Geron Corporation Aktie

Good morning, and thanks, everyone, who's joining us both here and on the webcast. We're thrilled to have the team from Geron here this morning.

And maybe with that, Harout, I'm just going to turn it straight to you. I'd love for you to kind of walk through what you view as an overview of the company and key value drivers for the business over the next, let's call it, 12 to 24 months?

Thank you, Corinne, and thank you for the Goldman Sachs team for the invitation to share why we are excited at Geron. So Geron is now a commercial stage company. In fact, we're almost to the day when RYTELO got approved in the U.S. for helping low-risk MDS patients after many decades of research and turmoils and shifting strategy like a lot of biotechs do. So now we are -- have emerged as a commercial stage company, really helping more and more patients in the U.S. and also now more and more internationally as we see that.

Our lead asset is RYTELO. It's the first telomerase inhibitor in the market that has been approved with the first indication in low-risk MDS with another Phase III in myelofibrosis post relapsed/refractory RUX patients. And we're excited as well to see once that data matures, how we can help further patients.

Great. And it's also nearing on an anniversary for you, which is 1 year with the company. So maybe you could talk about the key priorities you had when you took on the role and maybe provide a bit of a mark-to-market on where we are relative to those priorities. And then as you look forward, kind of where are you shifting in terms of your attention and strategic focus?

You're right. You're actually the first to note that I'm almost at the first year anniversary. It's been an exciting year, to be honest. I mean that this is kind of where -- as I reflect, I want to spend my time and really being part of something bigger where we can help more and more patients.

But when I joined in, the commercialization has already started. And maybe there was a bit of a discrepancy between what the market expected in terms of uptake and where we were. And that's where it's so important that we focus on what will it take to successfully commercialize an asset. And this is probably one of the good poster childs when people would say, drugs sell themselves, it doesn't work that way. And then I've done many of these launches over the years, especially as the U.S. Head of Hematology at Novartis. And none of the products that I've worked on come close to selling themselves, even back in the days of imatinib, that's probably the closest it will come ever, at least in my view.

But even there, the first few quarters, it took us quite a bit of time in educating people. So it really comes down to where we focus on is education, education, education, making sure that the U.S. hematologists, especially the community hematologists because this is a community-driven disease, really understand how to manage patients, what are the side effects they're going to see, what are the benefits they're going to see, why it's worth it and how do you help patients.

So we focus a lot on what typically is done in a more of a prelaunch stage, which I'm sure some of that was done, but really having that surge was my priority #1. Second was really making sure that we're injecting the team with updated oncology-based commercialization background folks. That was also very important and also making sure that our financial discipline is there so that we can continue to not just get RYTELO in the marketplace, but also ultimately get to a place where we can build a hematology company longer term. So really making sure that we tackle all of these 3 areas has been a focus for me in the first year. I think we've done a lot of advances in all 3 areas.

Okay. You mentioned already, but RYTELO has been on the market for about 2 years. Can you talk about the treatment paradigm and where RYTELO is currently being used? Maybe give us a sense for what portion of patients are seeing RYTELO at some point during their treatment journey?

Sure. So the low-risk MDS patient population has been -- this has been one of the interesting diseases. At one point back in the day, it used to be called even pre-leukemia. So the sense of urgency might not have been the same as some of the other areas of cancer. And that's been one of the areas where Joe can talk about as a trained hematologists who've seen a lot of those patients.

And also what's typical in oncology and hematology overall is whenever you're launching an asset, typically, you're going to get used later lines because first, there is a bigger unmet medical need where physicians have those patients who they've tried everything else and they're like, okay, a new option in this disease area, let me try RYTELO. So it does happen not just in the low-risk MDS, but across the board, I've seen it, where you start from lower -- later lines. And that's kind of what happened as well with us.

The key is as folks get more and more educated and the awareness is there, then you move up into where you're actually indicated. And that is in the second-line patient setting. So that's where our focus has moved very, very quickly into making sure that we're not just helping any patient, we're helping the second-line patient population.

And as part of that, the metric that we've been sharing with the market is what's the percentage of the first-line, second-line patients from the overall patients that we're getting. And I'm pleased to see that, that number has been going up gradually, but steadily and up.

So the last quarter that we have released that is 33% with a 12-month look back. The quarter before that was 30% with a 12-month look back and so on and so forth. So our aspiration is to really get to a point where any patient, and we estimate it's about 8,000 of them in the U.S. in the second-line patient really gets the benefit of RYTELO in that indication where we can help folks the most, where patients can stay on therapy the most and where that durability of response that we've seen in IMerge can really be replicated the most in that patient group.

Okay. So you're obviously working on this. But if there's a patient in the second-line setting that's not getting RYTELO, what are they getting instead? And when you go out to physicians in terms of education, what are you communicating to them about the profile of RYTELO versus the alternatives that are currently being used?

Yes. Maybe, Joe, you want to tackle that, because you've talked with a lot of hematologists and advisory boards in terms of what's the paradigm shift that we're seeing and what are people using in that area.

Yes. I mean, just to complete what Harout said earlier, in my fellowship back in the '90s, the standard of care for MDS was supportive care. So that's how far the disease has evolved from being viewed as just a symptom relief to actually a disease that can lead to death events that actually mimic lung cancer. So it's not that benign of the disease.

But the treatment paradigm has evolved over the years from transfusion and other supportive care to ESAs that was in the late '90s, early 2000. HMAs, lenalidomide for the 5-Del Q. And then in the 2020 time frame, Luspa was approved in the second line. and then in '23 in the first line. Luspa was exclusively in the RS-positive in the second line and then in the broader spectrum in the first line.

As a new drug, a new class of drugs actually, RYTELO, there's a learning curve, and that's the exposure that we have seen is patients do start at a later line and then they migrate to where the most benefit can be derived. Of all the classes of drugs available for MDS today, RYTELO has the broadest spectrum, and let me explain what that means.

All other drugs with the exception of the 5-Del Q for lenalidomide are symptom relief. They do not manage the disease foundation. RYTELO has the capacity to change the disease, a disease-modifying characteristics represented by the changes in the bone marrow mutational load, responses that are not seen with rate of response and durability of response.

The cytopenia that was not well understood in the early days of the launch. Now obviously, with the data correlating cytopenia with response, which we had speculated -- now we have the data to say this is an on-target drug also leads to that durable response in those patients who do manage that.

And the NCCN guideline, which was updated last fall, is a validation by the hematology community that this drug is a better drug for patients ahead of HMAs, which is the first version of the NCCN, if you recall, after launch, put it in the same bucket. Now it's ahead in the second line as a preferred agent. And it has activities in the RS-negative group, which is unique.

EPO level, serum EPO level, whether it's less than 500 or specifically over 500, that's unique. Transfusion burden, 4, 6 units or higher, that's unique. So that broad spectrum applicability allows the drug to continue to gain confidence in the prescribers' mind and eventually lead to more patients benefit from RYTELO.

What we are seeing are physicians now understanding how ESA plays a role in treating patients, and Luspa and how the sequencing are happening. They're realizing that they have a lot of gaps. So anecdotally, we're seeing at least in the key opinion leader world, physicians starting patients first-line RS negative group. Why? Because they know that the other agents do not affect those patients in a positive way. And those are patients that have the poor prognosis. We know Luspa does not work well, whereas RYTELO does have a positive effect.

Okay. And you just talked a lot about kind of the profile of RYTELO, but as you think about the uptake, and like, physician awareness is, where are you finding you're spending the most time on education kind of go out to the market and have these conversations.

The biggest, I would say, catalyst happened last year at ASH, when we had 2 key data sets. One was the cytopenia and correlation with response, which, again, was the gap in the mechanistic knowledge of the drug and that completed and filled that gap. And the other piece was the long-term landmark analysis, which showed that the drug is safe and effective in terms of the trend in OS, PFS and conversion to leukemia, almost dropping it by 50%.

So there's the early understanding of how the cytopenia is predictable, reversible and does not lead to clinical consequence. So that's the early safety component, if you will. And the long-term safety. So that's the 2 bookends showing that the drug is safe and efficacious in this disease.

Okay. You've mentioned at ASH that one aspect of your educational office is really centered around these medical conferences, and we're right in the midst of ASCO and EHA. So what can you highlight in terms of recent data sets that you have shared or are sharing in Stockholm over the weekend?

I would say the bulk of the data up to the ASH were mainly driven by the registrational trial IMerge.

Last year, we invested heavily in the investigator-sponsored research to make sure that we broaden the data set beyond just the MDS setting. And we are seeing a high enthusiasm and interest in studying RYTELO in the preclinical, clinical and in the real-world evidence. What we have -- what we are expecting and coming out of ASCO and now going to EHA are real-world evidence showing that in the real world, when RYTELO is used in patients that are not controlled as in a clinical trial, we are validating the results that patients do respond in a similar way.

The safety profile is as expected, which is, again, a very important aspect of when the drug goes to the market with all patients without any specific limitation in inclusion, exclusion and monitoring, we're seeing the same profile, which is very reassuring.

Great. And how do you think about these educational efforts kind of translating into launch metrics related to the front and second-line use and revenues? So how should we think about all the work you guys have undertaken over the past year kind of starting to translate?

Yes. Look, our story has been very clear, at least from the day I started to say, this is a growth story. It will be quarter-over-quarter. It will -- that's kind of our aspiration because sometimes I get asked like what's the inflection point? It's like there's thousands of patients, and we want to grow it quarter-over-quarter in a very steady manner. This is typically how in hematology, we've seen assets grow.

What is really great is and what Joe said is we wanted to make sure, first, the academic medical centers really understand and are bought into RYTELO. And that was important because there was a gap in terms of when you do your clinical trials predominantly ex U.S. and then you're launching in the U.S. and you have like 5 people involved in your clinical trials, there is a question. I mean it just is, unfortunately.

So the faster we wanted to make sure we engage that medical experts in really understanding and really test driving RYTELO from a clinical setting in a development setting. And that's where the surge of ISTs has happened in the last year to really make sure that any other medical questions that they would like to explore into is we have that opportunity to collaborate. So that's on the academic medical centers.

But of course, they're not the ones who see the bulk of the patients. So you need the AMC experts to really share their experience with the rest of the community, but they're not the ones who really drive the vast majority of the volume usage. That happens still in the community. That's where we have reset our segmentation. We've reset our positioning. We've reset our messaging to really tailor it towards that second line, simplify it to the community physicians who might see a prostate cancer in the morning, might see a lung cancer in the afternoon, and then they're seeing this low-risk MDS patients, usually elderly patients.

So in their mind, it's like, well, I have these more severe cancers to deal with. So really making sure that the sense of urgency, how do you treat them, how do you hold those, all these things are -- that's kind of being rolled out. We're in the midst of really doing that on the community setting. And we deployed a lot of the cash that we've saved from making sure that we have a more simple organization, streamlined organization. We redeployed many of that into that non-personal promotions, the digital aspects that we can reach more and more physicians in the community.

Corinne, just to add, I've been at Geron now since November '24. And in my first few months at the podium in these medical conferences, imetelstat RYTELO was either not mentioned at all or mentioned but not so much positive. And I've seen the transition over the next few months in '25, and now we're seeing RYTELO, at least with the academic medical center speakers, which actually is how things trickle down to the community docs, they're actually understanding and explaining the role of imetelstat. They're seeing the value firsthand now, which they didn't have before. And that will translate eventually to physician understanding the best placing of RYTELO in the treatment paradigm, and that will carry forward.

We're also seeing in ad boards as well as in CME events, physicians, the pre and post when you ask them a question, how once they understand the mechanism and the data, they understand how to place the drug as opposed to reacting to little knowledge, which was unfortunately at the time of launch.

Okay. So one of the reasons for the first and second line is because of duration of therapy. Could you put a bit of a finer point on what the duration of therapy you're seeing is across the broader patient population versus what you could achieve if you are getting it in the second line or even frontline?

Yes. I mean, IMerge has been predominantly a second-line patient population and that duration of therapy was called 8 months, 7.8 months to be more precise. And we're seeing that mimic in the real world for a like-to-like patient population. So whenever they are using it in the second-line setting, we're seeing that 8-month duration happen.

The difference is that we have much more later line setting patients in real world than we have in IMerge, where the duration of response is lower, predictably lower. And that's one of the things which we really want to make sure that we tackle because there is a reason why that duration of response is lower. These are sicker patients. RYTELO is good. It does help those patients as well, but it can do much better, good if you use it in the second-line setting.

And the one thing I would just say about this market, Corinne, is it's always good when a drug's indication NCCN guidelines really comes together with the tailwinds from the market. What do I mean by that is our indication is in second line, the NCCN is really supporting that positioning over there. But also as the market, which has been really ESA dominant for many, many years, EMAs have launched in the last 5, 6 years, starting in the second line, now moving squarely into the first line. That is a good thing for patients overall, where EMAs have shown better efficacy than ESAs in the frontline setting.

So the more they move in that frontline setting, that second-line setting opens up even more for RYTELO. And that's where to one of your earlier questions, what if they're not using RYTELO, what else are they using? Well, we still see, for example, usage of HMAs in that patient population, which even the NCCN now in the past few months, when they upgraded their guidelines, we are a preferred second-line agent. There is a reason for that. And that's kind of where we want to make sure that education search that we've been doing really happens so that we're used in that second-line setting with the durability of response that goes with it.

Okay. On that point, you've said that about 33% of patients on a look like a 12-month look back view are in the front and second line. Where do you think that could go at steady state if doctors are kind of using it the way your education would suggest they do?

Yes. I mean, hopefully, the idea is to grow it quarter-over-quarter. And that's really the case. I mean, this is a large market, Corinne, that even with a good asset like Luspa, they're not getting every first-line patient. And still, it's like a $2.5 billion business, right? So these are thousands of patients who can be helped. And our aspiration is to grow that in the second-line patient population quarter-over-quarter. And really, over time, folks can see the steadiness of those curves.

Okay. What about the average dose you're seeing for patients in RYTELO? And I think in IMerge, there was something like 50% of those patients saw some sort of dose reduction. Could you talk about the dose intensity you're seeing over the duration of therapy?

Do you want to tackle that?

Yes. So there are -- obviously, there's a spectrum of management of patients. When patients are managed according to the label, they tend to stay on the drug. And you have a different approach. You have a dose reduction and resumption at the higher dose that was started, which is the 7.1 milligram per kilogram every 4 weeks or they go down and they stay down or they go down and they have a second reduction of dose. So there's hold, there's reduction and there's resumption.

Patients tend to respond even when their dose is reduced after and sustained responses. So the key education that we've been entertaining is to make sure that patients are maintained on drug as opposed to what we have seen in the first few months after launch. Cytopenia was observed and patients were dropped after 1, 2 or 3 cycles, which is not doing patients any favor. So that's the approach that we have been educating. And again, the ASH data validates that point that cytopenia is -- has to be seen in a positive way, not as a negative. It's not a safety. It's an on-target observation.

So maybe could you speak a little bit more about this, like what the dose intensity is today versus kind of what it could be if you are able to get through these educational efforts and get more physician understanding around keeping patients on drug?

I mean it's -- again, tailored to the individual. Every patient is different. So you can't say everybody has to treat the patient equally. Some patients actually, in my view, need to have a higher dose escalation, which is not something that we have studied in the past, but something that we would look forward in the future.

And this happens in oncology quite a bit. I mean, I remember back when we launched everolimus, I mean, it was the same thing where withholding dose, reducing dose, these are things that oncologists and hematologists are used to. So we're not discovering a new path over here. What we're doing is making sure that there is a proactive education in terms of what they're going to see once they put a patient on RYTELO, what that data is and how do you go through it? And how do you go through it? It's quite simple between withholding dose, reduction of dose. And you get that durability of response that we've seen in IMerge, including dose tactics. It's not like those were perfect patients, no one reduced the dose. It's part of life. That's kind of what we're saying is you can mimic IMerge and actively manage the patient.

What's the -- if you can share kind of impact on revenue at different dose levels? Does it scale like linearly? Or is it...

I mean it can. Obviously, the more folks use the RYTELO appropriately, that's kind of what we want them to do. But our guidance and our aspirations do take into consideration that some people will have to dose escalate -- de-escalate or withhold doses mimicking IMerge. We don't have a reason to believe that somehow every patient is going to get on therapy.

I mean, if that was the case with 8,000 patients, I mean that would be a very, very different number. So our guidance and all that takes into consideration how IMerge was. And what I'm also excited about our efforts for this year is in addition to the ISTs that have been launched is starting to have some of those real-world evidences start to report back where we're seeing a mimicking of IMerge in the real world.

That's a good thing because sometimes in oncology or hematology, you don't necessarily have this. And for me, that was a very important validation for us that if we are able to get our educational pieces going in the way we are, we're going to get more and more patients in the second-line setting, which will give a lot of those physicians the ability to say, "Oh, I can actually see those results but have read about in IMerge, and that would really have that positive reinforcement.

Sure. You mentioned earlier that you kind of took a fresh look at tiering of the physician market and how you would go to market with that population. I guess what can you share at this point about how you are tiering the prescribers? And what percentage of patients are seen by the doctors that you're now able to kind of both directly and then indirectly reach?

Yes. So one of the things of having the benefit of fresh eyes, especially with our Chief Commercial Officer and I would say also our medical affairs head is really taking -- stepping back and leveraging their experiences in having dealt with these patient populations and these physicians and really understanding where is the source of business going to come from, not where it is today, but ultimately, where is it's going to come from. And this is a 80% community-driven disease. It really is.

So in the beginning, it does happen where our proportion of our sales will be more from the academic medical centers. It's just -- they're the first ones to start off with. But we also want to make sure that ultimately, if we're doing our job right, 80% of that is going to come from the community. So community physicians with high volume loads are really our priority #1.

I mean, those happen to be also the toughest accounts to get into, because everybody is doing that. But that's where even some of the revamping we've done in our field force in terms of making sure that we really have the connections. I mean, in a biotech setting, it's very different than a big pharma setting. In a big pharma setting, you're kind of developing people over time. In biotech, at least in a company like us, we don't have that time. That luxury doesn't exist. Everybody coming in has to hit the ground running very rapidly. We almost have a joking way of saying, after 2 paychecks, you're no longer new. And we pay every 2 weeks. So...

1 month.

It really is. So it's a very different shift in terms of how a commercial company works. Very different than a development company where it's all about precision. Let it take however many years it will take. We really need to get the precise. And that's important because you're dealing with FDA, you're dealing with very important things. But that changes.

The company needs to kind of change with it. So that's where our targeting now is very much on -- our efforts are on the high-volume ones, but also we have now a lot of capital deployed into digital and non-personal, where we can reach the tail end of those folks, but not necessarily having the rep chase down every single person, but really making sure that they're getting their information from online from where they actually do get in or from the regional meetings.

And that's another area where we spent quite heavily versus our previous approaches is there are a lot of regional meetings. Some of them are announced, some of them are more lucky, where it's 50 hematologists, 60 hematologists, they get together over a weekend, really discussing certain topics.

So what we have said in the marketplace is whenever that's happening and there is an MDS topic, RYTELO should be on the agenda, being debated, and we should be part of that partnership conversation. So that's another area where there's been a redeployment of cash really taking away from some of the areas that helped us get here, but not necessarily -- especially in R&D, not necessarily in need for us to carry that forward because a lot of that search has already been done.

What are the metrics that you as the management team are tracking to ensure this strategy is working? And can you share anything around kind of how those metrics are tracking right now?

Yes. So internally, we have almost reset our entire way of how we track performance, how we track early indicators, not just lagging indicators like sales because those happen -- if everything else goes well, then in a few months, you'll get the sales, but really tracking some of the early indicators in terms of effort, precision of where we target, making sure where our bulk of investments are going rapidly. So we've been really revamping our eyes and ears from that side.

What we have shared publicly is other than our sales numbers, obviously, is the demand growth, that is a very important metric. We also have shared our number of new accounts that have ordered RYTELO for the first time because that's also another metric in terms of activation of new accounts, and that has been steadily going up 150 to 100 accounts every quarter. And also our source of business in terms of patient type.

So first line, second line versus the later line. So ideally, we would want to see demand growth. We would want to see the right patients in terms of first, second-line patients versus later line patients and getting more and more sites to actually use it for the first time. Even I would say our rewarding system internally has shifted -- in the first year, it's typical that you're rewarding any kind of performance. But now we're not in that stage. Now it's about what are we actually rewarding is second-line performance. And that's going to be very important in terms of what you kind of shift is what you usually get.

Right. You do anticipate clinical -- a clinical update later this year from myelofibrosis. I guess what are the range of potential outcomes out of that interim update? And how do you plan to share it or communicate it with investors?

Yes. So other than low-risk MDS, I mean, we're very excited to have completed a Phase III in terms of enrollment in another high unmet medical area of not just myelofibrosis overall, but relapsed and refractory to a JAK inhibitor, in this case, ruxolitinib. And that's a patient population that needs additional options.

So we were very interested to see the Phase II data. And that's where we started the Phase III. Now it's fully enrolled. Data is maturing as of last fall. We have said that interim analysis based on the projection of events because it is a primary endpoint is overall survival, is before end of this year. That's on the IA.

And then if we keep on going, the full maturity of the data would be in the second half of 2028. What we have all seen in our previous career is that most of the time, those trials typically take the full maturity time line to -- for the data to mature. But of course, we're going to be ready to do an interim analysis with the high-quality data. And usually, because we want to stay blinded to that, the DMC will take a look at it.

The DMC has been meeting on a regular basis for the last several years anyway. So the range of outcomes can be stopped for futility where that's not helping anybody or even with the minimal alpha that we're spending in the interim analysis, stopping for overwhelming efficacy, which would be the best case outcome. Most of the time, it will be where they tell the company, keep on going.

And our intent is that we communicate whatever they tell us accordingly with the marketplace. So this is a big deal. So we're very excited about it, but we, as a company, can continue our lower-risk journey as we let that data mature. And then once we get there, we look forward to helping more patients as well in the myelofibrosis period.

Maybe a quick question on funding, which is how are you thinking about funding to profitability at this point? And are there any adjustments that you anticipate making to your commercial infrastructure now that you're reviewing it, et cetera, and have had it in place for about a year?

Yes. We did that review very rapidly, Corinne, because that was one of the things which was very important. It was primarily driven by simplifying our organization. We had at one point like 6 layers of people reporting to each other for a tiny biotech with one drug, one indication. And that's not how companies can really thrive and go. So we really made sure that we declutter the organization and we did that very rapidly and really actually helped us move forward.

So from that side, it gave us the option -- not just the ability to move forward in terms of impact, but also extend our cash runway, which gives us optionality. So now that's one of the things which is very special, in my opinion, about Geron is, we have an asset that's growing. We have another Phase III that's maturing, and we have the cash runway to keep on going and to, at one point, rise up to our real aspiration of building a hematology company with the $400 million plus cash that we have and another $200 million plus coming in every year in a very simplified manner. So that's really something that we're very excited about.

Sounds like much to come. And with that, I think we're basically at time. So thank you guys both for joining us. Thanks, everyone, who joined us here as well.

Thank you very much.

Thank you.

Analyst working for Jason Zemansky. Welcome to the first day of the Annual Bank of America Vegas Healthcare Conference. We want to welcome Geron Corp. With me, I have -- sorry, I have Harout Semerjian, CEO; as well as Joe Eid, CMO. Welcome, guys.

Thank you very much, Jackie.

Great. So just to get us started, maybe to start broadly for those less familiar with Geron, can you give a quick overview of the story and your focus on blood cancers?

Sure, of course. And thank you for Bank of America for this invitation. Very happy to be here today sharing why we're excited at Geron as we progress with the company. So Geron is a company that has graduated to be a commercial stage company, really battling hematological diseases. We have launched our first asset, which is a telomerase inhibitor called imetelstat, RYTELO is the trade name, really trying to help more and more lower-risk MDS patients around the world. And now it's been about 18 months or so that we have launched, and we continue to grow and which is something we're really proud of.

So as a company, we are very excited to be growing and helping more and more patients in lower-risk MDS as the first indication, but also we do have another indication, hopefully, that would have a readout in myelofibrosis as an interim in the second half of this year. So we can -- I'm sure we're going to talk about that as well.

Absolutely. Yes, that's a great intro. So maybe just to talk about the RYTELO launch. So as the launch evolves, what leading indicators do you view as most important RYTELO is gaining durable traction? And what should investors focus on over the next several quarters as proof points?

Well, I mean, it's -- our story is really one of focused execution at this point. So the most important metric, obviously, is our net revenue, which is an indicator of how we are able to advance and help more and more patients. And we're very happy to report that in Q1, we have made $51.8 million of net revenue. It's our biggest quarter ever. So that's something that we're very pleased with. But of course, the job will continue, and that's one of the things that we're going to be doing. At the same time, we've been sharing multiple different milestones with the investor community in terms of how many accounts are ordering RYTELO for the first time since launch, and that number is now 1,450 accounts across the U.S., which is really good.

How much of our sales are coming from first-line, second-line patient population rather than the later-line patient population. That number has gone up to 33% as well in addition to our demand growth, which has grown 6% quarter-over-quarter and our revenue of 8% quarter-over-quarter as well. So these are all metrics that we continue to share with the market, and we plan to as well continue to share them over the next quarters to come that really would show our ability to get more and more patients to benefit from RYTELO in the low-risk MDS patient population.

Understood. And so you've been very clear that the second-line setting represents the core opportunity today. So how confident are you that RYTELO becomes foundational in this setting over time?

Look, we're very excited about RYTELO's opportunity in the second-line patient population in low-risk MDS. What we have communicated to the market is that in the U.S., there is more than 8,000 patients who can benefit from RYTELO. In the second-line patient population, we've refined our positioning so that all our messaging is focused on that second-line patient population. Our indication is in that second-line population. The NCCN guidelines support us in that second-line population. We also know that there are multiple more patients that can benefit from RYTELO in other lines of therapy, more advanced lines of therapy. But our focus is really in that second-line patient population, and we've been seeing growth quarter-over-quarter in that patient population. So we will continue to do our work from that side as a holistic company across commercial, medical and the idea is to grow that over time.

Sure. So part of this journey, cytopenias have come up quite a bit. And so you previously described them as predictable on target and potentially correlated with response. How are you driving this messaging and physician confidence?

Yes. Maybe that's a question. I'll turn to Joe. He's a hematologist. He's a trained hematologist and deals with these patients as well in the clinic, obviously, and he's our Chief Medical Officer. So Joe?

Yes. I mean, cytopenia for RYTELO is on target because we see a predictable pattern. Patients drop -- have a drop in their platelet and neutrophils in about 2 cycles on average. That's the majority of cases. And within 2 weeks after that drop, they recover in over 80% of the time. So this is what the IMerge data has shown. And we correlated and we presented the data at ASH that those patients that tend to have this level of cytopenia tend to have the most robust response overall. And the reason that, that happens is the drug does not work on the symptoms of the MDS being just improvement of anemia. It works on the disease itself. It's a mechanism of action that is directly correlating with that drop in counts and the recovery and eventually improvement in the symptoms and the anemia.

The message that we have presented at ASH, the data is what is continuing in '26, making sure that we're bridging that gap in awareness and bridging the gap of how to manage patients because it's critical that physicians who are very familiar with the hem/onc space in terms of treatment, adverse events, et cetera, including cytopenia, they manage those patients on RYTELO properly so that they adhere to the treatment. And all they have to do is follow the label, how to dose manage, how to reduce, give a patient a break, resume treatment without dropping the patients at that point, which is critical. And now that we are telling them the cytopenia is correlating with response, it's better to maintain patient on drug.

And there's an analog in MDS with lenalidomide, which has the same pattern. The difference is lenalidomide works in one specific group, which is the 5 deletion q group. Our drug has a broader spectrum beyond the 5 del q, and that's a good correlation between our drug and experience they have with lenalidomide. A lot of this messaging, Jackie, we've been pulling it through our engagement with the medical community as well. So it's not just about an ASH presentation. Now people know that the drug works in terms of durability of response, and that's a good thing. Now they also have a reason to believe of the why. Why is it important that you got to manage the cytopenias that are predictable. They happen in the first couple of cycles whenever they do happen. And what are you going to get in return in terms of efficacy for those patient populations.

Understood. So earlier today, you released a press release announcing you'll be presenting the first real-world evidence of RYTELO at EHA. What readouts should investors be focusing on?

Yes. Before I turn it to Joe, maybe just a kind of a framing around that. One of the areas that we've been heavily investing in over the last couple of years is really the real-world evidence and additional investigator-initiated trials. There has been a lot of interest from the medical community in terms of really seeing what else can we learn from RYTELO as we go with the launch. And that's been very good in terms of that engagement. And maybe today, Joe is in a situation where him and his team were able to get one of those very important trials as well move forward. So Joe?

Yes. A couple of things, Jacqueline. Our IMerge trial was mainly run in the European markets with very few sites in the U.S. So the hands-on experience was limited. The real-world evidence data that will be presented at ASCO and EHA is based at Moffitt Cancer Center and satellite setting. And that is reflecting on the real-world application versus what the IMerge trial, which is a controlled study. And what we have found in that study, which has 2 components, a retrospective component, which will be presented and then a prospective, which is accruing patients as it goes forward.

The data is actually replicating the data from the IMerge, which is very comforting and providing confidence that if you manage patients appropriately, first line, second line, third line and beyond, the data that is observed is on par with IMerge. In some cases, actually, it's better, in particular, when we see a well-managed patient do better. And that's the message that I would convey from that real-world evidence. It's, again, a replication of the data in the real world in the clinic as opposed to a controlled setting.

Understood. So you mentioned on your Q1 earnings call, you would communicate your EU commercial strategy for RYTELO in LR-MDS by the end of the year. Can you discuss what strategies you're considering?

Sure. So as you know, RYTELO is a fully owned asset for Geron, and we have rights around the world, which is a very good situation to be in. And we actually have the EMA approval. So from a regulatory perspective, ex U.S. is also derisked. And that's important to know. Sometimes we forget that part. Now how do we bring the therapy to patients more and more. And that's something which is on our mind. Obviously, 90% of our focus and our team's focus is on the U.S. and making sure that, that happens. But we also believe that we have a global aspiration and duty to help more and more patients. We are seeing many other companies not necessarily wanting to move forward given -- and we understand why. I mean it is a volatile world.

MFN is a real topic. It is something that everybody is thinking about as we progress. At the same time, we know that we have multiple different options. So as an example, partnership is always an option for us. A wholly-owned asset that we have full rights on an asset that's made $51.8 million in the last quarter and a company behind it that's saying it's $220 million to $240 million in terms of net revenue for this year. That's not too many of those assets are lying around. At the same time, we do know that what we don't want to do which is the old classical model in Europe, where you invest 50, 60 people in Germany or in France or other areas, those days are probably not the most beneficial in terms of cash allocation and resource allocation.

At the same time, one of the things that we have said in our Q1 call is we are also seeing additional types of companies emerge in Europe where we can potentially partner with, but in very restricted manners, where they can be our extension in certain areas, be it contract sales organizations and others where some of the things that are important for us in terms of the pricing as an example, we're very close to it, and we're guarding it very carefully. But at the same time, we can partner. So what we have said is we're in the middle of looking at all these different options, and we plan to come back to the market with an update on our EU strategy before end of year.

Great. So in these last couple of minutes, maybe we can shift to your pipeline, specifically IMpactMF. So what gives you conviction that imetelstat can translate into meaningful benefit into myelofibrosis, particularly in the relapsed/ refractory post-JAK inhibitor setting?

Great question...

Yes. I mean the first foray of imetelstat in the clinic in the heme space was in essential thrombocytosis, which is caused by malignant megakaryocytes. That's the precursor of a platelet. They tend to secrete fibrin, which causes fibrosis in the marrow. That study showed almost 100% complete remission with half of that group of patients having the myelofibrosis mutation in the JAK load. And that was the basis for the IMbark study, which was 109 patients randomized to a high dose of imetelstat versus low dose. And in that study, there was improvement in the symptoms, but more importantly, almost tripling of the survival, also indicators of disease modification parameters such as reduction in the VAF or mutation load as well as reversal of myelofibrosis in the marrow, symptom relief, cytokine reduction.

That was the ground to give the company confidence to go into registration stage, which is the IMpactMF trial. It's a 2:1 randomization with an overall survival endpoint, which is unique in this space. And this trial is comparing the high dose of imetelstat, RYTELO, which is higher, 8.9 milligram given more frequently every 3 weeks against best available therapy. So on that basis, we have confidence in the science, and we're hoping that this will read out to help patients.

Great. Well, it was great having you guys here. And yes, thanks for having you guys.

Thank you for the opportunity.

Thank you.

Hello, and welcome to Geron Corporation First Quarter 2026 Earnings Call. [Operator Instructions] Please be advised that today's conference is being recorded.

I would now like to turn the call over to Dawn Schottlandt, Senior Vice President, Investor Relations and Corporate Affairs. You may begin.

Good morning, everyone. Welcome to the Geron Corporation First Quarter 2026 Earnings Conference Call. 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 our 2026 financial guidance, our current RYTELO commercialization strategy and related opportunities in the U.S. and the EU, the therapeutic potential of RYTELO, other anticipated clinical and commercial events and related timelines, the sufficiency of our financial resources and other statements that are not historical facts, which, of course, involve risks and uncertainties that could cause actual events, performance and results to differ materially from those contained in these forward-looking statements.

Therefore, I refer you to the risks and uncertainties described in today's earnings release and under the heading Risk Factors in Geron's most recent periodic report filed with the SEC, which identify important risk factors that could cause actual results to differ materially from those contained in these forward-looking statements and future updates to Geron's risks and uncertainties disclosures, including its upcoming quarterly report on Form 10-Q. Geron undertakes no duty or obligation to update its forward-looking statements.

Joining me on today's call are several members of Geron's management team: Harout Semerjian, Chief Executive Officer; Ahmed ElNawawi, our Chief Commercial Officer; Dr. Joseph Eid, Executive Vice President of Research and Development and Chief Medical Officer; and Michelle Robertson, our Chief Financial Officer.

With that, I'll turn the call over to Harout to review Geron's progress and strategy.

Thank you, Dawn, and good morning, everyone. In the first quarter, we made progress on our 2026 strategic priorities. We grew RYTELO through focused commercial execution and advanced our European commercial and pricing strategy while maintaining our financial discipline. We also further strengthened our leadership team by welcoming Timothy Williams, our new Chief Legal Officer and Corporate Secretary for Geron, along with 2 new Board members, Patricia Andrews and Constantine Chinoporos. Collectively, they bring decades of experience leading and advising biopharmaceutical company and will be instrumental as we execute on our strategic priorities and drive commercial growth for RYTELO.

RYTELO first quarter net revenue was $51.8 million, an increase of 31% year-over-year and 8% quarter-over-quarter, placing us on track to achieve our 2026 net revenue guidance of $220 million to $240 million. We continue to see strong tailwinds in the treatment landscape complementing our refocused commercial strategy and driving RYTELO demand. We are focused on 3 key initiatives fueling our RYTELO U.S. growth strategy. On the commercial side, we're continuing to increase awareness and education for RYTELO amongst U.S. health care professionals with a refined engagement plan to help identify appropriate second-line patients faster, and complementing our field force efforts by increasing our in-person and digital presence across hematology forums through accelerated investment in our surround sound approach.

From a medical affairs perspective, we are expanding our research partnerships and investigator-sponsored trial programs with the U.S. hematology community to increase our knowledge and real-world experience with RYTELO. Growing RYTELO demand in the U.S. market remains our priority. And we know from patients at HCP, there is an unmet need for low-risk MDS treatment options in Europe and an interest in RYTELO to help address that need. This quarter, we engaged in conversations with European medical experts, made progress with health technology assessment and conducted detailed research to better understand the European pricing environment.

As a biotech company, we have an obligation to make our medicines available to patients, but we also have a responsibility to maintain a value that reflects our innovation and support our next wave of growth. We know the demand in Europe for RYTELO is real, and we are exploring an agent commercial strategy that could maximize RYTELO's value in Europe while maintaining its pricing integrity in the U.S. We expect to communicate our commercial plans for Europe before the end of the year once we have clarity on pricing and market opportunity.

Financial discipline remains another top priority for Geron. We reported total operating expenses for the first quarter of [ $50.4 million ], down about 9% year-over-year, a testament to our financial discipline. A few first quarter dynamics such as annual bonus, severance from last year's restructuring and CMC investments to strengthen our supply chain for RYTELO led to a decrease in cash, which was in line with our expectations. We are on track to achieve our 2026 total operating expenses of $230 million to $240 million.

With that, I'll turn it over to Nawawi to provide more detail on RYTELO's commercial performance and execution.

Thank you, Harout. RYTELO's first quarter performance was incredible. Our strategy is built to support sustainable growth and ensure RYTELO reaches more eligible patients at the right point in their treatment journey when they are most likely to benefit. In the first quarter, we were able to grow demand 6% quarter-over-quarter and approximately 12% increase in prescribing accounts, expanding our footprint since launch to approximately 1,450 accounts. First and second-line patient starts on a rolling 12-month basis was 33%. RYTELO has the potential to make the biggest impact for lower-risk MDS patients in the second-line setting, which we currently estimate to be approximately 8,000 patients in the U.S.

This patient segment is our primary commercial focus and our strategy is supported by the current NCCN guideline. The movement of luspatercept into the first-line setting, backed by RYTELO's broad label and growing real-world experience. And last but not least, the IMerge data, including the data presented at ASH 2025, suggesting treatment-emergent cytopenias are consistent with on-target activity. Our commercial execution is focused on 3 core initiatives.

First, targeted engagement with high-volume community accounts. We are prioritizing centers that treat earlier line and second-line patients with our field engagements. Additionally, we continue to engage with lower volume accounts for those privately seeking salvage patients through digital tactics. Second, we are investing in the most effective marketing channels. This includes a strong emphasis on digital non-personal promotion and third-party educational platforms to create what we describe as 3D surround sound for RYTELO, ensuring consistent, high-quality messaging across multiple touch points.

Third, we are executing cross-function through effective account management, leveraging data presented at ASH 2025 to proactively address the cytopenias and highlight the potential association with response while positioning RYTELO as the standard of care in appropriate second-line patients regardless of their RS. We believe our commercial strategy and investments are well aligned to bring RYTELO to eligible lower-risk MDS patients in the U.S. and position us to grow demand in 2026.

I now turn it over to Joe to discuss our Medicaid and scientific engagement.

Thanks, Nawawi. In the first quarter, we continue to engage closely with the hematology community to increase RYTELO's share of voice. Since the start of the year, we've had a presence at several medical meetings, including the Aplastic Anemia and MDS International Foundation, ASCO, and the 2026 Pan-Hematology Clinical Updates meeting. These are targeted peer-to-peer conferences that provide the opportunity for more detailed clinical dialogue and practical discussion among healthcare professionals. We are also looking forward to attending ASCO and EHA, where we will engage with hematologists to articulate the clear differentiation of imetelstat in low-risk MDS based on clinical efficacy, quality of life benefit and mechanism of action, generate advocacy within the KOL community and support investigator interest in research opportunities aligned with our medical strategy.

These medical meetings enable us to further educate the hematology community on RYTELO's deep body of scientific evidence. Our messaging continues to be focused on the ASH 2025 data suggesting treatment-emergent cytopenias are consistent with off-target activity. We are seeing increasing interest from community hematologists understanding these data and learning how to incorporate these insights into their clinical practice. We were pleased to further reinforce the significance of these data with our recent publication in Blood Cancer Journal that examined the association between treatment-emergent cytopenia and clinical responses to RYTELO.

We are also engaging with academic centers to support the high interest in imetelstat to advance ISTs and real-world evidence studies. Notably, we are seeing increased interest from centers in Europe wanting to contribute to preclinical, clinical and real-world evidence data generation. We expect initial real-world evidence data to be available in the second half of 2026. In addition, we are pleased to have achieved the inclusion of imetelstat in the National Comprehensive Cancer Network or NCCN, chemotherapy order template. This inclusion positions imetelstat as an active therapeutic versus supportive care for lower-risk MDS.

The order template provide healthcare practitioners with clear guidance on administration, enabling imetelstat to be seamlessly incorporated into oncology practice workflows and supporting standardized and appropriate administration across treatment centers. This follows the NCCN guideline update in September 2025, recommending imetelstat as the preferred second-line treatment option in lower-risk MDS.

Turning to our Phase III IMpactMF trial in relapsed/refractory myelofibrosis. The fully enrolled trial is projected at this time to reach the interim analysis death event triggered in the second half of this year. Imetelstat works on the foundation of the disease, which is why we believe it has the potential to be a first-in-class therapy in myelofibrosis. In myelofibrosis clinical trial conducted with imetelstat, we saw evidence of disease-modifying activity correlating with clinical benefit and overall survival through a reduction in mutation burden, specifically JAK2, CALR and MPL driver mutation. An improvement in bone marrow fibrosis and reduced telomerase activity, which is important as telomerase is significantly upregulated in cancers.

For our IMpactMF trial, overall survival is the primary endpoint, and our confidence in this endpoint is supported by encouraging survival outcomes observed in the Phase II EMBARK trial, which informed the design of the IMpactMF trial. While our base case from a planning perspective remains progression to the final analysis in the second half of 2028, reaching the interim analysis represents an important milestone as we continue to advance the potential beyond lower-risk MDS. An earlier positive outcome would represent an upside scenario to our plan.

I'll now hand it over to Michelle to walk through the financials.

Thank you, Joe, and good morning, everyone. For more detailed results from the first quarter, please refer to the press release we issued this morning, which is available on our website. Our first quarter 2026 results reflect our dedication to commercial execution and financial discipline which positions us well to achieve our 2026 financial guidance and advance our strategic priorities to create long-term value for patients and shareholders.

In the first quarter, total net revenue for the 3 months ended March 31, 2026, was $51.8 million compared to $39.6 million in Q1 2025. Gross to net reductions increased to 21% for the 3 months ended March 31, 2026, compared to 13% for the same period last year. As volume increased, there was wider 340B utilization and expanded GPO contracting, which we foresee continuing as the business matures. For the remainder of 2026, we expect gross to net to be in the low to mid-20s. Research and development expenses for the 3 months ended March 31, 2026, were $15 million, consistent with $15.1 million in expenses for the same period in 2025.

For 2026, we expect continued investment in CMC and our clinical development program and lower employee costs driven by the decrease in headcount as a result of the workforce reduction in December 2025. Selling, general and administrative expenses for the 3 months ended March 31, 2026, were $35.4 million compared to $40 million for the same period in 2025. This change was primarily due to lower general and administrative personnel-related expenses and decreased headcount, partially offset by additional investment in marketing programs. For 2026, we expect continued investment in our RYTELO commercialization strategy and lower G&A personnel-related expenses driven by a decrease in headcount as a result of the workforce reduction in 2025.

Total operating expenses excluding cost of goods sold for the 3 months ended March 31, 2026, were $50.4 million compared to $55.1 million for the same period in 2025. The reduction is primarily related to decreased headcount as a result of the workforce reduction in December 2025. As of March 31, 2026, we had approximately $341 million of cash, cash equivalents, restricted cash and marketable securities compared to $401 million as of December 31, 2025. As a reminder, in the first quarter, we typically see a larger cash outflow due to the timing of annual bonus payouts. In addition, severance related to the strategic restructuring we announced in December 2025 was paid out in cash in the first quarter.

The decrease in our cash also reflects CMC investments to strengthen our supply chain for RYTELO. We are reiterating our 2026 financial guidance. We expect RYTELO net revenue of $220 million to $240 million with a greater portion of growth anticipated in the back half of the year. Our total operating expense guidance of $230 million to $240 million reflects strong financial discipline and investment to support our commercial strategy. We are in a strong financial position and are on track to achieve our 2026 financial guidance as we execute on our strategic priorities to grow RYTELO while maintaining financial discipline.

With that, I'll turn the call back to Harout for closing remarks.

Thanks, Michelle. We continue to build a patient-focused performance-driven culture at Geron, marked by a high level of cross-functional collaboration. Last month, we hosted our first all company national meeting, which was a great opportunity to bring this energized group together and rally around the mission, values and goals that drive us. We have the right team in place to execute on our strategic priorities, bring RYTELO to eligible patients and achieve our 2026 financial guidance. For the remainder of 2026, we are focused on growing RYTELO in the U.S., pursuing pathways to bring RYTELO to patients outside the U.S., advancing our IMpactMF trial, remaining financially disciplined and evaluating opportunistic innovation as we build Geron into a leading hematology company.

Thank you again for your time and interest in Geron. Operator, we're now ready to start the Q&A session.

[Operator Instructions] Your first question comes from the line of Tara Bancroft of TD Cowen.

So I have a question on MF. So I know we've been hearing this theme that physicians are very data sensitive in terms of awareness. So I was wondering if you had any updated thoughts on how you'll communicate the MF interim analysis this year. Like would you consider giving any numbers in that release at all? And then with that, I'm also wondering if you think that the interim outcome could have any read-through to potential uptake of RYTELO in MDS.

[ IMpactMF trial ] as you know, is fully enrolled, and we do project that we will do our interim analysis in the back half of this year. So that's still on track. Typically these thing, Tara, you know, the DMC would meet and obviously, we're blinded and we continue to want to stay blinded, depending on the outcomes obviously. But the highest likelihood, at least from a planning perspective, we see is that they tell us keep on going. And if they tell us anything else, then all the material, obviously, that we would communicate to the market accordingly.

But Joe, do you want to add anything more?

Yes. Tara, I think your question is how do physicians react to it. The second is disease or indication where you do have a proof of concept and an overall survival impact. So it definitely will have an effect, a positive effect because our message at MDS is that this is a disease-modifying agent, and having this proof of concept in Phase III with overall survival from an MF would definitely enhance and augment that awareness and that value [indiscernible] hematology.

And our next question comes from the line of Gil Blum of Needham & Company.

Congrats on the progress. Just a quick one for us. As it relates to European markets, you guys said you may have conducted some market research. Just sounding -- listening to your messaging, it kind of sounds like you're considering moving forward on your own. Is this fair? Or is this still a question mark?

Gil, yes, in line with what we have said is we want to explore all options to bring RYTELO to patients in Europe. As you know, the European opportunity from a patient numbers perspective can be in line with U.S. opportunity. So it's quite significant from a patient numbers perspective. Of course, the second part of that is the pricing, which is a very key inflection point for us. That needs work, and that's kind of the work that we're doing.

If you think about options for a company like us, it's really 3 different areas. One is the classical built-up model. The second on the other end is a full partnership with another pharma. We are not doing the first to be clear. That's not where we're pursuing a very big classical buildup. That's really not for us. Partnerships are always an option. But also what we are seeing in the marketplace still is an emergence of new models and new partners in Europe that can complement what we're doing because there are a lot of companies, U.S.-based biotechs that are having to put their thinking cap on and see how they can serve European patients. Many of them are choosing not to do anything about it, which we think is unfortunate for patients and for the mission.

But at the same time, we want to make sure that we're doing a thoughtful work. So we're pursuing all these different opportunities, Gil. And before the end of the year, we will update the market in terms of where we land and what we think is the optimal way to bring RYTELO commercially to ex U.S. market.

And as a follow-up, will there be real-world data from imetelstat in low-risk MDS patients presented sometime this year?

Yes. Maybe I'll hand it over to Joe to address that question, it's a good question.

Yes. Gil, we have a slew of research -- investigator-sponsored research, including real-world data that will be presented at the upcoming meetings in the second half of this year as we have been saying. Some of it will include the real-world utilization in MDS and how it's playing out in the real world. And the early indication that we have mentioned in the past is that the data reflects the IMerge data from responses as well as [indiscernible].

And our next question comes from the line of Corinne Johnson of Goldman Sachs.

So I think you've talked about this one L2L share, and it's been pretty stable in the 30% range. Maybe you could talk to us about the tactics you're using to increase adoption in the earlier line population. And when you think we could start to see those educational efforts flowing through to changes in actual prescribing patterns in a more meaningful way?

Yes. I think if I heard you right, your question was about the first-line, second-line share of patients versus later. Okay, yes. So what we are communicating today, Corinne, is the share of our utilization in the first line, second line versus the later line is 33% this quarter with a 12-month look back. As you remember, last quarter, it was at 30% with a 12-month look back. So we continue to make progress in getting more and more of our patients in the first line, second line. And that's how we see our performance going forward is continuous progress, continuous growth quarter-over-quarter and that's the strategy we're pursuing, iterating our guidance for the top line between [ $220 million and $240 million ].

Our next question comes from the line of Emily Bodnar of H.C. Wainwright.

In terms of the 6% increase in demand in this quarter, what's your confidence in the sustainability of that for future quarters in 2026? And were there any seasonality impacts or other factors that you could specifically point to that helped increase demand in the first quarter?

Yes. Thank you, Emily. Yes, look, I mean, we're very pleased with where we are in Q1, where we have landed is in line with our expectations in terms of both top line growth, but also on the investment side. And our plan is to continue to grow quarter-over-quarter. That's the strategy we're pursuing regardless of seasonality, different things that will happen every year. We know that. But at the same time, we do expect a gradual and continuous growth quarter-over-quarter. This is one where we are communicating -- we have communicated that.

We have a guidance for the year in terms of the top line. And we have also communicated that we think that growth would be more accelerated in the second half of the year, purely by the fact that we have done significant surgeries in Q4 and Q1 and a lot of these programs do need time to kick into action. And we want to continue to fuel this growth quarter-over-quarter. It's not -- we don't see it as like a total transformation inflection point between one day to the other. This is a story for us of continued growth quarter-over-quarter. We do believe that the potential is tremendous in this low-risk MDS area, and we look forward to serving more patients and continuing to grow the business.

[Operator Instructions] And our next question comes from the line of Stephen Willey of Stifel.

Just curious about the data you're seeing on the treatment duration and persistency front. I know that you've been in the market now, I guess, messaging the correlation between cytopenias and clinical benefit. Has that driven any measurable improvement in patient persistency over the last 4 to 5 months? And I just have a follow-up.

Yes, what we see in real world is really quite close to what we've seen in IMerge data in terms of patients -- average duration of patients staying on therapy on RYTELO. What we are pursuing is more patients in the first line, second line, and that would obviously increase the persistency of patients on treatment, right? So this quarter, we're up to 33% versus last quarter with a 12-month look back at [ 34% ]. So we want to see that number continuously and gradually grow. But within the line, at this point, what we see is really in line with what IMerge has shown us in terms of average duration of patients on therapy.

Okay. And then I just guess with the business approaching breakeven and presumably some level of confidence into achieving profitability, at least on a non-GAAP basis before the end of this year. Just curious how active some of the peripheral BD efforts might be right now. And just whether or not there's a specific stage of development that you're looking for in an asset and whether you think there's both the appetite and bandwidth to potentially execute on a transaction before the end of this year?

Yes. Thanks, Steve. Look, I mean, ultimately, our main focus is on growing RYTELO, especially in the U.S. for the time being, exploring ways to bring RYTELO to ex U.S. patients as well. We continue to do that. We have a healthy cash position with even more disciplined from a financial perspective to ensure that we're executing per plan but doing it in a financial disciplined manner. And that provides us, Steve, with a lot of different optionality in terms of wanting to do deals, not having to do deals, staying opportunistic, looking at where else can we build our company in terms of our long-term aspiration of building hematology company that's consistent and sustainable.

So that's ultimately where we want to go. So we do have optionality, Steve. It's too early for us to comment on will we do a deal or not. We're always in the market looking for opportunities, but our very focused efforts are now on execution and making sure that RYTELO grows in line with our expectations and really by focusing on those 8,000 patients in U.S. in the second line, which we believe we can really help more and more of them as the quarters come.

I'm showing no further questions at this time. I'll now turn it back to Harout Semerjian for closing remarks.

Thank you very much, everyone, for joining our call today. We look forward to updating on our progress over the next quarters to come. Thank you very much. This concludes our call.

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

All right. Good morning, everyone. I'm Nicole Germino, one of the biopharma investment bankers here at Barclays. And today, we are joined by Harout Semerjian, President and CEO; and Joseph Eid, Executive Vice President of Research and Development and CMO of Geron.

Thank you both so much for being here today. So Harout, to kick us off, you have a robust experience in big pharma and biotech. What are the reasons that attracted you to Geron? Since joining the company in August of last year, what has the company done in 2026 to align Geron for success?

Yes. Thank you very much, Nicole, and thanks for Barclays for -- this is a very nice invitation and the opportunity to continue to share our Geron story.

Yes, you're right. I've been in pharma for more than 30 years between pharma, biotech and particularly in hematology/oncology for 20-plus years. And really what attracted me to Geron and what keeps me motivated 6 months in is a drug that works. First of all, imetelstat, a new option for lower-risk MDS patients and really one where we can actually make a difference for even more patients with a more robust and refined commercialization plan.

And that's what we've been doing over the last few months and really making sure that we are reaching more and more patients. In 2025, we did announce that overall in the year, we have in our first full commercial year, sold $184 million of sales, which is a very good starting point. But more importantly as well, we have given guidance that, that growth will continue and accelerate in 2026 with a top line guidance of $220 million to $240 million and doing it in a more cost-effective manner even from before, and that's where we have also given guidance on the operating expenses side of $230 million to $240 million, which is a significant drop as well from before as many of the major trials that we have are now fully enrolled, such as in MF and whatnot. So it's very exciting, and that's why I joined, and that's why I'm very excited about where we are.

Great. So Joe, for folks less familiar with the MDS market opportunity, can you walk us through the patient journey, the treatment paradigm and where RYTELO fills the gap?

Yes. I mean myelodysplastic syndrome is a spectrum of disease. You have the low risk, the high risk, which is closer to leukemia, acute myelogenous leukemia. Patients tend to present mainly with complaints of fatigue, and quality of life drop off. They get diagnosed when they have a CBC showing low hemoglobin. And then a bone marrow biopsy shows that the patients have mutations and diseased marrow.

Typically, they go on, on erythropoietin-stimulating agent, ESAs, PROCRIT, ARANESP or most recently, luspatercept, which has moved into the first line or if they have specific mutations, they have a deletion 5q, for example, lenalidomide is an option. Otherwise, those patients tend to be more and more transfusion dependent over time. And that's where those drugs don't work anymore, and they have to move on to other therapies.

HMAs were the mainstay after that first bolus of drugs. What happened over the last 18 months now, RYTELO was approved in the first line for ESA ineligible or unlikely to respond such as high EPO 500 and beyond or high transfusion burden and second line and beyond. The difference between all other drugs that existed with the exception, I would say, of lenalidomide, and I'll come back to that, and imetelstat is the fact that our drug works on the disease, not on the symptoms.

It's not just stimulating hemoglobin rise by the erythropoietin stimulation or the maturation, which is ESAs and [ EMA's ] role, our drug actually works on the clone itself that's causing the MDS. That leads to eradication of the clone, cleaning out of the marrow, creating space for the normal hematopoiesis to recover, and that's how our drug works. And that's why we see the best response and durable response to our drug as well as now with the landmark analysis beyond 40 months, we're seeing patients with overall survival, PFS and conversion to leukemia, all trending in favor of RYTELO arm.

Those patients, again, back to your journey, those patients eventually either evolve into leukemia or have comorbid conditions adding to it because of the low hemoglobin, transfusion dependence, iron overload as a result of that, developing allergies to the transfusions. They have very poor quality of life, and they tend to have shortened survival. So it's a cancer sometimes the misnomer of low risk makes it feel like it's a benign disease. It's not. It is a cancer and has to be viewed as such.

So when you look at the scripts over the past few quarters, are you capturing mostly late line? And what are your strategies to capture more patients in earlier line of therapy?

Yes. We've been updating the market actually on 3 major KPIs. One is the demand growth, obviously, when you're launching a new therapy, how much demand growth there is. And we're pleased to report 9% growth in the last quarter, which is Q4 2025. We also report on how many new accounts have bought RYTELO for the first time since launch, and that number is now in the 1,300 with the addition of another 150 accounts for the first time.

And then the third metric, which we also share is how much of our business is first line, second line versus later lines. And that number has been about 30% as reported in the last quarter with a 12-month look back. So we are pleased to see the uptake, obviously, in this disease area, but we also know that we have more work to do, and we have much more opportunities as well. And that's where we're very focused on making sure that we leverage the market dynamics where luspa is moving more into the front line, HMAs are moving more later lines and that second-line opportunity is becoming much clearer for us. And over time, hopefully, we move more and more patients and report on that KPI.

Okay. And as you mentioned earlier, you posted fourth quarter results with $48 million in sales and then $184 million for full year 2025. And then you've guided to 2026 revenue guidance of $220 million to $240 million, which is -- which implies about 20% to 30% year-on-year growth with sales weighted towards the back half of the year. What gives you confidence in your 2026 financial guidance? And what are going to be the drivers behind the growth for back half?

Yes. No, we really believe in RYTELO. First, it's -- as I said, it's a drug that works in a patient population that's very desolate, as Joe really kind of highlighted the patient journey that goes not only from a very significant impact on the quality of life, but also from a survival perspective. So we believe we can help much, much more patients. So we're very excited about where the market is going by itself with that openness of the second-line patient population.

Unfortunately, it's not like we're curing patients in the first-line setting. All those patients will transfer into a second-line need at one point, and we will be there to really help them. But also from our side, our refined strategy in terms of really focusing on that second-line patient population, simplifying our messaging given that 80% of the patient population actually is seen in the community.

And that's where really understanding the intricacies between what we need to engage with academic medical centers with in terms of research, additional engagements and how do we really become effective in the community setting in terms of simplifying the message, identifying who the patient is and how can we help that patient move forward.

A lot of these really gives us confidence that we are on the right track, that we're growing, we're expanding our base and we can help more patients. And that's why even in the beginning of January, first day of JPMorgan, we gave the guidance for 2026. And we want to wake up every day with this refined team that we've done deliberate choices in the last quarter of 2025 to really simplify our own organization to be even more impactful so that we can move together and deliver on what our commitments are.

Great. So with the favorable FDA label and your positioning in the NCCN guidelines, what are the levers to drive further growth? Is it going to be focusing on the community setting or laying the groundwork post REBLOZYL? How are you thinking about this?

Yes, it's actually all of the above in many ways. So we are pleased, obviously, that those patients have more and more options in the first line with luspatercept moving there in the last 18, 24 months. But we also are very keenly aware that those patients, unfortunately, will move on to a second-line setting. So we do want to make sure that in the community, how RYTELO is used is very important.

And maybe Joe can comment on what have we shared data at ASH on this particular area, but also from the academic medical centers, really making sure that we are leveraging our collective knowledge of decades of knowing these hematologists across our careers and really making sure that we're really having the dialogues needed for RYTELO growth, not just for the patients of today, but also exploring additional opportunities. But maybe you want to comment as well.

Yes. I mean as the first-in-class telomerase inhibitor, RYTELO mainly enrolled patients out of -- in Europe and very low hands-on experience in the U.S. So that created a little bit of unknown to the community in the U.S. And what was also very apparent of the profile of the drug is that it causes cytopenia. So a new class of drug, not understanding why patients have cytopenia and how to manage was what we wanted to bridge.

And over the last, I would say, a year plus now, we've now informed physicians of the mechanism of action and that the cytopenia is on target, which leads to patients actually being responders. So what we presented at ASH was data linking the cytopenia, which is predictable, resolvable and manageable without any clinical significance when compared to placebo to patients actually responding, and those are the robust responders. So it is almost like a clinical biomarker.

And that obviously gives confidence to physicians. Now coupled with that data, we also showed the long-term benefit, which I mentioned earlier, that also gives the safety long term, not just the short term, which again builds on that confidence.

Okay. So it sounds like the cytopenias are not a reason for pushback to not start...

Hematologists are used to managing cytopenia day in and out. Most of their patients actually have some sort of cytopenia, not knowing what it is and how to manage it was mainly the gap, I would say. That's been now not just informed, but also, as I said, providing confidence that that's actually a good thing if we see.

Okay. Harout, can you talk about the ex U.S. total addressable market for RYTELO? And how are you thinking through the ex U.S. commercial plans?

Sure. Yes. We do have RYTELO rights across the world, which is also quite good to see for a company of our size. And we actually have $400 million of cash as well. So it's also good to have the fuel to do things as you want. One of the things which over the last many, many years, we've learned is really making sure that we understand any market we want to get into, especially with an evolving landscape, right?

So at one point, I still remember when Europe used to be as big as the U.S. from a value perspective, and that number start changing over the years to 60-40, 70-30. And in some cases, as we look at other assets in the marketplace, such as luspa, for example, where I think they're selling about $2.5 billion, $2 billion of that is in the U.S. and about $0.5 billion is ex U.S. So there are still many patients.

And from a patient number perspective, is as big as the U.S. So in the U.S., we say about 8,000 patients in the second-line setting, and there isn't any reason why that shouldn't be the case in Europe. Of course, we want to make sure that we are helping more and more patients. And the guiding glide for us is that RYTELO needs to be everywhere helping patients. We don't necessarily ourselves need to be everywhere in every country, but we can definitely keep our optionality open.

So what we're doing currently is working and engaging with the HTAs, the health technology assessment processes around Europe because we do have an EMA approval, which is very good. But as you know, in Europe, it's -- that tells you that it's safe and effective. Somebody still needs to pay for it and at what price and at what comparison; so we're doing that work anyway regardless of if it's us who's going to market it or if we partner with somebody else. All these options are all on the table.

We want to be very deliberate about it. We are not in a hurry to really get some cash injections. We have that. What we are in a hurry for is patients and making sure that we're helping more and more patients. So over time, that would say, but that work is ongoing. And these are no regret moves because regardless of whoever is going to do it, and I've worked and lived for 10 years in Europe and launched multiple drugs and some more successful than others. So we learned and there's a lot of battle scars. So we really want to make sure that we understand that market before we actually go and pick.

Great. And so beyond focusing on the commercial execution for RYTELO this year, you also have a Phase III IMpactMF trial in relapsed/refractory MF with interim data in the second half of this year. Can you remind us about the trial design, the interim readout and what you're looking for as good data?

Yes. So this is a Phase III trial built on the back of a Phase II randomized trial looking at a high dose and low dose, 9.5 milligram per kilogram given every 3 weeks. So it's a higher dose and more frequent than the MDS treatment. That IMpact trial showed an advantage in survival as well as symptom relief. So the Phase III is designed to have a 2:1 randomization to imetelstat versus best available therapy in the relapsed/refractory myelofibrosis population, meaning that they have been exposed to JAK inhibitors and either did not tolerate or failed with an endpoint of overall survival as primary endpoint and secondary endpoint of symptom relief.

That trial has an interim analysis, as you mentioned, projected to fall sometime in the second half of this year. It's driven by death events. And depending on where that trajectory takes us, obviously, that interim analysis will be triggered.

It's a very interesting one because, I mean, I've been involved in myelofibrosis for many years, but starting from ruxolitinib ex U.S. And these are areas where the size of the market has grown over time beyond people's expectation and certainly my expectation. So to have a new mechanism of action in a disease area that's been JAK after JAK, that's very exciting.

Doing a large randomized trial with 300-plus patients across multiple countries, that's exciting. Having an overall survival that can really make a difference, that's very exciting. Obviously, the downside of that is these are trials that take much longer.

But that's kind of behind us where it's been already enrolled and now we're waiting. So be it the interim analysis, which what we're seeing is that we think that from a planning perspective, these trials usually take the full time to mature, and we'll be ready for it. That's one of the reasons of having a good balance sheet from a cash perspective is we're not dependent on these. It's nowhere in the stock anyway. So it's very exciting, and it would be an all on upside, but we have to wait for the data.

Okay. I mean having said that, why did you pick OS as the primary endpoint given the fact that it does take a long time? What's the benefit of it?

Yes. The IMpact trial, which was the Phase II trial was designed with the JAK inhibitor endpoint and OS as a secondary endpoint. And in that trial, we saw an improvement of survival between the high dose and the low dose, which is almost like a placebo control, almost tripling the benefit in overall survival. We also confirmed that with a historical matched cohort, which confirmed again the value of that high dose given every 3 weeks. So that confidence in the data gave us the benefit to design this trial with the OS endpoint.

Maybe, Joe, could you also address the MOA of RYTELO in MF and how it's differentiated from the other drugs?

Yes. I can go back to the first trial in hematological malignancies that was done in essential thrombocytosis. MF is 1 of 5 diseases under the umbrella of myeloproliferative disorders, essential thrombocytosis, polycythemia vera, myelofibrosis, CML and CMMoL. They all have some commonalities in terms of what's triggering their disease. In ET, for example, the essential thrombocytosis, the foundation of the disease is the malignant megakaryocytes, the malignant progenitors of platelets.

And those platelets secrete fibrin, okay? The first trial of RYTELO, imetelstat, at the time, it was in 9 patients with ET, 9 out of 9 patients responded. Biologically, those patients, the majority of them, 8 of them had the JAK2 V617F mutation. Now why is this important? Because that's the same mutation that you see in the myelofibrosis. So that gave impetus to having a myelofibrosis trial. That was the IMpact trial.

And in that trial, as I mentioned, we had that overall survival. But the megakaryocytes are a specific target, especially those mutated one. Once you clean those megakaryocytes, the fibrin starts clearing out of the marrow. And in that myelofibrosis IMpact trial, we saw fibrosis resolution. No JAK inhibitor does that. And then you have normal hematopoiesis recover, which leads to the secondary hematopoietic organs, which are the liver and the spleen.

Normally, those are the main hematopoietic organs in an embryo. As we grow in age, the bone marrow becomes the main and those organs stop producing hematopoietic cells. So that reversal takes time. And that's why in the IMpact study, we saw evidence of the OS and evidence on the symptom relief. It just it was taken longer than the typical 24 weeks that you see with JAKs. So that's the evolution that we saw with that IMpact trial that gave us confidence. But again, it's a drug that works on the foundation of the disease, and that's what we also see in the MDS. Our drug works on the mutated cancerous cells.

And it sounds like you're also improving the quality of life effectively?

Yes, because it does increase the cytokines and improves the symptoms. And overall, once you have normal hematopoiesis, your organs obviously shrink and you're back to normal.

Okay. I guess lastly, Harout, can you talk about how there's this disconnect between how the market thinks about the opportunity for RYTELO and what's in the stock?

Yes. Obviously, I mean, I'll leave it to you guys to comment on the stock itself. But what we're getting excited about is we have a first indication in lower-risk MDS. In our first full commercial year, we just posted a net sales of $184 million. So why is that important? Because it kind of puts a very clear baseline in terms of what's the potential of the drug starting up.

And we all agree that if a lot of things are done differently as well in terms of really engaging with that U.S. hematologists upfront as big pharma does that number could have been even higher. So that's where we're very excited about the -- giving guidance for 2026. In the beginning, we used to say about growth, then double-digit growth. Now we're actually showing what that is between 20% and 30%, so that's our baseline.

Then we have $400 million plus in the bank, which actually gives us a lot of optionality of not necessarily pursuing certain deals that doesn't make sense for us. We have an asset that is fully around the world is within our control, which is really great. And then we have now a fully enrolled myelofibrosis trial that has taken years to enroll and tens of millions of dollars, but now that's all behind us.

And if the data is anything close to what we think and what we hope it is, that's a transformational area and another disease area that is as big as MDS. So there's a lot of excitement from that side, Nicole. At the same time, we're very keen on that performance and execution is really the first clear step, and that's why we're very focused on doing that. This year, we've given guidance of how that would look like, what do we think the shape of the curve would look like. And we've been very transparent about that. And now it's all about execution and as we have our second indications and beyond mature.

Great. Well, thank you so much, Harout and Joe, for giving us an overview of Geron. And with that, we'll go over to the next panel.

Thank you very much.

Thank you.

Thank You.

Hello, and welcome to the Geron Corporation Fourth Quarter 2025 Earnings Call. [Operator Instructions]. Please be advised that today's conference is being recorded. I would now like to turn the call over to Dawn Schottlandt, Senior Vice President, Investor Relations and Corporate Affairs. You may begin.

Good morning, everyone. Welcome to the Geron Corporation Fourth Quarter 2025 Earnings Conference Call. 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 our 2026 financial guidance, the expected benefits and other impacts of our strategic restructuring plan, our current RYTELO commercialization strategy and related opportunities, the therapeutic potential of RYTELO, other anticipated clinical and commercial events and related time lines, the sufficiency of our financial resources, our ability to access additional debt financing and other statements that are not historical facts, which, of course, include risks and uncertainties that cause actual events, performance and results to differ materially from those contained in these forward-looking statements.

Therefore, I refer you to the risks and uncertainties described in today's earnings release under the heading Risk Factors in Geron's most recent periodic report filed with the SEC, which identify important factors that could cause actual results to differ materially from those contained in these forward-looking statements and future updates to Geron's risks and uncertainties, including in its upcoming annual report on Form 10-K. Geron undertakes no duty or obligation to update its forward-looking statements.

Joining me on today's call are several members of Geron's management team. Harout Samerjian, Chief Executive Officer; Ahmed ElNawawi, our Chief Commercial Officer; Dr. Joseph Eid, Executive Vice President of Research and Development and Chief Medical Officer; and Michelle Robertson, our Chief Financial Officer. With that, I'll turn the call over to Harout to review Geron's progress and strategy.

Thank you, Dawn, and good morning, everyone. The strategic alignment work we completed in 2025 positions Geron for growth in 2026 and places us on a path to becoming the hematology powerhouse in the long term.

In 2025, we made deliberate choices to evolve the company into a more commercially minded organization. We strengthened our leadership team, developed a more focused commercial strategy and improved financial discipline by aligning our financial resources and people to our growth priorities. RYTELO's growth strategy is built on 3 initiatives, 2 commercially driven and 1 medical affairs.

From a commercial side, we are continuing to increase awareness and education for RYTELO amongst U.S. health care professionals with a refined engagement plan to help identify appropriate second-line patients faster and complementing our field force efforts by increasing our in-person and digital presence in hematology forums through accelerated investment in our surround sound approach. From a medical affairs perspective, we are expanding our research partnerships and IST programs with the U.S. hematology community to grow our knowledge and real-world experience with RYTELO. Nawawi and Joe will discuss these initiatives in more detail.

As for our Q4 2025 and full year results, RYTELO's fourth quarter net revenue was $48 million, in line with our expectations. For the full year 2025, we delivered RYTELO net revenue of $184 million, a meaningful number for hematology drug in its first full commercial year. Total operating expenses for the full year 2025 were approximately $265 million, in line with our previous guidance of $250 million to $260 million.

Looking ahead, we're laser-focused on operational execution and delivering for patients. Our RYTELO net revenue expectations for 2026 is $220 million to $240 million, with the underlying assumption of driving consistent RYTELO quarter-over-quarter demand growth. Our 2026 total operating expenses are projected to be between $230 million and $240 million, a roughly $20 million year-over-year reduction at the midpoint. This guidance reflects a streamlined company aligned to create near- and long-term growth and value.

The market opportunity for RYTELO is clear, and it is validated by the IMerge data, RYTELO's FDA label and the NCCN guidelines. We are confident in our RYTELO revenue growth strategy and our ability to execute it.

With that, I'll turn it over to Nawawi to provide more details on RYTELO's commercial performance and execution.

Thank you, Harout. RYTELO's performance in 2025 establishes a solid base for us to execute our commercial strategy and further grow demand in 2026. In the fourth quarter, we achieved 9% demand growth for RYTELO compared to the third quarter, a 13% increase in prescribing accounts, expanding our footprint to approximately 1,300 accounts. First and second-line patient starts on a rolling 12-month basis was 30%.

Based on our analysis, we believe market conditions for RYTELO in second-line lower-risk MDS are favorable. The movement of luspatercept into the first-line setting has further clarified the second-line opportunity for RYTELO in appropriate patients, which is well positioned based on the IMerge data, NCCN guidelines, our label and the growing real-world experience. Our commercial strategy is designed to ensure that RYTELO reaches more eligible patients at the right point in their treatment journey and when they are most likely to benefit from RYTELO.

Our commercial execution is focused on 3 core initiatives. First, targeted engagement with high-volume community accounts. We are prioritizing centers that treat earlier line and second-line patients with our field force engagements as we continue to engage with lower volume accounts or those primarily treating salvage patients through digital tactics.

Second, we are increasingly investing in the most effective marketing channels. This includes a strong emphasis on digital, nonpersonal promotion and third-party educational platforms to create what we describe as a 3D surround sound for RYTELO, ensuring consistent, high-quality messaging across multiple touch points.

And third, we are executing cross-functionally through effective account management, leveraging data presented at ASH 2025 to proactively address the cytopenias and highlighting the potential association with response while positioning RYTELO as the standard of care in appropriate second-line patients regardless of their RS status. In terms of patient opportunity, our primary commercial focus in 2026 is on eligible second-line lower-risk MDS patients, which we currently estimate to be approximately 8,000 patients in the U.S.

RYTELO's broad label supports treatment of earlier and later lines of therapy, but second line is where we believe RYTELO has the potential to make the biggest impact on patients' lives. For us, this patient segment aligns with RYTELO's therapeutic profile and NCCN guidelines and represents a meaningful market opportunity for RYTELO. We believe our commercial investments are well aligned to drive impact. and we remain disciplined in deploying resources where we believe they can generate the greatest return. I now turn it over to Joe to discuss our medical and scientific engagement.

Thank you, Nawawi. Our medical and scientific efforts in 2025 played a critical role in increasing RYTELO''s share of voice within the hematology community, and we plan to continue to engage closely with the community throughout 2026. Educational activities at meetings such as SOHO and ASH translated into increased awareness with more health care providers sharing positive feedback as they gain experience treating appropriate patients and observing meaningful clinical benefit. This growing confidence is reinforcing RYTELO's role in the treatment landscape. IMerge is a data-rich trial with analysis beyond the primary endpoint continuing to inform the field.

Data presented at ASH 2025 highlighted insights suggesting treatment-emergent cytopenias are consistent with on-target activity, helping to deepen understanding of treatment effect, inform clinical practice and further strengthen engagement across the hematology community. We also expanded our engagement with academic centers to support the high interest in imetelstat to initiate more ISTs, and we are also seeing increased interest in community centers wanting to contribute to preclinical, clinical and real-world evidence data generation.

We have aligned to support over 10 ISTs and real-world evidence spanning mechanistic studies, combination and sequencing, early line use and new settings. We are seeing increasing interest from both academic and community centers to participate in evidence generation, and we expect initial real-world evidence data to be available in the second half of 2026.

In addition to large scientific congresses, as we move into 2026, we are placing increased emphasis on smaller peer-to-peer medical meetings such as the Aplastic Anemia & MDS International Foundation, FLASCO meetings and other similar forms. These settings allow for more detailed clinical dialogue and practical discussion among health care professionals, which we believe is particularly important for a therapy like RYTELO as physicians and other health care providers refine patient selection and treatment sequencing.

Our presence at these meetings supports more meaningful education, facilitate experience sharing among peers and further amplifies RYTELO's visibility and credibility in the hematology community. We view this targeted engagement as a valuable complement to larger meetings and an important driver of sustained awareness and adoption. Finally, our fully enrolled IMpactMF trial in relapsed/refractory myelofibrosis is projected at this time to reach the interim analysis death event trigger in the second half of this year.

Overall survival is the primary endpoint, and our confidence in this endpoint is supported by encouraging survival outcomes observed in the Phase II EMBARK trial, which informed the design of the IMpactMF trial. While our base case from a planning perspective remains progression to the final analysis in second half of 2028, reaching the interim analysis represents an important milestone as we continue to advance imetelstat's potential beyond lower-risk MDS. An earlier positive outcome would represent an upside scenario without planning.

I'll now hand it over to Michelle to walk through the financials.

Thank you, Joe, and good morning, everyone. For more detailed results from the fourth quarter and full year, please refer to the press release we issued this morning, which is available on our website. Q4 and full year 2025 reflect both the progress we made with RYTELO and the financial discipline we exercised to manage operating expenses and provide the flexibility to make the best investments that have the potential to drive near- and long-term value. In the fourth quarter, total net revenue for the 3 months ended December 31, 2025, was $48 million compared to $47 million in Q4 of 2024.

For the full year 2025, total net revenue was $184 million compared to $76 million for the full year 2024, reflecting a full year of RYTELO commercial availability. Gross to net deductions increased to 17.7% for the 12 months ending December 31, 2025, compared to 14.5% for the same period last year.

As volume increased, there was wider 340B utilization and expanded GPO contracting, which we foresee going forward as the business matures. For 2026, we expect gross to net to be in the high teens to low 20s. Research and development expenses for the 3 and 12 months ended December 31, 2025, were $16 million and $74 million, respectively, compared to $23 million and $104 million for the same period in 2024.

The year-over-year change was due to lower clinical trial costs and manufacturing expenses as we began to capitalize inventory after the approval of RYTELO. We expect our research and development expenses to decrease slightly in 2026, primarily due to lower labor costs driven by a decrease in headcount as a result of the workforce reduction in December 2025, partially offset by higher clinical trial costs related to our potential ISTs.

Selling, general and administrative expenses for the 3 and 12 months ended December 31, 2025, were $42 million and $159 million compared to $43 million and $146 million for the same period in 2024. The full year 2025 increase was primarily due to an increase in sales and marketing full-time employees and additional investment in marketing programs. We expect our selling, general and administrative expenses to decrease in 2026, primarily due to lower G&A labor costs driven by a decrease in headcount as a result of the workforce reduction in December 2025, partially offset by higher marketing costs due to continued investment in our RYTELO commercialization strategy.

Total operating expenses for the full year 2025 were $255 million, in line with our previous guidance of $250 million to $260 million. The strategic restructuring announced in December 2025 has been completed, and we accounted for substantially all the expenses associated with the reorganization in Q4 2025. As of December 31, 2025, we had approximately $400 million in cash, cash equivalents, restricted cash and marketable securities compared to $503 million as of December 31, 2024.

Our balance sheet remains strong and was further strengthened with the recent amendment to our Pharmakon loan agreement, extending potential access to an additional $125 million in capital through July 30, 2026. Also, as a matter of corporate housekeeping, we plan to file a new shelf registration and ATM with our 10-K on February 27. The strategic actions we took in the back half of 2025 position Geron for a year of growth in 2026.

We are reiterating our 2026 financial guidance. We expect RYTELO net revenue of $220 million to $240 million with a greater portion of growth anticipated in the back half of the year. Our total operating expense guidance of $230 million to $240 million reflects strong financial discipline and investment to support our commercial strategy. With that, I'll turn the call back to Harout for closing remarks.

Thank you, Michelle. Building on a year of strategic alignment across the organization and energized engagement with the hematology community, we enter 2026 with a clear opportunity in second-line lower-risk MDS, a commercial strategy designed to reach the right patients at the right time, a European approval that gives us the ability to engage ex U.S. and a strong balance sheet that gives us flexibility to opportunistically innovate.

Our priorities for 2026 are clear: drive U.S. commercial growth, pursue pathways to bring RYTELO to patients outside the U.S. and remain financially disciplined to evaluate opportunistic innovation as we build Geron into a leading sustainable hematology company. Thank you again for your time and interest in Geron.

Operator, we're now ready to start the Q&A session.

Our first question comes from Tara Bancroft with TD Cowen.

So I know you've emphasized growth inflection that you expect in the second half of the year to meet guidance. So I'm curious if you can go into more specifics on the commercial or physician behavioral milestones that we should specifically watch for in the first half of the year to gain confidence that, that inflection is on track? And also in that, I'd be curious to hear which of these factors most underscore your confidence in guidance.

Thank you, Tara. It's Harout here. Thanks for the question. Yes, great point. I mean, obviously, as we enter 2026, we are very focused on our executional plans. A lot of the difficult decisions and realignments we had to take in the back half of last year are all behind us, and we're starting the year with a very energized team going forward.

I would say the Q4 demand growth of 9% is an important metric for us because it is forward-looking, and that's something we always look at. From what we see, obviously, we're not going to comment on Q1, but we -- what we have seen from IQVIA and others is in line with our expectation. That's why we're reiterating guidance of growth of a top line between $220 million and $240 million.

Now you guys can see that versus the $184 million that we have delivered in 2025. That is a meaningful growth, and we're very excited about that. We are seeing certain green shoots. But at this point, let's leave it at that. The team is super focused on execution with this refined messaging, with the refined targeting on high-volume accounts really making sure that we're more focused on not just scientifically super accurate messaging, but really ones that are impactful and can make the second-line opportunity more of a reality. So that's kind of where our focus area if that helps.

[ id="-1" name="Operator" />

Our next question comes from Gil Blum with Needham & Company.

So you kind of mentioned a focus on the second line here. Do you guys have any insight as to how many second-line patients you currently have? What is the proportion to the third-line patients? Is there any information you can share there or at least qualitatively?

Yes. Well, what we have shared is a few things actually that can help with your question. One is that we've shared that we have about 8,000 patients in the second-line setting that we are targeting. Obviously, lower-risk MDS in totality is a much bigger number, but our focus is on that second-line patients who move from a frontline and more and more luspatercept and then they move into second line.

Unfortunately, as you know, those patients are not getting cured. They are going to be moving into a second line. And then with the recent update on the NCCN guidelines with RYTELO becoming a preferred second-line agent ahead of HMAs, which kind of pushes HMAs into later lines. So that really opens the opportunity for the second-line patient population. So that's really important for us.

So almost 8,000 patients where -- that we believe can really benefit from RYTELO in the second-line setting. We have also shared in this call, Gil, that now that we have mature 12 months data in terms of patient split, around 1/3 of our patients are coming from first, second line. So multiple data points over there that also indicate to our focus, why we're focused on these, where we stand from a first line, second line versus later lines.

Obviously, there's always going to be later line patients. But what we're saying is our focus is really strictly on the second line where we're putting all our efforts, energy and funding over there. So that's really the secret sauce for our growth strategy going forward.

Thank you. very helpful. And maybe another question. So you mentioned 9% demand growth and about 15% increase in prescribing accounts in the fourth quarter. What do you think the cadence is to see that translate into the revenue side?

Yes. I mean, obviously, these are -- they go hand-in-hand with different timings. You have gross to net. We have catch-ups, true-ups that we have to do from that perspective, just like what we did in Q4. So demand growth is really for us the key in terms of getting more and more patients to grow, getting more accounts who have not ordered before to start ordering, which is another 150 accounts we have added in Q4. And those things are really important that they continue.

So with the refined strategy of really focusing on the high-volume community accounts in addition to the academic medical centers, that we always had that focus on. But really, this would be one on the community side, and that's where a lot of our focus is going to be. And we believe that would drive consistent growth in terms of demand. And that's our focus is consistent growth over -- quarter-over-quarter as we progress in 2026.

[ id="-1" name="Operator" />

Our next question comes from Emily Bodnar with H.C. Wainwright.

Maybe one on the ordering accounts. So obviously, you've been increasing the cadence pretty consistently quarter-over-quarter. I'm kind of curious how many accounts do you think there potentially could be at peak? I guess, how many are there in total for these approximately 8,000 second-line patients? And then maybe on the expense side, your guidance kind of estimates potential for you to break even later this year. Is that something that you're kind of reaching for? And maybe just discuss profitability in general.

Sorry, Emily, can you repeat the second question? I was having a hard time in hearing it probably from our side.

No problem. Just on the expense side with your guidance for revenue and expenses, it looks like you could potentially break even in the second half of the year. So maybe just comment about your thoughts on profitability.

Got it. Michelle, maybe you want to take the second half of the question, and I'll take the first one.

Sure. Yes. Thanks, Emily. Yes, we definitely see a path to profitability, but that is not our focus in 2026. I mean we reduced our operating expenses in the fourth quarter. We reduced our operating guidance for 2026. But remember, we also want to invest heavily in the commercial strategy as well as additional investments in ISTs. So we do see a path to profitability, but for 2026, with our strong balance sheet, we're really focusing on making the right investments to have the biggest impact short term and long term.

Yes. Thanks, Michelle, for that. And for your first question, Emily, there is tremendous ways to go. I'll put it like that. It's -- if you look at those 8,000 patients who are clearly in the second-line bull's eye of our focus area within the lower-risk MDS, Don't forget that this is a community disease more than academic medical center disease. So typically, it's about 20% in the AFCs and 80% in the community.

So we really want to make sure that we're making inroads in the community, and that's where a lot of the patients are, and that's where a lot of our focus is, especially in the high-volume accounts. So part of what Nawawi and his team has done recently is really retool our marketing mix so that we complement what the field is doing with what we call our 3D surround sound efforts so that we can reach more folks deeper with the high volume, but also broader through digital and nonpersonal effects so that we can get the best of the worlds in a cost-effective and meaningful manner.

[ id="-1" name="Operator" />

Our next question comes from Corinne Johnson with Goldman Sachs.

You mentioned that you have approximately 30% of patients in the first and second-line setting that are currently on therapy. Could you help us think through what that needs to be in order to reach your guidance for the year? And then you also mentioned, I think, a 13% increase in prescribers quarter-over-quarter. But could you speak to any patterns with respect to converting like a new prescriber to repeat prescriber and what you're seeing there with respect to depth metrics?

Sure. Thank you, Corinne. Yes. I mean our guidance is -- the underpinning of that is we need more centers who use it for the first time, but we also need more repeat customers, especially in the high-volume accounts. Both of them are important. So the fact that we are adding on a quarterly basis 150 accounts is a good thing in our opinion because that kind of deals with the breadth.

And of course, our focused efforts and really being even more supportive of the high-volume accounts that talks to the depth of a prescriber. So we actually need both. It's not one or the other. Both of them are important, but that's where the efforts from our side might be slightly different, and they are customized to the customers' needs. So we're focused on both, Corinne.

[ id="-1" name="Operator" />

Our next question comes from Stephen Willey with Stifel.

I was curious to what extent you're seeing EVO as a second-line competitor. I know there's a lot of discussion around being placed ahead of the HMAs. But do you have any insight as to the proportion of patients who are failing frontline luspatercept and then getting treated with an ESN? And then I just have a follow-up.

Yes. Thanks, Steve. Maybe, Joe, you want to shed some light on the question is if something else is used in the front line, what's the role of EVO that we're seeing in second line?

I mean, with the move of REBLOZYL to the first line, we're seeing a shift in the treatment paradigm where it was a sequence of ESAs and luspa in the past. Now we're seeing luspa becoming more dominant in the first line. And as far as the biology goes, ESAs do not work as well post luspa. And that's where, at least from a physician perspective, what we are hearing from the KOLs is that they move in their treatment plans from a luspa to imetelstat as a second-line preferred drug, not ESAs.

Yes. And that's a very important shift in the market, Steve, as far as we're concerned because not only are we focusing on the patients that we can help the most, but the market shifts are, in our opinion, also in our advantage because it's no longer about just competing with luspa on the same patient. It's really about making sure that folks get the right treatment in the front line.

And more and more, we're seeing luspa move up. But of course, if you're losing that in the front line, you're not going to use the same thing again in the second line. And to Joe's point, EMAs after -- ESAs after EMAs, the data is not that great, at least the ones that we've seen. And now with HMAs moving further out with the recent NCCN guidelines, that really opens the door for that second-line patient population.

And that's why we have streamlined our messages, made it even simpler where we're saying it's regardless of our status and really making sure that we're focused on those patients because we do believe that between the FDA approval, between the NCCN guidelines are really very helpful for those patients that we're focusing on.

That's helpful. And then just curious if there's anything you can say about what the plans for the European approval might be here going forward. I know there's obviously a lot of discussion around MFN pricing. Just curious if you've crystallized that ex U.S. strategy at all.

Yes, great question. Thank you. Well, so we do have a European approval, right? So that's one thing which is actually derisked, which is a great thing. But of course, European approval without funding is a much more limited positive outside.

So we really need to make sure we understand the HTA piece. And now more and more in addition to that is the MFN impact, obviously. So it does mean we got to be more careful about and more thoughtful about how we're moving forward. One thing that hasn't changed, Steve, is at the end of the day, it's really about the number of patients that we can help and at what price for innovation can we have a case to negotiate with the large countries such as Germany, France and others.

Our focus currently is on making sure that we are making inroads on understanding and really synthesizing the HTA processes and the HTA ability to command a premium that we believe RYTELO deserves and making sure that we have that crystallized and in parallel, having conversations with like-minded partners where we assess between us doing some of that work, which, as you know, more and more is getting pressured for U.S. biotechs, but also it's important that we engage with partners who actually see the opportunity the way we see it and not just be afraid of the paying for innovation part with the larger payers. So that work is ongoing, Steve.

Those things actually take months. Unfortunately, these are not short cycles, but they are very important ones regardless of whoever is going to commercialize the asset, you need a good HTA understanding in terms of how we can really help the RYTELO dossier overall. So that work is ongoing, and that's why we're saying we're going to be opportunistic about Europe and really making sure that meanwhile, we're super focused on our U.S. focus and growth over here as we have those conversations.

[ id="-1" name="Operator" />

That concludes today's question-and-answer session. I'd like to turn the call back to Harout Semerjian for closing remarks.

Thank you, everyone, for joining our call. We look forward to updating you on the progress over the next several quarters. So thank you very much for joining our call today.

[ id="-1" name="Operator" />

Ladies and gentlemen, this concludes today's call. Thank you all for joining. You may now disconnect.

Hello, and welcome to the Geron Corporation Third Quarter 2025 Earnings Call.

[Operator Instructions]

I would now like to turn the call over to Dawn Schottlandt, Senior Vice President, Investor Relations and Corporate Affairs. You may begin. 

Good morning, everyone. Welcome to the Geron Corporation Third Quarter 2025 Earnings Conference Call.

Before we begin, please note that during the course of this presentation and question-and-answer session, we will be making forward-looking statements regarding future events, performance, plans, expectations, and other projections.

Including those relating to the launch, commercial opportunity, and therapeutic potential of VYTELLO, anticipated clinical and commercial events, and related timelines.

The sufficiency of Geron's financial resources 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 results to differ materially from those contained in the forward-looking statements and our future updates to those risk factors.

Geron undertakes no duty or obligation to update our forward-looking statements. 

Joining me on today's call are several members of Geron's management team: Harout Semerjian, Chief Executive Officer; Michelle Robertson, Chief Financial Officer; and Dr. Joseph Eid, Executive Vice President of Research and Development and Chief Medical Officer.

Ahmed ElNawawi, our Chief Commercial Officer, will be introducing himself at the beginning of Q&A. 

Before handing the call over to Harout Semerjian, I'd like to say I'm truly energized to join Geron. This is a company that can change the lives of patients with blood cancers.

The work ahead of us is real, but in my 3 weeks here, my confidence in our ability to deliver has grown every day. With that, I'll turn the call over to Harout. 

Thank you, Dawn, and good morning, everyone. I'm very excited to be hosting my first earnings call as CEO of Geron.

On this call, we will provide a commercial overview, an update on medical affairs and our pipeline, and end with an overview of our financials. Three months ago, I joined Geron because I saw a company with real promise, a differentiated product that is effective, and it addresses a high unmet need in lower-risk MDS. 

Over these past months, I've been deeply impressed by the strength and dedication of our organization. The culture here is patient-focused and resilient, giving me conviction that with improved alignment, we can build an execution-oriented organization that brings the promise of RYTELO to more lower-risk MDS patients. 

Let me share 4 reasons that support our belief. First, RYTELO is a compelling drug. It has demonstrated meaningful efficacy in lower-risk MDS, and it is differentiated in its mechanism of action and clinical profile. 

Second, lower-risk MDS is an area of high unmet need with few, if any, potential treatments being studied in the clinic that can provide the differentiation that RYTELO can as a telomerase inhibitor.

There is a clear opportunity for RYTELO to be an important therapeutic option in lower-risk MDS. 

Third, there is an opportunity to accelerate growth with the right strategy and improved execution. And fourth, the company is well capitalized. We have a strong cash position, which we believe is sufficient to support the robust commercial and medical affairs engagement needed to increase RYTELO utilization. 

Now, let me provide you with an overview of our Q3 commercial performance. Net product revenue was $47.2 million for the third quarter.

During the quarter, demand for RYTELO was down 3% compared to last quarter. New patient starts in the first and second line increased to 36% compared to 30% in Q2. 

However, new patient starts did not offset the discontinuations we saw from patients using RYTELO in later lines. It is clear we have work to do on establishing RYTELO as a second-line therapy in eligible patients with low-risk MDS and educating HCPs on treatment management.

Prescribing accounts increased by 15% in the quarter, with approximately 150 new ordering accounts added in Q3, expanding our footprint to 1,150 accounts. 

Lastly, we completed the first shipment of RYTELO to Germany under a named patient early access program. We're preparing for the planned commercialization of RYTELO in select EU markets in 2026.

Q3 was an important quarter for us as we took stock of what we need to do to ensure RYTELO reaches more patients. 

We're assessing both internally across people, processes, messaging, and overall effectiveness, and externally with our customers to amplify partnerships and ensure the appropriate usage of RYTELO.

We recently announced the addition of Ahmed ElNawawi as our new Chief Commercial Officer. 

ElNawawi is an experienced commercial leader with an established track record of launching multiple global oncology products and leading commercial teams in both biotech and pharma.

He brings a wealth of expertise to Geron to execute a strong commercial strategy to support RYTELO's growth. 

With the recently announced additions to the executive leadership team, along with existing team members, we can realign to accelerate momentum and grow RYTELO. I'm confident we can realize the full value of RYTELO and build a bright future for Geron. 

We believe Geron and RYTELO can be transformational in the lower-risk MDS space with improved execution. We have already identified 4 initial actions to step up our execution and support future revenue growth. 

First, we need to substantially increase awareness for RYTELO among U.S. HCPs through a comprehensive, well-coordinated account plan. Our market research is clearly telling us that education is key to increasing usage in the appropriate patients.

This is especially critical when an HCP prescribes RYTELO to the first few patients.

Our field-based commercial and medical colleagues have sharpened their approach to customer engagement aimed at educating HCPs on how to use RYTELO, identifying the appropriate patients to start therapy, expanding reach into the community, sites improving conversions and retention, and effectively managing patients on therapy.

We believe, over time, this push to increase awareness for RYTELO will grow our U.S. prescriber base and drive sales in the U.S.

Second, we need to significantly and consistently increase our in-person and digital presence in hematology forums. We are just starting to do this through expanded relationships with U.S. KOLs and increased engagement with key patient advocacy groups.

A good example of this would be Geron's efforts at this year's Society of Hematologic Oncology Conference in September in Houston.

At the conclusion of this conference, we noticed a surge in engagement from physicians who participated in our multiple advisory boards and other engagement activities, with a positive change in Geron's external perception.

We received anecdotal feedback that more physicians are beginning to shift their thinking on RYTELO, not just as a third or fourth line option, but as a therapy worth considering earlier.

That shift won't happen overnight. But as we continue these efforts throughout 2026, we expect to see an impact on RYTELO utilization.

Lastly, we're excited to expand our IST program with U.S. clinical sites and HCPs to address additional key medical questions about potential uses of imetelstat and the benefits of telomerase inhibition.

The IMerge trial predominantly enrolled sites in Europe. We have work to do to collaborate with U.S. HCPs and give them opportunities for additional research with imetelstat.

These initial initiatives are just the beginning as we expect to identify additional opportunities to improve execution in the near term. It is important to recognize that the pull-through of the improved execution to revenue growth will take time.

As for the additional utility of RYTELO, we recently completed enrollment in our IMpactTMF Phase III clinical trial evaluating imetelstat in relapsed/refractory myelofibrosis.

We currently project the interim analysis to occur in the second half of 2026, with the final analysis projected in the second half of 2028.

Our base case is for the trial to run to the final analysis, as is the case for the majority of trials with overall survival as the primary endpoint. Should we see an opportunity to help patients with data from the interim analysis, we will be ready to explore the next steps rapidly.

Success in myelofibrosis could double our addressable patient population.

Finally, before handing it over to Joe, I want to reiterate my optimism in Geron's future.

Our priorities are clear. We are working to maximize the impact of RYTELO for patients today while advancing our first-in-class telomerase inhibitor to benefit more people tomorrow.

With that, I'll now hand the call to Joe to review clinical and medical affairs progress.

Thank you, Harout. On today's call, I will highlight our upcoming presence at ASH, medical affairs actions we have taken to improve RYTELO execution, including events at SOHO and investigator-sponsored research.

And then I'll provide an update on our Phase III clinical trial in relapsed/refractory myelofibrosis.

First, we had 5 abstracts accepted for ASH. The data feature a new clinical and translational analysis of imetelstat across lower-risk myelodysplastic syndrome and myelofibrosis.

Two abstracts, including an oral presentation, will feature new analyses from the Phase III IMerge trial.

The oral presentation offers insight into how early cytopenias observed with imetelstat are on target pharmacological effects and may be associated with treatment response, offering valuable context for interpreting treatment patterns and managing patient outcomes.

This data will help us educate HCPs to better understand, anticipate, and manage these effects, helping to ensure patients are appropriately maintained on therapy.

The other IMerge abstract highlights a 42-month landmark analysis of long-term outcomes from the trial. While the analysis was not prespecified, the totality of the data and the results of the landmark analysis suggest a favorable trend for imetelstat in overall survival, progression-free survival, and time to progression to AML compared to placebo.

Both abstracts highlight the value of the unique mechanism of action of RYTELO in lower-risk MDS disease and its management.

There will also be 3 additional posters, including data from the EMbark and IMproveMF trials in MF and the investigator-sponsored trial, IMpress, in high-risk MDS and AML. We plan to continue our medical engagement at ASH.

We are planning an advocacy forum that is designed to bring together patient advocacy organizations and professional societies to raise awareness and provide education on lower-risk MDS and the use of RYTELO as a treatment option. This is the first event of this nature hosted by Geron.

In addition, we are planning to engage with an increasing number of hematologists at ASH, both in one-on-one and group settings. These engagements help us convey new data to physicians as well as collect insights that can help refine our strategy.

Our presence at ASH will build upon the primary medical affairs efforts taken this quarter that focus on 4 strategic initiatives: community site penetration, initiation of ISTs, awareness and education ramp-up, and KOL and advocacy alignment.

We strongly recognize that in order for RYTELO to be successful, we need to be successful in the community setting, where approximately 80% of lower-risk MDS patients are treated.

Last quarter, we described how we are focusing on increasing HCP awareness of RYTELO, particularly in the community setting, as well as academic

centers that were not part of the Phase III pivotal trial. 

Our team has been actively engaged with these sites directly at an important medical meeting. The expansion of our medical affairs field team has allowed us to refine our targeting model, better prioritize mid-disile physicians, and improve awareness among community sites.

We continue to intensify our messaging via webinars and peer-to-peer educational efforts. 

In our most recent awareness trial utilization tracking, we observed positive shifts in physician understanding of RYTELO's efficacy in terms of robust and durable hemoglobin response and appreciation of cytopenias being on target based on RYTELO's unique mechanism of action. 

In parallel, we continue to support several investigator-sponsored trials exploring imetelstat in diverse hematological settings, including combination regimens and earlier line use, as well as real-world evidence.

We expect that these independent studies will help build external validation and broaden the clinical and real-world evidence base for imetelstat. We observed high interest in investigating imetelstat in preclinical, clinical, and real-world evidence settings.

We received a good number of proposals, and we decided to fund a number of these proposals that we expect to commence generating data in 2026. 

We are also actively engaging with KOLs and advocacy groups to broaden the reach of RYTELO's data narrative. Our goal is to help key opinion leaders become ambassadors, reinforcing that RYTELO can be considered alongside existing therapies in earlier lines rather than a drug of last resort.

These efforts are starting to yield early results. Post-engagement surveys suggest that physicians who initially expressed reservations about cytopenia now report a better understanding of the mechanism of action, dose adjustment strategies, and monitoring protocols. 

Our data confirmed that physicians who have used RYTELO in practice view its profile more favorably than those who have not. As many of you know, the Annual Society of Hematologic Oncology meeting was a major touch point this quarter.

Our team presented real-world case studies, translational biomarker data, and longer-term follow-up from earlier treated patients. The reception was constructive.

Among key opinion leaders, we are seeing a growing perspective that RYTELO deserves a position as the #2 option for eligible patients with lower-risk MDS after standard CSA therapy, especially in certain high-risk subpopulations. 

This is supported by the recently updated NCCN guidelines that now recommend RYTELO as a treatment for use in low-risk MDS patients with serum EPO over 500 ahead of HMAs.

A central theme during the SOHO meeting was how RYTELO's use fits with luspatercept. We made the case that RYTELO and luspatercept can be complementary rather than mutually exclusive, i.e., that RYTELO does not need to displace luspatercept, which can be used sequentially or in stratified patient segments based on its approved label and NCCN guidelines. 

This narrative struck a chord, and we believe it could help ease some of the challenges in physicians' minds. 

On the clinical front, I am pleased to report that our IMpactMF trial is now fully enrolled with 320 patients from 26 countries. This is a Phase III trial in relapsed/refractory myelofibrosis and is the first MF clinical trial with overall survival as the primary endpoint.

We expect to have an interim analysis in the second half of 2026 and the final analysis in the second half of 2028, subject, of course, to achieving the specified number of death events. 

With a high bar set for the interim analysis, we are planning for the trial to conclude at its final analysis. This is typical for a trial with the primary endpoint of OS. 

To close, our medical affairs and R&D teams remain fully aligned with our commercial team. Our combined efforts are focused on evidence generation, physician engagement, and data dissemination to support broader adoption of RYTELO in lower-risk MDS.

I'll now turn the call over to Michelle to go over our Q3 financials. 

Thank you, Joe, and good morning, everyone. For more detailed results from the third quarter, please refer to the press release we issued this morning, which is available on our website.

As of September 30, 2025, we had approximately $420 million in cash and marketable securities compared to $503 million as of December 31, 2024.

Total net revenue for the 3 months ended September 30, 2025, was $47 million compared to $28 million in Q3 of 2024. Gross to net increased from Q2 to Q3 due to increases in the Medicaid mix rate, fees from new GPO contracts, and returns from several customers where their supply of RYTELO had reached its expiration date. 

As of September 30, 2025, ending inventory at distributors was on the high end of our range of 2 to 4 weeks. Research and development expenses for the 3 months ended September 30, 2025, were $21 million compared to $20 million for the same period in 2024.

The change was primarily due to increased CMC and personnel-related expenses. Selling, general, and administrative expenses for the 3 months ended September 30, 2025, were $39 million compared to $36 million in Q3 last year. 

The change was due to an increase in sales and marketing headcount and additional investments in marketing programs. For fiscal year 2025, we expect our total operating expenses to be between $250 million and $260 million, below our previously announced guidance of $270 million to $285 million.

We continue to focus on efficiencies and prudently manage our spend while continuing to prioritize investments in our RYTELO commercialization strategy, commercial supply redundancies, and post-marketing commitments, as well as preparations to launch RYTELO in selected EU countries in 2026. 

Overall, with our current cash and marketable securities and anticipated net revenues from expected U.S. sales of RYTELO, we believe that Geron remains in a strong financial position to fund projected operating expenses for the foreseeable future.

I'll now turn the call back to Harout for closing remarks. 

Thank you, Michelle. In closing, I want to reinforce 3 key takeaways from this call. Number one, shifting physician behavior and building a brand in hematology takes time. 

The urgency across our organization is understood, and we're fully committed to the patients who are depending on us. Number two, improving alignment and generating momentum, is our focus.

And lastly, RYTELO is a drug that works. With the right execution, we believe it can be positioned for long-term success. We appreciate your support.

Before we begin our Q&A, I'd like to hand it over to Nawawi, our new CCO, to say a few words introducing himself. Nawawi?

Thank you, Harout. Let me start by saying thank you for the opportunity to be part of that Geron team.

I am halfway through my third week, and what I have seen through my one-on-ones and team meetings with the entire commercial organization is that we are deeply committed to patients.

We have a drug, RYTELLO, that has the potential to address an unmet need in low-risk MDS patients. With improved alignment and our focus on driving operational excellence, I am confident we can grow revenue by delivering RYTELO to eligible patients.

Thank you, Nawawi. Operator, we're ready for Q&A.

[Operator Instructions]

Your first question comes from Tara Bancroft with TD Cowen.

So I have one very quick one and then a real one. So the first one is just being, if you can perhaps, Michelle, give us a little bit more insight into the current gross to net that you mentioned increased this quarter.

Wondering if the previous mid-teens range still applies or if we should amend that. And then, so demand being down 3% this quarter, it's nearly flat. But I'm curious to hear more about what drove that.

I know you stated that discontinuities in later lines are a big factor, but I'm curious to hear if there were other headwinds that you can speak of this quarter that you observed, like reluctance to reorder or seasonality, but basically, looking for any outlook on those for Q4 that may perhaps be reversing?

Tara, thanks. Yes. So I believe that the mid- to high teens are still applicable for the forecast.

What we did 1 year in, it's reasonable to review your launch assumptions, check the channel mix. And in our case, we had an increase in the Medicaid channel mix.

So we've increased our reserves for those rebates. And going forward, that will kind of moderate itself. We did have some returns. So we also looked at our rate of returns and trued that up and adjusted that and increased that moderately.

And then we did expand our GPO contract business. So we had some additional fees this quarter, and we'll see those going forward also. But we still feel confident that we'll be in the mid- to high teens going forward.

Tara, thanks for the questions. Yes, I mean, you'll see basically what we're doing a lot.

There's a lot of resetting and making sure that we have a strong base going forward. Regarding your question about the demand side, I mean, it is at 3%. That's the accurate number. I agree with you. It's flattish, given that our base number of patients where we are, a few patients can make a difference one way or the other.

So keeping that in mind, what we're seeing is that we are getting new patients, but the discontinuation of patients who existed or who came in on the brand, they're really later-line patients. And unfortunately, those patients are much more beaten up, and they don't stay on therapy for very long.

So what we really want to make sure that we are doing is we're getting the right patients upfront in the early setting, and that's going to happen by really driving the education, the brand awareness and the additional actions we're taking beyond just sending in a rep, that's where we believe that by doing the surround sound, that can drive the right patients to start on therapy.

And that's where we're saying we have work to do on that part, so that's the focus area that we have.

The next question comes from Stephen Willey with Stifel.

I guess you talked about the growth in ordering accounts, I think, 15% sequentially.

Do we know anything about just the breadth of prescribing at this point and how many of those ordering accounts have either already written the script and/or are new to the brand? And I just have a follow-up.

Yes. Steve, thanks for the question. Yes, I mean we're pleased to see the continuous increase in the number of new accounts coming on board.

So another 150 accounts have ordered RYTELO in this quarter versus last quarter. So that puts us this year to more than 500 new accounts ordering RYTELO versus last year.

So the breadth of folks getting on board, we're pleased with that. I think the work we have is making sure the depth is there and the right patients are the ones who are being put, namely, earlier lines of patients.

So repeat business was about 80% of accounts that have reordered in the last quarter. So we're pleased with that. So I think that's not our bigger challenge where we want to focus on is getting the breadth of patients, especially having the first patients, especially in the community, to really have a right start, we call it.

So basically, get the right patient on, know how to manage effectively the first few patients, especially in the community setting. And that we believe will lead to a depth of prescription, which can really be helpful for patients.

So that's some of our focus areas.

The breadth of accounts is actually going in the right direction in terms of additional accounts over time, coming on board with RYTELO.

And then, do you have any idea what the average duration of therapy looks like at this point? I know you're talking about use primarily occurring in these later-line patients.

I know the label calls for 6 cycles, I guess, at a minimum. I'm just curious what you're seeing, if anything, on the duration of therapy side.

Yes. Thank you, Steve. What we have said is that in the real world, we're seeing that the therapy duration is in line with IMerge in a similar patient population.

So, keeping in mind that in IMerge, there were predominantly more second-line patients. And in the real world, there are more third, fourth, and fifth-line patients. That's where the difference is happening.

So that's where we want to make sure that we continue to encourage physicians to use RYTELO in earlier lines of therapy to really mimic what we're seeing in IMerge and beyond because currently, it's apples to oranges and IMerge is most second line and in real world, it's more third, fourth line, which is shorter than that 8 months that we've seen in IMerge.

The next question comes from Corinne Johnson with Goldman Sachs.

This is Anubham on behalf of Corinne. Can you talk about the revised operating expense guidance for the year? Where are you finding the savings or the efficiencies in the budget?

And what should we expect with respect to the OpEx cadence for the next year?

Yes. Thanks. So I mean, we're not giving guidance just yet for the 2026 full-year spend. But for 2025, in the past, I have mentioned that we have levers to pull, particularly around some of our CMC investment.

And we've also slowed down just some of the infrastructure, organizational infrastructure investments related to IT systems, and we were able to pull in our full year OpEx this year to the $250 million to $260 million. So we feel pretty confident in those numbers.

The next question comes from Emily Bodnar with H.C. Wainwright.

I had one on your sales force. I believe a few quarters ago, you mentioned that you would have the sales force fully hired by the third quarter.

So I'm curious if that's been completed. And also any commentary you can give on what metrics you're using to evaluate the sales force, and their impact on demand generation? And also, if you can give an update on your EU partner search, if that's still ongoing.

Thank you, Emily. Good question. So yes, we have reported last quarter that we have hired our field force. And I would say our customer engagement folks, because it was beyond just the commercial people; we also doubled our MSLs in the field.

So both have been done in the last quarter.

The training has happened over the summertime. And now we do have an effective customer engagement folks, both on the commercial side and also on the medical side.

Where the focus has now been is not just on the number of bodies that we have, but on the effectiveness of all the customer-facing folks, and then with the head office people, to really be effective, to be outcomes-focused rather than activity-focused.

So there is quite a bit of work happening in the background on the operational excellence type, and that's where I'm very excited with Nawawi coming on board and together with the rest of the ELT, that we really drive the appropriate uptake of RYTELO in the right patients.

So that's regarding the sales force and the execution piece.

Regarding the EU, we remain excited. I mean, we do have an approval in the EU, which really sets us apart, and we're very excited about that. We want to make sure that we're good stewards of our investments.

That's where the focus at this point of our own internal efforts are on the U.S., obviously, for 2 reasons: the U.S. being the largest market, but also the fact that IMerge has had much more robust uses in Europe rather than in the U.S.

So from our own efforts, we're focusing on the U.S., but then also making sure that we're having the dialogue with appropriate potential partners in Europe and beyond. The whole idea is that RYTELO, we believe, needs to be everywhere, helping patients across the world.

We don't need to be everywhere as a Geron ourselves.

So those conversations are happening as we speak. But we want to make sure that it's the right people, it's the right timing. We are always having the patient in mind.

So we're pleased to start seeing that we have our first named patient sales happening in Germany, but we will make sure that it's really the appropriate setup whatever we come up with, especially now that we have half of the ALT is new and there's a reset that we're doing internally and ensuring that we have the appropriate conversations given how much collective partnership opportunities we have across the world.

So stay tuned on that. That's ongoing, and we will update the market as we have new updates.

[Operator Instructions]

Your next question comes from Faisal Khurshid with Leerink Partners.

Just wanted to ask if you could characterize your level of confidence that you figured out what the issues are and that you truly believe that awareness is the main lever to pull here.

And then also, if you have any updated views on the timeline to see a return to growth here based on your efforts and expanded field force?

Yes. Thank you, Faisal. I mean, look, we will not be here if we don't have confidence. I mean, we have very high confidence.

I personally have high confidence, and every leader who is here has high confidence, be it newly joined or folks who've been here and who really believe in RYTELO.

So confidence is definitely there. It's a prerequisite, but that's not enough, Faisal. Positive thinking is not where we're going. We really are focused on the execution of key areas such as brand awareness.

I mean, that's one of the prerequisites, in my opinion, at least, that we want to make sure that more and more hematologists, when asked, do you know RYTELO in lower-risk MDS.

The answer is yes. We want to make sure that physicians know how to use it, be it in academic centers or be it in the community.

That's why we're really increasing our search on the ISTs because having hands-on experience with a drug like RYTELO by our U.S. hematologists is an important aspect of what we do.

At the same time, on the community level, we want to make sure that our community physicians who are dealing with all kinds of different hematology and oncology situations and lower-risk MDS might not be the largest pool of patients they have, but they are able to effectively select the right patients and put them on the right therapy, manage the first couple of cycles of the adverse events so that they can get to the efficacy that we've seen in IMerge and others.

So from a confidence perspective, Faisal, we definitely have the confidence. But beyond the confidence, we do believe we have the right identification of the diagnosis and some of the key programs that are now in place, and we look forward to continuing to update the market on that.

At the same time, we are saying that these things do take time. I mean, it just is. And there is nothing wrong with that. It does take time. So we want to be also very open in terms of these are not light switch moments.

We have the cash, we have the people, we have the plans, and we look forward to updating you as we start expanding our demand.

And then, do you have a timeline that you're willing to kind of guide the Street? I don't know when we should expect growth.

No, we're saying at this point, this is a 2026 growth story, Faisal. And we are not giving any guidance at this point on our top line, but we look forward to that being something that we plan to tackle in the near future. So we're assessing at this point.

But we think now we've put our heads down, get to work. And in 2026, this is a growth story over there. But we're not giving any specific guidelines in terms of is it's going to start growing on March 31 or April 15. That's not what we're saying.

But we are very confident about the trajectory. And as you're seeing, I mean, this has been a very important quarter to really level set many of the things that we need to do to ensure that we're doing the right things and then over time, growing the demand appropriately.

This concludes the question-and-answer session and will conclude today's conference call. We thank you all for joining. You may now disconnect.

Hello, and thank you for standing by. My name is Tiffany, and I will be your conference operator today. At this time, I would like to welcome everyone to the Geron Q2 2025 Earnings Call. [Operator Instructions] I would now like to turn the call over to David Borah, Head of Investor Relations. David, please go ahead.

Good morning, everyone. Welcome to Geron Corporation's Second Quarter 2025 Earnings Conference Call. Before we begin, please note that during the course of this presentation and question-and-answer session, we will be making forward-looking statements regarding future events, performance, plans, expectations and other projections, including those relating to the launch, commercial opportunity, therapeutic potential of RYTELO, anticipated clinical and commercial events and related time lines, the sufficiency of Geron's financial resources 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 results to differ materially from those contained in the forward-looking statements and our future updates to those risk factors. Geron undertakes no duty or obligation to update our forward-looking statements. With that, I'll turn the call over to Dawn Bir, Interim President and Chief Executive Officer.

Thank you, Dave, and good morning to everyone on the call. I'll begin on Slide 4. Earlier today, the company issued a press release announcing the appointment of Geron's new President and CEO, Harout Semerjian. He has joined today's call and will provide brief comments before we open the call for Q&A. I'm also joined by several members of our management team: Michelle Robertson, our Chief Financial Officer; Jim Ziegler, our Chief Commercial Officer; and Dr. Joseph Eid, our Executive Vice President of Research and Development.

Our top priority remains the successful commercialization of RYTELO in the United States. We are executing with precision across our enhanced and aligned commercial and medical affairs strategies established this past quarter. We see that they're beginning to translate into measurable results and believe that we have implemented the right strategies that will drive continued commercial success.

Q2 RYTELO net revenues were $49 million, representing an increase of approximately 24% over the first quarter. This was driven in part by increased demand from new patient starts. At the end of Q2, our inventory remained within our target range of 2 to 4 weeks.

Last quarter, we outlined new strategic plans to bolster RYTELO sales growth in the U.S. I'm happy to share that the team has been productively executing those strategies and very quickly implementing important initiatives. Today, Jim and Joe will provide an update highlighting these recent and significant advancements.

Our first priority is to increase brand awareness among the highest decile of U.S. hematologists treating the greatest number of eligible lower-risk MDS patients. We have seen an increase in RYTELO awareness, both aided and unaided, among those physicians treating LR-MDS patients. This is driven by Geron's wide-reaching and aligned commercial and medical affairs educational efforts.

Our second priority is to ensure that physicians are not only aware of RYTELO, but have a comprehensive understanding of how and where to prescribe confidently and successfully. We're pleased that our HCP market research in Q2 indicated a higher willingness to prescribe RYTELO in the first 12 months of a patient's therapy, aligned with the approved label and NCCN guidelines.

And our third priority is to expand U.S. KOL support and advocacy through aligned messaging, education and engagement efforts. By expanding our commercial sales force and customer-facing roles by over 20% and doubling the size of our medical affairs organization, we believe that we're on track to achieve the KOL support warranted by RYTELO's unique mechanism of action and differentiated therapeutic profile. Our new hires have completed training and are now deployed to educate and inform key accounts and HCPs. We expect to begin seeing their impact by year-end. Jim will provide additional details on RYTELO performance during the quarter.

While still early in our execution, we're happy with how our sharpened commercial strategy and focus is showing early signs of success. We continue to keep a close eye on demand and sales trajectories and expect to make any necessary adjustments to ensure RYTELO is being adequately and appropriately prescribed.

Turning now to our European strategy. We continue activities to support launch in select EU markets next year. Jim and Joe will provide additional details later during this call. We are pleased with the recent enrollment momentum in the Phase III IMpactMF trial and expect enrollment to be completed by year-end. Today, Joe will provide more details on this trial, including recently presented data at several medical meetings.

Lastly, in early March, I stepped into the role of Interim President and CEO on request of the Board of Directors to lead the company at a critical time during the search for a new CEO. In less than 6 months, we quickly pivoted, resetting the path of the organization. We are confident that the important work that was done over the last 2 quarters now positions Geron for future success. On behalf of Geron's Board of Directors, I'm extremely pleased to welcome and to announce the appointment of Harout Semerjian as Geron's new President and CEO.

Harout is a seasoned commercial leader who brings more than 30 years of experience and focus within hematology and oncology and a vast network of deep relationships with important physicians and thought leaders in this space. I believe that Harout will complement Geron's seasoned leadership team while leveraging his experience to drive shareholder value. I'll remain invested in and committed to Geron's success as a member of the Board of Directors.

I'll now turn the call over to Jim for a commercial update.

Thanks, Dawn, and good morning, everyone. Today, I will provide a second quarter commercial performance and progress update. Quarter-over-quarter demand growth in the second quarter was 17% higher compared to the first quarter. These promising second quarter results were delivered by our cross-functional team that is executing our plan of action. I want to acknowledge the sales leadership team for focusing on leading their teams and delivering results, all while recruiting, hiring and training our expanded sales force. Our field teams are working together to transition accounts and relationships during this period of expansion and change. Looking forward, we expect the expanded team and planned initiatives to begin having an impact by year-end.

In addition to the net revenue and demand growth metrics, we are pleased to provide updates across previously reported performance indicators on Slide 7. At the end of the second quarter, there were approximately 1,000 sites of care that have utilized RYTELO launched to date. This is an increase of approximately 400 new sites since the beginning of the year.

Of the accounts that previously ordered, approximately 2/3 have reordered in the second quarter. The rolling 3-month claims data as of May 2025 estimates that approximately 30% of RYTELO new patient starts were in first and second lines. As HCPs gain clinical experience with RYTELO, we expect use in earlier lines to increase. Over time, we also expect our focus and execution on the commercial plan of action to support our efforts to increase use in earlier lines.

We are encouraged by our recent market research that shows that when HCPs who treat lower-risk MDS are informed about RYTELO, the majority indicate that they will prescribe RYTELO. We believe that when HCPs are aware and informed, their likelihood to prescribe is strong. Therefore, we must execute our plan to increase awareness and educate HCPs on RYTELO's strong product differentiation so their intent to treat translates into actual treatment decisions with RYTELO.

Payer access continues to strengthen with approximately 90% of U.S. covered lives now under favorable RYTELO medical coverage policies that are consistent with the FDA label and/or NCCN guidelines. This is an increase from 85% reported in the first quarter earnings call. We are pleased with this strong level of access, especially among top national payers.

We remain focused on the successful commercialization of RYTELO in the U.S. On Slide 8, I will reinforce our commercial strategies and plan of action to drive continued growth. Our first priority is to increase RYTELO brand awareness by increasing our presence and share of voice across HCP targets to treat the majority of lower-risk MDS patients. Last quarter, we announced an expansion of our customer-facing teams by more than 20% to improve our reach and message delivery, especially for higher decile HCPs to treat the greatest number of RYTELO-eligible lower-risk MDS patients. I am pleased to report that almost all of the commercial new hires, including key account managers, oncology clinical educators and regional marketers are now trained and deployed in the field, and we expect to see their impact by the end of the year.

The hiring process was highly competitive, and we added very experienced and accomplished individuals that we expect to make a strong team even stronger. Some level of disruption is expected as we expand and regions and territories change. Our sales colleagues have demonstrated strong teamwork and communication to make these transitions as efficient and least disruptive as possible.

We are also making incremental investments in the second half of 2025 towards community-based educational and outreach initiatives. These initiatives are designed to drive broad reach and awareness, especially for community HCPs who treat fewer lower-risk MDS patients and may not see a Geron team member as often.

Our second priority is to improve HCP prescribing confidence and clarity by reinforcing RYTELO's strong therapeutic profile and product differentiation, especially focusing on second-line post ESA or ESA ineligible patients to drive earlier use aligned with our approved label. We believe RYTELO is a highly effective novel treatment with a strong label, favorable NCCN guidelines and broad U.S. payer coverage. We are also making incremental investments in omnichannel initiatives designed to expand the reach of our key marketing messages for lower-risk MDS treaters and complement the messaging efforts of our sales team.

Our third priority is to generate stronger KOL support and advocacy through engagement and education. Increased KOL advocacy is essential to building broader support and use of RYTELO given the limited number of U.S. clinical trial investigators and patients who participated in the Phase III IMerge trial. Our newly formed regional marketing team is hired and beginning to work with top KOLs in developing and executing peer-to-peer and community-focused education initiatives to support appropriate use for RYTELO.

In summary, our second quarter performance results reflect the strong execution by our cross-functional teams. Our patient-centric team has the conviction to help make RYTELO accessible for treatment-eligible patients, and in doing so, deliver continued growth over the coming quarters and years. While we remain focused on U.S. launch performance, our three priorities in the EU remain HTA submissions, EAP programs and commercial distribution. Pending favorable pricing and reimbursement, we intend to take a measured approach to commercialization in select EU4 countries and do not plan to launch RYTELO in Europe independently. In the meantime, we maintain financial discipline in our investments for the planned EU4 launch. I will now turn the call over to Joe, who will provide a medical affairs and clinical development update.

Thank you, Jim. I'd like to start with a general update of the medical affairs organization and highlight several important accomplishments from last quarter. During our last call, I mentioned the actions we are taking to enhance community awareness of RYTELO, improve HCP confidence in how and where to prescribe and bolster KOL advocacy within the lower-risk MDS HCP community. Both initiatives are being successfully implemented, and we are receiving positive feedback across the board from our external stakeholders.

We have doubled the size of our overall medical affairs team. We expanded the team to concentrate on payer-focused MSLs and restructured our publication planning and health economics outcomes research processes. We have a more streamlined and coordinated account management process, which is more efficiently aligned between our medical science liaisons and commercial field teams.

We are focusing on increasing HCP awareness of RYTELO, particularly in the community setting and in academic centers that were not part of the Phase III pivotal trial. We are increasing our efforts to educate and inform the U.S. prescriber community and key thought leaders. Subsequently, we are seeing deeper involvement with high-priority HCPs and MSLs and a broadening support of RYTELO within the MDS community.

Switching now to the IMpactMF Phase III trial in relapsed/refractory myelofibrosis. The study is now over 95% enrolled, and we expect to complete enrollment before the end of the year. As a reminder, this is the first MF trial where overall survival is the primary endpoint. Therefore, the time line for interim and final analysis are tied to the number of death events. Based on current assumptions of death events, we expect the interim analysis to occur in the second half of 2026 and a final analysis in the second half of 2028. We will monitor the death events as the trial advances and make any changes to our assumptions on that basis.

As we highlighted on our last call, we are very excited about the potential to expand imetelstat in this indication. We have several presentations at the most recent American Society of Clinical Oncology Annual Meeting and at the European Hematology Association Annual Congress, showcasing our progress with the myelofibrosis program and underscoring our confidence in telomerase inhibition as potentially transformative new mechanism of therapeutic action. We also had a handful of presentations highlighting new analysis on how RYTELO has the potential to deliver meaningful benefit across a range of low-risk MDS patients.

Having a strong presence at venues like ASCO and EHA is an important priority for Geron's medical affairs strategy, and we were extremely pleased with the multitude of opportunities to highlight the incredible work the company is doing. We also plan to have a strong presence at ASH. With that, I'll hand the call to Michelle to review our Q2 financial results.

Thank you, Joe, and good morning, everyone. For detailed results from the second quarter, please refer to the press release we issued this morning, which is available on our website. As of June 30, 2025, we had approximately $433 million in cash and marketable securities compared to $503 million as of December 31, 2024. Total net product revenue and total net revenue for the 3 months ended June 30, 2025, were $49 million.

As RYTELO was approved by the FDA in June of 2024, there was only approximately $780,000 of net product revenue in Q2 of 2024. Gross to net remained in the mid-teens percent from Q1 to Q2 within the range of previous guidance. The increase in RYTELO net revenues from Q1 to Q2 was driven by increased demand from new patient starts. As of June 30, 2025, our inventory was within our target range of 2 to 4 weeks.

Research and development expenses for the 3 months ended June 30, 2025, were $22 million compared to $31 million for the same period in 2024. The change was primarily due to lower clinical trial costs associated with the decrease of activity in our IMerge MDS study after FDA approval of RYTELO in 2024 as well as manufacturing and quality costs that were capitalized in the current period now that RYTELO is approved versus being expensed in the prior period.

Selling, general and administrative expenses for the 3 months ended June 30, 2025, were $39 million, roughly unchanged from the same period last year. For fiscal year 2025, we still expect our total operating expenses to be in the range of approximately $270 million to $285 million. This includes expenses associated with our continued investment in our RYTELO commercialization strategy, investment in commercial supply redundancies and post-marketing commitments as well as preparations to launch RYTELO in selected EU countries in 2026.

Overall, we believe that Geron remains in a strong financial position to achieve our corporate objectives with access to additional debt funding through our Pharmakon loan agreement. With that, I'm pleased to welcome Harout, who will provide brief remarks before opening the call for Q&A.

Thank you, Michelle, and good morning, everyone. I'm thrilled to be joining Geron at this pivotal time as we accelerate RYTELO's promise to lower-risk MDS patients in need of new options. Over the last period, I was deeply impressed by the Geron team's commitment to the mission at hand from the Board of Directors to the management and team at large. I look forward to connecting with our analysts and shareholders soon after my onboarding. Thank you. And with that, we will open the call for questions. Operator?

[Operator Instructions] Your first question comes from the line Tara Bancroft with TD Cowen.

Congrats on a great quarter, and we also want to offer a very warm welcome to Harout. Great to see you. So my question is, if you can offer maybe how many active patients are now receiving RYTELO? And I understand that 30% of new patients have been in the front and the second line, but I'm curious how much of that 17% increase in demand during Q2 was from true second-line or frontline patients just to get an idea of any nearer-term new messaging and outreach impacts that you're seeing.

It's Jim Ziegler here. As you know, in the buy-and-bill market, we don't get perfect data. So we rely upon different methodologies to assess new patient starts. This could include market sizing reports from syndicated agencies, our specialty pharmacy as well as patient chart audits. Based upon that, we estimate our number of new patient starts. So if you use some simple math, because we don't have that data, of the 1,000-plus accounts that have prescribed RYTELO to date and 2/3 of them have reordered in this previous quarter, you know the minimum threshold is going to be 600-plus patients. So we use methodologies, but we don't report it specifically because it's not perfect data.

Okay. Yes. No, that makes sense. And so of that 17% increase in demand, you don't necessarily have that data for how many of those specifically are second line or frontline patients, just to confirm that?

Not accurate data. We have good projections, and that's why we do some of the market research and again, the syndicated data, which I shared on the call. Right now, the market sizing reports that we get suggest that first and second-line use is approximately 30%.

Your next question comes from the line of Peter Lawson with Barclays.

Jim, maybe just on the back of Tara's question, just how sustainable is that 17% quarter-over-quarter demand growth? And I have a follow-up.

Sure. Peter, we focus on our business drivers. The business drivers are new patient starts by line of therapy and duration of treatment. And as you know, for a product that's often approved in the relapsed/refractory setting, physicians tend to use it in later lines. As they gain confidence, they move it to earlier lines. And that's what I would suggest the market research data has shown us that over the past couple of quarters, the intent to prescribe is high, and we're seeing positive trends over the past few quarters of physicians using RYTELO more in the first and second line. And I just reported that it was 30% approximately in this last survey.

Got you. Is there any additional data points around this kind of KOL scientific advisory strategy like how many new KOLs were added into the efficacy group or other data points you can share with us?

Sure. Maybe I'll take the first part and then invite Joe to ask as well. So KOLs are critical to our strategy. Given the limited number of KOLs that participated in the trial, we have a very concerted and appropriate effort against the KOLs. So as an example, we've taken some incremental budget, and we're increasing our KOL engagement, speaker programs, initiatives at large conferences and congresses and efforts like peer-to-peer programs. We funded that, and they will be executed throughout the course of the year and into next year. And that's where we're placing a lot of our KOL efforts. Joe?

Thanks, Jim. And Peter, to give you a little bit more of the color, we obviously are engaging with scientific leaders of all backgrounds and stature. So we have different tiering, if you will, where the engagement is also tailored to their interest, their needs and our interest. And in that case, we have speakers, we have advisory meetings. We have publications. We have study designs and feedback that we collect insights from these various thought leaders. And that allows us, one, to manage our strategy well to respond to their needs and their patients' need, but also allows us to set our clinical development strategy, our medical performance and make sure that we are responding to the needs and enhancing knowledge and awareness in the community at all levels with the community docs and academic physicians. And that's how we approach this from a medical point of view and clinical development.

Your next question comes from the line of Faisal Khurshid with Leerink Partners.

Allow me also to kind of extend my best wishes to Dawn and also welcome to Harout. So Jim, thank you for that overview of the commercial plan of action. Could I ask you to sort of comment on like diagnosing? Like what do you think was the biggest issue that held back the launch in like 4Q and 1Q? And then consequentially, which of the strategies that you've employed in 2Q do you think had the biggest impact in the quarter and then going forward through the year as well?

Faisal, this is Dawn. I'll jump in real quickly and then turn it over to Jim. So as I entered the role, we quickly pivoted and identified strategies that we really believe are going to make a difference in the long term. Number one, of course, is increasing awareness of our product. Number two is ensuring that there's real comfort and clarity in prescribing. And number three, it's really engaging that KOL audience and gaining their support and their advocacy. And so that quick pivot happened in March, and we're really pleased with what we're seeing today and really focused on moving forward. And so Q2 was really encouraging. We expect that the efforts that are in place today will really play out over the next couple of quarters, and we expect to see long-term consistent growth. And I'll turn it over to Jim to provide additional comments.

Thanks, Dawn. Just to build on Dawn's point and to share my confidence and enthusiasm going forward. On brand awareness, we conduct a lot of market research. What I can share with you is that when physicians are educated and informed about our product profile, there's a statistically significant difference in the brand perceptions along efficacy, safety, MOA. When physicians understand our product profile, their intention to prescribe is high. That gives us confidence. And we're starting to see that play out in some of the early data and the trends as we get hyper focused on our strategy and the execution. Just to note on execution, all credit to our customer-facing teams, the existing team, executing the existing plan of action delivered the results that we just reported in the second quarter. The impact of the incremental sales team as well as the incremental investments will play out by the end of the year and end of next year. So that gives me tremendous confidence that we can execute and we can deliver the results that we all expect.

Got it. And can I ask a follow-up on duration of therapy? Because I know you've kind of said in the past that it was sort of tracking a little bit below where you'd like to see it. And now you're seeing the kind of proportion of utilization in frontline and second line increasing nicely quarter-over-quarter. Do you have visibility on seeing that play out in duration of therapy quite yet? Or is that something that you sort of need to gather more data on?

Thanks. It's similar to my previous answer in the buy and bill, we don't get perfect physician and therefore, patient level data. So again, we use different market research methodologies, SP data and our patient chart audits to assess that. I'll state what is intuitive and obvious, but I think it's helpful. In our IMerge trial, we reported that the duration of treatment was 7.8 months. As you know, when physicians start a new therapy approved in the relapsed/refractory setting, they tend to start it in later lines. As you go from first to second, third line plus, not only does the number of patients generally decrease, but the duration of treatment or the duration of response tends to decrease. So remember, right now, the majority of our patients are third line plus. But as I reported, we're starting to slowly move into the earlier lines as physicians gain confidence with RYTELO.

Your next question comes from the line of Stephen Willey with Stifel.

Let me also extend a warm welcome to Harout. Just curious, maybe, Jim, if there's anything that you can qualitatively say about early 3Q demand trends. I know you provided some color here on early second quarter trends on the last call. Just wondering if there's anything that you can say here that maybe dovetails with some of the improvement in metrics that you're seeing.

Sure. Thanks for the question. So as you know, claims data is available weekly to syndicated audience. We rely primarily on our own internal sales data. And what we see in both sources of data is that there can be some week-to-week fluctuations, which is why we focus primarily on trends, rolling 4-week, rolling 8-week and increasingly rolling 13-week averages. Without sharing confidential information on the early trends, we have cautious optimism that we will continue to drive demand and execution going forward.

Okay. And then maybe just a quick question on myelofibrosis and enrollment. Has there been anything just rate limiting on the screen failure front? I guess if I look at ClinicalTrials.gov, I mean, you've got 200-plus sites that are open and activated. I think over the last 12 months, you've maybe enrolled about 80 patients or 25% of the trial. So is there a rate-limiting factor here in terms of just your ability to recruit patients into the study?

I mean at this juncture, obviously, there are no further obstacles. Usually, you see a hockey stick shape of enrollment where most of the difficulties are seen in the beginning when you're opening sites, when staff are being trained, that's why you see the highest level of screen fail. But as you progress in the study, and we are now at the tail end of that study, you see awareness of the protocol, the nuance of the inclusion/ exclusion. So you see a drop in the screen failures. And we're seeing enrollment that is very strong to the point that we are very confident that this study will complete enrollment by year-end.

Your next question comes from the line of Gil Blum with Needham.

Let me also add my congratulations and love to Harout. So we kind of got up this question a little bit, but is there any anecdotes you can provide about the type of physicians that are currently prescribing RYTELO in earlier lines? Any particular features there, where they are, what their experience is like?

Sure. I can provide some anecdotal information. So consistent with our label, we get some utilization in the ESA in eligible patients. We also get earlier line use when physicians have prescribed and have had patient success previously in later lines of therapy. Joe, do you want to add anything?

Yes. I mean, if I understood your question, I mean, we're seeing prescribers in the community and in the academic centers. And we're seeing that awareness improvement over time. And I've said that on prior calls, RYTELO is definitely a different class. It affects the disease, not just the symptoms. And we see the highest response from a hemoglobin point of view in the MDS therapeutic arena. So all of these are attributes that physicians and patients are obviously appreciating. And the more awareness and experience they have, the more progression we'll see to increase the prescription, but also the setting in terms of line of setting that these patients are being treated with RYTELO.

Maybe a quick follow-on. When you don't see retention, is there any explanation that you're receiving from those centers or they just kind of fall off?

Market research would suggest that some of the discontinuations might be from cytopenias, but we see that as an opportunity to further educate physicians. And then I guess what we're most excited about is some of our data generation efforts to really help educate these physicians with our own internal data as well as potentially real-world data going forward. So we're putting a significant effort to make sure that once we have a patient that they have the best chance for outcomes and patient success.

Your next question comes from the line of Emily Bodnar with H.C. Wainwright.

I'll also extend my welcome to Harout. I guess along the line of questioning with the first-line, second-line usage, I'm curious what you think is kind of a realistic split that you can get to with first-line, second-line usage first, third line? And if you have any, I guess, additional data you can discuss with what physicians are typically using ahead of RYTELO for those third-line use cases?

Sure. If I give you our expectation and percentages around first and second line, I'd be in danger of giving guidance. So what I would say is that consistent with products approved in the later line, it is our intent and our objective to make sure that consistent with label, we have appropriate use in first-line ESA ineligible patient population as well as ESA relapsed/refractory patients regardless of second line plus. In terms of data, the most common used treatment out there -- remains ESA. Of course, luspatercept continues to grow, especially in first line with the COMMAND data. But regardless, we think we have a highly differentiated product, which, again, consistent with label. We're going to compete for that ESA ineligible patient in first line and then the ESA relapsed/refractory patient because we believe we have a highly differentiated product. And again, as market research suggests, when physicians understand our product profile, their intention to prescribe is high, and it's our obligation to make sure that we pull that through in our execution.

Your next question comes from the line of Greg Harrison with Scotiabank.

I wanted to ask how you're thinking about the EU commercialization strategy? And if there are specific attributes you're may be looking for in a partner? And if you could also comment on the potential timing of an agreement that you may announce.

Great questions. Thanks, Greg. So I think maybe some context is helpful right upfront. Only about half of the products approved in the U.S. wind up commercializing ex U.S. Fundamentally, the biggest barrier is often the reimbursable rate that is achieved ex U.S. We're really no different. So our #1 commercial priority is to make sure we secure the highest possible reimbursable rate. And as you know, in Europe, it's a country-by-country and negotiating effort. So that's our top priority across the board. In terms of partners, we have engaged a number of different partners on every front, including HTA, EAP and distribution. In terms of commercialization itself, what I want to reinforce is we are maintaining financial discipline in our investments. We're not building out ahead. We're going to make sure that we have strong reimbursement in the countries that matter most. And we're engaged with a partner right now that could potentially help us commercialize in the EU4 and in additional countries and regions should we get that favorable reimbursement. And that's where we're spending all of our commercial effort right now, which is getting strong reimbursement.

Your next question comes from the line of Corinne Johnson with Goldman Sachs.

Maybe a couple from us. You mentioned that 30% of the patients were second and first line in May. I was wondering if you could contextualize for us where that came from, maybe like the prior time that you ran those metrics. And then I know you're recalibrating the sales team and you expect that to really start flowing through by year-end. But I'm curious what leading metrics you're following to kind of understand how that recalibration is translating to improved demand?

Corinne, thanks. The source for this is outlined in the slide itself. So what we're using is the same source. It's IQVIA claims data based upon a rolling 3-month average. I will remind everyone that there's a lag in this data. So we just got the latest data, which is met recently, which is how that number was calculated. So we use the same methodology, the same partner to assess the trends over time. In terms of the field force, I'm really excited about the -- okay. Great. I don't know where I lost you. So anyway, the sales force metrics that we look at, obviously, are sales performance at the regional and territory level. We look at, obviously, execution metrics like reach and frequency and calls on top targets and physicians.

That concludes our question-and-answer session. I will now turn the call back over to David Borah for closing remarks.

I'd like to thank everybody for their time and attention today, and we look forward to meeting with you all soon. Thank you.

Ladies and gentlemen, this concludes today's call. Thank you all for joining. You may now disconnect.