Geron Corporation ($GERN)

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.