Good morning, everyone, and thank you for joining us at the first day of the Needham Health Care Conference. It is my pleasure to have with me today Harut Simerjian, the president and CEO of Jiran, as well as Joseph Eid, the chief medical officer of Jiran. As a reminder, you can enter a question through the ask a question box at the bottom of your feed. But, Haru, maybe just to set the stage for whoever is unfamiliar, high-level overview of the company story.

Sure. Thank you, Gail. Good to see you. And thank you for needing for this opportunity to share a bit more about the geron story as it's been unfolding. So we are a commercial stage company focused in hematology, oncology. We have launched the first telomerase inhibitor, Imitalstat, in the marketplace as of middle of 2024. So we're in that first initial two years of launch phase, trying to help low-risk MBS patients around the world, hopefully, but now starting with the U.S., based on the IM-rich data that was released. 2025 was a very good year for us. We have reported $184 million of net revenue, and we started the year with a guidance that we have given in terms of our growth ambition of $220 million to $240 million of net revenue in 2026 with an even more streamlined team and investments that we had in 2025. So we're off to races, and we're happy to be here to share that story.

So maybe on a personal level, you've started, you've been around now for a little bit, but you're still a little new to Jiron. What attracted you to this story and what do you think has changed since you've joined?

Yeah, I've been in the pharma business for more than 30 years now. The vast majority of that time, Gil, as you know, has been in hematology, oncology with a large player in this area for many, many years. So for me, having this opportunity to be in a company like Geron where we have an asset that has gotten approval, as you know, many biotechs don't even make it to this point. So we're very fortunate to actually have an FDA approved asset in lower risk MDS was something very attractive for me. So when I was talking with a lot of the physicians and a lot of folks who I know, in this disease area, you know, efficacy matters. And really making sure that we have a drug that is able to have that durable responses, for me, was very important. So that's where I started with. And then, of course, you know, having a company where we actually have funds, we have $400 million on our balance sheet where we can actually, you know, get things done. That was also very important. That wasn't always the case in some of my previous companies, so this was also something fortunate over here. So, yeah, I've been here now seven, eight months in Geron, really, you know, putting together the team, the vision, together with the team, so that we can really tackle the 8,000 patients who are second-line lower-risk MDS patients in the US. So we believe that we have a tremendous opportunity to help those patients and make a great business case and have Geron ultimately become a hematology powerhouse. So there's been multiple things that have attracted me to here, Gil, be it from the drug to the company, to the fuel in the tank, and to really a vision that we can all stand on and really work together as a team to make it happen.

Thank you. Very helpful. And maybe a good place to start, just reminding us what the standard of care is for low-risk MDS and where Rectal is positioned.

Yeah, I mean, just maybe a little bit of a stepping back, Gail. Myelodysplastic syndrome is a spectrum of disease. You have the low-risk MDS and you have the high-risk MDS. The high-risk MDS is very close to acute myelogenous leukemia. And as a whole, MDS is a precursor to leukemic transformation, and that's why it's considered a cancer and not a benign condition. The treatment for many years was transfusion and support. Then ESAs came into the scene in the early 2000s for anemia of cancer. And then in 2020, Lusparacept was approved for low-risk MDS, initially in the second plus line, and in 2023, it was approved for first-line MDS. The other drugs that are also utilized include lenalidomide for specifically the 5-DEL-Q and hypomethylating agents, HMAs, like azacitidine, the cytabine. And those initially were used in a broader spectrum. But as the field has evolved, we see now a transition in the clinic and endorsed by NCCN guideline for ESAs or LUSPA in the first line, with LUSPA making a move into capturing more of that first line. And then depending on whether it's ESAs or LUSPA, the second line preferentially is now Imitalstat with NCCN guideline pushing the HMAs into the third line and beyond. And that's, you know, the current paradigm of treatment where imatelstat is anchored in the second line, but also has applicability in first line, and that's in the label for ESA ineligible for EPO levels over 500 and high transfusion burden. As well as we know, ESA is not functioning as good after loose paracept. That also becomes, you know, an imatelstat positioning.

And maybe just spend a second on RS negativity. I mean, there is clearly less of a benefit for LUSPA in RS negative patients. Is that something we're seeing in practice? I mean, the label covers everything.

I mean, lusparacept was approved, if you recall, in the second line exclusively in RS positive on the basis of the medalist trial. The command trial, which is a first-line population, included RS negative, albeit at a fraction of the epidemiology, meaning about 30% compared with more than double in the normal epidemiology. The overall study results were positive when compared with ESAs. But if you look at this ESA subpopulation, they do not benefit as much. And if anything, physicians now see that as a vulnerability or an Achilles heel for Luspericep. And they see Metelstat as a drug that works in all these situations, RS positive, RS negative, high transfusion burden, high mutation burden. So because the difference of treatment or mechanism of action for the treatment is also at the basis of those differences. So you see ESAs and EMAs more of a supportive care, whereas a metallostat is more of a disease-modifying agent. It acts at the basis of the disease. We have now many data pointing to that, that it's an on-target drug against the mutated clones of MDS. Now, anecdotally, we've seen physicians in the clinic now starting to transition from blind check ESAs or blind check LUSPA to the profile of patients. If patients tend to have ESA, RS negative, for example, ESAs are not very good at that population, albeit maybe better than LUSPA, and LUSPA, you know, not a good option. They're opting for Imitalstat, which has actually benefited of this patient. I've had, you know, few KOLs talk to me about their first-line patients come in with RS negative profile, And they're putting them on IMITELSTAT, seeing a much more robust response than when you see in the later lines of therapy, which is expected. So that is reassuring. And it's, again, in line with the mechanism of action of IMITELSTAT.

How would you say the reception of RETEL has been by physicians? And is there any difference between what you're seeing from academic centers and, let's say, the community setting?

Yeah, there definitely are. I mean, so, you know, one thing to keep in mind, Gil, is that when we were doing the iMerge trial, the, you know, our own pivotal asset, 90% of those patients were enrolled XUS. So that's one thing which is kind of important to keep in mind is reception is really tied with a familiarity before a launch, right? And that's where, you know, to be honest, we've had to do a lot of awareness and education for our U.S.-based hematologists, be it on the academic medical centers, but more on the community side to really understand the mechanism of action of Ritello. Why is it different? How do you get to that durable responses? And, you know, whenever you see a cytopenia, how do you deal with it? And it's been an ongoing educational journey so far. So what we have seen is more and more of these anecdotes where folks who might not have known about it before are using it, using it well, using it in the right patient population. And with the recent cytopenia data that was presented at ASH, and maybe Joe can talk about that, that also is now giving further boost to the story of why Ritello is an appropriate second-line agent. Joe, do you want to talk about the cytopenia data?

Yeah, I mean, when I mentioned that this drug mechanism of action is on target, the target is being the mutated MDS clone. So cytopenia that is seen with imetelstat is the reason for why the drug works. Because you're targeting those mutated clones and you're clearing the marrow of the disease to make space for normal hematopoiesis to recover. So we see a predictable cytopenia within the first two to three cycles, and we see a predictable recovery within two to four weeks in over 80% of patients with lower level of cytopenia. And those patients, and this is what was presented at ASH, those patients that tend to have cytopenia tend to be the ones that have the most durable, robust response. And that's, again, consistent with how we understand the mechanism of action to be effective against this disease.

So some of our own research has shown that retail is currently, the use is concentrated in later lines right now. How are you working on improving adoption in earlier lines, especially the topics we touched on, like virus-negative patients?

Yeah, so you're right. I mean, this is something which we have also disclosed on our full year 2025 results, Gil, is 30% of our business, we believe, is coming from the first line, second line patient population, meaning 70% is coming from third line plus. you know generally speaking in oncology or hematology whenever you launch an asset you do start getting more you know traction in the later lines that's something which is not you know a typical that happens uh often the key is to start moving more into the lines that you're approved in as fast as possible right which in our case is in that second line setting so you know that's kind of where we're doing a lot of our education, to really make sure that we are getting the appropriate patients. We have fine-tuned our strategy recently, where we're really focusing on that second-line patient population, which we believe in the U.S. is about 8,000 patients, so it's not an insignificant number of patients who can potentially benefit from Immetelstat based on the label, based on the NCCN guidelines. But of course, we always anticipate that there will be a subset of patients who are in that third line or beyond who need options. This is a disease where recycling of therapies does happen sometimes. So we do see that. But ultimately, what we want to see with more education, with more focus, and with really also our investments that we have been putting beyond just field force or medical people in the field is we've been investing heavily on the non-personal promotion, on the digital, you know, platforms as well, as well as regional meetings beyond just ASH and EHA to really make sure that that education gets so that we can ultimately get to the patient population that we believe we can help the most, which is the second line, lower-risk MDS population.

So what would you say a typical patient experience refers to how it looks like? And kind of as a related point, what happens when a community doctor sees these kind of side of peanuts? Do they see a new drug or how are you guys? Maybe we'll start with that part.

And Joe, I mean, you're a trained hematologist and you've dealt with patients like this, so

he can give you a real world example of that. Yeah. I mean, as you know, the majority of our patients on clinical trial for the eMERGE was done outside the US. So the hands-on experience in the big institutions as well as in the community was minimal. So we've been improving awareness by engaging scientifically at congresses, in clinics, in peer review forums, in those small peer-to-peer meetings. And the whole purpose of that is to make sure that we bring the science and the data to their attention so that they are aware of the data. So that's one piece. The other piece is obviously having good experience. And the good experience starts with the education on the mechanism of action. That cytopenia, for example, presentation at ASH, which has been published recently, also, again, links the cytopenia to the benefit of the drug. And that's one actually key component in this disease specifically, because there is an analogue that the hematologists are very familiar with and they're comfortable with, which is lenalidomide in the 5-del-Q subpopulation of MDS. Now, that specific mutation responds to lenalidomide, and those patients tend to have cytopenia. And in the lenalidomide case, that cytopenia was also correlated with the response to lenalidomide. So that's the backdrop, if you will. Our drug, Imitalstab, in addition to the 5-DELQ, it has actually activity across all mutations that we have tested that cause the MDS disease. So that understanding and that linkage to a known analog is also a way to reassure physician that when you do see cytopenia, instead of what we saw in the early days, patients were dropped off because physicians didn't understand why there was cytopenia, what to do with it, and what to expect. Now we have the full story that it starts in the bone marrow, that this drug is on target, it works on those clones, that's why you see the cytopenia, and then to reassure them that most patients do not have bleeding or infection because those are ineffective hematopoietic clones, and that actually is also supported by the IMERS trial, where the placebo incidence of bleeding or infection was similar to the one seen on the metal set, which was minimal. And more importantly, patients do recover. And then now we have the full story, which is those patients that you do manage as opposed to interrupting drug and getting patient off drug, you manage them through those few weeks. And those patients tend to be the best responders over time. So that's a totally complete transformation in the understanding of how the drug works and how you manage your patients.

Thank you. Very helpful. And maybe kind of as a follow-on there, the treatment burden, right? This is an infused drug. Can you compare this to, you know, the preceding standard of care and how do these things match? I mean, you know, if there's cytopenias, you probably also need to

of GCSF, et cetera? Yeah, I mean, on trial and in the real world, what we're seeing is if patients do receive any growth factor, it's no more than one injection. They're not getting the weeks or the days of support. Again, you have to think of the MDS patient differently than the chemo, for example, patient, where, you know, you have an intact barrier, no mucositis, no diarrhea. You have a very transient cytopenia, not prolonged. All these are factors why patients become susceptible for infection and bleeding. And then we're not indiscriminate like chemo that indiscriminately kills all the clones in the bone marrow, the good and the bad. and Mattelstat targets the bad clones. So all of these are reasons why we don't see a difference in incidence of these cytopenia effect, whether it's bleeding or infection, between active arm and Mattelstat and placebo. And that's what we're also getting from the real-world application.

So Ritkel generated about $184 million last year. company guided to 220 to 240 for this year. So more backhanded. What gives you confidence

of this 20 to 30% growth? Yeah, great question, Gil. And we actually put that guidance out to like first day of JP Morgan, right? So, you know, very early on in the year. And it's really driven by our conviction of, you know, how much potential does Ritello have? And, you know, let's say Q4, we had to take some tough decisions in terms of a major rift that we have implemented, primarily driven by, you know, the need to simplify the organization because we wanted to make sure that we have, you know, more investments in areas that really will move the needle for the ongoing and the going forward business rather than more historical reasons. So we have taken big sums of money from areas where it was needed at one point to get a drug approved. But after that, it just becomes more helpful for the company to, for example, invest in digital, you know, forums, non-personal promotional, you know, forums, regional meetings beyond ASH, and things of that nature. So that's where we've been really, you know, focusing on. So we have a streamlined strategy in terms of the focus on the second line patient population, and that's how we're all, you know, aligned as a company, that that's where we're going to focus on. We have the focus on the high-volume accounts that, you know, we really kind of read our accounting and our targeting to ensure that we don't shy away from, you know, high-volume accounts just because they're harder to get in. That's really where, you know, we have a single purpose, you know, to do with a drug that we have and making sure that we're really, you know, amplifying our educational assets in a way that also includes this digital, as I mentioned, and then really work and engage with the medical community on other areas. There has been a lot of enthusiasm about the mechanism of action that Ritello provides, this telomeres inhibitor, for example, right? So that's driving a lot of medical conversations, which in turn is driving a lot of ISTs and investigation or initiated trials. And we have announced recently that there are 10 of those, more than 10 of those actually, that we have aligned with from a strategy perspective and approved for it to be funded. So this would include a lot of adjacencies across, we're not obviously reproducing iMERGE, but there are a lot of other areas within hematology and oncology in general where, you know, a telomerase inhibitor can play a role. And the more we're engaged with our physicians to understand that, the better it is. So between that, between our strategy, between our rejuvenated team, the focus, the increased investments in where it matters, we felt confident to have guidance from the beginning of the year that shows a significant growth, right? From moving from $184 to take the midpoint of the $220 to $240, that's $230 million, right? You're looking at almost a $50 million uptake or, you know, so that's really very exciting for us, and we believe there's 8,000 patients in the U.S. that we can help, and we're waking up every day making sure that that's getting done.

Maybe a question on uh the frontline dynamics are you guys still seeing uh patients who receive esa and then i mean i've gotten the the sense that you know biologically that doesn't necessarily make the tonic sense uh both of those drug push the merit of produce more um but i'm just wondering if there's still like two lines of of something you know basically factor yeah joe maybe you want to

take from a mechanistic perspective, you know, ESA, LUSPA, and then I can comment on the market

dynamics in general. Yeah. So let's think of ESA as the erythropoietin stimulating agents. And EMA is the, LUSPA is the erythropoietic maturation stimulator. So you have drugs that kind of work in a sequence where the ESAs stimulate the progenitor and the EMAs stimulate the more mature cells and make that maturation faster, they come out of the marrow faster. We know that LUSPA works better than ESA when you compare it in that same population. the fact that EMA matures the cells ESAs does not work on that population after so in that sense ESA and that's what we see in the clinic is not as effective post LUSPA and the best option for these patients is actually metelstat because that you know population is still healthier and will benefit more and longer from a drug like imetalsat, which works on the disease. So mechanistically, that's the sequence that if one is to use one drug before, LUSPA has the better data, ESAs does not work as much after.

And that's exactly in line with what I was suggesting about the overall market where it's going. We are actually seeing tailwinds rather than headwinds, you know, going forward, Gil, specifically on this topic, because as LUSPA, which used to be predominantly a second line agent, moves more and more into frontline setting, given mechanistically how Joe, you know, eloquently described it and the data over there that they have shown they are better than the ESAs. We think that will, you know, continue over time. Unfortunately, even when that happens, it's not like, you know, every patient is getting cured. You will need additional options in the second line setting. And that's where we are appropriately positioned, regardless of whatever is the front line, to really help patients, second line patients with Ritello. And I will just add one more, you know, dynamic that has happened in the marketplace is the NCCN guidelines. that have also been recently updated, where now Ritello is a preferred second-line agent ahead of HMAs. It's also a very valuable market dynamic that we shouldn't overlook it, because even after HMAs, not many things work out. So it is more appropriate, in our opinion, that it's kept more for later lines of patients. But really, you know, the first dynamics is really where, you know, Ritello is a solid second line agent. And that's where we see some of the tailwinds as well, helping in addition to our own efforts.

Very helpful. So you guys have an EMA approval, but you're not launched XUS. Maybe just give us an idea of how you guys are thinking about XUS markets.

yeah no great question i mean you know so immittal stat is a wholly owned asset we have the rights you know geographically everywhere in the world and in addition to our fda approval we actually have an ema approval as of last year uh we haven't fully commercialized it uh in these countries obviously um and as you know many biotechs ourselves included there's a lot of debates and discussions today, especially in the world of MFN, how do you go about doing it in a way where it doesn't impact us back home and our U.S. business, obviously. We're of the belief that Ritello, our drug needs to be everywhere. We don't necessarily need to be everywhere. So there are conversations we're having with potential partners, but there are also conversations that we're having about what are the other optimal ways that we can bring Ritello to the marketplace in European countries in particular. Because as you know, a lot of centers in Europe actually enrolled patients on Immintelstat. And we have even more ambassadors and more folks who support Immintelstat because they've seen the value of it in the clinical trial setting, even more than the U.S. To be honest, I mean, it did hurt us in the U.S. with the need for this surge of education. But on the European side, we have a very, you know, robust footprint of physicians who have been involved. So, you know, it's currently where, regardless of where the commercialization efforts go, Gil, what is really clear is we have to be very close to the pricing, you know, component of it. and we have to do it in a way which is, you know, gated as well. So currently we have a lot of efforts on the HTA processes in terms of really understanding how would we assess value based on the different parameters of the HTA processes going into the different, you know, large European countries and making sure that appropriate measures are taken for Ritello to be, you know, up against, you know, decent comparators when it comes to that. So that work is ongoing, and depending on that work and depending on what we believe we can get, you know, pricing, because, again, this innovation issue is a real issue, and we all know that, and we all succumb to the fact that we need, you know, more and more countries to recognize innovation. We're one of those companies that have been really going at it for 35 years, and finally we have an approved drug, and that innovation has a value. So we're doing a lot of that work on the HTA side, and depending on the outcomes of that in a gated fashion, we would decide on next steps beyond that.

Great. I do want to spend some time on the myelofibrosis program. um we're finally progressing on this one and may see some pretty interesting data so just maybe start with the impact mf trial design and what should we expect in this upcoming interim later this year assuming everything uh falls into place yeah yeah i mean maybe uh gill

get to give a little bit of context of the uh impact mf the phase three trial this is a phase three trial in a two-to-one randomization of Imitalstat versus best available therapy, looking at overall survival as a primary endpoint, as opposed to symptom relief, spleen size and symptom relief. The data that gave us confidence to go into this space with the phase three registrational setting is the EMBARC trial phase two data. It's a randomized trial with close to 110 patients randomized to two doses of Imetelstat, a high dose and a low dose. The high dose is actually higher than the MDS dose and given more frequently every three weeks. That trial showed benefit in symptom relief as well as overall survival. And the overall survival was so dramatic, almost tripling the benefit between the high dose and the low dose, as well as when compared with the historical match control, that the benefit in that population, which is the relapse refractory to JAK inhibitor population, had a very significant overall survival. So the study is designed with an overall survival on that ground. And we believe, again, coming out of that, that this would be a paradigm shift if we proceed with a trial that ends up positive in this population, which is, again, a relapse refractory to JAK inhibitors. now as far as where what what the study design and what we're looking for being that this is an overall survival endpoint the milestones are driven by death events so the projection of the death events are that we will probably hit an interim analysis by the second half of this year which is what we have stated in the past and the and the final analysis will be let's call it two years beyond that. The DMC has been meeting regularly to review the data on this trial two to three times a year since the inception of this trial. So our assumption is that the DMC is most likely to inform us that the study will continue to proceed to the final analysis because the interim analysis has a high bar like any other overall survival study that's designed that way, and that would be a good thing, which means that the totality of the data still continues to favor the continuation of the trial.

Okay, that makes a lot of sense to us. How has the standard care at best available therapy changed? I mean, the study has been going on for a while. Is there a drift there as well?

So, the standard of care has shifted in the sense that there used to be one JAK inhibitor. Now, there's multiple JAK inhibitors. But what we are also seeing with the JAK inhibitors, our patients are recycled very quickly from one to another JAK inhibitor in a rapid sequence. Overall, cancer support and management of patients with cancer has improved, including management of patients with myelofibrosis. That by itself is a condition that improves patients' outcome and patients' well-being. However, there's no evidence that any particular JAK inhibitor has improved survival. And that's the differentiation, I would say, between a study designed like ours, which is focused on overall survival, because our drug has that evidence from the phase two, versus the JAK inhibitor, which is more of a symptom relief, which is why they usually use those different endpoints. Overall, the study has taken longer in the sense that patients are living longer on our IMPACT trial, which is, again, an indication that patients' well-being with this disease has improved somewhat over the years, but not to the point that, again, we have that major differentiation in survival.

So maybe kind of to touch on this in one more direction, what would you consider a clinically meaningful improvement in overall survival as it relates to systemic care?

I mean, it's defined in the statistical plan, and this is a high bar for overall survival, but it has to be statistically and clinically significant for FDA, obviously, to grant us

approval. So maybe kind of looking, you know, from the 50,000-foot view, any last kind of messages you want to highlight to investors? What do you think people are not catching on to as it relates to Jaron?

Yeah, I mean, look, it's, you know, Jaron is now a commercial company with an asset that, you know, last year we sold $184 million. And we all agree we can do better. And that's why we put a guidance for 2026 that shows what better means. and it's a meaningful growth for our base business in low-risk MDS. We have really reset our own way of working and making sure we're really engaging very effectively with the marketplace and making sure that that educational piece is really, really there because it's not every day that you get a drug that actually has a durable response where the response is a year and above in a low-risk MDS patient population. And yes, there are many cases where cytopenias happen. We are talking about the hematology patient, you know, hematural hematology group that is used to dealing with this. What was missing is making sure that we're really having the dialogue as to the why they're seeing that. And that's in the data that we have released in ASH and making sure that that engagement happens. And so we do have a very solid base case in the U.S., but also an opportunity geographically to expand the XUS. with a very strong balance sheet of 400 million and above. That gives us a lot of optionalities to pursue that. On top of that, we have a fully enrolled trial in the myelofibrosis setting with an overall survival as the primary endpoint. I mean, that data can't get more conclusive like that, right? So it either works or it doesn't. That's the upside of it. The downside is it does take years to mature that data. And luckily, meanwhile, we have the MDS business to, you know, grow and expand as we get to the MF readout. So I think where the opportunity here at Geron is that you have a commercial asset that is, you know, de-risked from a regulatory perspective, obviously, de-risked from a clinical perspective in the MDS business with potential to grow and help the 8,000 patients in the U.S. and, you know, thousands more XUS and with a very meaningful readout in the MF field and who knows where else can do, you know, and then on top of that, we can use our balance sheet for additional optionality. Our vision is to build a hematology powerhouse over time. That's where we want to go, starting with the lower MDS, getting into the MF and then really interrogating where else can we go with telormase inhibitor or any opportunistic innovation

that we might do after that right with that um i think we can conclude uh again thank you for for joining us and joseph as well thank you thank you very much bye-bye