All right. Thank you for joining me. We've got Geron here with us. I think our last session of the morning before lunchtime for everybody. Thank you so much for coming down. We've got a ton to talk about.
Yeah.
Maybe I'll just give you guys a minute or two to go over what's top of mind for you, for investors, as we head towards the end of 2025 and into 2026.
Absolutely. Thank you very much, John and Evercore, for this opportunity to share why we're excited about Geron, about RYTELO, about the low-risk MDS community overall. Geron is a commercial-stage company. It's been for the last year with a new, exciting therapy called RYTELO, imetelstat, which is a first-in-class telomerase inhibitor, really helping low-risk MDS patients. We've launched now. It's been five quarters of our launch. We reported in the last quarter $47.2 million of sales in the U.S., net sales only. It's a real drug. It's a real potential. Many of us have joined over the last few months as well to really further drive that potential into patients. We're very excited about what we have in front of us, not just in MDS, but also, I'm sure we'll talk about our additional programs in myelofibrosis.
Oh, certainly. Let's start with that launch that's ongoing. Obviously, RYTELO has showed great efficacy in the clinical trials, especially durability in the pivotal study, very impressive. Commercial uptake over the past year disappointed a lot of folks' expectations. Can you walk us through the now that you've got a year of commercialization under your belt, you've seen sort of how this is going in the commercial setting. Can you walk us through the disconnect, the apparent disconnect between strong clinical data that you would expect to drive a lot of interest from the space and real-world uptake?
Yeah. No, it's a great question, John. That's what's one of the things, to be honest, I was looking at a quarter ago when I joined Geron, is any physician I ask about the value proposition that RYTELO can bring in, there's consistency in what I hear in terms of the drug is effective. This is a novel class. We need new therapies for these patients. The durability of response, specifically in transfusion independence, is real. That's really kind of something needed. Then folks look at other therapies that have launched in this space, such as Luspatercept, for example. Now they're selling what, like $2 billion plus a year. It really kind of shows you the potential that any novel therapy that actually works in a disease area has over there. Yet our launch has been more, let's call it modest over here.
I think for me, the way to describe it is anybody who tells you that drugs sell themselves probably should take a look at Geron, because this is a great example of a drug that actually is effective, safe. Yet there is definitely room for improvement in terms of uptake, be it in the U.S., where we have the FDA approval, but also in Europe and other areas where we do have the approval. We have been really focusing on operational excellence and on execution, be it on the commercial side, be it on the medical side, something that has been going on for a number of months. Of course, over the last few months, I can talk about it more because I have been here, to really make sure that the right patient is put on RYTELO, not just any patient or the last-line patient.
Because in oncology and hematology, it's quite normal that you first start off with the later-line patients. At one point, you've got to start moving to where the trial has been designed. Our IMerge study has been predominantly second-line patients, where we've shown a lot of very good data. We want to make sure that every second-line patient actually gets the benefit of RYTELO.
That is on label, but critically, that is not where the initial uptake had been at the time of launch.
Correct.
Can we talk about what that trajectory looks like in 2026? You've talked about that as a growth year and a year for reacceleration. You've mentioned moving into earlier lines as being a key driver there. How do you get there? What are the levers that allow you access to those second-line patients where presumably durability and length of time on therapy are the major drivers for revenue? How do you get access to those patients where previously prescribers had been hesitant to give them to you?
Yeah. I mean, the way we look at it is it's two things. What are the things we can control, but also where is the market heading? Both of them are quite important. What we can control is making sure that the IMerge data as it has been done, that that's really communicated well, that that's really across our hematology environment in the U.S. One of the things which, to be honest, played against us is the fact that we have 90% plus of our pivotal trial enrollments are ex-U.S. We are launching in the U.S. However, we have a lot of physicians who we know very well and on very good relationships over the years. We've had both myself and Joe, we have a lot of extensive connectivity with that network. They're telling us, "We don't know you guys.
We don't know you within the context of Geron, within the context of RYTELO, because the trials were done ex-U.S. We really need to make sure that that message and awareness is really covering across the country. That is something in our control that we can do. Something else from a tailwinds perspective that we can benefit from is we do have Luspatercept in this disease area that has been moving into the front-line setting, which is great news for patients that are looking for options in the front-line setting. That opens the opportunity even more in the second-line setting, because last we checked, it's not like Luspa is curing patients. Unfortunately, all these patients will be at one point relapsing, and they need new options. That is where IMerge comes in. We are able to demonstrate a very durable transfusion independence, a very durable response.
Like a replica.
Exactly. The story has become one of coexistence rather than just a competition. Between what's in our hands and between where the market is going, we do believe that these two forces are going to be very important to fuel the growth for RYTELO in 2026. John, you may or may not know, but in September, the NCCN guideline was actually updated exactly in the direction that Harout was describing, where now we are not on par with HMAs. We are ahead of HMAs, which means we are immediately after the Luspatercept first-line line.
That's a great point. Now, you've mentioned the relationships you have with KOLs who maybe were unaware of the trial results, or at least didn't have first-hand experience from the trials. Those are folks that are major drivers of potential uptake across the space here. The potential benefits that the trials show, as you say, maybe they ought to sell themselves, but you still have to get in front of these KOLs. Can you talk a little bit about how that process has been going over the past few months, how you're making traction, and maybe how you can report what's resonated with those KOLs?
Yeah. No, that's a great question. Back in the day, I used to be the global brand lead for Gleevec and CML. If there is a product that would sell itself, it's probably Matt Nay would have been the poster child of that. I can tell you stories about that. Maybe I'll tackle your question in two ways. One, a few things from my side on the commercial side, and then have Joe maybe mention some things also on the medical side and some of the bigger accounts. On the commercialization side, hematologists are quite a concentrated group. It's not as diverse as a breast cancer group. The ability to connect with them, have that role is very important because it's a much tighter group, at least that's been our experience, and making sure that we're visiting the right people.
We're visiting them with the right segmentation and targeting, differential messaging, folks who are using Luspatercept in the first line versus ones who are not using it in the first line, folks who really know how to handle typical run-of-the-mill hematology side effects, such as the neutropenias, thrombocytopenias, versus others who might be in the community, who might be seeing an MDS patient in the morning and a lung cancer patient in the afternoon. How do we ensure that we make their life easier? There is significant focus from a commercialization perspective to make sure that our messaging is really resonating with the practice of the person in front of us. It is not about spending more money just for the sake of money. It is really to tailor our needs in a way that really makes sense. Maybe, Joe, you want to comment on some of those.
John, when you're launching a drug, there's an approach to three different groups of physicians, physicians that you could qualify as allies, meaning those are the physicians who were part of the study design, strategy, execution, and are at the podium. The second group that's neutral, that's informed but not really involved. The third group, which is negative. In our situation, most of our allies' group were outside of the U.S. because that's where the experience was. We had to overcome that gap. In some experiences where we had a big institution like MD Anderson, for example, where we had zero engagement, zero involvement from the investigators with our drug, they were not just neutral. They were on the negative side. Actually, they had data produced by their telomerase expert who speculated that maybe telomerase can cause leukemia in this population.
After obviously engaging and providing data and answering questions and providing them a drug to do their own experiment with our drug as opposed to a surrogate, it turned out that they found that the drug is on target and it does not cause leukemia. There you go. Since then, they have also treated patients, and they are representing us at the podium, talking about their experience, first-hand experience with RYTELO after Luspatercept, and praising the value of this drug in terms of robust response as well as durability of response in patients otherwise that were bedridden.
Yeah. There's an actual component from the patient, but there's also an emotional component. You've got to kind of go through that journey.
Makes sense. All right. Now, I want to get back to both of those things in a little bit more detail. Before we do that, as we sort of think broadly about 2026 growth, as we think broadly about reacceleration, potential reacceleration of revenues, and I know you're hesitant about the sort of guidance you're giving, can you tell us what kinds of metrics you're excited to see internally, what you would plan to share with the street? When they're available, what are the sorts of things that we should be looking for to signal that you're on this track?
Yeah. No, we're not hesitant about guidance. We're not giving guidance. That's just the clear. Look, we have multiple things we're very excited about. And many things, like we are sharing certain metrics. For example, we are sharing new accounts that have not ordered before are ordering now. We have shared that number. Now we have 1,150 accounts, and that's an increase of 150 accounts in the last quarter versus the quarter before. That's a good metric. Another metric is where is our source of business coming from? 36% of our patients are now coming from the first-line, second-line, lower MDS setting versus the later lines. That's up from 30% the quarter before. These are kind of early indicator things that are important. However, what we had reported in the last quarter is that the demand is not where we want it to be. Why?
Because you have a lot of patients who are on the late lines, and those are dropping off as new patients coming in. That bucket has been quite leaky. We really want to make sure that we get the right patients involved and on therapy because that first mathematically increases the duration of response, which is something we monitor. There are KPIs regarding the brand itself. There are KPIs about the awareness itself. There are KPIs that we look at our operational effectiveness itself from a field perspective. What we're doing, are we going to the right places and all that? The sales piece itself is really a lagging indicator. That's kind of a you do everything else right, over time, you're able to report hopefully better sales outcomes.
We have quite a bit of work that we have done over the last few months in terms of really getting our connectivity with the market and really making sure we understand where our business is coming from and where it's not going to come from. Those are things which I'm very excited about because.
New accounts opening, proportional accounts opening.
New accounts opening, new patients coming in, demand, our ability to kind of impact the potential of the drug in terms of awareness levels of folks, usage, repeat usage in certain areas. How is the AMCs in the academic medical centers viewing the drug versus the community doctors? Those are very different things. The share of podium on the AMC side, how many new ISTs are people asking us to do? How much there is engagement to further study RYTELO? There are multiple areas that we're looking at that gives us a good picture.
Are there particular levers in getting into those key segments? I'll say specifically, like AMCs. Are there particular levers that are going to drive engagement with KOLs, get them to the podium, get them to be talking to their peers and leading the education versus community docs? Are they caring about different things?
Yeah. Maybe, Joe, you can comment on the AMCs and not comment on the community.
There's definitely a difference. Physicians in big institutions want to have their own experiments, their own questions with their own patients and labs. Since Harout joined us, we've had now a number of actually, there's an excitement to have RYTELO in those experiments. We got a number of proposals that we are now in the process of contracting after approval. Those will address questions within MDS as well as beyond MDS in the clinical as well as in the preclinical space and real-world evidence. Those are the drivers for those physicians to not just do the experiment, but also to publish, to present, and talk about RYTELO.
On the community side, it's a bit different because in academic medical centers, it's about their personal experience, share of podium, all that. On the community side, we've got to make their life easier. They're seeing all kinds of patients. Our role is really to make sure that we're plugging into their practice and making sure that we're really helping them help patients. That's where the simplification of the messaging comes in important. How do you tackle the patients in the first couple of cycles where 80%-85% of potential neutropenias, thrombocytopenias happen? Why it's important to hold the dose and get to that efficacy that we've seen in IMerge. It's a bit different, but we've got to be able to do that. That's really one of the key levers of success.
Especially as you want to push into earlier lines, I imagine.
Correct.
That's predominantly in the community.
Correct. John, I do not know how many of the audience here are going to ask. We have five posters approved, two of them specifically for the MDS from the IMerge study. One is an oral presentation talking about efficacy and safety of RYTELO. On the efficacy, we have now proven that this drug improves survival, PFS, and reduces conversion to AML. That is the first time ever a drug in MDS second-line plus that does that. The second one is as important, which is, again, the awareness of safety and what does it mean when we talk about cytopenia, which has been one of the hurdles that we have heard. Again, we speculated and hypothesized that because the drug works on ineffective hematopoietic cells and reduces and kills those cancer cells in the bone marrow, that cytopenia is related to that mechanism of action.
If anything, now at the podium this weekend, we'll see that this correlates, this cytopenia correlates with the best response. It's important that patients and physicians understand that and manage those cytopenias so they don't panic and stop the drug, which has been one of the issues that we're trying to address.
That makes sense. Let's touch because we only have a couple of minutes left. Let's definitely touch on myelofibrosis, IMpactMF, finished enrollment this year. It's a unique trial. Design's a little bit different than others in the MF field. Can you talk a little bit about what drove the decision-making in the phase three design and how you hope to leverage those endpoints?
Yeah. Maybe, Joe, you can tackle that. Then I'll add a couple of.
Yeah. The phase three was based on a successful phase two. I would put successful in quotation because the initial design was a JAK inhibitor design, TSS, spleen symptoms. Based on the timing of those endpoints, the drug or the study was deemed negative in the sense that we did not hit the exact endpoints at the exact time frame. When those time frames were extended, the symptoms were much better. More importantly, when the drug, and this was a two doses randomized, high and low, there was definitely a difference for the high dose in overall survival. That was the first time ever in a relapse refractory myelofibrosis study that we have a survival advantage almost tripling what a historical cohort would have.
On that basis, the phase three study was designed with the bold conviction that this drug is not just doing symptom relief, which we can. It is actually transforming the disease from a deadly disease to a manageable disease with extension of life.
Yeah. Now it's fully enrolled. As of September, again, a tiny biotech leading this global phase 3 trial. Now it's a matter of waiting for the events. The projections currently show us that the interim analysis would be sometime in H2 2026. The full analysis would be sometime in H2 2028, all depending on events, obviously. Our base case is that this trial will go until full analysis. Of course, we'll be ready for interim analysis in case we have a positive upside. This is a very exciting field. It can almost double our potential patient addressable market.
Yeah. Very exciting and very unique trial design in the MF space. In our last couple of seconds here, I would love to return to a topic that you mentioned a little bit earlier on expenses. It's not good enough to spend more money to spend more money. You have to be more targeted. You lowered OpEx guidance for this year, maybe paradoxically in the face of an underperforming launch that you want to reinvest in. Can you talk a little bit about how you're managing expense discipline versus the need to aggressively approach the market, have an active sales force?
Absolutely. We get that question quite a bit, like, can you throw more money at it and the problem goes away? No. It does not work that way. We really need to be very disciplined in what we do. We have the funding, which is fantastic. Given in a market like this, the fact that we actually can keep on going without having to go back to the capital markets, that is a good thing. At the same time, we have to be disciplined. I mean, I have faced it over the last few years in my other companies where it is so important to have the fuel that you need. We have reduced our OpEx guidance for this year to say somewhere between $250 million-$260 million.
We think that even for next year, we do not see a major uptake about that because we have what we need from the market perspective. It is really about how do you become the maestro, how do you manage all this, and making sure that we have the right targeting that is happening and not just we are just throwing spaghetti at the wall. We are going to be much more surgical. The areas where we need to invest in, we are going to be doubling up. In other areas, we might not be. This is kind of our approach in low-risk MDS. Of course, with the MF, the bulk of that trial is now behind us because it is already fully enrolled. Once we see what is happening with the data there, we can rapidly accelerate as per need.
Meanwhile, there's no need to have everything on the high alert. Very surgical in expenses, but very assertive in terms of driving value.
Excellent. All right. Thank you guys so much for joining us. Hope you have a wonderful conference.
Thank you very much.
Thank you.