Just on time. All right, we can get started. Hi, everyone. I'm Tara Bancroft. I'm one of the senior biotech analysts here. Thank you for coming to TD Cowen's 46th Annual Healthcare Conference. Our next session, we have a fireside chat with Geron. From Geron, we have the CEO, Harout Semerjian, and the CMO, Joseph Eid. Thank you guys both so much for joining us here. It's a privilege to have you. I thought, you know... Actually, before I get started too, any of you in the audience, if you have a question, please raise your hand, you know, stand up, wave to me, we'll make sure that you get heard too. Harout, maybe to start, can you give us some high-level thoughts? I like to ask in a way, you know, since you are now not that new in this role. Not anymore. How your thinking has evolved about priorities at the company and, you know, how you're gonna get to this growth story that you've been talking about since you started. Yeah. Thank you, Tara, and thank you for TD Cowen for the invitation. It's a privilege to be here. Yeah, Geron is a commercial stage company in a very novel class of telomerase inhibitor. I mean, we're very excited about our commercial, you know, being now a commercial company after many, many years of being a development company. We have our first asset in the market, RYTELO, which we just reported last week that its first full year of commercial sales has reached $184 million, which is really an exciting place to grow because next year we're saying we have a growth story with $220 million-$240 million of guidance on the top line that we have given. Our priorities have not changed in the last few weeks, Tara. We're really all about execution so that we can grow in line with what we believe RYTELO deserves to help more and more patients in the U.S. and abroad. Okay, great. Let's dig into that guidance a little bit more. you know, the $220 million-$240 million, it's a pretty meaningful- Mm-hmm growth from the around $190 million, I'm gonna round up, for 2025. Maybe you could tell us a little bit more about what underscores your confidence in guiding to that range. Yeah, we're very excited with where we end up the year, more importantly, what's coming in 2026. As you said, it is a, it is a very meaningful growth. It just puts RYTELO in a place where we believe it deserves, really helping more and more of the second-line, low-risk MDS patients. Really what drove our excitement and our confidence in giving that guidance is two things. One is internally, what are we doing? Second is, where is the market going? We believe both of them are positive in favor of RYTELO. Starting with internally, in the back half of last year, we've done a lot of fine-tuning, refinement of the strategy, of the people, of the organization. As you know, as an organization, we've become a much more streamlined organization, much more effective in really reaching patients and stakeholders. That's one area. Also the refinement of the strategy, really focusing on the second line. That becomes more important especially when 80% of the business is actually in the community setting. It's really important that we're much more streamlined on our messaging so that we can get more and more folks going on. We've refined our messaging, we've refined our investment, not just from a field perspective, but really investing heavily in what we call the surround sound. A lot of digital, non-personal promotional areas that really help in addition to our field efforts, reach more and more customers. That's really important. That's from an internal perspective of what we have been doing. Also, if you look at the market, where the low-risk MDS market is going, more and more we see in the frontline setting, luspatercept is getting used more and more, which is great for patient, it's great for everybody. To be honest, it's also great for us because that's one area that they're gonna be helping more and more patients in the frontline setting. We're also excited with the NCCN guidelines that have recently been updated in the fall of 2025 that clearly shows that RYTELO is a preferred second-line agent ahead of HMAs. If one of the competitors is moving in the frontline, HMAs are moving more in the down, you know, the downstream. That second line, market opportunity, which we think is about 8,000 patients in the U.S., we clearly can make a difference over there. Between what we're doing internally, where the market is going externally, we have confidence, and that's we're looking forward to every day executing based on that guidance. Okay, great. You know, kind of the next obvious question would be, with that guidance range, what would it take to be able to beat that, and maybe your level of confidence that in actually doing so? Yeah. Well, let's achieve the guidance first. Yeah. I mean, that's gonna be key because, as you said, you know, getting from $184 million to $220 million-$240 million, I mean, that's a, that's a real guidance. It just, you know, demonstrates our enthusiasm and our ambition. We really need to work on all levels. First of all, we need to get more second-line patients. It doesn't mean we're not gonna be, you know, getting third-line patients or above. Of course we are, but our focus is on the second-line patients. We need to get more second-line patients. What that does is two things. One is, as it's a funnel, you have more second-line patients than anything else, so we get more patients. Those patients actually stay more on therapy than third-line, fourth-line plus patients. That's gonna be really important that we get that. And we show consistent growth quarter-over-quarter. That's at least the aspiration, with the thinking that in the second half of the year, you know, just from math perspective, the growth would be higher than the first half of the year. The idea is that we grow over time, we get more demand, we get more patients, earlier alliance patients. We're also able to have more meaningful dialogues with the community physicians to ensure that they understand how to put patients on RYTELO, how to manage patients on RYTELO, and how to see patients to the efficacy that we believe RYTELO can give them, especially with the newer data that we have shared in ASH 2025. Yes, we will definitely talk about the ASH data, which I thought was very interesting. Maybe a little bit more on cadence this year, because you mentioned consistent growth quarter over quarter in each quarter, right? I know you've emphasized in that guidance, it's a little bit more back half weighted. Maybe you could tell us more about what we can look for in messaging from you and different metrics that you might provide, to, you know, see that that is coming. Of course, I mean, this is our aspiration. Business is... I mean, I wish it was always a linear line. It usually never is, but that's still the aspirational part. It's two things. One is consistent growth, but also growth that, you know, in the second part of the year would be higher than the first part of the year. That's kind of we're saying both things at the same time. You know, we do share three metrics from more of a leading indicators perspective. One is demand growth. I mean, what really underpins all this is how much more patients are getting put on it, and that the closest metric we have is how much drug is getting to the accounts from the wholesalers, right? That's, that's an important one. We have reported a 9% growth in the last quarter. The other metric that we share is how many new accounts have ordered RYTELO for the first time since launch, because, you know, we think that's also an important metric in order to show the breadth of prescriptions. At one point, that KPI might not be the same because not every account they're not created equal. Mm-hmm Especially as we focus more and more on the high volume accounts. Then the third one, which we had shared, is the percentage of our business in the first line, second line setting versus later line settings. Now that we have 12 months of data, we have shared actually over the last 12-month look back, that number was about 30%. You know, one out of three patients, currently on RYTELO is in the first line or second line setting, and we hope that that grows as well over time. You know, we have already, you know, few meaningful KPIs that we have shared from a leading indicators perspective. And those are important thing. Of course, from the market perspective, the market does see the weekly IQVIA as well, which, you know, we have commented before that generally, directionally, it's in the right direction. Obviously, these are never, you know, perfect match, either from a timing perspective or the quantity perspective. Directionally, they are more or less in line with what we see as well. There, there are multiple indicators for folks who are paying attention about where we're going. Yeah. Okay, great. Yeah. That 9% demand growth is a great metric to follow. You know, I think what would be helpful to hear from that is, you know, if you're already seeing that, could we see that level of revenue growth in Q1 over Q4? Is that something that we should expect? I wouldn't comment on Q1, but I would say, generally speaking, these two things end up kind of converging at one point. Mm-hmm. Remember, RYTELO sales is still fairly in its first, you know, 24 months, where there are movements that happen, and we have commented that in Q4. There's been a lot of true ups as well, one times, one-time offs, you know, kind of resetting some of our gross to net and things of that nature, which we don't typically see it in a Q1 setting. That's one of the reasons why we wanted to make sure that all that is behind us in Q4. You know, over time, that would converge, not necessarily, you know, from a Q1 perspective. Yep. Okay, that makes sense. Maybe then on average, what is the time to paid remittance, like from prescription to recording revenue? How long would you say that takes on average? Yeah, it really depends, to be honest. I mean, it's tough to answer that. Generally speaking, accounts would not I mean, the whole idea is accounts will order RYTELO when they have patients. Mm-hmm. You know? else- Mm-hmm ... why would they, you know, hold that kind of, high-end, drugs to do that? Once they're, once that pull is happening, then the idea would be afterwards they will come and, you know, the accounts will buy from us as well. That's usually the sequence of things that would happen. It really depends on the time, but those are not very long cycles. Okay, great. With your focus on post luspatercept patients, coming from receiving luspatercept in the front line and receiving RYTELO in the second line, especially in the community setting, what do you think that community doctors especially need to see in order to actually start prescribing it, at a much greater rate in the second line specifically? Maybe Yeah, I would just maybe slightly, you know, call that our focus is on second-line patients. Mm-hmm. You know, regardless of what they're taking in the first line. Yeah. What we are seeing more and more is luspatercept is getting used in the front line. Yeah. so with that, we're getting more patients in the second line after l uspatercept, which is very good on multiple sides, and it's good news, for patients. That's kind of where our focus is. If you wanna, tackle the rest. Tara, Yep. Mm-hmm. The IMerge trial was mostly second line, and that is the data that will be obviously has been communicated with physician. We have also, you know, been doing a lot of engagement, scientific engagement, as well as publication to give confidence to physician, one, to identify the patients and how to manage patients on treatment. The publications also from the luspatercept, you know, post-luspatercept treatment shows also that ESAs are not effective. That data is available in the public domain. All of that information with our scientific engagement as well as the commercial engagement is gonna be helping physician identify the patient in that second line. Mm-hmm. Prescribe RYTELO. Okay, great. Right now, could you just remind us REBLOZYL use in the frontline, like what% of patients is it now used in? Is it like 30%, 50%? I don't know if you've given any color about that. That's probably more of a BMS question. Yeah, yeah. You know, but, what we do see is it's increasing over time. Mm-hmm. You know, since their approval in 2023. That's a good thing because they have shown that they're better than the ESA. You know, so be it. That's great. I mean, to Joe's point, it is important that if you are using an EMA like luspatercept, you know, using an ESA afterwards is not necessarily, you know, the best thing for the patient. Mm-hmm. If that's not really an option, HMAs are getting more relegated into the third line based on the new NCCN guideline update as of the you know, for fall. That's where we're really, you know, our enthusiasm in helping those patients in the second line comes up. Maybe just to add another you know, kind of fine point on the strategy between the academic medical centers and the community. In the academic medical centers, our medical team, you know, led by Joe, has been doing a very good job in terms of really engaging those medics in order for them to really understand what RYTELO can bring, given the fact that many of them have not been part of the pivotal trials since 90% of the patients in the pivotal trial were, you know, these trials were conducted ex US. Yes, you do gain some maybe cost efficiency and things of that nature, but you do end up paying a bit of a price in the, in the launch, which is something that we are definitely course correcting over here. The AMCs by themselves are not gonna be enough to get the business to where we need to be because 80% of those patients are actually in the community. Mm-hmm. That's where now the second part of our strategy in really making sure that we're engaging with the community doctors in a very meaningful way, and that's really, you know, more driven from a commercial perspective, given our breadth and availability. That's where, you know, simplifying the message becomes very important. Do we work in RS-negative even more than-- Of course, we do. Mm-hmm. Really get the message much more, you know, focused, really tackle the high volume accounts more than just any account. That's why, you know, I was mentioning not every account is the same. And making sure that they understand the value of the ASH data of why you wanna treat those patients and why actually if you do see cytopenias in the beginning, that's actually an on target effect. How do you deal with that in a very simple manner? Just follow the label. It's not rocket science. Mm-hmm. As a hematologist, most of them deal with this across. There is a lot of work being done slightly differently for the Academic Medical Centers, where they're much more interested in the science and the mechanism of action. That's why, you know, we have disclosed last week that we have more than 10 ISTs or ISRs that are, you know, now approved, and then we got going on it. On the community side, it's really more the fine-tuning, the simplifying, the, you know, the targeting. It's really the groundwork that needs to happen. That's, that's something that actually excites us as we do that in Q1 and move on. Okay, great. Yeah, that makes sense. I promise my next question will be on the ASH data, but I wanna go back to one of the metrics that you gave about more frontline use and, you know, just trying to think about it in context, right? With the fact that investigators were mostly ex U.S.- Mm-hmm. In the beginning, one of the major challenges was trying to raise awareness about the drug and the trial. You're seeing the fact that you're seeing frontline use when IMerge was primarily a second-line trial is really interesting. I'm actually curious, who are the doctors that are prescribing in the frontline? Are they more academic, community? Are they high volume, low volume? Are they involved in ISTs? Like who? Maybe you could tell us a little bit more about who they are. Maybe anecdotally. Yeah. Maybe it's also- Anecdotally, actually, we have had physicians prescribe RYTELO in first line and tell us why. In particular, the RS-negative population is not well served by the REBLOZYL in the first line. That's the go-to drug actually in that group. You know, I've heard it from a handful of physicians. These are academicians who know the data, who have worked on both drugs, and they see the value in it. When you started the launch, how has that evolved, especially post that data? I mean, cytopenia as a general theme is not something that hematologists will shy away from managing. Mm-hmm. The why and how to manage was probably not optimal when we launched the drug, given that the hands-on experience was mainly ex-U.S. Over the course of, you know, 25, what we've done is actually give confidence and confirmation that the cytopenia observed in the clinic is on target. It's not a side effect. It's on target. The drug targets the mutated that manifest in adverse event. More importantly, those events are predictable. Those cytopenias happen in the first two cycles, and they do also predictably recover within two weeks in 80% of patients. We see patients recover, and they have the robust response in their hemoglobin and stabilization of their white cells and platelets. The data that we presented at ASH actually confirmed that those patients that do happen to have cytopenia are actually the ones that get the most robust response. It is somewhat of a clinical biomarker. Given that we are talking about MDS, there's an analog. Lenalidomide is a drug that data, you know, again, validate term benefit, but also we're seeing over time the safety of the drug from an OS, PFS, and conversion to leukemia. The 45-month landmark analysis showed that, you know, RYTELO is actually benefiting patient long-term, not just short-term. Okay. Wonderful. Maybe now we can move on to ISTs. I know you've mentioned that there are several, but I'm curious, what are the major focuses of each of those trials? Like what are the ISTs hoping to learn? Really, what is it that most excites the physicians who wanna participate in them to actually conduct them? Yeah. I mean, one indicator of, you know, interest is physicians spending time writing proposals and asking for funding, right? Drug for that matter. Being that we are the only you know drug in that 1st in class telomerase inhibitor, we kinda cornered that market, right? Physicians are coming to us from all angles, the preclinical, clinical, and the real-world evidence. Mechanistically, this is gonna be useful for us to continue to inform physician of how the drug works, also it helps us on the second generation TI that is in our pipeline. The clinical is very broad and is enhancing our data beyond the IMerge trial, beyond MDS. Meaning, you know, different lines of therapy in the MDS, sequence and combinations, as well as looking at different indications. Those could be used as a signal for either development further or combination safety and efficacy or even a NCCN guideline listing. All of the data that will be generated will enhance the knowledge and applicability. The real world is trying to replicate the knowledge from the handful of patients, let's call it the 200 patient on the IMerge, to you know, more in the thousands patients data that will also validate a lot, but also uncover other discoveries in terms of where are those patients, how are they benefiting in the real world. We are seeing that spectrum of interest, and we are supporting all of these in our IST program. This is one area where we increased the funding over the last few months because we do believe, and we are aligned with the physician community to say, "Yeah, we have a new telomerase inhibitor in the marketplace." Pretty much every doctor who goes through medical school has learned about it. Until, you know, recently, it was more sci-fi than anything else. Now we have the first approved, FDA-approved drug in the marketplace. Where else can this benefit? Really having, you know, that ability to, you know, engage with the medical community across, not just we're not talking about MDS only, where else can this help? Even in some solid tumors in other areas, because we do know TI is involved in multiple different areas. That is very exciting, and that kind of only can help, RYTELO on the long term, and of course, you know, on our first generation, but also, you know, as we do our TI work, beyond that. Okay, great. I do wanna make sure we have time to get to MF, but I wanna ask you briefly on EU launch plans. You know, well, just in general, what is the plan there, and what could the market look like once you add the EU? I mean, one of the things which is really great about RYTELO, this is a fully owned asset for Geron, right? We have the rights in the U.S., ex-U.S., and international markets. We actually have an European EMA approval, which is, you know, a big plus from a safety and efficacy perspective. Of course, in Europe is a very different funding mechanism than it is over here. You know, we gotta go through the, you know, funding mechanisms per major country. Those are, it takes months to go through that journey. Each journey is a bit different than the other country. We're following is RYTELO needs to be everywhere helping patients. We are more of a, you know, kind of, you know, U.S. based biotech, but we do wanna make sure that we have those conversations. Having those intelligent conversations with potential partners is a very important aspect. One of the key aspects of that is making sure that we understand the pricing strategy to maximize the price in line with the innovation that we're bringing. Don't forget, we've been doing this for the last 30 years. We've been investing, you know, for the last 30 years to bring our first telomerase inhibitors to market. That commands a premium. How do we pull that through in different European countries? How do we do it in a way where there is an MFN, you know, situation going on over here, right? Those two things become very important. That work, we are doing it ourselves, so that we really understand the pricing, and then we'll have the dialogues that are needed. We do see this as an opportunity. We know luspatercept, for example, it's selling about, what? Two and a half billion dollars around the world. About half a billion dollars of that is in ex-U.S. markets. It's quite meaningful as a market, let alone the patient benefit. Okay. Wonderful. All right. Next major data catalyst. Very excited to see the interim analysis for the phase III MF trial. Maybe you could tell us with that interim analysis, what should we expect to see? Is it, you know, that the trial is moving forward? Are we gonna have some data? Any numerical data points in that? Or just a communication that we're moving on to the full analysis, and then after that, maybe some benchmarks to think about either that or the full analysis. How should we compare it? Yeah, maybe I'll kick it off and then, Joe, you can, you can add on it. We are conducting a overall survival trial, a phase III trial, post-Rux, right? These are all patients who have relapsed or refractory to ruxolitinib. This is a very large market in the myelofibrosis world. There are so many, you know, folks who are trying to show that survival benefit. We have enrolled, you know, our patient population, 320 patients or so, two to one randomization. That data is now maturing, you know, since the fall. There is a interim analysis built up, which we project that will be in second half of this year. We project because it's a survival event. We project that the full analysis will happen in H2 2028 if the trial goes on. These interim analyses for survival driven trials are usually a very high bar from a statistics perspective. We haven't talked about what's the, you know, the SAP over here, but these are very high bars. That's why we have also said that from a planning perspective, we think that this will go all the way to maturity. Now, if we are going to be doing the interim analysis, and of course, if that bar is met, that would be best case scenario for everyone, especially for the patients who need additional options. We will announce that when the time comes. Most of the time, the way these things work is the DMC will take a look at it because we plan to stay blinded. They'll take a look at it, and they'll answer us to say, you know, "Keep on going," or stop for different reasons. Typically what we've seen at times like this is most of the time they will come back and say, "Keep on going," which that would be a very good thing to do because they, you know, they already are meeting regularly and taking a look at that data anyway. If that happens, you know, the plan would also be to announce that we're doing exactly what they told us, keep on going. Those are kind of the two things. I mean, none of that is captured in today's talk anyway, you know. All this is a potential upside, but it's a large area of high unmet medical need coming in with a novel therapy with overall survival data from the beginning. If that data holds anywhere close to what we've seen in the phase II, that would be a very good day for patients and for Geron obviously. Yeah. The only thing that I can add is the fact that it's an OS, you know, a primary endpoint based on a phase II data that was randomized to a high dose and a low dose, which was more like a placebo control, that actually almost tripled the survival of patients on the, you know, trial dose. That gives us the confidence in the design of the phase III. All right. Thank you. I feel like... You wanna take one more minute? I love asking this question. Please. What do you think is the most underappreciated right now about Geron? Well, look, I mean, it's been very interesting seeing the Geron story, even from the outside before I joined. You know, when there was the clinical trial, people were like, "Oh, you know, that is the risk from a clinical perspective, the risk from a regulatory perspective." In our estimate, there's 8,000 patients in the U.S. that can benefit from RYTELO. Even in a year where we all agree that we can even do better, we just reported last week $184 million of net revenue. We're just getting started. You know, the other day somebody asked me, "Oh, can this be a half a billion-dollar product?" I'm like, "Well, I'm just giving you guidance, second year, $220 million-$240 million. Okay, where do you think this can go, right? Again, I think the overall story has been underappreciated, and we understand some of the reasons in terms of you know, you always wanna get up and running to a great start in terms of a launch, a commercial launch. Biotechs get to those what is deemed for a finish line from a development perspective, a starting line from a commercial perspective. Those two things are very, very different. We don't deal with our launch as the finish line because now we're a commercial company. We don't underestimate what we need to do. That's kind of our focus is like, you know, ultimately speaking, if we had a cash need to go out to the marketplace and all that, but that's not where we are. We are a company with $400 million of cash and cash equivalents on our balance sheet. We're in a very healthy situation to really drive forward the story of RYTELO. Really some of the green shoots that we're starting to see, anecdotally some of the discussions we're having, that really gives us a lot of enthusiasm to say, "Yes, we had a good year in 2025, and we can have a much better year in 2026." We're giving guidelines on the top line and on the bottom line. I think it's really a matter of you're gonna have some people who are more avant-garde kind of believing in it, and some folks who would want to see a bit more evidence, and that's okay. that's what we will wake up every day to execute on the plan and really demonstrate the power of RYTELO for patients. Great. Thank you so much. I know we're up on time.