NCCN guidelines. Today, 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 RYTELO to expand use in earlier lines of treatment, including first line ESA-Ineligible, and second line ESA-relapsed refractory patients. In Europe, we estimate that the EU4 total addressable market for RYTELO is approximately 80% of the U.S. Later in this call, Joe will provide an update on our ongoing Phase III relapsed 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 relapsed refractory myelofibrosis patients, and the EU4 total addressable market is approximately 9,000 JAK inhibitor relapsed 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 RYTELO in the U.S. On Slide 8, I will highlight our strategy, plan of action, and thoughtful investments to support this priority. First, we are working to improve RYTELO 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 a 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 to treat the greatest number of RYTELO 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 who treat fewer lower risk MDS patients and may not see a key account manager as often. Second, we are working to increase HCP prescribing confidence through clinical experience and patient success stories. We believe there is an opportunity to reinforce RYTELO’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 confidence and clarity through education and strong messages that reinforce RYTELO’s product differentiation through the expanded field team, especially targeting our higher volume, lower risk MDS treaters. We are also enhancing our omnichannel 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 RYTELO, given the limited number of U.S. clinical trial investigators and patients who participated in IMerge. 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 RYTELO’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 positions 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 RYTELO 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 RYTELO 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 RYTELO. 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 RYTELO new patient starts were in the 1st and 2nd lines. We expect to see an increase in second line use as HCPs gain more experience with RYTELO and become more comfortable prescribing it in earlier settings. Our recent market research evaluating intention to treat suggests physicians intend to use RYTELO in earlier lines of therapy. Payer access continues to strengthen with approximately 85% of U.S. covered lives now under favorable RYTELO 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 European markets is dependent on strong reimbursement and favorable pricing. We are engaging established third party partners across commercial, market access, medical affairs, 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 U.S. sales performance. We remain confident in the long-term potential of RYTELO 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 RYTELO. I will now turn the call over to Joe Eid, 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 RYTELO, 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 clinical engagement. 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 RYTELO'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 RYTELO, 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 RYTELO'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 RYTELO's safety profile, which has generally been that RYTELO 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 IMerge data showed that the exposure to imetelstat 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 imetelstat. Looking ahead, we are excited about the upcoming American Society of Clinical Oncology and European Hematology Association annual meeting 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 imetelstat research interest from investigators, and given its unique mechanism of action, there is eagerness to evaluate imetelstat in new settings as well as new indications. As Dawn 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 an access program to provide RYTELO to eligible patients with low risk and intermediate one MDS. I'd also like to provide an update on our IMPACT MS Phase III trial in relapsed refractory myelofibrosis and discuss why we're excited about expanding imetelstat in this indication. As you know, we based the IMPACT MS Phase III trial on our single arm Phase II 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 imetelstat. These significant observations gave us confidence in pursuing the registrational study in relapse refractory myelofibrosis. Our confidence also stems from the unique mechanism of action of imetelstat. Telomeres are repetitive DNA sequences at the end of chromosomes and serve as protective caps that can help maintain the stability and integrity of these chromosomes. Telomerase is an enzyme that maintains telomere length in rapidly dividing cells. Telomerase is upregulated in more than 90% of cancers, including myelodysplastic syndromes, and leads to cell division uncontrollably without reaching the Hayflick limit thereby evading oncogenic senescence. RYTELO is the first and only telomerase inhibitor approved by the FDA for certain lower risk MDS patients and is being evaluated in relapsed refractory myelofibrosis in a Phase III ongoing trial. We are very encouraged with the continued interest in the IMPACT MS Phase III 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 MS Phase III trial is designed with a 2 to 1 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 III trial, we also have the Improved MS Phase I trial, which is a frontline myelofibrosis study of the imetelstat in combination with a JAK inhibitor. This trial completed the dose escalation stage. We were encouraged to be able to dose ruxolitinib and imetelstat at the maximum intended doses of each without observed dose limiting toxicity. We also observed fewer cytopenias than seen in the IMerge 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 myelofibrosis. This is a great opportunity for patients with unmet need and for imetelstat's continued growth. We believe that this is an important opportunity to investigate whether imetelstat 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 31, 2025, we had approximately 457.5 million in cash, cash equivalents, restricted cash and marketable securities compared to 502.9 million as of December 31, 2024. Total net product revenue and total net revenue for the three months ended March 31, 2025 were 39.4 million. There were no products or net revenues in the first quarter of last year since RYTELO was approved by the FDA in June of 2024. As Dawn mentioned, Q1 RYTELO net revenues were down approximately 8 million from Q4, while demand in the 13-week period through the week ending March 28 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 RYTELO. Gross 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 at the FDA approval of RYTELO in 2024, as well as manufacturing and quality costs that were capitalized in the current period now that RYTELO 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 RYTELO 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 RYTELO commercialization strategy, investment in commercial supply redundancies, post-marketing commitments, as well as initial preparations to launch RYTELO in selected EU countries in 2026, including the HCA evaluation process. We will be able to provide additional details as we approach the planned launch next year. 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 RYTELO is a differentiated product for the treatment of certain patients with lower risk MDS, a disease with high unmet 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 RYTELO 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 imetelstat 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 RYTELO's success here in the United States. And lastly, we're excited as we look towards the future. Our pivotal Phase III trial evaluating imetelstat in relapsed refractory MS patients with an overall survival endpoint, if successful and approved in this setting, could potentially double the commercial opportunity of RYTELO. 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.

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

Hi, good morning. So, I'm hoping just with the inventory impacts potentially behind you, demand is improving in recent weeks 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?

Hi Tara, it's Dawn Bir. 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 of April over March; so, what we anticipate is continued momentum building into Q2 and sustaining throughout the year through 2025.

Okay, thanks so much.

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

Good morning. This is Teresa Vitale on for Greg Harrison. Thanks for taking our question. Just curious if you can comment on your commercial efforts to drive the assessment of efficacy for patients on this luspatercept to an earlier stage in order to help promote switching to RYTELO, and maybe what are KOL citing as their reasoning behind. Any hesitation in switching patients from standard of care and prescribing RYTELO and earlier lines of therapy.

Teresa 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.

Let's start by discussing perceptions, behaviors, and results. We conduct ATU market research, which focuses on awareness, trial, and utilization. It begins with awareness. Our research indicates that when physicians are aware of RYTELO's product profile, they perceive it more favorably compared to those who are not familiar with it. This positive view applies to both efficacy and cytopenia management. In our latest ATU, we observed a notable improvement in the perception of cytopenia management, particularly among those who have used RYTELO, as it is regarded as significantly more manageable than for those who have not used it. Regarding efficacy, recent data shows that perceptions surrounding second-line RS negative have shifted positively and are being recognized as a key differentiator. I mention this to highlight that the messages from our field force are resonating with physicians, and we anticipate that these perceptions will lead to behavioral changes. The positive data point I shared earlier indicates around 20% utilization in both first and second lines, which is an improvement over earlier results. These are promising indicators for sustained growth, and I want to commend our customer-facing teams, including the CAMs and oncology clinical educators, for effectively delivering the message, as we noted earlier that impactful messaging results in significant outcomes.

Yeah, maybe to compliment Jim's answer, you specifically asked about luspatercept. Obviously, as we know in the IMerge study there was a limited number of patients who had received luspatercept, given that it was in the early days of its approval. However, we did have subsequent trials that did include patients who have received luspatercept and we presented data at ASH last December that showed the activity of imetelstat, post CSA, post luspatercept, 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 imetelstat have experienced the positive benefit of this on their patients, and that is encouraging. The efficacy is somewhat unparalleled in the 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 or just the dynamics there that we should be thinking about as the inventory been burnt 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 specialty pharmacies and specialty distributors were using history to project the future going forward. So, as the trend started to flatten the inventory increased. The 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 RYTELO, but that's all buy and build products. So, while the inventory was probably at the higher end, 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 you think that kind of stabilized kind of issues, I guess slower than expected pull through, and stocking, you think that's in a good spot for 2Q?

We do Peter, thanks. Yes.

Thank you. You mentioned having around 1300 high-priority healthcare professionals. How many of these are currently being reached by the field team? What is the frequency of their visits, and what target do you have for that metric in the second half of this year?

Peter, we're not going to get 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 1300, 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 push-backs of physicians who are less interested and I have a follow on?

Going back to the market research, I would say that for those who have not used RYTELO or are not necessarily informed by our key account managers, some frequently mentioned barriers include cytopenias or a lack of patients. However, that situation changes significantly when we consider physicians who have treated or are aware of RYTELO. We believe that ongoing outreach and delivering compelling messages, particularly to our targeted accounts, will help alter those dynamics. It's important to note that physicians who have used RYTELO and are familiar with it generally hold a much more favorable view of its product profile and utilization patterns.

If I may add, actually we've had several engagements with physicians who have not used RYTELO, 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. In those conversations we've had with many of those type of physicians. When we do discuss the mechanism of action and that the cytopenias 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 physicians' thinking and potential utilization in their clinics.

So just to focus on that point, would you say the main barrier is getting physicians to begin treatment? Is that accurate?

One second, Jim. When Reblozyl was launched, there was this so-called apathy among physicians converting from ESAs to luspatercept. To this day, we see patients in particular in the community setting on ESAs, even with high EPO levels over 500, all patients who have failed ESAs, that's been the pattern for 20 plus years in the clinics, and that's the reason for many of those barriers that we are seeing initially in the luspatercept journey and some of that we're seeing for the imetelstat 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 and G&A?

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 Stephen Willey of Stifel. Your line is open.

Yeah, good morning. Thanks for taking the questions. Joe, I guess you talked about 900 accounts having ordered to date. Can you 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?

Stephen, 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, Stephen.

Okay, and then can you also just comment in terms of what you're seeing with respect to luspatercept utilization in the frontline setting both in terms of RS positive and RS negative and do you have any sense that these patients are subsequently stepping through an ESA as a second line option, or is it just too early into the luspatercept 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 luspatercept based upon the command data, and if that happens and continues to grow, we're expecting duration of treatment fairly consistent with their study. In terms of switch, we can't promote specifically post-luspatercept, our labeled indication is ESA relapsed refractory or ESA ineligible. However, the NCCN guidelines is a bit broader.

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

Hi, good morning. Thanks for giving the questions. I'm curious for physicians who have used RYTELO 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?

Yeah, 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, you commented did not reorder RYTELO, if you can provide any reasoning that you're hearing for that.

Nothing specific at this point. It could just be simply dose interruption due to 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 and market research.

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

Hey, thanks for taking the questions. Maybe first on the inventory part of this, Michelle I think you previously communicated that the distributors were maintaining 2 to 4 weeks of inventory in the channel. So, what's the day supply today, I guess, or at the end of first quarter. And then I have a follow up.

Sure, thanks, Kalpit. 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 3.5 weeks and as of the end of Q1, it was on the lower end of three weeks.

Okay, makes sense. And then, at this point in the launch, are your new patient starts consistently exceeding the discontinuation, or are you starting to see some of those early patients who received imetelstat 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 patients starts have to fill the funnel and continue to drive. The promising data that I share on this call is that, based upon the most recent new patients starts number 25%, approximately 25%, and we're in 1st and 2nd lines. 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?

In the first quarter, cash burn is typically higher due to bonus payouts and some early investments in inventory.

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

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

Thanks Faisal. 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 sales-force perspective in market research, delivering the right message to the right physician 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.

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