Great. Thank you. Good morning, everyone. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler. And before I begin, I am required to point out certain disclosures regarding the relationship between Geron and Piper Sandler, which are located at the back of the room and also at the registration desk. Geron's imetelstat is currently under regulatory review by the FDA and EMA for the treatment of transfusion-dependent anemia in lower-risk MDS patients, and the company is preparing for a potential commercial launch in the U.S. in the middle of this year. Here to update from Geron is CEO, Dr. Chip Scarlett. Chip, thanks for being with us.
Yeah, thanks a lot, Ted. Appreciate it. Well, it's a real pleasure being here. I don't think we've presented for many, many years at Piper, and appreciate the opportunity. Since it's a pretty short period of time, we'll go directly into it. I do need to inform you about our forward-looking statements. So during the course of the presentation, I may be making forward-looking statements regarding future events, performance plans, expectations, and other projections regarding our businesses further identified in our corporate investor presentation and SEC filings. Actual events and results could differ materially from those statements as addressed in the risk factors in our SEC filings, and we undertake no duty or obligation to update any of our forward-looking statements to reflect future information, except as required by law.
So I thought I'd start off today by just refreshing those of you who are not familiar with the story of what imetelstat is and what the mechanism of action is, because it's quite relevant to the rest of the story. So this is our investigational first-in-class telomerase inhibitor. We've been developing telomerase inhibition as what we believe a highly relevant opportunity to target a very important pathway, particularly in heme malignancies. So malignant hematopoietic stem cell clones, which are the source of disease in myeloid heme malignancies such as lower-risk MDS and myelofibrosis, rely on continual upregulation of an enzyme called telomerase to support uncontrolled proliferation. So imetelstat was developed specifically to target telomerase .
When it binds to that target, to telomerase, it inhibits its activity, and that results in apoptosis of the malignant clones in the bone marrow and recovery of effective hematopoiesis. So that's sort of the fundamentals of this drug and our foray now for well over a decade into heme malignancies. Just two seconds on the lower-risk MDS patient experience. So these patients are generally elderly patients. I say that with a grin and bear it look, because I'm now in that classification from an age perspective. The majority actually are treated under Medicare Part B. Generally speaking, patients come to a general physician. They get referred to a hematologist when they have an anemia of unknown origin. They eventually become symptomatic after getting the diagnosis.
There's some watch and wait, and they get treated predominantly with erythropoiesis-stimulating agents, ESAs, EPO for short. Some cases, HMAs and lenalidomide, although that is becoming increasingly rare. And the core of treatment has been and continues to be blood transfusions. Eventually, as patients become increasingly transfusion-dependent, and the disease continues to progress, and all of these bad things that you see to the right occur, then this is the role for a variety of different drugs that have been under development for a while. Because this is a fairly short presentation, I'm not gonna give you a whole lot more about the background. I'm happy to take questions from folks.
But we actually had our phase III results that came out almost exactly a year ago, actually 11 months ago. And that was a study called IMerge, and we have been driving towards an FDA approval ever since we filed the NDA in the summer, and we have a PDUFA date now, which we'll talk about in a second, in mid-June. There are a couple of things to really point out about imetelstat, which in this case, I'm showing you some market research, but actually, this is whether it's market research by us or whether it's just speaking with KOLs or individual community physicians, it always comes across the same way. First of all, we have compelling transfusion independence and durable transfusion independence.
I would argue, in fact, that we have unprecedented durability of transfusion independence, having 16- and 24-week TI data. Certainly more robust than the current standard of care, which is predominantly luspatercept or Reblozyl. We also have compelling TI rates across various subgroups within the MDS population, and this is really quite important. That includes patients who have high transfusion burden, patients who are both RS positive and RS negative, and also we have activity in patients who actually have high EPO levels, which generally make them ineligible for either Reblozyl or ESAs. There is also a very predictable adverse event profile. We do see cytopenias. These cytopenias become very familiar to physicians who treat this patient population.
They are transient, they're short, they're manageable, and patients actually are treated today, both across the academic and also the community settings. The second indication that I'd like to just briefly discuss is an allied disease, relapsed and refractory or JAKi relapsed and refractory MF. And we'll see, and I'm going to just again, because we have a very short period of time, I won't even show a schematic of the, or design of the study. I would invite anyone who wants more detail. We have a very comprehensive deck in our the investor portion of our of our website, and I would encourage everyone to go there and take a look. So we're currently underway with a study called IMpactMF.
This is the first and only phase III trial in myelofibrosis with an overall survival as a primary endpoint. The reason that we are going for overall survival, which as far as, obviously, it's the only one out there today, is because we saw a really outstanding median overall survival in the Phase II Program, although that was uncontrolled. But compared to historical controls, and also compared to a real-world data study that in which we created a synthetic control arm using patients at the Moffitt, who were individually matched, if you will, having failed JAKis, individually matched to patients in the imetelstat phase II, we saw again, very dramatic differences in overall survival. So that encouraged us to do this large study.
It's a 360-patient—320, excuse me, 320-patient study, randomized 2-to-1 for imetelstat versus best available therapy. Best available therapy does not include a JAK inhibitor since these patients have all failed JAK inhibitors, and we expect an interim analysis, as I'll discuss in the last slide. We expect an interim analysis in the first half of 2026 and a final analysis in the first half of 2026. We believe that this study, if it reads out, would be very transformational for the field. And obviously, anyone who goes for the gold with a survival study, if that comes through, that becomes a very, very important opportunity in the treating the disease. These are large markets.
The total addressable market, or TAM, for lower-risk MDS, is made up of patients who are ESA ineligible, patients who are RS positive. That's the indication for second line for Reblozyl, or luspatercept, and patients who are RS negative, for whom the second line is not available from a labeling perspective. We expect to become part, that imetelstat will become part of the standard of care in lower- risk MDS, and that equates to roughly a $3.5 billion TAM, as of 2033.
In the MF patient population, there are approximately 24,000 patients who are treated in the U.S. and E.U., who are JAKi relapsed and refractory, and we expect to expand as a standard of care in relapsed refractory MF, and that's another additional $3.5 billion in TAM. So this is a very large market opportunity if we do in fact become standard of care in both of those indications. We have financial resources to support a potential commercial launch of imetelstat.
I think the key numbers are that we have $382 million on our balance sheet as of September 30, and we do expect to have financial resources to support our projected level of operations, including a launch, potential launch in the U.S. through the third quarter of 2025. So how will all of this play out? This is our view, at least today. We believe that there is a very significant opportunity for value creation associated with these different milestones. So on the left, you see U.S., E.U. regulatory filings. So, the U.S. NDA was accepted for review in October 2023. And the MAA for the EMA in lower-r isk MDS was validated in September 2023.
In 2024, we expect an approval in both the U.S. and the E.U.. The PDUFA action date is June 16 of 2024, and we would expect the review of the MAA to be completed by the end of 2024. Obviously, a launch would transpire after an approval, certainly in the U.S., and eventually, although, as we all know, it takes a little bit longer in the E.U.. And then I mentioned before, for relapsed refractory MF, we expect a phase III interim analysis in the first half of 2025. That's with the primary overall survival endpoint, and then an expected phase III final analysis beyond that, potentially in the first half of 2026.
We also have additional indications that we're sort of been started, and those include. We do have a small frontline study that is on in phase I. We're combining with ruxolitinib in MF, trying to bring the benefits of imetelstat earlier in the disease course. Right now, that's predominantly a safety study. There are overlapping issues of thrombocytopenia, as everybody knows, with ruxolitinib, and so we're just taking it a little bit slowly, but so far so good. And then we also have a consortium of academic hematologists, predominantly ex-U.S., have clamored to explore the potential value of the drug in relapsed refractory AML, and that's a study that has also just started.
So, that's what I had planned to say today, and I'd be happy to take any quick questions from the audience.
When it comes to U.S a re-
So, in the U.S., it's a pretty modest sales call universe, and we would expect to target that with 50-60 reps. Pretty typical for this type of disease and this type of indication. In Europe, we are sort of keeping our options open right now. As you know very, very well, Ted, it takes quite a bit of time for various reimbursement to come through even after approval. And so as of this moment in time, we've said that we would consider both partnering, but also potentially doing a self-commercialization in some of the larger markets and some other strategies. But we really haven't expanded on that too much. We got a longer ways to go, so we'll update that probably sometime later in 2024.
After this, I gotta go back to the West Coast. What should we expect from you?
There's a couple of very nice abstracts that sort of follow on from a lot of the things that you've already seen. In fact, if you want a sneak preview, since they've all been published, you can again go to our website to the investor section. Look, we have an updated corporate deck, and at the end of that corporate deck are a slide on each of the abstracts. The bottom line is they're showing some very, very beautiful data on the fact that we are able to treat patients even with historically difficult mutations to treat, and that's a whole story that I didn't have time to get into. The second is also we confirm that...
We confirmed the benefit of the drug in a number of other different areas. So I'll leave it at that since we're actually out of time, and I wanted to be on time if we could be. Other questions from people in the audience? I could probably do something quickly. Yeah. All right. Well, thank you very much. I appreciate the opportunity to present to everyone today.