My name is Derek Archila. I'm one of the senior biotech analysts here at Wells Fargo. I'm very pleased to have our next presenter, Rigel Pharmaceuticals. From the company, we have the President and CEO, Raul Rodriguez. Raul, thanks for joining us.
Thank you, Derek, and thank you for having us. It's nice being at your conference again, and it's a very productive meeting for us, so thank you. Appreciate that. Delighted to take you through the Rigel story, and, at the end, we may have time for some questions, so delighted to take. Important, forward-looking statements here. Please read those, important information. They're also available on our website. Let me start, by telling you what Rigel is. Rigel is a hematology-oncology company, and it's a company that looks to be much larger than we are today in hematology-oncology. And how we're gonna get to where we want to go is two ways: Commercial execution on our two approved products. One is Tavalisse in, approved for ITP. I'll tell you a little bit about that.
Our newest launch, Rezlidhia, in relapsed/refractory AML, and I'll certainly tell you a good deal about that. In addition to executing on the commercial available products, we're also looking at development and expansion. Development programs for our low-risk MDS program with our IRAK-1/4 inhibitor. I'll share some information there, and then soon we'll be sharing more information in terms of what we're doing with fostamatinib and olutasidenib in next set of clinical trials we hope to launch in the near future. We're also looking at continuing to in-license opportunities in hem/onc space, and I'll share with you what we're looking for there, as well as touch briefly on some of the partnered programs with the company. Let me start with our commercial products, and I'll start with growing sales of Tavalisse and ITP.
So Tavalisse is a Syk kinase inhibitor, and it was approved for the treatment of adult patients with chronic ITP who have failed one prior agent. Very typically, that's a steroid. This is an area where there continues to be significant unmet need. An area about 81,000 patients with adult chronic ITP in the U.S. Some of them, about 37, as you see there, are in watchful waiting. That is, they have some type of more mild disease that as yet hasn't progressed where they need therapy. Eventually, they all need therapy, and eventually, they go to first-line agent. Typically, the first-line agent is almost always a steroid. And that's where you start and see if, in fact, the disease responds to that.
But failing that, and most eventually do fail that, they go on to needing other agents, where we are approved in second, third, fourth, or fifth line. So that's where we're approved. About 24,000 patients in that second, third, fourth, fifth, and beyond lines that the product is approved with. But in reality, all these patients cycle, and so really the whole 81,000 over the longer term is what's available for treatment with the product. When you first launch the product, and we launched this product in mid-2018, about five years ago, we were primarily used in the more refractory cases, fourth, fifth line. There were some agents, Rituxan, Promacta that were used in first, in second or third line, and then we were used in more refractory cases.
Over time, our goal has been to get into the earlier lines. I'll show you on the slide here on the right. Initially, you see here, even in 2021, you know, close to just about, you know, 70%-60% of our cases were in the more refractory lines. The green and which is in third line, and the orange, which is in second line, relatively small still. Over the course of time, as we provide information to these clinicians on our product and the data supporting its use, and then they've gone to use it initially in more refractory cases, and success there allowed them or made them want to be using it in, say, third line and then eventually into second line. We've been able to grow the second and third line usage quite substantially.
So in the last 3 quarters, for example, we're a little over 70% in second and third line, which is a really great place to be. We still get some usage in more refractory cases, of course, but really very nice growth in the more earlier lines of therapy. That's really important for 2 reasons. 1, you see there, 75% of the post-steroid cases are in those second and third lines. So really, that's a large basket of patients in that category, and we're beginning to penetrate those lines. You know, it took some time to do, simply because the TPO agents for Rituxan are things that doctors are very experienced in using. They've been using it for 10 years before our product was approved or more, and as a result, displacing them took a level of familiarity and engagement that really required some time.
Well, important that we penetrate those early lines because many patients are there, number 1. And then number 2, as you see on the slide on the right, the response rates are so much better in second and third line. We're able to get patients over 30,000 platelets, 90, 80-some% of the time in the second and third line. So really, a very good performance, particularly in those earlier lines, especially compared to more refractory lines, where patients are just much more difficult to treat. So we're able to provide these doctors in earlier lines with a product that performs so much better, and this will have a cascade effect.
Once they've had good performance in second line or third line, they're likely to continue to use it in those patients, and maybe even if they're in third line, move it up, move the patient into second line to use the product. And this result, plus the excellent durability of benefit that we see here, where the product, once you have a response, you're able to hold that response for a good long time, has really been the compelling story of the product. So this has really been very good data and very good performance in the marketplace in terms of moving upline. The results has been really excellent growth for the product since COVID subsided. Prior to COVID, we were growing very nicely. COVID hit. We had to take our sales reps out of the field, go to Zoom calls.
Sales were relatively flat during those two years in 2020 and 2021 because we simply weren't able to see doctors, and frankly, the whole ITP market was flat. But then, beginning last year, we saw a reemergence. Clinics opened up, patients out there that previously were at home, not looking for new treatments, now looking for new treatments, and the result being that we've seen a very good acceleration of growth for Tavalisse post-COVID, such that the last three quarters has been the best three quarters, each quarter successively since launch. So we're really happy with the performance and growth of the product. A very steady product for us, reaching $21 million last quarter, and really provides the bedrock for us to grow the company and add on other products. So let me tell you about that next.
Oh, before I go on, in ex-US territories, we have partners that provide the product. Grifols in Europe, Kissei in Asia and Japan. We have a partnership with Knight in Latin America and with Medison in Canada and some of the Middle East countries. Of note, our partner, Kissei, conducted a phase three trial for Japan approval. Excellent results. They shared some of that at the ASCO meeting, and then now has launched the product in Japan, and they have been getting very good traction. So we look forward to their continued progress there. It's already approved in Europe, and our partner, Grifols, is selling it there, and we look forward to our Knight partnership when we do get approval in Latin America. Much smaller opportunity. But the...
All the major markets where ITP exists in Europe, Latin America, Asia, and North America, the product is available. Let me move on to our next product, which is expanding our commercial hem/onc portfolio with Rezlidhia, our new in-license. Now, about 14 months ago, July of last year, we in-licensed Rezlidhia from a company here in the Boston area, Forma Therapeutics. Really an excellent product, and I'll share why we were excited about this in-license. Pretty quickly, we engaged with FDA. We were able to get the product approved in December, about 3 months ahead of schedule, and we were able to launch the product in December, late December. Provide some information at the ASH meeting of December of last year, but really at the last minute. So we're really excited about this, this addition to the portfolio.
Rezlidhia is indicated for the treatment of adult patients with relapsed or refractory AML, who have an IDH-positive mutation. AML, you may know, is really just an awful diagnosis and a terrible disease, very aggressive, rapidly advancing, mostly in adults, more senior citizens than younger people. And it's a disease where there's a tremendous medical need. 20,000 patients diagnosed every year, a little over 11,000 succumb to the disease every year. So really a very, unfortunately, deadly disease. IDH-positive patients are about 6%-9% of those, and what we found is that, there's a real need for new treatments in this category, that address the mutation. And so we're excited about this targeted approach to doing it.
On the left side of this, you may be familiar. AML patients are divided into fit and unfit patients. Those that are fit undergo extensive chemotherapy and eventually go to transplant. They do relapse and were eligible for usage there. Unfit patients are treated with non-intensive chemotherapy, typically venetoclax and azacitidine, and then some of them relapse, and that's where we're eligible in the two orange buckets there that you see on the slide. So, our colleagues at Forma Therapeutics did this very nice and fairly comprehensive phase II clinical trial, looking at various cohorts as monotherapy and as combination therapy with azacitidine, looking at various subpopulations, and we'll be generating additional publications and information on these subpopulations as time goes on. But the key one was cohort one, as you see up there in the upper right-hand side.
This is where they enrolled the most patients, and that's the cohort that was what led to an approval for this product. The primary endpoint is CR/CRh rate, with secondary endpoints in overall responses, duration of responses, transfusion independence, overall survival, and of course, safety. And let me tell you why we were excited about the results from this cohort one in a very summary slide. What we saw is that the CR/CRh rate was about 35%. A very good result, especially considering this is a relapse refractory population. And perhaps the most important number on the slide is the duration of response, 25.9 months.
Recall, this is a disease that is rapidly advancing, and to be able to provide patients a durability of this response of over 2 years is really an impressive performance for this product, and that's what got us excited about the possibility of in-licensing and providing it to patients. In addition, the CR/CRh rate is mostly due to CRs. 92% of the responses were CRs, not CRHs, so higher quality responses. And for that group, the durability of response was 28 months. Again, a very impressive number for this really terrible disease and, and into the refractory setting. Transfusion independence was achieved for all dose groups, which is good. It's a well-characterized safety profile and does not require any cardiac monitoring, that leads to discontinuation. So really, there's a good deal more data, that has been published.
This result has been published earlier this year, and so, in January, so this is available for you to read if you so wish. But we're excited about this opportunity because it was such a nice fit with what we were doing with Tavalisse in the hematology/oncology area. Just, by way of background, there are about, 1,000 patients who are IDH positive in relapsed refractory AML on an annual basis. They come from both unfit and fit, relapsed refractory patients that we're available for.
So it's a patient population that is attractive for a company our size and an opportunity that we think is very exciting for Rigel in this setting. When we did some market research before we in-licensed the product, the market research told us three things: that they were looking for efficacious, targeted therapies, and obviously, this provided such a thing. For longer duration of responses, that was a key feature in products that doctors aspired to have, and that providing a good balance between the efficacy and the toxicity profile of the product. I think, olutasidenib, Rezlidhia is able to provide all of these in terms of what we're able to demonstrate and with data to support it.
So as you see here, we kind of check the boxes in terms of things that we're looking for in terms of a targeted therapy ability to provide a benefit. The CR/CRh rate is excellent. One thing that wasn't on the earlier slide is this estimated 18-month survival rate, 78%. Really an impressive number as you recall how deadly this disease is. Strong efficacy in this setting, excellent safety profile, and no cardiac monitoring required. So I think we're able to address many of the both patient and healthcare provider needs with this product, and we're pretty excited about it, as we launch the product this year. The performance this year has been very good.
We've sold about $95 million at the end of Q2 in terms of product sales, which is excellent, and shows nice increases in terms of bottles sold and bottles sold sent to patients in clinics, as you see there. So excited about the opportunity to do this, but we're just getting started. One of the things that we've done is at the ASCO meeting provide additional information to these clinicians. Now, we had the publication on the cohort one data in our hands. We also had this very nice publication by one of the important premier KOLs in this area, Justin Watts, where he took a look at the data for olutasidenib and provided this review article highlighting the product's benefit in this treatment area and expressing his favorable view of olutasidenib in the relapsed refractory IDH-positive setting.
In addition, now, one of the questions we received regularly from clinicians is, "How does your product work in the post-venetoclax setting?" We were able to provide at EHA, at middle of this year, this poster showing that in patients who failed venetoclax, we're able to provide equal benefit as we did in the overall patient population. So that's really a very nice result because it provided the clinicians' comfort that, "Okay, many of my patients are venetoclax start with venetoclax, and then once they relapse, then where do we go?" Well, this is a very good alternative for those patients. So we were delighted to provide that information. So good information available, especially at mid-year, from these two publications.
Then, what we've also done is now expand our organization in a more focused manner. In the middle of this year, we created an institutional business manager team, 8 sales reps that address academic institutions across the U.S. Lots of years' experience in hospital sales and also in hematology oncology. So they're well-poised to help us penetrate the key, a key segment, that being academic centers who treat AML, and numerous other activities to support them as well, that is helpful, that we launched in the middle of the year. And what we're planning is substantial number of publications, to help bolster the understanding of the benefit of Rezlidhia in this relapsed refractory setting.
So a lot of work going on in terms of helping us, in terms of being really well-poised beyond this point, to accelerate sales for this product with the sales team, good people, the right people, and the right data to support their efforts. So we're delighted by the prospects of this opportunity. Let me move on to the development programs, and we have two types of development programs in place. One is what I think are, we call more strategic, and some that are more opportunistic. The strategic ones are in hem/onc, and things that we want to move forward and execute ourselves. They include our IRAK-1/4 inhibitor program, and we're looking at other indications for both fostamatinib and olutasidenib in the hem/onc space.
And more opportunistic are things we have in terms of partnerships with our RIP kinase inhibitor with Eli Lilly and a COVID phase III trial with the NIH/NHLBI. That's in phase III. I'll focus on the strategic ones with the rest of this presentation, but touch a little bit on the RIP1 kinase, because there's some updates on that. So in terms of growing the company, beyond growing it with the current approved products and the currently approved indications, our efforts are in two phases. One is development options for fostamatinib. Here, we're considering steroid-refractory chronic graft-versus-host as a possibility. There was some data that we were able to publish from a collaboration we have at Duke, showing really nice results with fostamatinib in this setting, and we're considering that. For olutasidenib, we're considering several things.
One is moving into first line, and we're looking at the possibility there and what exactly, how exactly we might execute on that. Also, in combination therapies with other drugs, how the product might work there. And finally, other more challenging, difficult-to-treat populations, where we think this IDH inhibitor may have a real benefit. So we're looking at all three of those areas as possible ways of moving forward with ourselves or with academic partners. So that's a key part of our development, our growth strategy. The other one is a continuation of what we did with Rezlidhia: in-license a molecule and add it to our portfolio. What we have at Rigel is an excellent commercial organization that's able to bring in new molecules like Rezlidhia and sell it to both community-based hematology oncologists, as well as now academic-based hematology oncology areas.
And we're looking for products in hematology or transplant that are late-stage programs, and that we're able to leverage our current organization very well. By example, with Rezlidhia, we brought that molecule in a little over a year ago. We got it approved, we got it launched. We only added two headcount in order to do so. So it tells you the leverage we're able to get out of our commercial organizations today, and we'd like to continue to do that because we could add additional molecules that fit well, and that would be accretive to what we currently have and accelerate the growth of the products. So between these two efforts, development of olutasidenib and fostamatinib, and then licensing, we look to be major drivers of growth for the company.
Let me move on to our IRAK-1/4 inhibitor, which is a very interesting molecule. It's a molecule discovered within Rigel. IRAK-1 and 4 is important because it inhibits cytokines quite broadly. It inhibits the toll-like receptor pathway as well as the IL-1 signaling pathway, which are two key immune signaling pathways in cells. One in four does that much more profoundly than an IRAK-4 only molecule, which makes us excited because we're inhibiting with an IRAK-1/4, two key pathways that are critical, and we're doing so in a very profound manner. We've been able to show that we're able to inhibit almost 100% of some of these inflammatory cytokines, whereas with a IRAK-4 molecule, you can only inhibit partially.
We think this is an excellent tool to treat particularly difficult diseases, such as in hematology, oncology, and low-risk MDS in particular. So we're excited about this molecule discovered in-house. We've gone through phase 1 and have now initiated a phase 1b study that I'll show you a little bit of information on in a minute. But the opportunity here is tremendous, and we look for this molecule to show some very good data. I'll pass on this slide for a minute and then come back to what we're doing clinically. So this is a phase 1b study that we've launched, and this is a typical dose escalation study. We're enrolling three + three patients in each of these cohorts. We've completed enrollment in cohort one and cohort two, and now we're looking to go into cohort three.
And so we hope to begin enrolling cohort 3 later this fall, and hopefully even get to 4 later this year. Cohort 1 and cohort 2 are really more for safety. They're pretty low doses. We think we'll see efficacy more in cohort 3 and cohort 4. And once we get to dosing that, and then we are able to dose for 3 to 6 months. So, we hope to have some data from these two, cohort 3 and cohort 4, sometime next year, and be able to share that with you, because I think it should be a very exciting opportunity. We're looking at safety primarily, but secondary endpoints of transfusion independence, remission, overall response rates, obviously PK and some other biomarker work we're doing.
So we're very excited about this opportunity, and obviously, low risk MDS is quite synergistic to what we're doing commercially with both fostamatinib, Tavalisse, and Rezlidhia, olutasidenib. So we'll share that information with you as we get there. One of the other things I wanted just to touch base on is this RIP kinase inhibitor. We partnered this program with Eli Lilly, and there's two really components to this program. One is an immune, and one is a CNS. The immune is further along. We licensed to them a molecule, R552, which they have now put into a phase 2A study in rheumatoid arthritis. And we hope to have interim data with this program sometime next year. But it's an exciting molecule.
In Lilly's words, "This is the best-in-class RIP1 inhibitor," and they're looking forward to studying in RA. We think RA is an excellent opportunity. It's a big area. It's an area where there's a room for improvement, but it also is an area where success here bodes well for success in other areas such as psoriasis or IBD. So we're excited to see the data for both RA purposes, but also beyond RA purposes. So, we're delighted that they've started then, and we look forward to having that data next year. The second component is a CNS component. Our job there was to give Lilly a basket of CNS penetrant, RIP kinase inhibitors. We've done that, and now Lilly is working on selecting and doing some preclinical work on those molecules, and they look forward to putting that into human study after that.
So very nice program with some recent progress that we have to report on. We trust a little bit on the financials. This is a little busy slide, but I think it's useful. As you see there, the product sales continue to grow steadily. Tavalisse has had very good performance in the last 12 months, especially in the last 9 months in terms of the last quarters, every quarter being the best in terms of bottles sold to patients in clinics. And then sometimes there's up flows and downflows of inventory, as we listed there. But the trajectory is quite nice. And now with the addition of Rezlidhia, adding to that, you'll see we expect that number to continue to grow over time, which is really, really fantastic because that serves as the bedrock for the company.
Cash position is $64 million, which is a little higher than last quarter. So we're in a good cash position in our minds, and especially given that we have a products that are growing and will support the business overall. The objective is to reach cash flow break even. We don't have a guidance in terms of what, what quarter or year that will be as yet, but in the not that distant future, that would be the case. And that will allow us to fund other indications more fully from internal cash flows. So let me summarize what some of the catalysts are going forward. One is to continue to grow Tavalisse sales in ITP, and as you saw, very steady growth there.
We're gonna be delighted to continue that growth as the products becomes used in earlier lines of therapy, and those earlier patients have better results, so therefore stay on product longer, and seeing that continue to happen. The launch with Rezlidhia continued to go forward, and we look forward to providing additional data for new subsegments of the population, as well as using this new institutional-based business team to help us communicate more fully with clinicians in the academic centers. Later this year, we'll discuss what we're going to be doing with olutasidenib and fostamatinib in terms of next set of clinical trials we're doing there. Continue to enroll our IRAK-1/4 program and hopefully have data sometime next year on those more higher dose growth cohorts. We continue to look at in-license opportunities.
Some of that might be M&A related, to grow the business further, and we'll hopefully have announcements as appropriate there, and I look forward to our partners making progress with their respective programs, be it Eli Lilly or the NIH. So with that, I'll stop, and I think we have a little bit of time to answer some questions.
Awesome. Yeah, I can kick it off. Raul, maybe just first on kind of the ITP market and how you kind of see that evolving and, and where Tavalisse will continue to play a role. Obviously, we're gonna see maybe some FcRns enter the market, other small molecule, you know, drugs. So, I mean, does that kind of continue to remit you to kind of later line and kind of push against your kind of strategy to go earlier line? Like, how do you think that all plays out?
You know, what's very interesting is that it's an established area with the TPO agents being available now for 15 years, and Rituxan being available for longer than that and commonly used. Now, we're beginning to get a position in that area in those earlier lines and doctors becoming comfortable with the product, but it's taken about 5 years to do so. The data coming from FcRn, the lead one, frankly, is no better than what we have or the TPO agents have produced. So there's not an inherent reason to change that ordering. I also understand there's some pricing issues that they might have to price substantially higher, which may relegate them to the later lines, because that's where they start anyway. But if you price substantially higher, what we've seen is that this is a price-sensitive market.
We are priced equal to the TPO agents that are sold here, and they would have to be, too, unless their data is very different. But it's hard to beat 86, 94% response rates. You can't go much higher than that. And so I don't think that their entry into the market will substantially change the dynamic, where there's TPO agents, Rituxan, and ourselves used in first... in second and third line, and they, they probably would be relegated to later lines. I don't think it's gonna be possible, for, at least from the data shown so far, that that will be radically different.
Yeah, that's fair. I mean, in terms of, you know, what took so long to kind of move Tavalisse earlier line?
Mm-hmm.
I know you talk about 5 years. Is it really just the accumulation of the data, or was it just getting more experience with the drug? Like, if I recall correctly, when you guys launched, you know, there were some safety issues kind of associated with Tavalisse. I don't know if they were GI related, but have they kind of figured out how to best, like, titrate the drug and kind of get that experience that's led to more kind of, you know, basically penetration in the earlier line?
You know, so it's been 5 years since we launched the product, but remember, 2 of those years were COVID years, where our, our sales force was out of the field, hard to get access to doctors. We probably provided, in those 2 years of COVID, about a third as many calls as we did before that or afterwards. That is, it's just not as efficient in terms of being able to sell a product. So it's 5 years, but that is a caveat. I think, it just took years of doctors getting experience with the product and then feeling comfortable that they should move patients that are earlier on into the product. And it just takes being there, detailing the product consistently, them hearing about the products, speaker programs, talking about the products that got them to a comfort level.
Okay, I'll put a, I'll put a third-line patient on there." And then seeing positive results there, maybe a year later, "Okay, maybe I'll try this in second line now." And there's features to the product that differentiate it from both Rituxan as well as the TPO agents that they get, getting used to. You know, interestingly, the AE profile really has not been an impediment to the use of the product. You know, some diarrhea in some patients, but again, give Imodium, and that addresses that pretty well. So it's not an AE profile. It's just really a familiarity, comfort, experience. They, they-- Even though they are hem/oncs, they have established patterns that are difficult to upend, and it just takes some time to do so.
But it's delightful that we're at that point where, you know, we're seeing that we are changing the dynamic, and we are penetrating those earlier lines now. But that's just of late, really, in the last, you know, year or so.
Gotcha. And I wanted to ask a question on Rezlidhia. So just how do you think about that overall market opportunity? I know you put up some patient numbers, but, you know, why wouldn't a physician, you know, use Rezlidhia in that patient population, and what would they use instead?
Sure.
Or what was kind of standard of care prior, you know, in that kind of like, very refractory setting for IDH-positive?
Yeah. So, typical first-line patient in the U.S. is venetoclax and azacitidine. So, failing that, and if it's an IDH-positive patients, they were using an approved IDH inhibitor called Tibsovo, and that was the, you know, what they generally went to. There are some other things they used. If they used Tibsovo up front, then they would maybe use venetoclax and azo in the second line setting. So, it really takes getting doctors familiar with the data, and we're working very hard on that, providing data in various key subsegments. Like I said, post-venetoclax is essential, and we'll provide other segments, other demographics, to give doctors comfort. The patient, that's sitting in front of me would be a good candidate for, for Rezlidhia, and frankly, just they have to try it.
The benefit here is that really excellent durability, and so hopefully, they see that durability, and then we'll try it in another patient as well. So, it really requires them to try it first and know the product, know the data, get sufficient comfort in trying it in the first patient, having some results in that first patient, and then try it in a second patient. That's the dynamic that has to occur, and that's what we're working towards. Some doctors are, you know, and these tend to be more academic centers, are willing to try it earlier on. Doctors in the community settings, so not surprisingly, are a little bit more conservative in what they try, and they look for guidance from academic centers, which is why that institutional or academic business team is so critical.
Because it allows us to really address that audience that are probably, you know, early adopters of new technologies such as this. And I think we have the data that they've asked for us and continue to provide in order to help them help them use it. But it takes a fair amount of work, and it takes presentations, speaker programs, it takes a whole constellation of different things to begin to change established treating patterns, even though the disease is deadly and as rapidly advancing as AML. So, it's not that different, only maybe a little accelerated, actually.
Interesting. And then just in terms of the combos that you could look with Rezlidhia. So, what way would that be like combo with venetoclax, or is that a too toxic, you know, drug to do combo? Like, how, how would you think about combo therapy in this population?
So, in the relapsed refractory setting, we've tried some data with azacitidine already. So, we have some of that data, but there's opportunities there, that if you go earlier in line, what do you combine with? So, we're looking at several different options right now that look pretty attractive and what subsegments of, say, first line, which you'd like to try after. And so, we're looking at all those opportunities, and probably later this year, we'll have an answer to your question more precisely.
Interesting. And then just in terms of the... You know, you kind of talked about this kind of institutional sales force, and the academic. So, like, in terms of AML, what's the breakdown between kind of academic and community? And then I guess the same question for ITP, like, how much of the overlap are you getting, and can you leverage from the sales force?
So in ITP, it's primarily community-based, and a small set, percentage of it is actually academic, but it's primarily community-based. It's a chronic disease, and it's been around for... It's been drugs available for that setting, for a decade, so they are comfortable treating it now, and they know how to treat. There are some quirks. More academic center doctors are willing to go to 30,000 platelets count before they begin to treat. Hem/Onc that have less experience, they're a little nervous at 50,000 platelets, so they treat a little bit different. But there is very different, it's primarily a community-based disease. For AML, it's much more balanced. It's almost, we thought 50/50 academic versus community-based, but as we move forward, it may actually be more academic than community-based.
Keep in mind, this is in the relapsed/refractory setting. So even if someone's stabilized and are being treated with Vidaza in the community setting, if they relapse, they usually refer them to an academic center for subsequent drugs like this. So, it may be a bit more in academic centers, and so that's why this team is so critical that we just launched, working launch with.
Got it, and then maybe last question. I want to squeeze one in on the IRAK one-
Yeah.
- inhibitor. I guess, you know, we've seen some other IRAK-4s out there, and also there's also this, you know, I guess, line of thinking in terms of hitting IRAK-1 and getting that better efficacy. Maybe can you just kind of explain biologically what's, you know, why is it important to also hit IRAK-1 to kind of get that, you know, better, better efficacy that you're seeing with the, the combo?
You know, I exactly can't explain the reason why. The two work very closely in the cell in terms of MyD88, MyD88, mutations. And so if you inhibit only one, you still get signaling from IRAK, but if you only have IRAK-1, if you inhibit both, you really obliterate the signal or can obliterate the signal. So that is why it works, because they work very close in tandem. In fact, they're basically at the same level in the cascade. And so just hitting both really is just more effective.
Got it.
And it doesn't mean that you want to hit obliterate the signal, by the way, but it means you could back off the signal and inhibit it as much as you want, being able to go to 100%, whereas you can't do that with a 4.
Oh, yeah, I was going to follow up in terms of, like, the safety profile, again, in terms of the selectivity and of that molecule.
It's fairly selective for IRAK. It's a kinase inhibitor, so if you dose it high enough, you will get other kinases in there. And that's something we hope not to get to with the current dosing paradigm that we're looking at in this phase 1b trial.
Got it. Okay. Well, Raul, we'll leave it there. Thanks so much.
Thank you so much, everyone. Thanks.