Thank you for standing by, and welcome to the RYTELO FDA Approval Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star, followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press the star one. Thank you. I'd now like to turn the call over to Aron Feingold, Vice President of Investor Relations and Corporate Communications. You may begin.
Good morning, everyone. Welcome to the Geron Corporation RYTELO FDA Approval Conference Call. I am Aron Feingold, Geron's Vice President of Investor Relations and Corporate Communications. 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 therapeutic and commercial potential of RYTELO, the expected market for RYTELO, launch timing, availability of supply and patient access for RYTELO, key success factors for commercial launch of RYTELO, 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 filed with the SEC, which identifies important factors that could cause actual events to differ materially from those contained in the forward-looking statements.
Geron undertakes no duty or obligation to update our forward-looking statements. I'm joined today by several members of Geron's management team: Dr. John Scarlett, Chairman and Chief Executive Officer; Dr. Faye Feller, Executive Vice President and Chief Medical Officer; Anil Kapur, Executive Vice President of Corporate Strategy and Chief Commercial Officer; Michelle Robertson, Executive Vice President and Chief Financial Officer; and Dr. Andrew Grethlein, Executive Vice President and Chief Operating Officer. On today's call, Chip will provide opening remarks, followed by Faye, who will review the U.S. prescribing information for RYTELO, and Anil, who will discuss the U.S. market opportunity and launch plans. Chip will then provide closing remarks and will end with Q&A. Slides to accompany this call are posted in the Investors and Media section of our website, www.geron.com. With that, I'll turn the call over to Chip.
Thanks, Erin. Good morning, everybody. Thanks for joining us on this very special day for the low-risk MDS community, and particularly for patients who we've been working so hard to serve, as well as for our own company, Geron Corporation. RYTELO is now the first and only FDA-approved telomerase inhibitor. Today's approval of imetelstat, being commercialized as RYTELO, as the first and only FDA-approved telomerase inhibitor, is a testament to the power of our science, the excellence of our clinical and regulatory execution, and the authentic passion of our people to innovate treatments for patients in need. We're very grateful for the participation, commitment, and encouragement from patients and their families, advocates, clinicians, study coordinators, and site personnel, scientists, and Geron employees and collaborators, past and present, that made today's significant milestone possible.
Low-risk MDS is a blood cancer that often progresses to require increasingly intensified management of key symptoms such as anemia and resulting fatigue. These low-risk MDS patients frequently become red blood cell transfusion dependent, which has been shown to be associated with short and long-term clinical consequences that reduce quality of life, cause emotional and psychosocial issues, and shorten survival. It's our ambition to change the outlook for eligible patients with low-risk MDS who could potentially experience the meaningful clinical benefit possible with our medicine. The approval of RYTELO with low-risk MDS, with transfusion-dependent anemia broadly across ESA ineligible and ESA relapse and refractory subpopulations, regardless of ring sideroblast or RS status, has the potential to transform the treatment paradigm for these patients who remain in high unmet need despite currently available treatment options.
Approximately 10% of low-risk MDS patients are not eligible for ESAs and have very limited treatment options. RS-positive patients make up approximately 25% of low-risk MDS patients, and most continue to experience high transfusion burden despite available therapies. RS-negative patients make up approximately 75% of low-risk MDS patients and are a population particularly vulnerable to poor clinical outcomes. There are approximately 13,200 U.S. patients with low-risk MDS who need treatment for symptomatic anemia. We believe that RYTELO can become part of the standard of care and help address unmet need in low-risk MDS patients with transfusion-dependent anemia who are ESA ineligible, ESA relapse or refractory, RS-negative, and ESA relapse and refractory, RS-positive with high transfusion burden. With that, I'll turn the call over to Faye. Faye?
Thanks, Chip, and thanks to everyone for joining us during this landmark moment for the lower-risk MDS community. As a formerly practicing hematologist, I treated many lower-risk MDS patients with the ESAs and felt frustrated with the lack of additional options for my patients once they were relapsed or became refractory to ESAs. I am honored to be here launching a medicine that could help these high unmet need lower-risk MDS patients with transfusion-dependent anemia. Please refer to slide nine for the first page of the RYTELO FDA-approved prescribing information, and note that the full prescribing information is available on our website. As Chip mentioned, the FDA approved RYTELO across a broad lower-risk MDS patient population, regardless of RS status, who have limited current treatment options.
The approved indication is for the treatment of adult patients with low- to intermediate-1-risk MDS with transfusion-dependent anemia requiring four or more red blood cell units over eight weeks, who have not responded to or have lost response to, or are ineligible for ESAs. The recommended dosage of RYTELO is 7.1 milligrams per kilogram, administered as an intravenous infusion over two hours every four weeks. The label details pre-medication prior to dosing with RYTELO for potential infusion-related reactions and provides instructions for preparation and administration. There are two dosage forms and strengths approved for injection of 47 milligrams and 188 milligrams powder, each in a single dose vial for reconstitution. The label contains no contraindications, no boxed warnings, and no REMS program.
The warnings and precautions cover the most common grade three adverse reactions, thrombocytopenia and neutropenia, which were reported for 65% and 72% of patients, respectively, in the IMerge Phase III trial. These events had a median duration of less than two weeks, and in more than 80% of patients, were resolved to grade two or less in under four weeks. Clinical consequences of severe infection, febrile neutropenia, and severe bleeding were infrequent. Cytopenias were generally manageable with dose modifications, and the monthly dosing of RYTELO aligns to routine blood count monitoring for these patients. The warnings and precautions also refer to potential infusion-related reactions, as well as embryo-fetal toxicity.
The most common adverse reactions, with an incidence of 10% or more, with a difference between arms of 5% compared to placebo, including laboratory abnormalities, were decreased platelets or thrombocytopenia, decreased white blood cells, decreased neutrophils or neutropenia, increased aspartate aminotransferase or AST, increased alkaline phosphatase or ALP, increased alanine aminotransferase or ALT, fatigue, prolonged partial thromboplastin or PTT time, arthralgia, myalgia, COVID-19 infections, and headache. Clinically relevant adverse reactions in less than 5% of patients who received RYTELO included febrile neutropenia, sepsis, gastrointestinal hemorrhage, and hypertension. In the IMerge trial, the safety profile of RYTELO was well characterized, with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar side effects for hematologists who are experienced in managing cytopenias.
Overall, we are very pleased with this label and believe that it reflects the strength of our clinical data and the potential for RYTELO to be a practice-changing medicine and part of the standard of care treatment for patients with lower-risk MDS and transfusion-dependent anemia who are ineligible for or relapse refractory to ESAs. I want to take a moment to thank all the patients, families, providers, support staff, advocacy groups, scientists, and Geron employees, past and present, for their contributions. With that, I'll turn the call over to Anil.
Thanks, Faye, and thanks to everyone for joining us on this very important day for our company. It is a great privilege to deliver the first FDA-approved telomerase inhibitor for patients with lower-risk MDS with transfusion-dependent anemia. We are eager and ready to serve the eligible low-risk MDS community, and I'm happy to share with you our expected U.S. market opportunity and plans to provide RYTELO to these patients. On this next slide, we believe RYTELO offers a compelling value proposition for stakeholders. Low-risk MDS is a blood cancer that often progresses to require increasingly intensified management of key symptoms such as anemia and resulting fatigue. Many low-risk MDS patients with symptomatic anemia frequently become red blood cell transfusion dependent, which has been shown to be associated with short and long-term clinical consequences that reduce quality of life and survival.
There is a high unmet treatment need for patients with low-risk MDS, as many progress and are not responding to current treatments, achieving a durable response, or experiencing extended and continuous red blood cell transfusion independence. Currently, treatments for red blood cell transfusion dependent patients, relapsed or refractory to, or ineligible for ESAs, have significant limitations, underscoring the need for novel options. Moreover, as demonstrated in the IMerge Phase III clinical trial, RYTELO can offer eligible low-risk MDS patients meaningful clinical benefit, including durable and sustained red blood cell transfusion independence, increases in hemoglobin levels, and reduction in transfusion burden across key low-risk MDS subgroups, as described by Faye, irrespective of ring sideroblast status, baseline RBC transfusion burden, or IPSS risk category.
RYTELO was also shown in IMerge to have a well-characterized safety profile with generally manageable and short-lived thrombocytopenia and neutropenia, which are familiar side effects for hematologists who are experienced with managing cytopenias. The wholesale acquisition cost, or WAC, for the 188 milligram vial of RYTELO will be $9,884, and for the 47 milligram vial will be $2,471. RYTELO's price is based on a holistic and differentiated value we believe it provides to patients and payers to address the high level of unmet need among the low-risk MDS patients with transfusion-dependent anemia for which it is indicated. We believe imetelstat is uniquely positioned to address unmet need in low-risk MDS in these patients with transfusion-dependent anemia. This slide depicts the expected treatment landscape, as well as a simplified schematic reflecting the current NCCN guidelines.
As you may be aware, the NCCN guidelines, along with published results from randomized trials, remain among the most important factors that influence clinical and payer decisions and significantly inform prescribing behavior. The current NCCN guideline recommends ESAs as the preferred treatment option for the largest segment of frontline RS-negative patients. It is important to remember that many of these patients will show a loss of response to ESA treatment in the frontline setting in approximately 18-24 months. There also continues to be limited treatment options for patients with serum EPO levels greater than 500, and participation in clinical trials for ESA-ineligible RS-negative patients is encouraged by NCCN guidelines. From our perspective, these guidelines reflect a lack of effective new treatment options, in particular for those patients who are ESA-ineligible, high transfusion burden patients, and for RS-negative lower-risk MDS patients who constitute an estimated 75% of this market.
This is a need we believe RYTELO can powerfully address as a potential durable treatment that can be used broadly across these MDS subtypes. We expect to see RYTELO uptake across ESA-ineligible, ESA-failed RS-negative, and RS-positive high transfusion burden patients based on our latest market research, which was completed earlier this month with 37 community and 20 academic U.S.-based practicing hematologists. On the left-hand side of this slide, as you can see, our research suggests meaningful RYTELO use in frontline ESA-ineligible patients. The right-hand side of the slide shows the estimated second-line population, approximately 85% of which are expected to be ESA or luspatercept experienced. Our research suggests a broad use of RYTELO across the second line, regardless of frontline therapy, and particularly for RS-negative patients.
Our research supports the significant unmet treatment needs for the low-risk MDS patient population, and we strongly believe that RYTELO can play a meaningful role for eligible low-risk MDS patients moving forward. We plan to conduct a prioritized and targeted launch to a concentrated prescriber base of approximately 8,000 healthcare professionals. We also plan to cover approximately 2,200 targeted accounts, and 70% of the patients are expected to be treated in the community setting with low-risk MDS. As an infused product, RYTELO will be provider-administered. Medicare is expected to be the predominant payer, with approximately 84% of the patients falling under the Medicare umbrella. On this next slide, to support our RYTELO launch in the U.S., we have our in-house infrastructure fully in place, including our highly experienced oncology field teams, which are fully deployed and cover the entire U.S. market.
This includes 50 key account managers, our oncology clinical educator liaisons, the field reimbursement and national account teams, along with our field medical affairs teams. I've had the privilege of getting to know our field teams well, and I'm deeply impressed by their caliber, experience, and commitment to ensure RYTELO reaches the patients as quickly as possible. We recognize that RYTELO can only bring value and change lives if it is accessible to the patients who need it. That's why we are offering a wide range of resources to support access and affordability for eligible RYTELO patients, including our Reach for RYTELO Patient Support Program, which provides a range of resources that are designed to support access and affordability to eligible patients prescribed RYTELO. We are also engaging government and commercial payers to support access to RYTELO and have initiated the J-code submission process.
In addition, our medical affairs teams will today also submit our information packet that includes the RYTELO prescribing information and IMerge Phase III Lancet publication to support inclusion in the important NCCN guidelines. We expect that RYTELO will be available in the distribution channels by the end of this month for the 188 milligram vial and expect the 47 milligram vial to be available later this summer. Our Reach for RYTELO program will also be in place to support patient access and assist with pre-authorizations, as shown on the right-hand side of this slide. From our perspective, the following key strategic imperatives that we believe are critical to successfully launch RYTELO. First, we aim to ensure a positive first experience with RYTELO for eligible low-risk MDS patients and their prescribers. Second, our goal is to drive adoption among prescribers, building on our U.S.
prescribing information that supports treatment with RYTELO to help eligible low-risk MDS patients achieve the clinical benefits possible with RYTELO. And finally, we are supporting patient access with a comprehensive program that supports the patient's access to RYTELO. With that, I'll now turn the call back over to Chip for his closing remarks. Chip.
Thanks very much, Anil. We believe we're poised for a highly successful U.S. launch of RYTELO, which can address eligible low-risk MDS patients with transfusion-dependent anemia and potentially provide meaningful clinical benefit with a well-characterized and generally manageable safety profile. RYTELO is well positioned to become part of the standard of care across ESA-ineligible, relapsed refractory patients with lower-risk MDS and transfusion-dependent anemia. We're excited and well prepared for this launch with our highly experienced commercial organization and field teams leading our efforts. We'd like to thank all of our shareholders who have supported us through the journey to develop this innovative treatment, a first-in-class telomerase inhibitor, and which we believe will bring great value to patients, physicians, and stakeholders alike. Thank you, and Operator, if you would please open the line for questions.
Thank you. We will now begin the question-and-answer session. If you would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again. Your first question comes from the line of Tara Bancroft from TD Cowen. Your line is open.
Hi. Excuse me. Good morning and congrats on the approval and the great label. So can you describe more about your expectations for the cadence of the launch? Like, what are the lowest-hanging fruit to address first? And will there be a bolus of initial patients, things like that?
Anil?
Sure. Thank you for the question, Tara. I think boluses are hard, Tara, to define and quantify. What I will say is what's become very clear is we are launching in a sensitized market, and this market is dissatisfied with current options. As you say, the patients who are probably at the highest requirement for new therapies include patients who are either RS-negative, which is a large patient population, patients who are high transfusion burden, and patients who may have seen both ESAs and/or luspatercept and are looking for better treatment options. And I think we are going to see a mix of all of these patients, but in general, the unmet need within this market is very high, and RYTELO has differentiated data to address all of these subpopulations.
Okay. Thank you so much.
Thanks, Chip. Your next question comes from the line of Stephen Willey from Stifel. Your line is open.
Yeah. Good morning. Thanks for taking the questions and congrats on the approval and label. Really well done. So I guess maybe just a couple of quick questions. So not sure if you kind of want to walk through some of the levers that you contemplated, I guess, here in setting price. I'm not sure if A, could disclose what the average weight of an IMerge patient was, just out of curiosity. And then what's the visibility in terms of the completion of the J-code and just when you expect that to be online? Thanks.
Maybe Anil can take.
Oh, I can take your first one. Yeah. Go ahead. Go right ahead, Anil.
So I hope I remember all your questions. Let me start with the easy one first at the bottom. The J-code process obviously started today, and our expectation would be it takes typically, Steve, about 6-9 months to complete. There are calendar limitations, and we would definitely be meeting the July 1 guideline for submission, and we would expect 6 months, which means we would likely see Q1 2025 for a permanent J-code assigned to imetelstat. The second part is pricing, obviously, has multiple factors that go into it. For us, it is the clinical value to our patients. And what we see here is a highly differentiated drug, which hits a high level of unmet need. We have worked very extensively with a broad range of national payers in the U.S. We have shown our data.
We have spoken to the market characteristics, and we believe this price will be favorably received. We do not, given that the dosing is weight-based, each patient is different. We do not provide characterization on the average weight for these patients. As you know, the demographic of this patient population skews elderly, typically greater than 70 years of age.
All right. Thanks for taking the questions.
Thanks a lot, Steve.
Your next question comes from the line of Corinne Johnson from Goldman Sachs. Your line is open.
Good morning, team. This is Craig Johnson . Congratulations on the great news. To start us off here, the label indicates that the drug is indicated for patients who require four or more transfusions in eight weeks. What portion of the patients does this apply to?
Go ahead, Anil.
Great question, Craig. So Craig, just to step back for a second, I just want to note again that low-risk MDS is a progressive disease, and transfusion burden, as we have seen through all the clinical publications and real-world data, only continues to increase over time and continues to increase from one therapy to another. Our research and also data that was published by Dr. Rami at ASH 2023 showed from the real-world dataset, approximately 50% of the patients are high transfusion burdens, which are four or more. In addition, our research also indicates that transfusion burden in the eyes of a physician is a sliding scale, with many physicians, approximately 80% plus of the physicians we have gone to research with, indicating even one or higher on a regular basis is not satisfactory to them.
We expect the vast majority of the patients who are transfusion burdened to be provided access to RYTELO. In addition, the NCCN guidelines will help with our adoption as well. I'll just stop here to see if I answered your question.
Yeah. That's helpful. And just one more from us. So what is implied in regards to annual pricing based on the median dose and duration in the IMerge study?
Say that again, Craig. Can you repeat the question? I think I lost you on some middle part of your question.
Yeah. I'd be happy to. So I just wanted to get a little bit more color of maybe your expectations on annual pricing given the median dose and duration that you observed in IMerge.
So what I can speak to is the data that was there in IMerge, where the median treatment duration was approximately 8 cycles with imetelstat across the patient population studied. But what I'll also mention is what we have spoken to, and what is very clear, is that physicians in low-risk MDS look at the totality of clinical data. They look at a patient population from multiple dimensions. Some of the dimensions include achievement of transfusion independence, but importantly, they're looking also for markers of patient benefit, in particular, rises in hemoglobin and how the patient is feeling in terms of quality of life and visible reductions in RBC transfusions. So our expectation is that the dynamic in the marketplace that will prevail is if the patient is doing well and they are seeing meaningful clinical benefits, the totality of data is likely to prevail.
So our expectation is that these patients will be obviously treated to physicians' discretion, and many of these patients could be treated for a longer period of time than what is the median time reported on the IMerge Phase III trial.
Got it. Thank you very much. And again, congratulations.
Your next question comes from the line of Kalpit Patel from B. Riley. Your line is open.
Yeah. Hey, good morning. Many congrats on the approval yesterday. As you sort of model out the launch for imetelstat, what are your expectations for the real-world average number of cycles, considering that there are more RS-negative patients in the real world than in the clinical trial setting?
Kalpit, we have not provided that guidance. Our expectation is that duration of treatment across both RS-positive and RS-negative, and for all the populations we spoke about, is likely to be guided by the totality of clinical evidence and, as we said, across the factors which include achievement of transfusion independence, but also the clinical characteristics that we speak about that physicians monitor for patients, including what they are seeing for hemoglobin rises and how the patient is feeling and decreases in RBC transfusions. We will look at RYTELO. We expect RYTELO to behave in a similar way as well within this marketplace and provide more information when appropriate.
Okay. Okay. And one more question, maybe. Any thoughts on the weekly monitoring requirements for the first two cycles and every cycle thereafter? How similar or dissimilar is that from your clinical trial protocol? And does that weekly monitoring impact a particular group of physicians, maybe the community doctors? All I'm trying to ask is how reasonable is it to do this for those types of doctors?
Faye, do you want to go first?
Just to say I can take that.
And then I can add, yeah. Thank you.
Yeah. Yeah. I can take that. Hi, Cal. So it is consistent with what was done on the Phase III IMerge study, weekly for the first two cycles and then monthly prior to dosing in order to manage any potential dose modifications. This is pretty standard across four hematologists, I would say, as closer monitoring, especially in this patient population, is often merited regardless of what drug you're starting in the beginning of treatment as a patient adjusts to the new treatment and the side effect profile, while monthly before the infusions is pretty standard. I don't know, Anil, if you have anything to add.
The only other thing I'll add is, Kalpit, to your question, we also obviously shared our profile, and the weekly monitoring is also consistent. Many of these patients, as you know, are highly transfusion-burdened, and they are coming to the clinics once a week or at least more than once a month, many, many times to get red blood cell transfusions. So this has not been something that has been highlighted as a burden by both community and the academic facilities.
Okay. Great. Congrats again, and thanks for taking the questions.
Thanks, Kalpit.
Again, if you'd like to ask a question, press star one in your telephone keypad. Your next question comes from a line of Gil Blum from Needham & Company. Your line is open.
Hi. Good morning, everyone. Let me add my congratulations for the approval and some strong label. Could you remind us your ex-US strategy?
Neil, you want to take a first crack at that?
Sure. So our expectation, Gil, is that we would get our EMA approval in the first half of 2025. And we are keeping all our strategic options open that include a limited self-commercialization model or ex-US partnerships. And we are dictated very clearly by what is in the interest of Geron and, importantly, in the interest of patients and our shareholders. In addition, I think it's important to also mention that we are already heavily engaged with some of the key early launch markets in Europe, in particular with Germany, officially with the payer bodies there, which is all really important. So more to come on that in 2025. Okay. And.
Not sure anything you would like to add? Sorry.
No, no. It's good. My other question is, when should we expect maybe an update to the NCCN guidelines now that imetelstat is an approved product?
So our expectation, Gil, is that the low-risk MDS NCCN guideline updates, we should expect to hear somewhere within the next 2-3 months for imetelstat, which the request has been officially filed today as well, or will be filed, I should say, will be filed today as well. So within the next 2-3 months.
Okay. Great. Congratulations again.
Thanks, Gil.
Your next question comes from the line of Joel Beatty from Baird. Your line is open.
Hi. Thanks for taking the questions and congrats on the approval and the labeling. First question is, what metrics are you and internally and the sales force focused on as you execute the early launch?
So Joel, there are essentially three broad factors that we look at and we are laser-focused on. One is around access and affordability. But the sub-dimensions and the most critical pieces there for us are to make sure that the process for getting our submissions for NCCN guidelines is completed, the J-code submission process, which was also initiated today, and for the P-code as well. Those processes are extremely critical. We also monitor things which are around guidelines and pathways. All of these will take their natural course of time and are also heavily focused on making sure that we provide all the payer bodies, the information required for them to start their policy development process. So that's all the key metrics for access and affordability that we'll be laser-focused on. The second one we look at is obviously our launch awareness and detailing.
We are extensively engaged with our GPO channels. As you know, 70% of this market is community physicians. Almost all are part of two or three big GPOs. We have a very efficient process to make sure that we are able to reach the physician offices with news of RYTELO's approvals and are heavily engaged with the GPOs. That's a really important priority for us. I think kudos also to our sales teams, which over the last two months have already secured hundreds of appointments with physicians across low-risk MDS. Our job here is to amplify the engagement strategy and be able to make sure that we are able to positively engage with these physicians across the entire nation.
And then the last metric that we will continue to look at, obviously beyond sales, is how then patient service experiences and to make sure that we are providing a very seamless experience to customers. All these metrics are part and parcel of what we are really working towards. We'll provide appropriate information over time to make sure that people are informed around RYTELO adoption in the U.S.
Great. Thank you. And then on pricing, how much discounting do you anticipate compared to the WAC?
We are not going to provide that answer, Joel, but what I will tell you in general for low-risk MDS and for oncology, especially in the marketplace with buy and bill where we are, you do not tend to see a heavy amount of contracting, but I'll just leave it at that.
Great. Thank you.
Thanks, Joel.
That concludes our question and answer session. I will now turn the call back over to Aron Feingold for closing remarks.
Thanks so much to everyone for joining us today and for your questions and support. We look forward to keeping you updated on our progress. Have a wonderful rest of your day.
This concludes today's conference call. Thank you for your participation. You may now disconnect.