All right, good morning, everyone, and thank you for joining us at Needham & Company's 23rd Annual Healthcare Conference. So my name is Ethan Markowski, and I'm a biotech associate here at Needham. It is my pleasure to have with me today Chip Scarlett, Chairperson and CEO, and Anil Kapur, Chief Commercial Officer of Geron, with me today. As a reminder, any viewers who are watching through our conference portal are able to submit questions via the Ask a Question feature below the video feed. So with that, kind of get right into it. So Chip, maybe if you could start with introducing those who are less familiar with the story a little bit about the background of Geron and where the company is today. Yeah, thanks a lot, Ethan. It's a real pleasure to be with you and with the rest of the participants in this fireside chat. So it's a very exciting time for our company. We're looking forward to providing an overview, but before I begin, I do need to share brief forward-looking statements. During the course of this fireside chat, I may be making forward-looking statements regarding future events, performance plans, expectations, and other projections regarding our business as further identified in our corporate investor presentation and in SEC filings. Actual events or results could differ materially from these statements as addressed in the risk factors included in our SEC filings. Geron undertakes no duty or obligation to update our forward-looking statements to reflect future information, except as required by law. So for those of you who are unfamiliar with Geron, we were founded on the scientific hypothesis that inhibiting telomerase could kill malignant cells in a variety of different types of tumors. Geron is the only company to successfully develop telomerase inhibitor. Of course, we call our telomerase inhibitor imetelstat. And this drug is currently under review by the FDA and EMA. It is our lead product in a group of patients with transfusion-dependent low-risk MDS. We have a PDUFA date that is June 16, 2024. And so as a result of that, being pretty much around the corner in pharmaceutical terms, we're preparing to be ready for a US commercial launch at the time of approval. Beyond low-risk MDS, another key component in our path to value creation is our ongoing IMpactMF clinical trial. This is a phase III study in JAK relapsed and refractory MF patients. It's the first and only MF phase III trial with overall survival as a primary endpoint. Lastly, I should mention that these two lead indications represent a very significant commercial opportunity. We've estimated that the total addressable market is approximately $7 billion in 2031 across the U.S. and the EU. Maybe that'll complete my beginning statement. We can move on. Great. Yeah, no, that's a great overview. There's been a lot of attention on the recent FDA advisory committee meeting for imetelstat. I do plan on asking some more specific questions in a little bit, but maybe if you could just kind of summarize your take on the meeting and how you look about the future for imetelstat going forward. Yeah, I'd be happy to. Sort of a very high-level summary is that there were two sort of threshold questions that seemed to be addressed very directly. The first was the clinical benefit associated with transfusion independence. I don't think there was much doubt in the conclusion there that that was really spoken to. I suspect we'll talk about it a little bit more. That was really spoken to very eloquently, not only by many hematologists who commented on the value of transfusion independence, but also by many patients who came to the advisory committee. The second was, of course, we were very pleased that ODAC voted overwhelmingly in favor of the clinical benefit risk profile of imetelstat in these low-risk MDS patients who are transfusion dependent. That's, of course, the population that we studied. I would like to say, Ethan, before we go on, that a really big takeaway for me was the outpouring of support from the low-risk MDS community. That included not only hematologists, but also patients. Many spoke very eloquently at the ODAC about the burden of transfusion-dependent anemia and the tremendous need for new treatments, particularly for patients with difficult-to-treat subtypes like high transfusion burden and RS-negative patients. Right. Yeah, like you said, I think that was really apparent at the meeting. So thank you for pointing that out. You touched on it a little bit already, but one of the kind of key discussion points that was brought up throughout the meeting is it was unclear to some of the, especially, I would say, solid tumor physicians, whether achieving transfusion independence actually correlated to improving quality of life. It seemed like the hematologists argued that it definitely did, but maybe you can give a little more insight into how important achieving TI really is for patients. Yeah, it's actually stated by one of the panelists who's a hematologist that transfusion independence is actually the ultimate quality of life measure for her patients. Transfusions can provide short-term relief, but they also come with long-term clinical and quality-of-life consequences. And from a clinical perspective, a purely clinical perspective, frequent transfusions may lead to alloimmunization, thus difficulty in identifying a matched donor to support the continuous transfusion need. Patients can develop end-organ damage due to iron overload. But I think one of the things that really came out at the ODAC very, very, very clearly was that patients become tethered to an infusion chair in a way that a lot of people who are not intimately familiar with this disease don't really appreciate. For a patient in a more rural setting, it may take an entire day or longer than a day to drive to an infusion center to wait for blood to be cross-matched. Sometimes that blood has to then be brought in from another infusion center over the space of many hours. And then you don't just shove this in. You have to administer these units of blood carefully, especially at older patients who have challenges in their circulatory system. So patients really experience significant social and psychological burden in managing their healthcare. And again, anybody who wants to really hear the real improvement in quality of life should go listen to the patient's testimony at the open public hearing as to how getting off of transfusions had really changed their life for the better and how being on continuous transfusion dependency was really a terrible challenge for them to manage. Yeah. No, no, I agree. So one of the common investor pushbacks we hear is looking at the high rate of high-grade cytopenias that were observed in earlier clinical studies for imetelstat. Can you just touch on these briefly? How comfortable do you think physicians are at managing these cytopenias? And then maybe more importantly, the lack of these low blood counts translating to clinical events, how important do you think that is? So we've been studying this drug now in hematologic indications for well over 10 years. And the neutropenia and thrombocytopenia associated with the use of imetelstat have been very well characterized across all of these clinical trials. We know that these cytopenias very frequently occur during the first few cycles. They're generally very manageable and of short duration. As you mentioned, perhaps most importantly, there are very few clinical consequences associated with these cytopenias that would typically concern a hematologist. So the incidence in the IMerge phase III study of serious infections, bleeding events, hospitalizations, etc., were similar and not different in the placebo-treated arm. Those are patients continuing to get transfusions for the most part, and those patients who were treated with imetelstat. So from our market research and as we've heard from many different hematologists who spoke at the ODAC, this group of specialty physicians are very accustomed to managing hematologic AEs. And almost all of the drugs that they use have side effect profiles that can be associated with prolonged myelosuppression. So they spoke again eloquently as to their comfort level of this. This is part and parcel of their daily life. They follow patients' counts. They adjust dose. They hold doses as needed. And this won't be just for imetelstat. It's for many of the drugs that they use. So I think it's very clear to us that they're comfortable and does not present a major impediment to their adoption of the drug. Okay, and maybe one more from the meeting before we move on to some of the commercial preparation that you guys are doing. One of the points that the FDA brought up is that durability seemed to be significantly shorter, including all patients in the analysis versus only responders, which was about 40% or so. How should investors think about these results and maybe provide some additional context there on what your opinion of the data is? Sure. Well, I think I'd start off by saying that the reality is, and this would be true for most oncology or drugs or products used for treating malignant conditions, patients who don't meet criteria for any meaningful clinical response generally drop from treatment. So analytically, if quantitating durability of non-response really isn't very informative from a clinician's perspective, the durability of response, in this case for transfusion independence, has historically been a key outcome measurement for patients who've met a threshold transfusion independence response rate and can offer a very meaningful insight into the real clinical benefit seen, in this case, with imetelstat treatment. So, for example, patients who achieved at least an eight-week TI in the IMerge phase III study went on to have a median continuous TI of one year. That's a very meaningful outcome. It distinguishes imetelstat from many other products in the field. It was deeply appreciated in all of our market research. I think that came out very well in the conversations with the ODAC. Yeah, and I know you guys are also able to show meaningful, durable improvements in hemoglobin as well, which is another important point, I think. So I think moving on now to commercial preparation, like you mentioned, you have an upcoming PDUFA date. Maybe we could take a step back and remind everyone what the current standard of care is in the LR-MDS and where you plan on positioning imetelstat. Great. Well, I'll give the first commentary to this. And then if you have follow-up questions or other points need to be made, I'll invite Anil Kapur, who is our Chief Commercial Officer, to make additional points. The majority of low-risk MDS patients who have symptomatic anemia are treated with ESAs in the front line. And most will fail treatment in about two years. Luspatercept is also now approved in the front line and is the NCCN guidelines' preferred choice for RS-positive patients, which make up around 25% of the total low-risk MDS patient population, 25%-30%. Whereas ESAs are still preferred for the RS-negative patients in the front line, according to the latest version of the NCCN guidelines. Our IMerge trial addressed three main patient groups. So, first of all, front-line patients who were ESA ineligible given their high baseline serum EPO levels. There's a very high medical need that remains for these patients. There are so few options that the NCCN guidelines recommend participation in a clinical trial for these front-line patients with high baseline serum EPO. We addressed those in our study. Second, we addressed ESA-failed RS-positive patients, where there are also limited treatment options, including luspatercept and HMAs. We know from MEDALIST data and real-world experience, luspatercept is not effective in high transfusion burden patients. There remains in that group, that subgroup of patients, a very particular unmet need. Lastly, there's a very large segment of ESA-failed RS-negative patients who tend to have worse prognosis than RS-positive patients. That also creates a very significant need for durable treatment. Great, great. Yeah, and this next one might be more for Anil, like you mentioned. But luspatercept generated about $1 billion in sales last year. How are you currently, I know you've touched on it in the past, but how are you viewing the market opportunity for imetelstat when you put that into perspective? So I think we view this market opportunity as highly compelling. We continue to see, as Chip articulated, a very high level of unmet need across these three patient segments. We see associated dissatisfaction with high transfusion burden patients and lack of effective options for RS-negative patients. And our expectation, Ethan, is that imetelstat will be broadly adopted in low-risk MDS. And it's a large and a compelling value proposition. And our data that's in the public domain is highly aligned to the unmet need, which is always a good thing for patients and for physicians. Great. Many investors also ask us this, which is, aside from sales, are there any other key launch metrics that you plan on keeping track of and communicating to the public? Yeah, so we will track, obviously, multiple measures in addition to sales, Ethan, that will help us understand the imetelstat adoption and marketplace feedback. We will share appropriate details in our public disclosures. Great, great. And Chip, you touched on it, but I think it's an important point to kind of double down on. And imetelstat seems to be one of the only drugs so far that has demonstrated some activity in RS-negative patients, at least compared to luspatercept. What makes these patients so difficult to treat? And is there any mechanistic rationale that you know of to explain why imetelstat might work better in this population? Yeah, Ethan. Yeah, well, it's true that RS-negative patients are more difficult to treat than RS-positive patients. I think that's been borne out across a number of treatment-agnostic studies as well as many different studies that have tried to treat these patients with different agents. In general, RS-negative patients tend to present with multilineage cytopenias, whereas RS-positive patients usually or may certainly present predominantly with ineffective erythropoiesis with preservation of the other cell lines. I think I would just simply say, as you know, we've seen with IMerge phase III results that RS-negative, as well as RS-positive patients treated with imetelstat, which has a unique mechanism of action, have shown clinically and statistically significant improvements in TI, obviously, compared to the placebo control arm. So that really indicates a broader effect of imetelstat in these patients. I think I'll leave it there, but it's pretty clear that imetelstat's MOA probably leads to this ability to treat pretty broadly. No, I think that makes sense. So another question that has come up, especially recently, is a relatively few number of patients received prior luspatercept before imetelstat and IMerge, just based on the evolving treatment landscape. Do you think this will influence treatment decision-making from physicians at all, do you think? Or is it just something that might evolve over time as we get more data in patients? I'll take the first crack at that, and then Anil may have a follow-on commentary. I think first, mechanistically, we can't think of any reason that a patient wouldn't benefit from imetelstat after receiving luspatercept. They're very different MOAs. And additionally, there's a real significant unmet need in this population, and there are no controlled studies evaluating any other treatments following luspatercept. I would like to point that out. And we had a small number of patients, which Anil may want to comment on, in both our phase II and phase III, who had been previously treated with luspatercept. And we felt very comfortable with those results. So based on our discussions with KOLs and market research, I don't think we anticipate it being an issue in the real-world application. But Anil, anything else you'd like to add to that? Yeah, sure. So, Ethan, just two points. Both our phase II and phase III study had luspatercept pretreated patients. They included patients who went on to even receive 1-year TI. I think it's a proud fact for Geron that one of those abstracts was selected as a top 10, I believe, abstracts coming out of post-ASH, which is really not something that happens all the time, but it just shows you our value proposition. And to a point, yes, this always evolves post-commercial approvals because physicians use multiple different drugs, and then they report on their experiences. So I think this will also benefit us in the marketplace. And importantly, I do want to point, Ethan, to our public disclosures in terms of our sequencing studies where we ask physicians, "How do you see the treatment landscape evolve? And what is the sequencing that you see?" In particular, they tell us very clearly that if you have a high transfusion burden patient, if you have a prior luspatercept treated patient, or if you have an RS-negative patient, they prefer imetelstat as the drug of choice across all of these segments. So I think from our perspective, I come back to a high level of unmet need, a clinical data set that's pointing to an ability to meet those unmet needs, and physician feedback is very positive and receptive. Great, great. And moving maybe more towards a hypothetical question. We recently hosted a KOL call prior to your advisory committee meeting. And the physician expert on the call believed that imetelstat would likely have a black box warning and require a REMS program. And I know you guys may or may not be able to comment a whole lot on this, but just wondering if you agree with this sentiment from the expert, or if there's any additional comments you can make about the type of patient monitoring you think will be required, assuming approval. Yeah, sure, Ethan. So similar to the IMerge phase III clinical trial, and for that matter, in the phase II trials as well, we do expect that in a real-world setting, patients will be monitored for blood counts during the first few cycles. That's really part and parcel of almost any drug being given, and certainly any drug with effects that include cytopenias or myelosuppression. And we have extensive feedback from hematologists that they're very used to managing these heme toxicities. And they often point to their familiarity with lenalidomide, Revlimid, HMAs, and other agents that actually cause even more prolonged myelosuppression than we see in general with imetelstat. So I think that this will be, as Anil has already commented, I think this will be part and parcel of the treatment landscape as imetelstat becomes used more and more. I think that it will be something that these hematologists have said, especially, I refer you back to the ODAC. They were very clear in their comfort level with managing cytopenias as part of their ordinary course of treatment with patients with low-risk MDS. Great, great. And maybe another one for Anil, but Chip, feel free to comment as well. What else do you need to do to build out your team ahead of this commercial launch? And kind of a two-part question. You've touched on it in the past, but are you open to partnering imetelstat in areas outside of the US? What's your strategy look like there? Yeah, maybe I'll let Anil take the first part of that question. He can also address the ex-US part as well. Go ahead, Anil. Okay, so just on the first part, Ethan, our commercial preparation structurally and to raise the organization, those are largely complete. We have a full spectrum of functions, including field facing, medical affairs, all recruited, onboarded, very high-quality talent with deep operational experiences, knowledge of oncology, blockbuster drug launches, both in large companies and biotechs. So very proud of the talent that has come into Geron. And all this talent has been recruited internally and through referrals, which also speaks to a high volume for us in terms of their perceptions of Geron and our data. So very proud of that. Our key account managers, which is very much, as you always know, is the last part. Our expectation is to onboard them this month and get them fully field-ready for launch. From our perspective, the commercial organization is well spoken for and continue to engage and make sure that we are ready to speak about imetelstat upon potential approval. To your question around ex-US, I think Geron's stance is very clear, open. It has to be something which is always in shareholder interest and in the interest of patients. It is strategically an important decision. We look at both partnering opportunities, and we look at strategic options, including self-commercialization in select markets. We would be able to provide an update on this sometime later this year. Chip, if there's anything else you would like to add, please do so. Yeah, I think that's the gist of it. I think we'll leave it at that, maybe. Great, great. And I do want to save a little time here just to touch on some of the other programs, such as the myelofibrosis. Can you maybe start us off? I know you touched on it in the beginning of the chat, but maybe what's the current competitive landscape in JAK inhibitor myelofibrosis, and what potential advantages do you think that imetelstat has there? I'll take it. So first of all, I would say today's MF treatments are really dominated by JAKi inhibitors, JAK inhibitors, and JAK inhibitor combos. A new mechanism could be really well received based on our market research. I think the critical need right now is to demonstrate the ability to improve overall survival. This is needed in this quite serious disease. There has not been a study that is read out with an overall survival primary endpoint previously. We designed our phase III study, IMpactMF, to have that, to have an overall survival primary endpoint. I think it's pretty easy to say that if that study was positive, we think it would be transformational for relapsed/refractory MF patients. So we pretty eagerly look forward to that readout. Great. And you kind of answered my next question. But are you just really shooting for, or do you think that achieving the primary endpoint of OS benefit is considered clinically meaningful, or is there a higher bar in your view that you're shooting for outside of just the primary endpoint? Let me speak to that mostly from a clinical regulatory perspective. And then Anil may have a few comments about how we believe the market would adjudicate this. So from a, as I said before, I don't think we have any studies that have really convincingly shown in an overall survival, well-powered overall survival study that was designed with the primary endpoint, actually reading out with that primary endpoint of overall survival. So I think that's something that most people would say is the sine qua non of an outcome in a disease with very foreshortened survival. And we think that that would be, again, transformational. We will look at other key secondary endpoints, as you would expect, symptom responses, spleen responses, other PROs. But really, the study's powered to look at overall survival. It's a long study as a result. It's got a lot of patients. I think that we would really look to that as the key harbinger for the future in that particular patient population. Anil, do you have any other comments that you would say about if that study hits? If that study hits, Ethan, it is going to be transformative. A phase III trial with a survival endpoint, primary endpoint has not happened in myelofibrosis space. We are a completely different mechanism of action to the current standard of care and even evolving combinations. The research, our discussion with physicians is very clear. Our population is targeting, as you know, relapsed/refractory myelofibrosis patients, which is the vast majority of patients in this space. They tell us that if we are able to demonstrate survival, this drug would be transformative for MF and obviously would be very, very quickly adopted for the treatment of these patients. Great, great. Sorry if you mentioned this already, but can you just remind everyone what the readout timing looks like in myelofibrosis? Yeah. Our guidance has been that an interim analysis is anticipated in the first half of 2025 and a final analysis anticipated in the first half of 2026. The interim would be when approximately 35% of the planned enrolled patients had experienced death events. The latter, the final analysis would be when 50% had died. We'll provide updates when appropriate. Great. Maybe just a quick word on financial situation. I know you guys had a recent financing, the company did. What's your current cash position runway, financial outlook for the company? As of December 31st, we had approximately $378 million on the balance sheet. With the net proceeds from our recent $150 million offering, based on current assumptions, we believe we'll have sufficient resources available to fund projected operations into the Q2 of 2026. Great, great. Checking the Q&A portal, so feel free if there's any additional questions. While I'm looking, is there anything else that you want to kind of summarize or highlight from the company perspective, anything we might have missed or not covered in the chat? I actually think you covered all the key points. Thank you very much for that. Maybe I'd summarize by saying that this is a really exciting time for both the company, the investors, the investigators. We've had really remarkable outpouring of support from the heme community. This would be, if approved, this would be the first, only the third new drug approved in the last roughly 20 years in low-risk MDS. That's always cause for a celebration amongst people who need additional innovative improvements. So I think that we feel like the profile of this drug really sets it up to be very helpful for patients and something that we believe will also be extremely valuable from a return on investment perspective. Overall, very excited and look forward to a PDUFA date of June the 16th. Great. And as you were speaking, we did actually get one question in the chat. So maybe we can address that. Another common investor question is, how are you thinking about potential takeouts? We've heard maybe after a few quarters of sales, it'd be more likely. What can you comment on from that perspective? I'd start off by saying that this topic comes up frequently because of the relative dearth of late phase III or even recently approved or to be hopefully approved products in this space. It's kind of back to that third new drug in many years. So I think it comes up because of both the perception and the reality that there are relatively few late-stage assets available in either low-risk MDS or, for that matter, even in MF, although there have been other drugs that have been approved recently there. Overall, we remain open-minded. Our number one goal is, of course, to get this drug to patients. That's why we are prepared to launch the product, as Anil very nicely pointed out, to launch it with a lot of enthusiasm and an awful lot of belief that we will really be doing something special for patients. We also take into account the fact that we've had many long-term and very, very patient and loyal investors. We certainly want to see them rewarded. There are many ways that reward can come. But we look at all of that taken together and will adjudicate all the different possibilities as they come in the interests of both of those groups of individuals. Great, great. Well, looking at the chat, I don't see any more questions. So Chip, Anil, thank you for the time today. Thank you for attending our healthcare conference. Thank you. Really appreciate it, Ethan. Yeah, thank you. It was great. And appreciate the high-quality questions and the time you gave us to discuss our product here. Thanks. Right. Take care. Bye. Take care.