Geron Corporation ($GERN)

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 heard, 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. 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 lower-risk MDS patients after many decades of research and turmoil 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 lower-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, 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 almost at the first year anniversary. It's been an exciting year, to be honest. I mean, 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 focused 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 go. So we focused 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 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 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 those 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. I won't point back in a 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 that a trained hematologist, 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's 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 also 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 focus the most, where patients can stay on the 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 to physicians in terms of education, what are you communicating about the profile of RYTELO versus these 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, 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. 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 approved in the second line and then '23 in the first line. Luspa [indiscernible] 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 exposures 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 to 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, disease-modifying characteristics represented by the changes in the bone marrow load, responses that are not seen with 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. 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. People level -- CRE level, whether it's less than 500 or specifically over 500, that's unique. Transfusion burden, for 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 patient 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 poorer 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 happy last year at ASH. When we had 2 key data sets, one was the cytopenia and correlation of the 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 book ends joined that the drug is safe and efficacious in this disease.

Okay. You mentioned ASH, but one aspect of your education offers is really centered on 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 emerge. 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 high enthusiasm and interest in studying RYTELO in the preclinical, clinical and in the real-world evidence. What we have expect -- 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, 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'd ask what's the inflection point is that -- 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 gain in terms of when you do the 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 price to me. I mean, just it's unfortunately. So the faster we wanted to make sure we engage 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. 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 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. So in their mind is 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 deployed 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 speaker, 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 the issue.

Okay. So one of the reasons for this special 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 or 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 indication. And seeing guidelines really comes together with the tailwinds from the market. What do I mean by that, is our indication is in second line, then CN 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, the 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 kind of where we want to make sure that education surge 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 -- like a 12-month look-back view or 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 patients off some sort of dose reductions. Could you talk about the dose intensity you're seeing over the duration of therapy?

Harout, do you want to tackle that?

Yes. So 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 a week -- 4 weeks, or they go down and they stay down or they go down and they have a second reduction of those. So there's holds, there's reduction and there's resumption. Patients tend to respond even when their dose is reduced after then 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 the 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 just intensity is today versus kind of what it could be if you are able to get through these educational offers and get more on 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 patients 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 those, reducing those, 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 those reduction of those. And you get that durability of response that we've seen in IMerge, including those tactics. It's not like those were perfect patients, no 1 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, deescalate or withhold doses making 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 evidence 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. They're ability to say, "Oh, I can actually see those results, that have read about in IMerge and that would really have that positive reinforcement.

You mentioned earlier that you kind of took a fresh look at tiering of the physician like 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 directionally and then indirectly reach?

Yes. So 1 of the things of having the benefits of fresh eyes, especially with our Chief Commercial Officer and [indiscernible] medical affairs head is really taking -- stepping back and leveraging their experiences and 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 going to come from. And this is a 80% commodity-driven disease. It really is. So in the beginning, it does happened where our proportion of our sales will be more from the medical centers. It's just they're the first ones we 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 the -- 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 it or from the regional meetings. And that's another area where we spend 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, right how we 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?

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 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, you 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 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 myofibrosis 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 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 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 a 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 according with the marketplace. So this is a big deal. So we're very excited about it, but we, as a company, can continue our low-risk journey as we let that data mature. And then once we get there, we look forward to helping more patients as well as 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 were rapidly current because that was 1 of the things which was very important. It was primarily driven by simplifying our organization. We had, at 1 point, like 6 layers of people reporting to each other, for a tiny biotech with 1 drug, 1 indication. And that's not how companies can really thrive and go. So we really make sure that we declutter our 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 ongoing and to, at one point, rise up to our real aspiration of building a hematology company with a $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.