Good morning, everyone. Thank you for joining us at the first day of the Needham Healthcare Conference. It is my pleasure to have with me today Harout Semerjian, the President and CEO of Geron, as well as Joseph Eid, the Chief Medical Officer of Geron. As a reminder, you can enter a question through the Ask a Question box at the bottom of your feed. Harout, maybe just to set the stage for whoever is unfamiliar, high-level overview of the company story.
Sure. Thank you, Gil. Good to see you, and thank you for Needham for this opportunity to share a bit more about the Geron story as it's been unfolding. We are a commercial-stage company focused in hematology-oncology. We have launched the first telomerase inhibitor, imetelstat, in the marketplace as of middle of 2024. We're in that first initial two years of launch phase, trying to help low-risk MDS patients around the world, hopefully, but now starting with the U.S. based on the IMerge data that was released. 2025 was a very good year for us. We have reported $184 million of net revenue.
We started the year with a guidance that we have given in terms of our growth ambition of $220 million-$240 million of net revenue in 2026, with a even more streamlined team and investments that we had in 2025. We're off to the races, and we're happy to be here to share that story.
Harout, maybe on a personal level, you've been around now for a little bit, but you're still a little new to Geron. What attracted you to this story, and what do you think has changed since you joined?
Yeah. I've been in the pharma business for more than 30 years now. The vast majority of that time, Gil, as you know, has been in hematology oncology with a large player in this area for many, many years. For me, having this opportunity to be in a company like Geron, where we have an asset that has gotten approval, as you know, many biotechs don't even make it to this point, so we're very fortunate to actually have an FDA-approved asset in lower-risk MDS, was something very attractive for me. When I was talking with a lot of the physicians and a lot of folks who I know, in this disease area efficacy matters. Really making sure that we have a drug that is able to have that durable responses for me was very important. That's where I started with.
Of course, having a company where we actually have funds, we have $400 million on our balance sheet where we can actually get things done. That was also very important. That wasn't always the case in some of my previous companies, so this was also something fortunate over here. I've been here now seven, eight months in Geron, really putting together the team, the vision together with the team, so that we can really tackle the 8,000 patients who are second-line lower-risk MDS patients in the U.S. We believe that we have a tremendous opportunity to help those patients and make a great business case and have Geron ultimately become a hematology powerhouse. There's been multiple things that have attracted me to here, Gil.
Be it from the drug to the company, to the fuel in the tank, and to really a vision that we can all stand on and really work together as a team to make it happen.
Thank you. Very helpful. Maybe a good place to start, just reminding us what the standard of care is for low-risk MDS and where RYTELO is positioned.
Yeah. Just maybe a little bit of a stepping back, Gil. Myelodysplastic syndrome is a spectrum of disease. You have the low-risk MDS, and you have the high-risk MDS. The high-risk MDS is very close to acute myelogenous leukemia. As a whole, MDS is a precursor to leukemic transformation, and that's why it's considered a cancer and not a benign condition. The treatment for many years was transfusion and support. ESAs came into the scene in the early 2000 for anemia of cancer. In 2020, luspatercept was approved for low-risk MDS, initially in the second-plus line, and in 2023, it was approved for first-line MDS. The other drugs that are also utilized include lenalidomide for specifically the 5q deletion and hypomethylating agents, HMAs, like azacitidine, decitabine.
Those initially were used in a broader spectrum, but as the field has evolved, we see now a transition in the clinic and endorsed by NCCN guideline for ESAs or luspatercept in the first line, with luspatercept making a move into capturing more of that first line. Depending on whether it's ESAs or luspatercept, the second line preferentially is now imetelstat, with NCCN guideline pushing the HMAs into the third line and beyond. That's the current paradigm of treatment where imetelstat is anchored in the second line, but also has applicability in first line, and that's in the label for ESA-ineligible, for EPO levels over 500 and high transfusion burden. As well as we know, ESAs not functioning as good as the luspatercept, that also becomes an imetelstat positioning.
Maybe just spend a second on RS negativity. There is clearly less of a benefit for luspatercept in RS negative patients. Is that something we're seeing in practice? I mean, the label covers everyone.
Imetelstat was approved, if you recall, in the second line, exclusively in RS positive o n the basis of the MEDALIST trial. The COMMANDS trial, which is a first-line population, included RS negative, albeit at a fraction of the epidemiology, meaning about 30% compared with more than double in the normal epidemiology. The overall study results were positive when compared with ESAs, but if you look at this ESA subpopulation, they do not benefit as much. If anything, physicians now see that as a vulnerability or an Achilles heel for luspatercept, and they see imetelstat as a drug that works in all these situations, RS positive, RS negative, high transfusion burden, high mutation burden. Because the difference of treatment or mechanism of action for the treatment is also at the basis of those differences.
You see ESAs and EMAs more of a supportive care, whereas imetelstat is more of a disease modifying agent. It acts at the basis of the disease. We have now many data points pointing to that it's on-target drug against the clones, the mutated clones of MDS. Now, anecdotally, we've seen physicians in the clinic now starting to transition from a blind check ESAs or blind check luspatercept to the profile of patients. If patients tend to have RS negative, for example, ESAs are not very good at that population, albeit maybe better than luspatercept, and luspatercept not a good option. They're opting for imetelstat, which has actually benefited this patient.
I've had few KOLs talk to me about their first-line patients come in with RS negative profile, and they're putting them on imetelstat, seeing a much more robust response than what when you see in the later lines of therapy, which is expected. That is reassuring, and it's again, in line with the mechanism of action of imetelstat.
How would you say the reception of RYTELO has been by physicians, and is there any difference between what you're seeing from academic centers and, let's say, the community setting?
Yeah, there definitely are. One thing to keep in mind, Gil, is that when we were doing the IMerge trial, our own pivotal asset, 90% of those patients were enrolled ex-U.S. That's one thing which is kind of important to keep in mind is reception is really tied with a familiarity before a lot, right? That's where, to be honest, we've had to do a lot of awareness and education for our U.S.-based hematologists, be it on the academic medical centers, but more on the community side to really understand the mechanism of action of RYTELO. Why is it different? How do you get to that durable responses? Whenever you see a cytopenia, how do you deal with it? It's been an ongoing educational journey so far.
What we have seen is more and more of these anecdotes where folks who might not have known about it before are using it, using it well, using it in the right patient population. With the recent cytopenia data that was presented at ASH, and maybe Jo can talk about that also is now giving further boost to the story of why RYTELO is an appropriate second-line agent. Joseph, do you want to talk about the cytopenia data?
Yeah. When I mentioned that this drug mechanism of action is on target, the target is being the mutated MDS clone. Cytopenia that is seen with imetelstat is the reason for why the drug works. Why? Because you're targeting those mutated clones, and you're clearing the marrow of the disease to make space for normal hematopoiesis to recover. We see a predictable cytopenia within the first two to three cycles, and we see a predictable recovery within two to four weeks in over 80% of patients with lower level of cytopenia. Those patients, and this is what was presented at ASH, those patients that tend to have cytopenia tend to be the ones that have the most durable, robust response. That's, again, consistent with how we understand the mechanism of action to be effective against this disease.
Some of our own research has shown that RYTELO, the use is concentrated later lines right now. How are you working on improving adoption in earlier lines, especially the topics we touched on, like RS negative patients?
Yeah. You're right. This is something which we have also disclosed on our full year 2025 results, Gil, is 30% of our business, we believe, is coming from the first-line, second-line patient population, meaning 70% is coming from third-line plus. Generally speaking, in oncology or hematology, whenever you launch an asset, you do start getting more traction in the later lines. That's something which is not atypical. That happens often. The key is to start moving more into the lines that you're approved in as fast as possible, which in our case is in that second-line setting. That's kind of where we're doing a lot of our education to really make sure that we are getting the appropriate patients. We have fine-tuned our strategy recently, where we're really focusing on that second-line patient population, which we believe in the U.S. is about 8,000 patients.
It's not an insignificant number of patients who can potentially benefit from imetelstat based on the label, based on the NCCN guidelines. Of course, we always anticipate that there will be a subset of patients who are in that third line or beyond who need options. This is a disease where recycling of therapies does happen sometimes. We do see that.
Ultimately, what we want to see with more education, with more focus, and with really also our investments that we have been putting beyond just field force or medical people in the field, is we've been investing heavily on the non-personal promotion, on the digital platforms as well, as well as regional meetings beyond just ASH and EHA, to really make sure that education gets so that we can ultimately get to the patient population that we believe we can help the most, which is the second-line lower-risk MDS population.
What would you say a typical patient experience with RYTELO look like? Kind of as a related point, what happens when a community doctor sees these kind of cytopenias? Do they discontinue drug or how are you guys addressing that?
Maybe we'll start with that part. Joseph, you're a trained hematologist, and you've dealt with patients like this, so he can give you a real-world example of that.
Yeah. As you know, the majority of our patients on clinical trial for the IMerge work was done outside the U.S., so the hands-on experience in the big institutions as well as in the community was minimal. We've been improving awareness by engaging scientifically at congresses, in clinics, in peer review forums, in those small peer-to-peer meetings. The whole purpose of that is to make sure that we bring the science and the data to their attention so that they are aware of the data. That's one piece. The other piece is obviously having good experience. The good experience starts with the education on the mechanism of action. That cytopenia, for example, presentation at ASH, which has been published recently, also again links the cytopenia to the benefit of the drug.
That's one actually key component in this disease specifically, because there is an analog that the hematologists are very familiar with and they're comfortable with, which is lenalidomide in the 5q deletion subpopulation of MDS. Now, that specific mutation responds to lenalidomide, and those patients tend to have cytopenia. In the lenalidomide case, that cytopenia was also correlated with the response to lenalidomide. That's the backdrop, if you will. Our drug, imetelstat, in addition to the 5q deletion, it has actually activity across all mutations that we have tested that cause the MDS disease.
That understanding and that linkage to a known analog is also a way to reassure physician that when you do see cytopenia, instead of what we saw in the early days, patients were dropped off imetelstat because physicians didn't understand why there was cytopenia, what to do with it, and what to expect. Now we have the full story that it starts in the bone marrow, that this drug is on target. It works on those clones. That's why you see the cytopenia. To reassure them that most patients do not have bleeding or infection, because those are ineffective hematopoietic clones, and that actually is also supported by the IMerge trial, where the placebo incidence of bleeding or infection was similar to the one seen on imetelstat, which was minimal. More importantly, patients do recover.
Now we have the full story, which is those patients that you do manage, as opposed to interrupting drug and getting patient off drug, you manage them through those few weeks, and those patients tend to be the best responders over time. That's a totally complete transformation in the understanding of how the drug works and how you manage your patients.
Thank you. Very helpful. Maybe kind of as a follow on there, the treatment burden, right? This is an infused drug. Can you compare this to the preceding standard of care, and how do these things match? If there's cytopenias, you probably also need to give GCSF, et cetera.
Yeah, on trial and in the real world, what we're seeing is if patients do receive any growth factor, it's no more than one injection. They're not getting the weeks or the days of support. Again, you have to think of the MDS patient differently than the chemo, for example, patient, where you have an intact barrier, no mucositis, no diarrhea. You have a very transient cytopenia, not prolonged. All these are factors why patient become susceptible for infection and bleeding. We're not indiscriminate like chemo, that indiscriminately kills all the clones in the bone marrow, the good and the bad. Imetelstat targets the bad clones. All of these are reasons why we don't see a difference in incidence of this cytopenia effect, but whether it's bleeding or infection between active arm imetelstat and placebo. That's what we're also getting from the real-world application.
RYTELO generated about $184 million last year. Company guided to $220 million-$240 million for this year's, so more back-ended. What gives you confidence of this 20%-30% growth?
Yeah, great question, Gil, and we actually put that guidance out first day of J.P. Morgan, right, very early on in the year. It's really driven by our conviction of how much potential does RYTELO have. Let's say Q4, we had to take some tough decisions in terms of a major RIF that we have implemented, primarily driven by the need to simplify the organization, because we wanted to make sure that we have more investments in areas that really will move the needle for the ongoing and the going-forward business rather than more historical reasons.
We have taken big sums of money from areas where it was needed at one point to get a drug approved, but after that, it just becomes more helpful for the company to, for example, invest in digital forums, non-personal promotional forums, regional meetings beyond ASH, and things of that nature. That's where we've been really focusing on. We have a streamlined strategy in terms of the focus on the second-line patient population, and that's how we're all aligned as a company, that that's where we're going to focus on. We have the focus on the high-volume accounts that we really kind of redid our accounting and our targeting to ensure that we don't shy away from high-volume accounts just because they're harder to get in.
That's really where we have a single purpose to do with a drug that we have, and making sure that we're really amplifying our educational assets in a way that also includes this digital, as I mentioned, and then really work and engage with the medical community on other areas. There has been a lot of enthusiasm about the mechanism of action that RYTELO provides, this telomerase inhibitor, for example, right? That's driving a lot of medical conversations, which in turn is driving a lot of ISTs and investigator-initiated trials. We have announced recently that there are 10 of those, more than 10 of those actually, that we have aligned with from a strategy perspective. We're not obviously reproducing IMerge, but there are a lot of other areas within hematology and oncology in general where a telomerase inhibitor can play a role.
And the more we're engaged with our physicians to understand that, the better it is. So between that, between our strategy, between our rejuvenated team, the focus, the increased investments in where it matters, we felt confident to have guidance from the beginning of the year that shows a significant growth, right? From moving from $184 million to take the midpoint of the $220 million-$240 million , that's $230 million, right? You're looking at almost a $50 million uptake. So that's really very exciting for us, and we believe there is 8,000 patients in the U.S. that we can help, and we're waking up every day making sure that that's getting done.
Maybe a question on the frontline dynamics. Are you guys still seeing patients who receive ESA and then luspatercept ? I've gotten the sense that biologically that doesn't necessarily make a ton of sense. Both of those drugs push the marrow to produce more. I'm just wondering if there's still two lines of some basically factor.
Yeah, Joseph, maybe you want to take from a mechanistic perspective, say, luspatercept, and then I can comment on the market dynamics in general.
Yeah. Let's think of ESA as the erythropoietin-stimulating agents, and EMA, luspatercept, is the erythroid maturation agent. You have drugs that kind of work in a sequence, where the ESAs stimulate the progenitor, and the EMAs stimulate the more mature cells and make that maturation faster. They come out of the marrow faster. We know that luspatercept works better than ESA when you compare it in that same population. The fact that EMA matures the cells, ESAs does not work on that population after. In that sense, ESA, and that's what we see in the clinic, is not as effective post-luspatercept.
The best option for these patients is actually imetelstat because that population is still healthier, and will benefit more and longer from a drug like imetelstat, which works on the disease. Mechanistically, that's the sequence, that if one is to use one drug before, luspatercept has the better data. ESAs does not work as much after.
That's exactly in line with what I was suggesting about the overall market, where it's going. We are actually seeing tailwinds rather than headwinds going forward, Gil, specifically on this topic because as luspatercept, which used to be predominantly a second-line agent, moves more and more into frontline setting, given mechanistically how Joseph eloquently described it and the data over there, that they have shown they are better than ESAs, we think that will continue over time. Unfortunately, even when that happens, it's not like every patient is getting cured. You will need additional options in the second-line setting, and that's where we are appropriately positioned, regardless of whatever is the frontline to really help second-line patients with RYTELO.
I will just add one more dynamic that has happened in the marketplace is the NCCN guidelines that have also been recently updated, where now RYTELO is a preferred second-line agent ahead of HMAs. It's also a very valuable market dynamic that we shouldn't overlook because even after HMAs, not many things work out. It is more appropriate, in our opinion, that's kept more for later lines of patients. Really the first dynamics is really where RYTELO is a solid second-line agent, and that's where we see some of the tailwinds as well, helping in addition to our own efforts.
Wonderful, very helpful. You guys have an EMA approval, but you're not launched ex-U.S. Maybe just give us an idea of how you guys are thinking about ex-U.S. markets.
Yeah, no, great question. Imetelstat is a wholly owned asset. We have the rights geographically everywhere in the world. In addition to our FDA approval, we actually have an EMA approval as of last year. We haven't fully commercialized it in these countries, obviously. As you know, many biotechs, ourselves included, there's a lot of debates and discussions today, especially in the world of MFN. How do you go about doing it in a way where it doesn't impact us back home and our U.S. business, obviously? We're of the belief that RYTELO, our drug, needs to be everywhere. We don't necessarily need to be everywhere. There are conversations we're having with potential partners, but there are also conversations that we're having about what are the other optimal ways that we can bring RYTELO to the marketplace in European countries in particular.
Because as you know, a lot of centers in Europe actually enrolled patients on imetelstat, and we have even more ambassadors and more folks who support imetelstat because they've seen the value of it in the clinical trial setting, even more than the U.S., to be honest. It did hurt us in the U.S. with the need for this surge of education, but on the European side, we have a very robust footprint of physicians who have been involved. It's currently where, regardless of where the commercialization efforts go, Gil, what is really clear is we have to be very close to the pricing component of it, and we have to do it in a way which is gated as well.
So currently, we have a lot of efforts on the HTA processes in terms of really understanding how would we assess value based on the different parameters of the HT processes going into the different large European countries, and making sure that appropriate measures are taken for RYTELO to be up against decent comparators when it comes to that. So that work is ongoing, and depending on that work and depending on what we believe we can get in our pricing, and because at the end, this innovation issue is a real issue, and we all know that, and we all succumb to the fact that we need more and more countries to recognize innovation. We're one of those companies that have been really going at it for 35 years, and finally we have an approved drug, and that innovation has a value.
We're doing a lot of that work on the HTA side, and depending on the outcomes of that in a gated fashion, we would decide on next steps beyond that.
Great. I do want to spend some time on the myelofibrosis program. We're finally progressing on this one and may see some pretty interesting data. Just maybe start with the IMpactMF trial design, and what should we expect in this upcoming interim later this year, assuming everything falls into place?
Yeah, Joseph, do you want to take it?
Yeah. Maybe, Gil, to give a little bit of context of the IMpactMF, the phase III trial. This is a phase III trial in a 2:1 randomization of imetelstat versus best available therapy, looking at overall survival as a primary endpoint, as opposed to symptom relief, spleen size and symptom relief. The data that gave us confidence to go into this space with a phase III registrational setting is the EMBARK trial phase II data. It's a randomized trial with close to 110 patients randomized to two doses of imetelstat, a high dose and a low dose. The high dose is actually higher than the MDS dose and given more frequently, every three weeks. That trial showed benefit in symptom relief as well as overall survival.
The overall survival was so dramatic, almost tripling the benefit between the high dose and the low dose, as well as when compared with the historical matched control, that the benefit in that population, which is the relapsed refractory to JAK inhibitor population, had a very significant overall survival. The study is designed with an overall survival on that ground. We believe, again, coming out of that this would be a paradigm shift, if we proceed with a trial that ends up positive in this population, which is, again, a relapsed refractory to JAK inhibitors. Now, as far as what the study design and what we're looking for, being that this is an overall survival endpoint, the milestones are driven by death events.
The projection of the death events are that we will probably hit an interim analysis by the second half of this year, which is what we have stated in the past. The final analysis will be, let's call it two years beyond that. The DMC has been meeting on this regularly to review the data on this trial 2x to 3x a year since the inception of this trial. Our assumption is that the DMC is most likely to inform us that the study will continue to proceed to the final analysis, because the interim analysis has a high bar like any other overall survival study that's designed that way. That would be a good thing, which means that the totality of the data still continues to favor the continuation of the trial.
Okay. That makes a lot of sense to us. How has the standard of care at best available therapy changed? The study has been going on for a while. Is there a drift there as well?
The standard of care has shifted in the sense that there used to be one JAK inhibitor. Now there's multiple JAK inhibitors. What we are also seeing with the JAK inhibitors, that our patients are recycled very quickly from one to another to another JAK inhibitor in a rapid sequence. Overall cancer support and management of patients with cancer has improved, including management of patients with myelofibrosis. That by itself is a condition that improves patients' outcome and patients' well-being. However, there's no evidence that any particular JAK inhibitor has improved survival. That's the differentiation, I would say, between a study designed like ours, which is focused on overall survival because our drug has that evidence from the phase II, versus the JAK inhibitor, which is more of a symptom relief, which is why they usually use those different endpoints.
Overall, the study has taken longer in the sense that patients are living longer on our IMpactMF trial, which is, again, an indication that patients' well-being with this disease has improved somewhat over the years, but not to the point that, again, we have that major differentiation in survival.
Maybe to touch on this in one more direction, what would you consider a clinically meaningful improvement in overall survival as it relates to standard of care?
It's defined in the statistical plan, and this is a high bar for overall survival, but it has to be statistically and clinically significant for FDA, obviously, to grant us approval.
Maybe looking from the 50,000-foot view, any last messages you want to highlight to investors? What do you think people are not catching on to as it relates to Geron?
Yeah. Look, Geron is now a commercial company with an asset that last year we sold $184 million. We all agree we can do better, and that's why we put a guidance for 2026 that shows what better means. It's a meaningful growth for our base business in low-risk MDS. We have really reset our own way of working and making sure we're really engaging very effectively with the marketplace.
In making sure that educational piece is really there because it's not every day that you get a drug that actually has a durable response, where the response is a year and above in a low-risk MDS patient population. Yes, there are many cases where cytopenias happen. We are talking about the hematology group that is used to dealing with this. What was missing is making sure that we're really having the dialogue as to the why they're seeing that, and that's in the data that we have released in ASH, and making sure that that engagement happens. We do have a very solid base case in the U.S., but also an opportunity geographically to expand ex-U.S. with a very strong balance sheet of $400 million and above. That gives us a lot of optionalities to pursue that.
On top of that, we have a fully enrolled trial in the myelofibrosis setting with an overall survival as the primary endpoint. That data can't get more conclusive like that, right? It either works or it doesn't. That's the upside of it. The downside is it does takes years to mature that data. Luckily, meanwhile, we have the MDS business to grow and expand as we get to the MF readout. I think where the opportunity here at Geron is that you have a commercial asset that is de-risked from a regulatory perspective, obviously, de-risked from a clinical perspective in the MDS business, with potential to grow and help the 8,000 patients in the U.S. and thousands more ex-U.S., with a very meaningful readout in the MF field, and who knows where else can do.
On top of that, we can use our balance sheet for additional optionality. Our vision is to build a hematology powerhouse over time. That's where we want to go, starting with the low-risk MDS, getting into the MF, and then really interrogating where else can we go with telomerase inhibitor or any opportunistic innovation that we might do after that.
Right. With that, I think we can conclude. Again, thank you, Harout Semerjian, for joining us, and Joseph as well.
Thank you. Thank you very much, Gil. Bye-bye.