All right. Good afternoon, everyone. I am Stephen Willey, one of the senior biotech analysts here at Stifel, and glad to have with us in the next session, the CEO and Chief Medical Officer of Geron, Harout Semerjian and Joseph Eid. Thanks, guys. Appreciate the time, as always. Maybe we can just jump right into RYTELO. You've been in this seat now, Harout, for I think almost nine months or so. You've got a couple of quarters under your belt. Where do you think you've made the most tangible progress on the commercialization front, and where do you think there's still significant improvements to be made, and what are the strategies that you're emphasizing to help drive uptake?
Yeah. No, thank you, Stephen, and thanks for Stifel for this opportunity to really share why we're excited about RYTELO and Geron overall. You're right. It has been several months now since August last year, and it's been a very exciting journey. Obviously, my passion and background is in commercialization of oncological assets, and particularly in hematology, and this is one of the areas where attracted me to Geron, where we have a very good asset, RYTELO, imetelstat, first-in-class telomerase inhibitor. We have a very clear target population that we can help, which is the second-line, low-risk MDS population, with potential to grow even more with the upcoming readout of our phase III in myelofibrosis. We've been very busy over the last few months, Stephen, in really making sure that we are becoming a commercial company. That's really the big picture.
We have been a development stage company for many years, that really got us to a great outcome from a labeling perspective, from an FDA negotiation perspective. Of course, one of the things that I've learned the hard way, sometimes and over the years is what got you here is not what gets you to next level. Now it's all about awareness, making sure that we're engaging with the hematology community, redesigning our org chart, and making sure that we're really punchy with that patient population, getting the benefit of RYTELO to those patients through the medical community. That's kind of what we've been focusing on, Steve.
Mm-hmm.
Over the past several quarters, you're right. We have reported in December 2025 a full year net revenue of $184 million. We've guided to this year a growth story of $220 million-$240 million of net revenue that we believe we can achieve, and we've really organized ourselves in a way that we have high conviction that that's the right approach, and that's what we're up to.
Okay. Look, I think obviously sales are the barometer by which all of us, mostly yourself, are ultimately judged. What are some of the key metrics that perhaps we don't get to see that you're really focused on internally to gauge some of the progress that you've made here? Is it new patient starts? Is it depth, breadth of prescribing, line or duration of therapy? What are you most focused on in terms of your ability to assess what's happening out there?
Yeah. No, look, on the short term, it's an execution story. Of course, sales are the ultimate measure of our ability to reach more patients with RYTELO. It's a lagging indicator as well. We obviously look at a lot of additional leading indicators, some of them we shared publicly. As an example, demand is a very important indicator. We have shared now consistently as well the number of new accounts that have come on board since the launch of RYTELO. That is a good measure for the breadth of our reach, given that this is primarily a community-based disease with 80% of the patients being treated in the community rather than in academic medical centers. The third metric that we do share as well is where is our source of business: First-Line, Second-Line patient population versus Third-Line plus.
I'm pleased to report that we're making progress on all these different metrics. As an example, in number of accounts, recently we added another 150 accounts, and that number seems to be something that consistently we're adding quarter-over-quarter. Also seeing movement in the source of business. As you know, a lot of these hematology assets or oncology assets start from more advanced lines and start moving more forward. We have reported now the number is at 33% of patients coming from the First-Line, Second-Line.
It used to be 30% in the last quarter, and so on and so forth. There is multiple acceleration and augmentation of what we look for in terms of reach, frequency, our efforts, where are we targeting, clarity of message, what's being retained, all that things. Also we do report some of those KPIs as well, which are on the short term important because it does give a light on our confidence of why we think the sales will continue to grow and the guidance that we put out in the second week of January of this year.
Mm-hmm. Okay. Maybe just on the line of therapy front, right? I know, and again, this seemed to be a little bit of a headwind when the drug was first launched. I think a lot of utilization seemed to be occurring in Third-Line Plus patients post an HMA, where their bone marrow reserve has been depleted, and they can't really respond to therapy. That 1/3 utilization you're now seeing in front second-line, where do you think that number can grow to over time?
Yeah, that number, we do want to see that grow over time, Steve. That's one of the things that happened recently as well is that the NCCN guidelines have been updated in the fall of 2025, where now, RYTELO is a clear and preferred second-line agent ahead of HMAs. For particularly that reason that you just mentioned is HMAs are used in this space for two reasons. One is habit across multiple different diseases, where a community center might have ordered a bunch of HMAs, then they'll try it in different areas. To be honest, there weren't too many other good options as well. That was one they would reach out to.
Now we do have a good option, and having the patient exposed to RYTELO before it goes and gets their bone marrow nuked with an HMA is, we believe that's an important one, and we are very pleased to see that the NCCN guidelines as well were updated based on that. We want to see more and more patients in the second-line setting. We've refined our strategy to solely focus on the second-line patient setting, which we believe are around 8,000 patients in the U.S. At the same time, we know that there are multiple other patients in the third-line setting and others, they do get RYTELO as well.
We do want to see that number, which is now at about 1/3 of the patients coming in, move up over time because that's where we can give the most benefit to patients, we'll have the longest duration of responses, and it will impact and mimic our label and the NCCN guidelines, to be honest.
Okay.
Yeah. The other comment I would add is, at the time of launch, Reblozyl, luspatercept-aamt, was still anchored in the Second-Line. With their approval about a year before, they're starting to actually to move into the First-Line, which will create that space, which now with the NCCN guideline actually is focused on imetelstat as the preferred Second-Line.
Yeah.
That move is going to happen in the dynamic treatment.
Yeah, it's a good question, I think, or a good point, I should say. I've always kind of wondered how that progression from luspatercept-aamt into front line where we know, again, depending upon RS positivity, your treatment duration can be two years, right, if you're RS positive. There is this notion of there being a potential air pocket that gets created in that second-line setting as you get patients rolling onto luspatercept front line and experience this extension of benefit. What does the community versus academic uptake look like at this point? Does it reflect that 80/20 split that you talked about before? Do you see any tangible difference in either breadth or depth of prescribing between these two subgroups of physicians?
Maybe I'll tackle it from a logistics perspective, and also, Joe, feel free to comment from a type of response and the patient type as well in the community. Steve, as you know, this is a community disease. 80% of the patients are in the community. Our sales have been more in the 50/50 range, where AMCs versus community, which is quite typical when you first launch, because you do want to start with the academic medical centers. These are the physicians who will stand on podium. They need to have the right experiences, and quite honestly, we didn't have as many centers as we probably would have wanted who have participated in the U.S. in our clinical development program.
There is a need to accelerate the AMC experiences early on in a launch, which I think we have done a good job in doing it, but also for the long-term sustainability of the brand and to reach more patients where they are being treated today, which is in the community, we want to see that split of sales move forward. One of the leading indicators, as I mentioned, is the number of new sites who are ordering RYTELO for the first time since launch.
Mm-hmm.
That delta has been about 150 every quarter, so the last quarter was 150 more, and those accounts were predominantly in the community, Steve. That's kind of where one of the reasons why we're quite pleased with that progress because we are reaching more and more community physicians. Maybe Joe, if you want to add something on the community physicians and how they treat patients and how we're tackling that.
Yeah. Stephen, the MDS disease is a community disease, as Harout had mentioned. Patients come in complaining of fatigue. They do blood work. They found anemia. They do a bone marrow, that's when they determine that they have MDS. They go to their tool box, essentially, which is ESAs, luspatercept-aamt, HMAs in the past. Now with imetelstat, there's definitely a learning curve that's been ongoing; the community is kind of lagging to the AMCs. They do usually follow the lead of what the AMCs are doing. Now that the AMCs are becoming more and more comfortable and actually appreciate the value of imetelstat. You see that transition also happening in the community, obviously with the surround sound between commercial, medical, and other peer-to-peer interventions, that's how we reach the community at large, if you will.
Okay. I know you've been kind of aggressively messaging the data that you showed at ASH last year, highlighting this correlation between the emergence of cytopenias and clinical benefit. How has that messaging resonated with prescribers, and are you seeing any kind of real tangible evidence of improved patient persistency during these first few cycles of therapy where these cytopenias tend to be concentrated?
Yeah, for any new class of drug approved, there's always the question, how does it work and what do I expect? For RYTELO, those were the obvious questions for physicians treating patients with MDS. The how it works was definitely a gap that we addressed, and the data that we showed that actually patients who do have cytopenia, which was a hurdle, because when you treat a patient, and they have cytopenia, the initial reaction that we saw right after launch was one or two cycles and the patients are off treatment. The data that we showed at ASH showed that the cytopenia correlates with the best robust and durable response. Now, why is that important?
It's related to the on-target effect, so that's the mechanism of action, and it's also related to the fact that the patients who do have cytopenia is somewhat of a clinical biomarker. There is a relevant example in this disease, particularly with lenalidomide, that the medical community is very familiar and comfortable with, which is lenalidomide causes cytopenia in a specific del(5q) subgroup that tends to do the best when they have that cytopenia.
Yeah.
They have those two, I would say, point to guide them how to manage. Instead of stopping the patient treatment after one or two cycles, now all you have to do is manage the dose to get them through the two cycles, which again, in our IMerge study, which we're seeing also in clinical experience now, those patients tend to have the cytopenia within a predictable two to third cycle, and recovery within two to four weeks for the majority, over 80%. Most importantly, no bleeding and no infections. It's just a numerical drop, which is the cancer cells that are being targeted.
There was another parallel publication at ASH that was as important, which is the long-term safety and effect of RYTELO, which showed that at 45 months, the patients are doing better from an OS, PFS, and conversion to leukemia point of view. The robust responders that we see in the early part are the ones that's showing up at the end.
All in all, it's a safe and effective drug, both in the beginning and the end. You just need to manage how to treat your patients.
Yeah. The lenalidomide analog I think is a good one, right? Because I think the incidence rate of those grade 3-plus cytopenias is higher than what we've seen with RYTELO.
Correct.
Also?
With more consequences, actually.
Also usually associated with clinical sequelae as well too.
Yeah.
Great. Very true. I know we're going to be seeing some additional data at EHA next month. This is going to be real-world data generated out of the Moffitt Cancer Center. I think the abstract was published last week. What would you highlight as being the key takeaways of that, and what do you think investors should be the most focused on?
Yeah, well, let me step back and answer that. We have supported now more than 10 investigator-sponsored research spanning the spectrum of preclinical, clinical, and the real-world evidence. The real-world evidence that you mentioned is one of those coming out of the Moffitt. That particular study has a two component, a retrospective component, which is the subject of your question, and a prospective component that is accruing patients that will be published in the future. This covers from the launch period, early part, and as expected, it covers a lot of patients that were third-plus line therapy. We're very pleased, actually, with the data showing a replication of the imetelstat with actually a little bit more. Typically, there's a downgrade from a clinical trial where the population is very controlled, who gets in, how they're treated, et cetera.
When you see a real-world data that is similar to a phase III or even better, that give you the sense that, and confidence that your drug is working the exact way you expect it and there are no surprises. There's more data that will be coming both from company supported as well as what we are seeing is there's a big interest in imetelstat by the clinicians and investigators to evaluate this new drug.
Yeah. I think there was also an EHA abstract highlighting real-world data that compared RYTELO with luspatercept in the frontline setting.
I thought this was interesting, right? It didn't just include those frontline ESA and eligible patients for whom you're currently labeled. Are you actually seeing any evidence of off-label utilization happening in frontline ESA-eligible patients?
Again, there's this progression of awareness and acknowledgement of the value of imetelstat. Imetelstat, unlike ESAs and EMAs like luspatercept, which are supportive care, is a therapeutic agent. When physicians are thinking of patients long-term, especially when you're treating them in the frontline, you want to make sure that you give them the best option for the long term. Imetelstat offers both. It offers them the ability to respond better because we know earlier line will respond better and longer. Two, as a disease-modifying agent because our drug works on the disease, not the symptoms. Changing the trajectory of the disease is the object of first-line treatment. In this case that you're mentioning, the second EHA, which is again coming from an investigator who is not supported by any shape by Geron, which again, a reflection of the interest of the medical community in this drug.
They're evaluating from over 100 patients, a subgroup that is deemed First-Line. The details are not very detailed yet in the abstract, so we'll see more. The point is that they match it to age and hemoglobin between the two groups, and they're showing responses that are very robust, so it's very exciting to see that. What's missing, though, to your point, is our drug is approved in the First-Line with serum EPO level over 500. That would be a key factor because if our drug is matching equally or better to imetelstat, but they don't have that hurdle, the serum EPO, that's a big factor in the fact that ESAs do not actually work in serum EPO over 500 or even 200.
Our drug works across the EPO serum spectrum, and that would be again, a detail that we will pay attention to. The point I think that the investigator is making is that this drug, at a minimum, is equal to imetelstat in the front line, but with an eye that this is a disease-modifying agent for the future, which is the key, I think, in that abstract.
Okay. Maybe we can shift gears to myelofibrosis just to wrap up here. I know you have this interim OS analysis coming from the IMpactMF trial before the end of this year. I believe you also have an ASCO presentation that tries to contextualize the survival benefit you saw in the phase II study, relative to what's happening now in the clinical "real world." With respect to this upcoming OS analysis, this is also a futility look as well, if I remember correctly?
There are options for the DMC to recommend to Geron. Stopping the trial for efficacy, futility, or continuing to final analysis, which we expect is the likely scenario. The DMC has been meeting regularly since the inception of the trial, two to three times a year, and up to now, they've been saying continue. Anything related to safety, anything of the sort is unlikely to be, and every time that they meet, they have the efficacy and safety data to compare and to decide on, and so far they've been going on. In terms of the OS analysis by Moffitt, this trial was planned in the early 2020 and executed, but there's been also a report of delays in when the readout will be and final analysis due to the fact that overall, the patient population is doing better.
That's because the supportive care is better. There's been more JAKs, obviously, and more clinical trials available for patients. We see obviously in our IMpactMF trial that those patients are living longer than when the IMbark study was evaluated at the time. In order to make sure that we are tracking appropriately, the same group that did the IMbark historical control is also doing this analysis to see that how is the population faring now with advanced supportive care. Yes, the verdict is that those patients are doing better, but they're still dying from their disease.
That's where, again, we see the value of a drug like imetelstat, which has actually more value and justification in MF than MDS if you believe in the science that we have shared so far.
Okay. I believe IMpactMF also allows for patient crossover to the extent that control arm patients receiving best available therapy meet certain specific disease progression criteria. Can you just remind us what that criteria is and whether you've been able to see the percentage of patient crossover that's happening on a blinded basis, and whether or not you think that crossover could be a potential statistical headwind in terms of trying to demonstrate an OS benefit on an intent-to-treat basis?
Yeah. A very good point in the fact that in an OS trial you want to minimize the crossover because of dilution of effect. The study design has two stopgaps to ensure that this is limited. One, the statistical plan allowed to a set number that we want to make sure we go under in terms of percentage. The second is the way the criteria are used to allow the crossover. This is a company decision, a sponsor decision to crossover. Patients have to wash out a period, and just by waiting, time with no active treatment is a factor in decision-making of physicians and patient not to crossover. Again, remember, this is a relapsed refractory population. The point I'm making is that we do see those crossover, but it's limited in scope by design to make sure that we do not dilute that effect of benefit.
Okay. Maybe to finish up here, Harout, your 2026 revenue and OpEx guidance would suggest that sustainable profitability's within near-term reach here. How does this impact capital allocation decisions for you going forward, specifically as it pertains to things like business development, stock buybacks? Maybe just on the BD side, you've been in [hematology-oncology] hem/onc for a while now. How important is scale in this business in terms of just being able to have multiple products in the bag?
Yeah, look, our story is one of growth and optionality, right? Growth, we've delivered $184 million in 2025. We've given a guidance to your point, where our top-line revenue and our OpEx are more or less in the same ballpark. We definitely see a path to profitability. That's one option. At the same time, a lot of us have joined to build a hematology company, which means additional potential deals. We're on record for saying opportunistic innovation. Of course, the closer that is to home in terms of putting in the same reps back, another asset that has very high overlap, that would be more the bullseye. We're preparing the company to do two things.
One is really making sure that we get more patients who can benefit from RYTELO on RYTELO in the U.S., making sure that we're looking at our options ex-U.S., and advancing our myelofibrosis. The $340 million of cash that we have on our balance sheet, that's also a very healthy number. That also gives us optionality from a BD perspective. It's really more you can see the short-term strategy doubling down on execution, mid-term on the MF, and longer-term from a BD perspective, Steve. We have the fuel in the tank to actually go through that, and we have a very good drug and also a company now that's much more focused on the commercialization. That's why we're here. We're very excited about this, and that's kind of what we're building over the next short-term, medium-term, and long-term.
All right. Well, I think that's a great way to end things. Harout , Joseph, really appreciate the time, and thanks everyone for listening.
Thank you.
Thank you very much.
Bye-bye.