Good morning, thanks to everyone who's joining us both here and on the webcast. We're thrilled to have the team from Geron here this morning. Maybe with that, Harout, I'm just going to turn it straight to you. I'd love for you to 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, thank you for the Goldman Sachs team for the invitation to share why we are excited at Geron. 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 lower-risk MDS patients after many decades of research and turmoils and shifting strategy like a lot of biotechs do. Now we 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 a first indication in lower-risk MDS with another phase III in myelofibrosis post-relapse refractory RUX patients. We're excited as well to see, once that data matures, how we can help further patients.
Great. It's also nearing on an anniversary for you, which is one year with the company. Maybe you could talk about the key priorities you had when you took on the role, maybe provide a bit of a mark to market on where we are relative to those priorities, and then as you look forward, 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. This is 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. When I joined in, the commercialization has already started. Maybe there was a bit of a discrepancy between what the market expected in terms of uptake and where we were. That's where it's so important that we focus on what will it take to successfully commercialize an asset. This is probably one of the good poster childs when people would say drugs sell themselves. It doesn't work that way.
I've done many of these launches over the years, especially as the U.S. head of hematology at Novartis, 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. Even there, the first few quarters, it took us quite a bit of time in educating people. It really comes down to where we focused on is 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 go on.
We focus a lot on what typically is done in a more of a pre-launch stage, which I'm sure some of that was done, but really having that surge was my priority number one. Second was really making sure that we're injecting the team with updated oncology-based commercialization background folks. That was also very important. 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. Really making sure that we tackle those, these three areas, has been a focus for me in the first year. I think we've done a lot of advances in all three areas.
Okay. You mentioned already, but RYTELO has been on the market for about two 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. The lower-risk MDS patient population has been one of the interesting diseases. At one point back in the day, it used to be called even pre-leukemia. 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 hematologist who's seen a lot of those patients.
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." It does happen, not just in the lower-risk MDS, but across the board I've seen it where you start from lower later lines, that's what's happened as well with us. The key is as folks get more and more educated and the awareness is there, you move up into where you're actually indicated, that is in the second-line patient setting. That's where our focus has moved very quickly into making sure that we're not just helping any patient, we're helping the second-line patient population.
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. I'm pleased to see that that number has been going up gradually but steadily and up. 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, so on and so forth. Our aspiration is to really get to a point where
Any patient, 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, where that durability of response that we've seen in IMerge can really be replicated the most in that patient group.
Okay. You're obviously working on this, if there's a patient in the second-line setting that's not getting RYTELO, what are they getting instead? When you go out to physicians in terms of education, what are you communicating to them about the profile of RYTELO versus these alternatives that are currently being used?
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.
Just to complete what Harout said earlier, in my fellowship back in the 1990s, the standard of care for MDS was supportive care. 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. It's not that benign of a disease. The treatment paradigm has evolved over the years from transfusion and other supportive care to ESAs. That was in the late 1990s, early 2000.
HMAs, lenalidomide for the del(5q), and then in the 2020 timeframe, luspa was approved in the second line, and then in 2023 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 del(5q) 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 [audio distortion] load, responses that are not seen with [audio distortion] of response, 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 the 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. 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.
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, four, six units or higher, that's unique. That broad-spectrum applicability allows the drug to continue to gain confidence in the prescriber's 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 patient and luspa and how the sequencing are happening. They're realizing that they have a lot of gaps. 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 poorer prognosis.
We know luspa does not work well, whereas RYTELO does have a positive effect.
Okay. You just talked a lot about the profile of RYTELO, but as you think about the uptake and physician awareness, I guess, 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 two 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. The other piece was the long-term landmark analysis, which showed that the drug is safe and effective in terms of trend in OS, PFS, and conversion to leukemia, almost dropping it by 50%. There's the early understanding of how the cytopenia is predictable, reversible, and does not lead to clinical consequence. That's the early safety component, if you will, and the long-term safety. That's the two bookends showing that the drug is safe and efficacious in this disease.
Okay. You've mentioned ASH, one aspect of your educational efforts is really centered around these medical conferences, and we're right in the midst of ASCO and EHA. 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 broadened 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 are expecting, and coming out of ASCO, 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.
Yeah.
How do you think about these educational efforts translating into launch metrics related to the front and second-line use and revenues? How should we think about all the work you guys have undertaken-
Yeah.
...over the past year starting to translate?
Yeah, look, our story has been very clear, at least from the day I started, is to say this is a growth story. It will be quarter-over-quarter. That's our aspiration because sometimes I get asked, "What's the inflection point?" It's like, look, 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, what Joe said is, we wanted to make sure first the academic medical centers really understand and are bought into RYTELO. 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 five people involved in your clinical trials, there is a price to pay. I mean, it just is, unfortunately.
The faster we wanted to make sure we engaged that medical experts in really understanding and really test driving RYTELO and 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. That's on the academic medical centers, but of course, they're not the ones who see the bulk of the patients. 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 users. 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 patient, usually elderly patients. In their mind, it's like, well, I have these more severe cancers to deal with. Really making sure that the sense of urgency, how do you treat them? How do you hold those? All these things are being rolled out. We're in the midst of really doing that on the community setting. 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 2024. In my first few months at the podium in these medical conferences, imetelstat RYTELO was either not mentioned at all or mentioned with not so much positive. I've seen the transition over the few months in 2025, 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. 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 were the issue.
Okay. One of the reasons for this, especially 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 front line?
IMerge has been predominantly a second-line patient population, that duration of therapy was called eight months, 7.8 to be more precise. We're seeing that mimic in the real world for like-to-like patient population. Whenever they are using it in the second-line setting, we're seeing that eight-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. 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. 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? Our indication is in second-line. The NCCN is really supporting that positioning over there. Also as the market, which has been really ESA dominant for many, many years, EMAs have launched in the last five, six 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 front-line setting. The more they move in that front-line setting, that second-line setting opens up even more for RYTELO. That's where, to one of your earlier questions, if they're not using RYTELO, what else are you using? Well, we still see, for example, usage of HMAs in that patient population, which even the NCCN now in the last few months when they upgraded their guidelines, we are a preferred second-line agent. There is a reason for that, and that's where we want to make sure that education surge that we've been doing really happens so t hat 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 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 going to be using it the way your education would suggest they do?
Yeah, hopefully the idea is to grow it quarter over quarter, that's really the case. This is a large market, Corinne, that even with a good asset like luspa, they're not getting every first-line patient, still it's like a $2.5 billion business.
These are thousands of patients who can be helped, our aspiration is to grow that in the second-line patient population quarter over quarter, really over time, folks can see the steadiness of those curves.
Okay. What about the average dose you're seeing for patients in RYTELO? I think in IMerge, there was something like 50% of dose patients saw some sort of dose reductions. Could you talk about the dose intensity you're seeing over the duration of therapy?
Do you want to tackle that?
Yeah. 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 mg/kg every four weeks, or they go down and they stay down, or they go down and they have a second reduction of dose. There's holds, there's reduction, and there's resumption. Patients tend to respond even when their dose is reduced after, then sustain responses. 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 one, two, or three cycles, which is not doing patients any favor.
That's the approach that we have been educating. Again, the ASH data validates that point that cytopenia has to be seen in a positive way, not as a negative. It's not a safety, it's an on-target observation.
Maybe could you speak a little bit more about this, like what the dose intensity is today versus what it could be if you are able to get through these educational efforts and get more physician understanding around keeping patients on drug?
It's, again, tailored to the individual.
Right.
Every patient is different, you can't say everybody has to treat the patient equally.
Sure.
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.
This happens in oncology quite a bit.
Yeah.
I remember back when we launched everolimus, it was the same thing where withholding dose, reducing dose, these are things that oncologists and hematologists are used to.
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. How do you go through it's quite simple between withholding dose, reduction of dose.
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 what we're saying is you can mimic IMerge and actively manage the patient.
Let's see if you can share impact on revenue at different dose levels. Does it scale linearly, or is it-
It can. Obviously, the more folks use RYTELO appropriately, that's what we want them to do. Our guidance and our aspirations do take into consideration that some people will have to dose escalate, deescalate, or withhold doses mimicking IMerge. We don't have a reason to believe that. Somehow every patient is going to get on therapy. If that was the case with 8,000 patients, that would be a very-
Yes.
...different number. Our guidance and all that takes into consideration how IMerge was. 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 evidence start to report back-
Yeah.
...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. 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 that I have read about in IMerge." That would really have that positive reinforcement loop.
Sure. You mentioned earlier that you 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 both directly and then indirectly reach?
Yeah. 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 stepping back and leveraging their experiences in having dealt with these patient populations and these physicians, and really understanding where is this source of business going to come from. Not where it is today, but ultimately, where is it going to come from. This is a 80% community-driven disease. It really is. 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 who start off with. 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.
Community physicians with high volume loads are really our priority number one. Those happen to be also the toughest accounts to get into because everybody's doing that. 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. In a biotech setting, it's very different than a big pharma setting. In a big pharma setting, you're 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 two paychecks, you're no longer new. We pay every two weeks.
One month
It really is. 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. That's important because you're dealing with FDA, you're dealing with very important things. That changes. The company needs to change with it. That's where our targeting now is very much. Our efforts are on the high volume ones. Also, we have now a lot of capital deployed into digital and non-personal-
Okay.
...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 this-
Yeah.
...or from the regional meetings. 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 low-key, where it's 50 hematologists, 60 hematologists, they get together over a weekend, really discussing certain topics. 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. 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 especially in R&D, not necessarily in need for us to carry that forward
Sure
A lot of that search has already been done.
What are the metrics that you as a management team are tracking that ensure this new strategy is working? Can you share anything around how those metrics are tracking right now?
Yeah. 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. 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. 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.
That has been steadily going up 150 to 100 accounts every quarter. Also our source of business in terms of patient type. First line, second line versus the later lines. Ideally, we would want to see demand growth. We would want to see the right patients in terms of first line, 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. Now we're not in that stage. Now it's about what are we actually rewarding is second line performance.
Yeah.
That's going to be very important in terms of what shift is what you usually get.
Right. You do anticipate 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?
Other than low-risk MDS, 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. That's a patient population that needs additional options. We were very enthused 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 primary endpoint is overall survival, is before end of this year. That's on the IA. 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 careers, most of the time, those trials typically take the full maturity timeline for the data to mature. Of course, we're going to be ready to do an interim analysis with the high-quality data. 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. 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 on the interim analysis, stopping for overwhelming efficacy, which would be the best case outcome.
Yeah.
Most of the time it will be where they tell the company, "Keep on going.
Okay.
Our intent is that we communicate whatever they tell us according with the marketplace. This is a big deal. We're very excited about it, but we as a company can continue our low-risk journey as we let that data mature. Once we get there, we look forward to helping more patients as well in the myelofibrosis space.
Maybe a quick question on funding, which is, how are you thinking about funding to profitability at this point? 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?
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, six layers of people reporting to each other for a tiny biotech with one drug, one indication. That's not how companies can really thrive and go. We really make sure that we declutter our organization. We did that very rapidly, and it really actually helped us move forward. 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.
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. That's really something that we're very excited about.
Sounds like much to come. With that, I think we're basically at time. Thank you guys both for joining us. Thanks, everyone who joined us here as well.
Thank you very much.
Thank you.
Thanks, have a good one