All right, good morning, everyone. I'm Stephen Willey, one of the senior biotech analysts here at Stifel, and very pleased to have with us presenting from Geron, CEO Chip Scarlett, obviously coming off a successful ODAC. John's gonna be kind of-or Chip's gonna be walking us through, kind of a quick presentation. There'll be some time remaining for Q&A. I know we started a few minutes late due to some technical issues, but, I'm gonna hand it over to Chip, and as always, we appreciate your time.
Thanks a lot, Steve. Really great to be here, as always, with Stifel, with the Stifel Group. So good morning to everyone on the call, and I am indeed Chip Scarlett. I'm chairman and CEO of Geron Corporation. It's an exciting time for our company, as Steve mentioned, and we're looking forward to providing a corporate overview. We could have the next slide, Christian. Please take a look at our short and sweet forward-looking statements, and we'll move on. So, I'm happy to say that Geron is positioned for a very successful U.S. launch if indeed we're approved. We have a PDUFA date of June the 16th of 2024 for imetelstat in the treatment of transfusion-dependent anemia in patients with lower-risk MDS.
So assuming that approval occurs, we'll be addressing a very underserved patient population that has very few treatment options and translates in 2031 to a total addressable market of greater than $3.5 billion in the U.S. and the EU. With that PDUFA date just a couple of months out now, we believe our U.S. commercial preparations are on track for a very successful launch. And in addition to our lead indication in transfusion-dependent lower-risk MDS, we're also studying imetelstat in a phase III clinical trial in JAKi relapse and refractory myelofibrosis patients that's known as the IMPACT-MF clinical trial. This area also represents a very high unmet need as these MF patients face a very dismal survival prognosis today. We'll say a little bit more about that in the remainder of this presentation. Finally, I think we believe that we're very well-resourced financially to support these future potential milestones.
We had approximately $378 million on the balance sheet as of December the 31st of last year, and then in addition, we added net proceeds from our recent $150 million offering, that was done in part with Stifel. Based on current assumptions, we believe we'll have sufficient resources available to fund our projected operations into the second quarter of 2026. Next slide, please. As part of the NDA review process, the FDA recently held an oncology drugs advisory committee, obviously known colloquially as an ODAC, which Steve also mentioned, and the purpose was to review the clinical benefit-risk profile of imetelstat in the indication that we've proposed getting approved in. We're very pleased they voted 12 to 2 in favor of that clinical benefit-risk profile.
I'd just like to say, a really notable takeaway for me personally was the incredible outpouring of support from the hematology community in general and those who either take care of patients with lower-risk MDS or lower-risk MDS patients themselves, all of whom spoke out at the ODAC about the burden of transfusion-dependent anemia in this disease and a very deep need for new treatments, particularly for patients with difficult-to-treat subtypes such as high transfusion burden and RS-negative patients. Next slide, please. Let's take a quick look at the significant unmet needs across key transfusion-dependent lower-risk MDS patient populations. Approximately 10% of lower-risk MDS patients are not eligible for ESAs and represent a very high unmet need group. In addition, RS-negative patients make up approximately 75% of lower-risk MDS patients, and they are a population particularly vulnerable to poor clinical outcomes.
There's no therapies indicated for the treatment of anemia in RS-negative patients once they're relapsed or refractory to ESAs. RS-positive patients make up about 25% of the lower-risk population, and most who are high transfusion burden also lack effective treatment options. So these underserved subgroups that are at greater risk for disease progression, and they certainly have suboptimal survival, and are in need of more transfusion or sorry, and more treatment options. Next slide, please. So our IMerge phase 3 data has been received very favorably by surveyed practicing hematologists across both the U.S. and the EU key markets. In our market research that's been done with practicing hematologists in these markets, they point to several key attributes of imetelstat that resonate strongly and that if approved could help address these unmet needs.
This market research is based on the IMerge phase III clinical trial results, which were published in The Lancet last year. Hematologists in both community and academic settings emphasize the totality of clinical benefit, which includes the very compelling red blood cell transfusion independence rates across those subgroups, sustained reductions of transfusion units actually given, and continuous rise in hemoglobin levels. The hematologists also pointed to very meaningful durability of response, including at least 24-week TI data. And finally, they point to the well-characterized AE profile with largely manageable cytopenias, particularly given their familiarity with managing this kind of familiar profile of transient cytopenias that they see with other treatments. Next slide, please. So we believe today that we're well-positioned for the U.S. launch, assuming, again, potential approval. We've completed multiple critical launch readiness activities, and we plan to be ready to launch imetelstat in the market on potential approval.
Our commercial and medical affairs teams are fully integrated and preparing for the launch. This includes the recent hiring of our salesforce, or key MF and key account managers. Long lead time activities such as securing a trademark for our brand name, manufacturing of commercial supply, finalizing channel logistics, our distribution network, and our patient support providers have all been onboarded and are fully integrating our highly experienced commercial and medical affairs teams. So in addition, we continue to transition Geron towards a commercial company with the integration and adoption of various systems and processes to recognize and report revenues and the continued refinement of engagement plans with marketing, commercial access, payer, and reimbursement stakeholders.
I have to say, we're really excited by the caliber of talent and the deep oncology expertise that we've been able to add to our team who have, in general, a great track record of operational excellence. We're excited about the opportunity to bring this innovative therapy to patients. There's no question about that after many years, and we're confident in our readiness to launch imetelstat upon potential FDA approval. Next, slide, please. So I'd just like to mention briefly that our second phase III trial of imetelstat is in JAKi relapse and refractory patients. This is a very unique study in that it's the first and only phase III trial in MF with overall survival as a primary endpoint. Today, treatment of myelofibrosis is dominated by JAK inhibitors or therapies other than with other mechanisms of action in combination with the JAK inhibitors.
The currently available therapies have been approved based on their ability to improve symptoms and reduce splenomegaly. Once patients become unresponsive to JAK inhibitors, they experience treatment discontinuations that sort of total up to about 75% of patients after five years, and overall face a pretty dismal survival of approximately 11-16 months after they become unresponsive to JAK inhibitors. So we obviously believe that imetelstat could be transformational for these patients, and the trial design for IMPACT-MF that you see here is based on the IMbark phase II study in JAKi relapse and refractory MF patients. In that study, we saw an overall survival in the imetelstat treatment arm of approximately 30 months or nearly double compared to historical controls.
We also saw in a comparison of the IMbark phase 2 data, real-world data from a closely matched cohort of patients at the Moffitt, in which the improvement overall survival and lower risk of death for imetelstat treated patients versus patients treated with best available therapy was confirmed. So with regard to IMPACT-MF, as of November 2023, this trial is approximately 50% enrolled, and we look forward to keeping you updated on the progress of this trial. So if we could go to the next slide. I think I'd like to leave you with a couple of key takeaways before we go on to Steve's Q&A. First of all, our PDUFA date's approaching pretty rapidly. As we said, we had a very positive ODAC. Very excited by that. Our commercial preparations are on track, as I just went through.
The imetelstat phase III data in low-risk MDS showed unprecedented durability of RBC TI across multiple patient groups, addressing areas, obviously, of very high unmet need. We have an additional phase III trial of imetelstat ongoing in JAKi relapse and refractory. These indications represent some significant commercial opportunities with a total addressable market for transfusion-dependent lower-risk MDS of greater than $3.5 billion and for the relapse refractory MF opportunity of greater than also greater than $3.5 billion in 2023 across the U.S. and the large EU opportunities. Finally, we're financially resourced to execute on our expected timelines with $378 million on the balance sheet as of 2031 and to which we added net proceeds of $150 from a $150 million gross offering in March. Thanks again very much for the opportunity, Steve, to present a little quick overview for people who may be new to the story.
Let's go on to your question, Steve.
Yeah, no, of course. Thanks. So the ODAC was, you know, obviously a pretty significant de-risking event for the regulatory prospects of this drug. I thought you guys did a great job, particularly given I thought the FDA did you and the drug a bit of a disservice with the briefing document that had been published prior to the ODAC meeting itself. But I know that you had already put some of the top-level commercial infrastructure in place prior to the ODAC. Can you speak, I guess, to the pace of salesforce onboarding that's occurred just in the last month or so? And will you be prepared to launch if an approval is granted at any time prior to the actual PDUFA date itself?
Yeah, thanks, Steve.
Well, the commercial and medical affairs teams have been fully integrated into our company and have been planning for a launch for quite some time. We have extended offers to our field salesforce for our key account managers, and we expect to welcome them to Geron next week in order to begin their onboarding and training. So we expect to be fully prepared to launch on or very, very, very, very shortly after the PDUFA date.
Okay. You know, we still get some one-off questions just regarding labeling. And we'd just be kind of curious around your thoughts regarding the potential of a boxed warning. Does it matter whether or not from just the broadness of claims you'll get ESA ineligibles on a label?
and then whether or not there's going to be a specific requirement to step through an ESA prior to receiving imetelstat, and I guess, you know, what the implication of those patients receiving frontline luspatercept might be.
Yeah. Well, first of all, Steve, as you know from many of our ongoing interactions over the last little while, and appreciate your, your questions very much. I'm not going to speculate or comment on any ongoing FDA interactions, including labeling. It's, it's just not the right thing to do at this point in time. We're, we're really close to, to the PDUFA date. So, I think I'll leave, comments about sort of the regulatory process, that's ongoing aside.
But what I can say is that, as very similar in our phase III study, which will obviously form the basis for which we, we go forward into the marketplace, we expect that in a real-world setting, patients will be monitored for blood counts in the first several cycles. We would fully, fully support that and want to do that. We also have extensive feedback from hematologists, both in the community and also in the academic world, that they're very used to managing hematologic AEs. They point to the familiarity with lenalidomide, HMAs, and other agents that, you know, may cause prolonged myelosuppression even longer than, than we may see. That was a big feature, as you recall, of the ODAC. If anybody hasn't had the opportunity to, to look at that, I think it's still up somewhere, the whole recorded session.
But in any event, I think we feel very confident going forward that we will be able to deal with issues around warnings and precautions. And I think, again, our physician base is very, very comfortable with that in general for most of the drugs that they give.
Okay. I know IMerge had some fairly stringent cell count cutoff values for inclusion into the trial, both with respect to neutrophils platelets. I'm not going to ask you if you think that those are going to explicitly be stated on a label. But I guess, can you speak to, you know, what proportion of low-risk MDS patients who are presenting maybe post-ESA kind of fall underneath those cell counts? And can you maybe speak to the screen failure rates that we're seeing in IMerge as a function of either platelets being too low or neutrophils being too low?
Yeah. Well, first of all, I'd make the comment that, most, you know, I think most of the patients, who, actually, are presenting with lower-risk MDS and who are relapsing and refractory to ESAs actually have platelets greater than 75,000 and ANC levels above this threshold. You know, those were put in, at the same time that we were looking at a variety of different indications. As for the screen, as for the screen failure rates, I actually am not 100% sure. And screen failure rates, even if you end up looking at one of these issues, they're often far, you know, it's a, it's a much more complex interaction than just not hitting one particular number. So I just simply say that, that most, I, I think that in general, we don't see that as, as being a, a big issue for the, for the drug going forward.
We continue to see a high level of unmet need across, you know, the three patient segments I described earlier. We expect imetelstat to be broadly adopted in transfusion-dependent lower-risk MDS. Obviously, the commercial opportunity is very attractive.
Okay. Yeah, maybe just kind of digging into that commercial opportunity a little bit. I would say that's kind of where most of the questions that we're getting now are. I know you've kind of spoken to the magnitude of the addressable market opportunity being kind of north of $3.5 billion. But just with respect to launch kinetics, and I think we get this question a lot, I mean, how do you think about the luspatercept launch just as a proxy for how investors should be thinking about imetelstat uptake? Do you think it's fair?
I think that the question of how to model a launch based on a competitor that entered into a marketplace a number of years ago when there were even fewer opportunities is a little tough for us to really say. We know the overall opportunity is great. The actual, you know, kinetics of that launch are, we're not really quite ready to go there and make any predictions. I just would simply say again that I feel really confident that we will get there and whether it's over the space of, you know, a few first few months or later, I'm not 100% sure exactly how that will go, but that's pretty much what I think we can say today.
Okay. Just in terms of your kind of $3.5 billion+ estimate of the addressable market opportunity, you know, there's obviously a pricing and a duration of therapy assumption that's baked into that. We know that luspatercept is kind of up titrated to a higher dose level in the vast majority of patients. That doesn't really kind of reflect what the monthly WAC is. So I guess the first question is whether or not that assumption takes that into consideration just from a pricing perspective. Then, on duration of therapy, I know that we have, you know, mean and median duration of TIs from IMerge. But presumably in the real world, there's still going to be patients who perhaps lose their TI, but are still seeing clinically meaningful reductions in transfusion burden, improvements in hemoglobin.
So would you expect those patients to remain on therapy longer, specifically in the context of there not being a number of effective treatment options thereafter?
Sure. Well, first of all, I do think that luspatercept pricing, you know, it's an important consideration. It's a reasonable place for people to look. It's premature for me or us to comment on actual commercial pricing at this point. But obviously, we think the price is going to reflect the value that we bring to patients and payers, if approved. We know that these patients all face a pressing need for treatment options. That's why they come to the second line. We believe that we will be able to meaningfully address, you know, that.
As we improve quality of life and as we give them transfusion independence, I think we feel very comfortable that there will be space there for very appropriate, you know, compensation. I think that the, sorry, the second part of your question was, was duration of therapy. Oh, duration of therapy. Yeah. So it's a really interesting point. Although transfusion independence was both the primary and the key secondary endpoint of our phase 3 study, Steve, we also saw a very substantial improvement in, you know, reduction of transfusion, even in patients who did not achieve full transfusion independence. We saw that. We saw patients who fell away from complete transfusion independence continue on if they had meaningful reductions in transfusion burden. And very importantly, if they had increases in hemoglobin, which we saw quite dramatically in many of these patients.
So I think that, while it's a little hard to be absolutely predictive, I don't think you should see the end, you know, the need for a, you know, for a transfusion as ending the patient experience with imetelstat. I don't know why that would be the case. And, you know, transfusion, the actual decision, especially in the real world, to give a patient a transfusion is often dictated by, of course, you know, practice patterns in the individual country. But it's also, very much dependent on the individual patient, patient needs. And so, we're not in charge of that. The individual practitioner is in charge of it.
But I feel very confident that if patients have experienced significantly lengthy transfusion independence and on top of it, increased hemoglobin and, obviously, are continuing to see decreased transfusion burden over a large period of time, we feel that will translate to a very helpful therapy for those patients.
Okay. Maybe just in the last minute here, you do have an MAA submission that was recently accepted and validated. I think you guided to a regulatory decision, perhaps occurring before the end of this year. What are your strategic aspirations right now for commercializing in Europe? And how important is the preservation of, you know, these wholly owned rights that you still maintain on this asset to longer-term strategic optionality?
Sure. Well, first of all, I think you bring up an important point.
First of all, the MAA, I think our most recent guidance has been that we would expect a decision, as potentially in the early part of 2025. We are, we want to be very practical about commercializing in Europe. It is an important opportunity. As you know, it's a, it's kind of a slower rollout than in the United States. Individual countries come on board. And you're quite correct that there are considerations about maintaining our currently unpartnered and, and, you know, full value associated with the European rights. But there are also multiple different ways to look at that. And I could just simply say we're continuing to evaluate our strategic option of options for European commercialization. That could include self-commercialization. It could include partnering. And so we expect to be able to provide an update on that later this year.
Okay. Very good. John, or Chip, I appreciate the time. Thanks again for participating.
ll right. Well, thank you very much, Steve. Always a pleasure. Thank you.
All right. Thanks, everyone.