Jim Ziegler
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 US 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 opportunity.
On slide 7, we outlined the estimated US total addressable market for RYTELO 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 a 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 US Later in this call, Joe will provide an update on our ongoing Phase 3 relapsed refractory myelofibrosis clinical trial, IMpactMF, 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 US 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 IMpactMF clinical and regulatory milestones. Our top corporate priority is the successful commercialization of RYTELO in the US. On slide 8, I will highlight our strategies, 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 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 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 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 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 competence 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 teams.
Our commercial and medical affairs teams are also addressing and educating HCPs on appropriate cytopenia management to increase HCP prescribing competence. And Joe will highlight the key considerations on cytopenia management and expectations later during his section.
Third, we are working to generate stronger KOL support and advocacy across the US. We believe that increased KOL advocacy is essential to building broader support and use of RYTELO given the limited number of US clinical trial investigators and patients who participated in IMerge.
Our strategy is to strengthen US 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 in 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 engagement, 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 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 first and second 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.
Payor access continues to strengthen with approximately 85% of US covered lives now under favorable RYTELO medical coverage policies that are consistent with the FDA label and our 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 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 medical affairs and clinical development updates.
Joseph Eid
Thank you, Jim. I'd like to start by sharing several recent accomplishments from the medical affairs organization.
Since our last earnings goal, 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 on 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 HE award.
In fact, we are in the process of doubling the size of our overall medical affairs team since our last earnings goal. 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 three pivotal trial, which enrolled the vast majority of patients outside of the United States.
We are increasing our efforts to educate and inform the US 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 three 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 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 imetelstat research interests from investigators, and given its unique mechanism of action, there is eagerness to evaluate imetelstat in new settings as well as new indications.
As Don and Jim mentioned, our focus and top priority remains US 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 RYTELO to eligible patients with low-risk and intermediate one MDS. I'd also like to provide an update on our IMpactMF Phase 3 trial in relapsed refractory myelofibrosis, and discuss why we're excited about expanding imetelstat in this indication.
As you know, we based the IMpactMF Phase 3 trial on our single-arm Phase 2 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 a historical cohort. Second, we observed decreased bone marrow fibrosis or complete reversal after treatment with imetelstat. 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 imetelstat.
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 chief chromosomes. Telomerase 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 cells dividing uncontrollably without reaching the Hayflick limit, thereby evading apoptosis.
RYTALO 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 a Phase 3 ongoing trial. We are very encouraged with the continued interest in the IMpactMF 3 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 IMpactMF 3 trial is designed with a 2:1 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 3 trial, we also have the IMproveMF Phase 1 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 ruxolitinib and imetelstat at the maximum intended doses of each without observed NPD. 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 MS. This is a great opportunity for patients with unmet need and for geo-uncontinued 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.
Michelle Robertson
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 ending 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. 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 ending 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 activity in our Phase 3 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 ending March 31, 2025 were $40 million compared to $27.1 million for the same period last year. The increase was primarily due to higher personnel expenses related to additional headcount to support the commercialization of RYTELO in the US.
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 [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 GRON 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 Pharmakon if needed.
With that, I'll turn it back to Dawn.
Dawn Bir
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 US commercialization and 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 US 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 Imitelstat 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 3 trial evaluating imetelstat in relapsed refractory MF 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. Operator?
Operator
(Operator Instructions) Tara Bancroft, TD Cowen.
Tara Bancroft
Hi. Good morning. So I'm hoping just with the inventory impacts essentially 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?
Dawn Bir
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.
Jim Ziegler
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. 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% increasing growth of April over March.
So what we anticipate is continued momentum building into Q2 and sustaining throughout the year through 2025.
Operator
Greg Harrison, Scotiabank.
This is [Teresa Vitale] on for Greg Harrison. Thanks for taking our question. I was 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 RYTELO and maybe what are KOL citing as their reasoning behind any hesitation in switching patients from standard of care and prescribing RYTELO in earlier lines of therapy?
Dawn Bir
Thank you. 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.
Jim Ziegler
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 RYTELO'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 RYTELO 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 course 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. 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.
Joseph Eid
Maybe to complement Jim's answer, you specifically asked about the post-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 had received luspatercept. We presented data at ASH last December that showed the activity of imetelstat, post-CSA, 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 providing additional information about that specific topic.
In terms of hesitancy, as Jim has mentioned and I will reemphasize, physicians who are using Imitalstat have experienced the positive benefit of this on their patients. That is encouraging. The efficacy is somewhat unparalleled in this space where we are seeing robust hemoglobin rises and patients' quality of life improving.
Operator
Peter Lawson, Barclays.
Peter Lawson
Jim, maybe you could walk through the inventory issue. Was that due to a distributor stocking in 4Q? The dynamics there that we should be thinking about as the inventory has been burned through. Do you think that is corrected?
Jim Ziegler
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. Many of our SPs and STs were using history to project the future going forward. 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 products as well as other products in our category.
The third thing is perhaps there was some anticipation of pricing or reimbursement issues, which is not specific to RYTELO, but affects all buy and build products. 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. That explains the difference between the drop in net revenues, yet the 1% increase in demand.
Thanks for the question, Peter.
Peter Lawson
Great. Do you think that stabilized issues with slow and unexpected pull-through and stocking? Do you think that is in a good spot for 2Q?
Jim Ziegler
We do, Peter. Thanks. Yes.
Peter Lawson
Great. Okay. Thank you. 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?
Jim Ziegler
Peter, 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.
Operator
Gil Blum, Needham & Company.
Gil Blum
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 physicians who are less interested and have a follow-on?
Jim Ziegler
Going back to the market research, what I would say is for those specifically that have not used RYTELO 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 RYTELO. 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 RYTELO have a much more favorable view of the product profile and the utilization patterns.
Gil Blum
Just to hone in on that -- sorry, go ahead.
Joseph Eid
If I may add, actually, we've had several engagements with physicians who have not used RYTELO. The main reason that they have accused 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 physician thinking and potential utilization in their clinics.
Gil Blum
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?
Joseph Eid
(multiple speakers)
One second, Jim. I mean, when [Revlizir] was launched, there was this so-called apathy among physicians converting from ESAs to spatter 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 in the clinics, and that's the reason for many of those barriers that we are seeing initially in the spatter set journey, and some of that we're seeing for the imetelstat as well.
Go ahead, Jim.
Jim Ziegler
Nothing to add. Thanks, Joe.
Gil Blum
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.
Michelle Robertson
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. 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.
Operator
Stephen Willey, Stifel.
Stephen Willey
I guess you talked about 900 accounts having order 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?
Jim Ziegler
Yes, 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.
Stephen Willey
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 if 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?
Jim Ziegler
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 NCCA guidelines is a bit broader.
Operator
Emily Bodnar, H.C. Wainwright.
Emily Bodnar
I'm curious for physicians who have used Ritolo 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 discontinuation to date kind of reasonings for those and if that's kind of in line with your clinical data expectations.
Jim Ziegler
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?
Emily Bodnar
For the one-third of HCPs who you commented did not reorder RYTELO, if you can provide any reasonings that you're hearing for that.
Jim Ziegler
Nothing specific at this point. It could just be simply a dose interruption due to a cytopenia. As you know, in this buy-and-bill 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.
Emily Bodnar
Okay. And then lastly, if you can comment on the improved MS data that you're going to have at ASCO, what differences should we be expecting for a presentation at ASH?
Joseph Eid
I mean, we have 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 cohort of patients. So we are expanding, and we're adding additional JAK inhibitors to the combination.
Operator
Kalpit Patel, B. Riley Securities.
Kalpit Patel
Maybe first on the inventory part of this, Michelle, I think you previously communicated that, you know, the distributors were maintaining two to four weeks of inventory in the channel. So what's the data supply today, I guess, or at the end of first quarter? And then I have a follow-up.
Michelle Robertson
Sure. Thanks, Kalpit. Yes. 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 2 plus 2.5 weeks.
Kalpit Patel
Okay. Okay. Makes sense. 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 imetelstat start to roll off and offset the new starts?
Jim Ziegler
Kalpit, we don't have perfect data on this. Again, we use patient chart audits and marker research. In the buy-and-bill market, the data isn't at a patient-specific level.
But I can 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 based on 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.
Kalpit Patel
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?
Michelle Robertson
Well, Q1 cash burn is always higher due to payouts of bonuses and some early investment, yes, on the inventory side. That was front (inaudible)
Operator
Faisal Khurshid, Leerink Partners.
Faisal Khurshid
Hey, guys, thanks for taking the question. I just wanted 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 it to translate into, like, true revenue growth?
Jim Ziegler
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 positions 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.
Operator
That is all the time we have for questions. This concludes today's conference call. Thank you for joining. You may now disconnect.
