Geron - Q2 2024
August 8, 2024
Transcript
Operator (participant)
Hello, and welcome to the Geron Corporation Second Quarter 2024 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, and if you would like to ask a question during this time, please press star one on your telephone keypad. I would now like to turn the conference over to Aron Feingold, Vice President of Investor Relations and Corporate Communications. You may begin.
Aron Feingold (VP of Investor Relations and Corporate Communications)
Good morning, everyone. Welcome to the Geron Corporation second quarter 2024 earnings conference call. I am Aron Feingold, Geron's Vice President of Investor Relations and Corporate Communications. I'm joined today by several members of Geron's management team: Dr. John Scarlett, Chairman and Chief Executive Officer, Dr. Andrew Grethlein, Executive Vice President and Chief Operating Officer, Dr. Faye Feller, Executive Vice President and Chief Medical Officer, and Michelle Robertson, Executive Vice President and Chief Financial Officer. On today's call, Chip will start off with introductory remarks on commercial execution and value creation. Andy will provide a commercial and operations update. Faye will speak to medical and clinical updates. Michelle will provide a financial review, and Chip will close with some final remarks.
Before we begin, please note that during the course of this presentation and question-and-answer session, we will be making forward-looking statements regarding future events, performance, plans, expectations, and other projections, including those relating to the launch, commercial opportunity, and therapeutic potential of RYTELO, anticipated clinical and commercial events and related timelines, the sufficiency of Geron's financial resources, and other statements that are not historical fact. 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 filed with the SEC, which identifies important factors that could cause actual results to differ materially from those contained in the forward-looking statements. Geron undertakes no duty or obligation to update our forward-looking statements. With that, I'll turn the call over to Chip. Chip?
John Scarlett (Chairman and CEO)
Thanks, Aron. Good morning, everyone. Thanks for joining us. It was just eight weeks ago that FDA approved RYTELO, our branded name for Imetelstat, as the first and only telomerase. It was just six weeks ago that RYTELO became commercially available in the U.S. With our strong commercial infrastructure in place at launch and the efficient mobilization of our field teams, we've seen encouraging early launch results. As of July 31, 60% of the top decile 1-4 accounts have been reached by our team across both community and academic settings. This has led to gratifying uptake. We estimate, again, as of July 31, that approximately 160 patients have received RYTELO, which is quite encouraging, given the very early stage of this launch.
The enthusiastic reception for RYTELO that we've seen within the hematology community reinforces the unmet needs for lower-risk MDS patients with symptomatic transfusion-dependent anemia. Many of our customers are passionate about getting access to RYTELO for their patients, and we've seen a strong push across the U.S. to add RYTELO to formularies, treatment pathways, and EMRs, including in the community setting. In addition, the MDS NCCN guidelines were updated this July 25 to include RYTELO as a Category 1 and 2A treatment for lower-risk MDS patients. That is, RYTELO is now designated for use in both RS positive and RS negative first-line ESA in-eligible patients, as well as in both RS positive and RS negative second-line patients, regardless of prior first-line treatment. We believe that these favorable NCCN guidelines have put RYTELO in a strong competitive position.
During their portions of this call today, Andy and Faye will walk through how clinical, formulary, and treatment pathway decision-making is guided by the NCCN guidelines. With the introduction of RYTELO as a new therapeutic option, we're seeing increasing dialogue among hematologists, rethinking treatment approaches for eligible lower-risk MDS patients with transfusion-dependent anemia. Consequently, we believe that RYTELO can become part of the standard of care for both eligible first and second-line patients. As shown on this slide, from the approximately 13,200 U.S. patients with lower-risk MDS who need treatment for symptomatic anemia, approximately one in ten are ESA ineligible due to serum EPO levels higher than 500 milli units per ml. These first-line patients have limited treatment options. RS positive patients make up approximately 25% of the lower-risk MDS patient population, many of whom continue to experience high transfusion burden despite available therapies.
RS negative patients make up approximately 75% of lower-risk MDS patient populations, many of whom are particularly vulnerable to poor clinical outcomes and have few other treatment options. In support of our commercial opportunity, we believe we have strong regulatory exclusivity and patent protection in the U.S. for RYTELO for this disease. Following approval, we completed the listing of our patents in the FDA's Orange Book. We also received confirmation from the FDA of imetelstat's orphan drug exclusivity for lower-risk MDS into June 2031. We've also filed our applications for patent term extension, or PTE, including for our method of use patent covering MDS and MS. If the PTE application is granted and applied to this patent, we estimate that the patent term would extend through August 2037.
We believe this IP protection, as well as several key factors I'll discuss on the next slide, position us well to create long-term commercial value with RYTELO. Based on the clinical profile of RYTELO, the approved U.S. prescribing information, and now a great set of NCCN Guidelines, we believe we are well-positioned to build long-term commercial value with RYTELO. More specifically, first, there's a high unmet treatment need for patients with lower-risk MDS, as many patients progress and do not respond to current treatments, achieve a durable response, or experience extended and continuous red blood cell transfusion independence. Treatment options for red blood cell transfusion-dependent patients who are relapsed or refractory to, or ineligible for ESAs can have significant limitations, underscoring the need for novel treatment options such as RYTELO.
Second, as demonstrated by the totality of clinical benefit in the IMerge Phase III clinical trial, RYTELO can offer eligible lower-risk MDS patients meaningful clinical benefits, including durable and sustained red blood cell transfusion independence and reduction in transfusion burden. In IMerge, this treatment effect is consistent across key lower-risk MDS subgroups, including both RS-positive and RS-negative patients who are not eligible for ESAs, as well as both RS-positive and RS-negative patients who are relapsed or refractory to ESAs. RYTELO was also shown in IMerge Phase III to have a well-characterized safety profile, with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar adverse events for hematologists who are experienced with managing cytopenias. Third, from an EU perspective, we also have a marketing authorization application, or MAA, under review in transfusion-independent lower-risk MDS, which we expect could be completed in early 2025.
We're working to finalize our strategy for EU commercialization as we continue to explore our options in the interest of maximizing our ability to serve all of our stakeholders, patients, healthcare providers, and shareholders. We're continuing to engage in discussions with EU regulators, authorities, and payers as we assess those options, which include self-commercialization or partnering. Then fourth, from a clinical development perspective, our pivotal Phase III IMpactMF OS clinical trial in JAK inhibitor-relapsed and refractory myelofibrosis patients has now achieved approximately 70% enrollment. An interim analysis is still expected in early 2026. This JAKi relapsed refractory MF population represents a high unmet need population and significant commercial opportunity. Lastly, our highly experienced team is driving performance across our business, passionately serving patients and customers, and staying focused on quality and operational excellence.
I'm also happy to report today that we have had an exceptionally strong response to our Chief Commercial Officer search and that we've made great progress in identifying several candidates with strong leadership skills and a history of outstanding commercial execution. We expect to be able to make an announcement in the next month or so. With that, I'll turn the call over to Andy for commercial and operations update. Andy?
Andrew Grethlein (EVP and COO)
Thanks, Chip, and good morning to everyone on the call. We have built a strong commercial infrastructure that has enabled us to activate the launch effectively. First, we are pleased with the early awareness of RYTELO among prescribers and payers. Based on our market research before FDA approval in May 2024, of over 100 U.S. hematologists and oncologists, over 80% of those surveyed were aware of imetelstat. One in three surveyed physicians indicated familiarity with the clinical data, and a majority of these physicians looked favorably on the efficacy profile and mechanism of action, which is especially important for a first-in-class treatment. Payers are expressing high levels of interest and already have a strong understanding of the RYTELO U.S. prescribing information and IMerge Phase III clinical data.
From an operational perspective, both dosage strengths of RYTELO, the 188 mg vials and 47 mg vials, were available in our distribution channel for customers to order from specialty distributors as of June 27, 2024. Our distribution network is fully activated, with our specialty distributor network actively supporting customer demand across hospitals and community oncology clinics. Across the contiguous 48 states, RYTELO is available to HCPs within 24-48 hours from our specialty distribution networks. We also believe that RYTELO's inclusion in the updated NCCN guidelines has been important in spreading awareness among the prescriber community. The NCCN guidelines are a highly regarded resource in clinical decision-making for prescribers, as well as provide critical considerations from a formulary and treatment pathway development perspective. Generally, the top national payers and Medicare cover oncology medicines categorized as one or two-way treatment by NCCN guidelines.
Our patient access and affordability solutions are fully activated. Our patient hub is fully operational and supporting inquiries from HCPs and patients. Our J-Code application was submitted in July 2024, and we expect issuance of a permanent J-Code in the first quarter of 2025. We have seen a strong push by prescribers to add RYTELO to their formularies and EMRs that can help accelerate access in the meantime. Lastly, we engage with the major national payers within 30 days of launch and look forward to continued dialogue as they adopt our national coverage policies, which we expect to occur in the first quarter of 2025. On this next slide is a snapshot of our medical and commercial field teams that have been fully deployed to cover the entire U.S. market, supporting HCP and account education and uptake.
This includes 50 key account managers, our oncology clinical educator liaisons, field reimbursement access directors, and national account teams, along with our field medical affairs teams. We are pleased that since these commercial and medical field teams were deployed in June, there has been a strong level of in-person access to community and academic accounts and HCPs. We believe that the experience and relationships that our talented field teams bring to Geron have enabled them to quickly access these accounts. We believe that the strong RYTELO value proposition, commercial foundation, and the execution of our entire organization is driving encouraging early results over these first six weeks of launch. As we commented earlier, we estimate that as of July 31, 2024, approximately 160 patients have received RYTELO.
This demand was generated in part by reaching approximately 60% of top Decile 1 through 4 accounts and includes orders from roughly 115 unique accounts. We are seeing an encouraging range of customers ordering RYTELO in these early days, from small community to large aggregator accounts, with hospitals ranging from community, academic centers, teaching hospitals, and large health systems. In July, we kicked off our national speakers program with the launch of our national broadcast event, featuring medical experts, which garnered over 300 medical professional participants. These events are a critical component of our marketing strategy to make sure HCPs are aware of the new treatment option for their eligible patients. Overall, our teams have focused on delivering our launch objectives: supporting a positive first experience for HCPs and patients, encouraging adoption among prescribers, and facilitating patient access.
We believe our early performance reinforces that executing against these objectives can meaningfully drive awareness and uptake for appropriate patients. With that, I'll turn the call over to Faye for a medical and clinical update. Faye?
Faye Feller (EVP and Chief Medical Officer)
Thanks, Andy, and thanks to everyone for joining our call today. As Chip mentioned, on July 25, the NCCN published updated MDS treatment guidelines, including RYTELO, for the treatment of symptomatic anemia in patients with lower risk MDS. We believe that RYTELO's placement in the updated NCCN guidelines reflects the strength of our Phase III data, which showed the clinical benefit of Imetelstat, regardless of ring sideroblasts status or serum EPO levels, as well as the favorable U.S. prescribing information, where RYTELO is indicated broadly across RS positive and RS negative patients who are both ESA ineligible and ESA relapsed refractory. The MDS NCCN guidelines characterize lower risk MDS patients without the del(5q) abnormality and with symptomatic anemia on the basis of ring sideroblasts status and serum EPO levels, without specifying red blood cell transfusion burden.
Overall, and as shown in the purple comment boxes on the far right of this slide, these updated MDS NCCN treatment guidelines include RYTELO as a Category 2A treatment for both RS positive and RS negative first-line ESA-ineligible patients, and as a Category 1 treatment for both RS positive and RS negative second-line patients, regardless of first-line therapy. Diving into these guidelines in more detail. On the left side of the slide is a schematic representing the NCCN guidelines for the treatment of RS positive patients. For ESA-ineligible patients who have serum EPO levels greater than 500 milli-units per ml, imetelstat is included as a Category 2A first-line treatment. For RS positive ESA-eligible patients with serum EPO levels 500 milli-units per ml and below, imetelstat is included as a Category 1 treatment, second-line after luspatercept.
Additionally, as shown in the 2+ line at the bottom of the schematic, imetelstat is included as a Category 1 treatment for later lines of therapy after ESA or luspatercept treatment in these RS positive ESA-eligible patients. On the right side of the slide is a schematic representing the NCCN guidelines for RS negative patients. For ESA-ineligible patients who have serum EPO levels greater than 500 milli-units per mL, imetelstat is included as a Category 2A first-line treatment. For RS negative ESA-eligible patients with serum EPO levels 500 milli-units per mL and below, imetelstat is included as a Category 1 treatment, regardless of prior first-line therapy with either ESAs or luspatercept.... Turning now to a clinical development update from our myelofibrosis program.
Our pivotal Phase III IMpactMF trial of Imetelstat in JAK inhibitor-relapsed/refractory MF, the first and only Phase III trial in MF with overall survival as the primary endpoint, has reached approximately 70% enrollment as of August 2024. A per-protocol interim analysis has been planned when approximately 35% of the planned enrolled patients have died, which we anticipate in early 2026. A final analysis is planned when approximately 50% of the planned enrolled patients have died, which is currently anticipated in early 2027. If the interim analysis is statistically significant, we would plan to file a supplemental new drug application with the FDA based on the interim analysis. As an overall survival study, the timeline for the interim and final analyses is dependent not only on the rate of enrollment, but also on the event rate or patient death rate in the trial.
Today, treatment of myelofibrosis is dominated by JAK inhibitors or therapies with other mechanisms of action in combination with JAK inhibitors. Once patients become unresponsive to JAK inhibitors, which leads to treatment discontinuation for approximately 75% of patients after five years, they face a dismal overall survival of approximately 11-16 months. We believe that if our trial is successful and imetelstat is approved in this indication, it could transform treatment for these myelofibrosis patients. Lastly, we are also evaluating imetelstat in the IMproveMF Phase I study as combination therapy with ruxolitinib in patients with frontline myelofibrosis. Our main goal for this combination study is to determine the safety profile of the regimen of ruxolitinib and imetelstat, as well as to explore potential activity of imetelstat in a frontline MF disease setting. Part 1 of the study is designed to be dose-finding.
In July 2024, after no dose-limiting toxicities were experienced by the first three patients in the dose level four cohort, or Imetelstat sodium 9.4 mg/kg, the Study Evaluation Team, or SET, unanimously recommended expanding the cohort per the trial protocol. This is the final step before dose selection and progression to part two of the study that is designed for expansion and dose confirmation. We hope to provide an update from part one of the study at an upcoming medical meeting. With that, I'll turn the call over to Michelle for a financial update. Michelle?
Michelle Robertson (EVP and CFO)
Thanks, Faye, and good morning, everyone. For detailed Q2 2024 financials, please refer to the press release we issued this morning, which is available on our website. Now let me bring your attention to a few highlights from the quarter. As of June 30, 2024, the company had approximately $430 million in cash, cash equivalents, and marketable securities. Total product revenue net for the three and six months ended June 30, 2024, was approximately $780,000. RYTELO became available for prescribers to order from specialty distributors as of June 27, 2024. Total revenues for the three and six months ending June 30 were $882,000 and $1.2 million, compared to $29,000 and $50,000 for the same period in 2023.
The increase in revenue is due to product revenue from U.S. sales of RYTELO that commenced in June 2024. Total operating expenses for the three and six months ended June 30 were $70.2 million and $126.7 million, compared to $52 million and $92.1 million for the same period in 2023. Cost of goods sold was approximately $17,000 for the three and six months ended June 30, which consisted of cost to manufacture and distribute RYTELO. R&D expenses for the three months and six months ended June 30, 2024, were $30.8 million and $60.2 million, respectively, and $35.5 million and $62.7 million for the same periods in 2023. Our clinical development costs for IMerge Phase III have decreased as we move into the long-term follow-up stage.
Selling, general, and administrative expenses for the three and six months ending June 30th, 2024, were $39.4 million and $66.5 million, respectively, and $16.5 million and $29.4 million for the same periods in 2023. The increase in selling, general, and administrative expenses primarily reflects higher commercial launch expenses, increases in headcount, and stock-based compensation recognized due to the vesting of performance-based stock options upon FDA approval of RYTELO. As of June 30th, 2024, we had 220 full-time employees. We plan to grow to a total of approximately 230-260 employees by year-end 2024. Our projected full year 2024 operating expenses are expected to be between $270 million and $280 million, which is unchanged from our prior guidance.
Based on our current operating plans and assumptions, we believe that our existing cash, cash equivalents, and marketable securities, together with our projected revenues from U.S. sales of RYTELO, will be sufficient to fund our projected operating requirements into the second quarter of 2026. I will now turn the call back over to Chip.
John Scarlett (Chairman and CEO)
Thanks, Michelle. To close, we're encouraged by our early commercial launch performance and the feedback we're receiving from customers and payers. We're pleased with our strong execution to date, but also recognize that we're still in the very early stages of our U.S. launch, with many more patients to serve and many more customers to engage.
... We have conviction that RYTELO can become part of the standard of care for eligible patients in this high unmet need, lower risk MDS treatment paradigm and bring differentiated benefits to patients. In addition to our launch in lower risk MDS, we're also advancing our imetelstat development program in myelofibrosis, which, pending positive outcomes from the trials, we believe will contribute significantly to the commercial value proposition for RYTELO in the future. Thank you, and we'll now open the line to questions. Operator?
Operator (participant)
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 that your phone is not on mute when called upon. Thank you. Your first question comes from the line of Tara Bancroft with TD Cowen. Your line is open.
Tara Bancroft (Director and Senior Analyst)
Hi, good morning, and thanks for taking the questions. I guess to start, I would love to get a better sense of expectations for the year and what you're targeting. For that, I know you're probably not providing revenue guidance, but I think it would be helpful to know whether a couple of things, whether you think a J-code could be finalized potentially before January, and other metrics like how soon you think the field team will hit 100% of the target prescriber base? Thanks.
John Scarlett (Chairman and CEO)
Thanks a lot, Tara. Appreciate the questions, which you're quite correct. We have limited ability to answer, six weeks into the launch. I think we're really happy with where we've ended up in such a short period of time, and think that that is, we hope that that's a harbinger of performance as we continue on. I think the J-code, I think we're guiding to the first quarter because we're honestly not 100% sure when it will come. History suggests that there is some variability at the end, but, you know, we gave that guidance, and I think we'll stick by it for the moment.
As we get a little bit closer, we may or may not have more information, but as of the moment, I think we would still stick to the early, early, earlier part of the year. I think with regard to metrics on the sales force, wow, the sales force is completely engaged, as you can imagine. I don't actually have any predictions available to any of us on that, but I do know that they are as, what's the best word for it? They are as enthusiastic and as hardworking a group of both, you know, KAMs, not only the key account managers, but also the folks responsible for trade and channel and for all of the various activities involved in a sophisticated commercial launch.
I think it's probably all we can say today, but thanks, thanks for the question. Look forward to, to seeing this all, evolve, over the remainder of the year.
Tara Bancroft (Director and Senior Analyst)
Great. Thank you so much.
John Scarlett (Chairman and CEO)
Sure.
Operator (participant)
Yep. Your next question comes from the line of Carter Gould with Barclays. Your line is open.
Carter Gould (Senior Analyst)
Good morning.
John Scarlett (Chairman and CEO)
Hi, Carter.
Carter Gould (Senior Analyst)
Congrats to Chip and team on the early days here. Appreciating that it's early, how would you... I guess that initial 160 patients, would you characterize that sort of as a bolus or potentially something more sustainable? Again, I appreciate it's early, but would these sort of, you have a sense if these patients were sort of identified by clinicians ahead of the launch or sort of more spontaneous use? And then on the patent term extension side of things, my understanding, or as I recall, I think sort of USPTO has, I think statutorily has, like, 14 months to respond to your extension. Is that correct, and is that a fair characterization of the timeline we should expect to hear back on this front? Thank you.
John Scarlett (Chairman and CEO)
Okay. Thanks, Carter. So with regard to the initial uptake and demand and the question of a bolus, you know, you only know a bolus for sure when you see it in the rearview mirror, right? I mean, if the trend line continues, it's not a bolus. If it slacks a bit at some point, I guess you would say it is a bolus. All I can say, Carter, is we did not, in our own thinking, model in a bolus. I think we've been pretty consistent about that and how we've said it. So it's a little hard to know exactly where this will go from here.
We do think this is all very indicative of a strong degree of organic demand that really reflects all of the great things that really happened, starting with the ODAC, which seems like a million years ago, but it wasn't. And then we got, of course, an excellent, very clean label.
And then, with the NCCN guidelines that really place this as a forefront of potential standard of care in this space, I, I think all we can say is we're just seeing a tremendous amount of interest on the part of HCPs, on the part of accounts, and when that, whether that's, whether this is gonna reflect a bolus or not, we, we don't really know, but I, I don't think that's something that we've anticipated, given the, the buy and bill nature of, of the, of the mechanics around all of it. With regard to the PTE, I wish it was 14 months. That would be great! I, I don't know if it's statutorily there or not. I guess it is.
But when we've spoken to our IP counsels, and others, we're seeing anywhere from 3-5 years for the PTO to really get back with definitive, "Yes, you can apply it to this patent, you can apply it to that patent," et cetera. So I would not be holding my breath on that. It's out of our hands. We've done everything we can to make these applications, but the historical performance has been pretty slow.
Carter Gould (Senior Analyst)
Understood. Thank you.
John Scarlett (Chairman and CEO)
Sure. Thank you-
Operator (participant)
Your next question comes from the line of Stephen Willey of Stifel. Your line is open.
Stephen Willey (Managing Director)
Yeah, good morning.
John Scarlett (Chairman and CEO)
Steve.
Stephen Willey (Managing Director)
Thanks for taking the question.
John Scarlett (Chairman and CEO)
Mm-hmm.
Stephen Willey (Managing Director)
-and, congrats on the progress. Appreciate some of the early metrics here, but just curious, of the 160 patients that have started therapy, can you comment-
John Scarlett (Chairman and CEO)
Mm-hmm
Stephen Willey (Managing Director)
As to how many of those patients are actually paying for drug? Is there a yet-to-be-worked-out reimbursement process for some of these patients?
John Scarlett (Chairman and CEO)
I think I'm gonna let, probably either Andy or Michelle, take that. I have a few comments, but they may be in a better position to answer that question. Andy, do you have any thoughts about that?
Andrew Grethlein (EVP and COO)
I think it's way early, Chip, to know, although what we do know is that we haven't had any issues with any of the submissions that have been made to date. You know, these patients have just gone through their first cycle.
John Scarlett (Chairman and CEO)
Great.
Michelle Robertson (EVP and CFO)
Yeah, I mean, I guess I would add that, again, as Andy said, we haven't received any pushback. I mean, we have a hub set up, a reimbursement process. Even with the temporary J-code, you know, our customers are pushing this through formularies, and so it has—reimbursement has not been an issue so far.
Stephen Willey (Managing Director)
Okay. That's-
John Scarlett (Chairman and CEO)
Steve, I guess. Yeah.
Stephen Willey (Managing Director)
Yeah.
John Scarlett (Chairman and CEO)
Steve, I guess the only other comment I would have, which may or may not be helpful in this regard. Remember, everyone, this is predominantly a Medicare population, and while we don't have as fine-tooth insight into the exact breakdowns of where reimbursement is coming from, we know that the majority of it is PHS, and that's historically not had a lot of pushback, as long as you have the NCCN Guidelines where they are today for us in Category 1 and Category 2A. So again, early days, we may be able to give a little bit more insight into this, but I think it bodes, the current situation as we see it bodes well for the future.
Stephen Willey (Managing Director)
Understood. And, again, I guess understanding that it's early, but do you have any early information on just whether or not you're seeing patients who are newly starting RYTELO being switched off of other salvage therapy? And I guess in your conversation-
John Scarlett (Chairman and CEO)
Yeah, sure.
Stephen Willey (Managing Director)
with physicians, is that a dynamic that you expect to play out as the launch proceeds?
John Scarlett (Chairman and CEO)
Yeah, I'll take that, and then I'll invite my colleagues to make any additional comments, if any. Look, I think we just naturally expect that some of these patients will be, as you said, patients from the third line, if you will, or second or third line, for sure. That would be natural in the availability of a new agent, and so forth. But we don't really have a way to characterize that. Our information that comes to us on an individual patient data is very limited, extremely limited, if any at all. We're really seeing the demand from accounts flowing into the specialty distributors and occasionally to a specialty pharmacy. And that's what we're really able to infer and figure out the dynamics on.
We don't—I, I'm not sure when and exactly how much fine-tooth detail we're gonna get on individual patients. I think that's gonna take some more anecdotal information and eventually perhaps even some studies or whatever. I don't wanna promise anything here. Of course, we're deeply interested in knowing the answers to all of that. But six weeks in, I can tell you right now, Steve, we're just not really 100% sure exactly the circumstances of these of these patients and exactly the buckets, as it were, that they're coming out of. We're just grateful that they're there.
Stephen Willey (Managing Director)
Understood. And then maybe just one quick question for Faye. Can you just remind us what the DLT window in the IMproveMF trial is? And for a patient who progresses on frontline rux, are the next-gen JAK inhibitors allowed in best available therapy?
Faye Feller (EVP and Chief Medical Officer)
So, um-
Stephen Willey (Managing Director)
Faye?
Faye Feller (EVP and Chief Medical Officer)
... so the first question. Hi. Hi. So the first question is about IMproveMF, correct?
Stephen Willey (Managing Director)
Correct.
Faye Feller (EVP and Chief Medical Officer)
DLT window. The cycle length is 28 days, so the DLT window is one cycle length. The next question was about MYF3001 or is whether next-gen...
Stephen Willey (Managing Director)
Whether the next-gen JAK inhibitors-
Faye Feller (EVP and Chief Medical Officer)
JAK inhibitors
Stephen Willey (Managing Director)
... are available therapy-
Faye Feller (EVP and Chief Medical Officer)
Okay. Yeah
Stephen Willey (Managing Director)
... in the Best Available Therapy control.
Faye Feller (EVP and Chief Medical Officer)
No, there are no JAK inhibitors allowed on the BAT arm.
Stephen Willey (Managing Director)
Okay. Thank you very much for taking the questions.
John Scarlett (Chairman and CEO)
Thanks you. Thanks.
Operator (participant)
Your next question comes from the line of Corinne Johnson with Goldman Sachs. Your line is open.
Corinne Johnson (VP)
Hey, good morning, guys. Maybe if you could just help us think directionally about the trajectory of new patient growth from here, probably through, like, the early launch period. Do you anticipate that kind of the new patients coming on therapy will come at a relatively steady clip, that it could be more lumpy, or that it would accelerate over time, and maybe precedent would be helpful as you think about the answer there? And then in terms of just target engagement, you mentioned obviously the top 60% of your top or 60% of the top decile accounts. I guess, I guess how many patients on average or, like, from a range are these accounts treating? And of that, like, what portion would be eligible for RYTELO? Thanks.
John Scarlett (Chairman and CEO)
I'll take the first one, which is the directionality, and as you said, the smoothness versus the lumpiness. I mean, I'm gonna say the obvious, Corinne, so forgive me. This is only the second new product launch in the last 12 years in lower-risk MDS, or maybe there's been a few others, but they've been very modest launches. And so we... All we really-- we don't have a lot to go on on this, and six weeks isn't very much. I will say that, maybe something that might be helpful is that we haven't seen a particularly, so far, in all of six weeks, we haven't seen a particularly lumpy, you know, you know, accretion of patients. It's been pretty steady.
But it's hard to do a trend line based on that. Maybe then next time we talk, we'll have a better feel for that. But I don't see any particular reason, other than just natural variation as things go on, that we would expect anything different than what we've seen to date, but don't really know. In terms of target engagement, just a couple of comments about this. These accounts are a very wide variety of accounts. So some accounts are large hospital systems. Some accounts are individual practitioners. Everything in between that you can imagine. The top deciles tend to be, you know, larger aggregator accounts, many physicians. So I don't have an exact number of physicians, but I'm not sure how helpful it would be because it is such a wide variety.
What we do know is that we've had really good traction getting in. We've had excellent traction speaking to these accounts in person. The number of accounts touched and reached, including the vast majority in person, is growing every day. So Andy, again, I don't know if you have any insight into this, but I'd invite any help we can give Corinne here.
Andrew Grethlein (EVP and COO)
No, I think, I think that's it, Chip. Yeah. I mean, it's... Account activation is accelerating. We believe that, so we're pretty, pretty pleased so far. And the top deciles, we obviously modeled based on flow of prior treatments when they, when for that launch, but I don't know that, you know, it's more proportionality. I don't think we can give patient numbers per account right now.
Corinne Johnson (VP)
Okay. Thank you.
Andrew Grethlein (EVP and COO)
Yeah.
John Scarlett (Chairman and CEO)
Mm-hmm. Sure.
Operator (participant)
Your next question comes from the line of Gil Blum with Needham & Company. Your line is open.
Gil Blum (Senior Analyst)
Hey, good morning, everyone, and thanks for including our questions. So I know this is very early, but is there any information you can provide about the split of these patients that were dosed, you know, RS positive, RS negative, front line, second line?
John Scarlett (Chairman and CEO)
Yeah.
Gil Blum (Senior Analyst)
Whichever information you have. Thank you.
John Scarlett (Chairman and CEO)
Yeah, Thanks, Gil. Thanks for the question. We don't have it. It's not the kind of information that would come in at this moment in time. We get this is pretty much demand information that we're able to give you. This is, you know, the number of vials going out the door and what we eventually, I think we will try very hard to get that. We're as interested as anybody in the nuances of, again, which buckets these patients are coming in. But as of today, no, we don't have that. And it will take some tweaking of our information sources and how we get that over the next several, I would think, many quarters, perhaps, to actually get a really accurate view on that.
But as of today, we just don't know.
Gil Blum (Senior Analyst)
Thanks, Chip. That's very helpful.
John Scarlett (Chairman and CEO)
Sure.
Gil Blum (Senior Analyst)
Another question and then a kind of related one. How long do you think it would take till you start getting feedback from treating physicians as to the outstanding challenges they're having at giving the drug or-
John Scarlett (Chairman and CEO)
Mm-hmm
Gil Blum (Senior Analyst)
... any other kind of bottleneck? Thank you.
John Scarlett (Chairman and CEO)
Yeah, thanks. Well, I think that boils down to the people that we have deployed in the field. Again, I'd invite Andy to comment about that, 'cause if you remember that slide that he showed, we've got a really varied group of people out in the field, and I feel quite good about that. But Andy, you might wanna just run through sort of how we-
Gil Blum (Senior Analyst)
Sure
John Scarlett (Chairman and CEO)
... get feedback.
Andrew Grethlein (EVP and COO)
...Yeah, I mean, we have several channels, obviously, but I think our med affairs team that's in the field and our medical affairs hub, which is fully active, is right now probably the main source of flow of certainly information requests. It's way early to start getting specific feedback. Again, given that we're only six weeks in, most of these patients are just through one, a single cycle of treatment. But we have seen a strong, and I think we're a strong volume of med info requests across a range of different areas, you know, from efficacy and safety to dosing and you know, reactions to the prescribing information. So that I think that bodes well that physicians are interested and becoming more and more educated about treating with RYTELO.
Gil Blum (Senior Analyst)
All right. Thanks for taking our questions, and congrats on the launch.
John Scarlett (Chairman and CEO)
Thank you.
Operator (participant)
Your next question comes from the line of Kalpit Patel with B. Riley Securities. Your line is open.
Kalpit Patel (Analyst)
Yeah. Hey, good morning, and thanks for taking the question. For the launch, I guess, do you have an early estimate or early sense of what the gross to net adjustments would be for third quarter, and how you anticipate that to shift over time, maybe into fourth quarter or maybe 2025?
John Scarlett (Chairman and CEO)
I appreciate the question. I think Michelle is probably the best person to answer that question. Michelle?
Michelle Robertson (EVP and CFO)
Yeah. Thanks, Kalpit. I mean, we obviously only had one week for the June close in our gross-to-net calculation. So I mean, it's a pretty straightforward gross to net breakdown of components, I mean, because it is a primary Medicare population. So, you know, we know the PHF is gonna be one of our largest so deductions in the gross to net. But I would say it's too early for us to really be comfortable and we need more data as the July sales close out and as well as the rest of the quarter. But we'll have a pretty good sense after a full quarter worth of sales.
Kalpit Patel (Analyst)
Okay. Okay, and, you know, as a follow-up, how are you viewing the current sell side consensus estimates for RYTELO in the second half of this year under your current launch projections?
John Scarlett (Chairman and CEO)
Um, Michelle-
Michelle Robertson (EVP and CFO)
I mean-
John Scarlett (Chairman and CEO)
I think it's yours as well.
Michelle Robertson (EVP and CFO)
... I would say that from a— Oh, sure. So I would say from a consensus perspective, as I mentioned before, I think that we need to sort of sit down, you know, with you guys and go through some of the assumptions, because they're definitely mixed among the different models and sort of mixed versus our internal models. And I think it's a lot on the annual cost per patient. There's a lot of variance between the models there. So which I think is probably contributing to that, would be duration of therapy, and you know, penetration is pretty varied. So I think that we'll look to give guidance on that post this earnings call.
Kalpit Patel (Analyst)
Okay. And then one last one on the NCCN Guidelines. I guess, were there any surprises based on where imetelstat is positioned in all the different subgroups of the treatment algorithm? And do your internal estimates of the percentage of lower-risk MDS patients that could be treated with RYTELO change based on this positioning?
John Scarlett (Chairman and CEO)
Yeah, I'll take that one, and then if Faye listens in and has anything else to contribute, I'd encourage her to do it. It's a great question, Kalpit. So first of all, I think if you go back to all the way back to top-line results, you know, close to a year and a half ago, 2 years ago, we identified at that point in time a couple of, you know, really big pockets of value here. The first one was, of course, that we thought that we were effective regardless of RS status, and so in both the RS positive and the RS negative. Second of all, we did have enough patients, although not a ton, of del(5q) patients, previously treated.
As we used to say, that was a highlight of the previous year's ASH, that we saw some really good results there. So we thought that previously treated lower-risk MDS patients who were not doing as well as physicians would like would be important. We thought that the high transfusion burden patients would be very attractive. And then we also identified that it looks like the patients who had serum EPO levels greater than 500, that is officially, you know, the ESA-ineligible patients, had done pretty well. And so we actually saw from our Phase III results pretty much the makings of where we ended up today.
What I can say is the label, which, of course, did have some transfusion burden requirements on it, as you would expect, based on the clinical trial, that didn't actually translate over to the NCCN Guidelines, which is interesting. Frequently is not the case in... as NCCN looks at treatment algorithms, if you will. And then all the other pockets really are completely there. So I have to say, I don't think what the pleasant surprise was that there were no unpleasant surprises. I think we just got a wonderful NCCN guideline affirmation of what we've always seen as the value in these various different areas. So I don't think that. I think it's pretty much what we were hoping for and what we had always imagined.
Faye, I don't know if you have any other comments about it, and it's a great question, though.
Faye Feller (EVP and Chief Medical Officer)
Well, yeah, Chip, I think you put it well. I think the only surprise was a pleasant one. We received everything that we were asking for, and they're strong Category 1 and 2A.
John Scarlett (Chairman and CEO)
Yeah
Faye Feller (EVP and Chief Medical Officer)
... guidelines and are a strong reflection of the data of the clinical trial. So all in all, a good result.
Kalpit Patel (Analyst)
Okay. Thanks very much for taking the question.
John Scarlett (Chairman and CEO)
Yeah. Thanks, Kalpit.
Operator (participant)
This concludes the question and answer session. I'll turn the call to Aron for closing remarks.
Aron Feingold (VP of Investor Relations and Corporate Communications)
Thank you so much for joining us today. We appreciate your interest in Geron and look forward to keeping you updated during this very exciting time for our company. Goodbye.
Operator (participant)
This concludes today's conference call. We thank you for joining. You may now disconnect your lines.