Hi, good afternoon. Welcome to the JPM organ Healthcare Conference. My name is Raji Gunasekera. I'm with the healthcare investment banking team. Today, I'm pleased to introduce, we have the Rigel Pharmaceuticals team and their CEO, Raul Rodriguez. Thank you.
Thank you, Raji. I appreciate the invitation. Thank you to our JP Morgan colleagues for having invited us. It's a pleasure to tell you a little bit about Rigel. So we will do the presentation, and at the end, we have a little bit of Q&A. So first of all, before we start, some important forward-looking statements. Feel free to read this, it's a lot of text, on our website. So Rigel is a hematology-oncology commercial-stage company here in the Bay Area, and there's two parts to the story I'd like to tell you about. One is commercial execution, where we have two products on the market at present: TAVALISSE, for the treatment of immune thrombocytopenia, ITP, and then REZLIDHIA, our newest product, for the treatment of relapsed refractory AML in IDH1 patients, mutant patients.
The second part of the story is what we're doing in terms of development and in our expansion plans for the future. I'll tell you a little bit about what we've done in the fourth quarter and last year, our plans for REZLIDHIA, exploring this opportunity in IDH mutant cancers in AML, MDS, and glioma. Some exciting developments there. I'll also give you an update on our R289, an IRAK1/4 molecule, R289, in phase I-B trial for lower-risk MDS, and discuss a few things in terms of what our objectives are in terms of in-licensing, where we're looking at late-stage opportunities that leverage our current capabilities and resources. Finally, a little bit of an update on our partner programs with Eli Lilly, our RIP1 program. So some exciting things to tell you in two different pieces.
Let me start with commercial execution. Well, it was a fantastic year for us in 2023. Record sales for our products. We reached $104 million for the entire year, 36% growth over prior year, a really great achievement. TAVALISSE, the main driver of this growth, was approximately $94 million, 24% growth over a prior year. We had a fantastic achievement. Things were a little flat there in 2020 and 2021 as the pandemic hit us, and we had to pull our sales reps out of the field. But then in 2022 and now in 2023, growth has really accelerated, as you see on this chart. So really fantastic performance by TAVALISSE, now in its fifth year on the market.
Our newest addition, REZLIDHIA, reached $10.6 million, about 10% of our total this past year, and in particular, Q4, where we grew 45% over the prior quarter. It's still at launch, still lots of opportunities here. I'll discuss that a little bit with you, where we're going with REZLIDHIA. But I would say this is an outstanding year and outstanding performance by both of these products, and a tribute to our commercial, our medical teams, our entire company, in having been able to achieve this at this point. Let me go a little bit into TAVALISSE in ITP, immune thrombocytopenia, where our objective is to continue to grow sales. TAVALISSE is indicated for the treatment of thrombocytopenia in adult patients with chronic ITP who have had an insufficient response to a previous treatment. Typically, that's a steroid.
Let me tell you a little bit more about the market. So there are approximately 81,000 adults with chronic ITP in the U.S. About 37,000 or so of these are in watchful waiting. And by that, I mean they either have some milder form of disease or they're in some temporary remission, but almost all of them eventually need some kind of treatment. The first-line treatment, about 20,000, as you see on this slide, are treated with steroids. Prednisone, dexamethasone are the two primary treatments there, and eventually, they need other things as their disease progresses, and that's where we come in. So we're indicated for this post first line, second line, and beyond, in lighter green here, where the arrows are pointing.
Every one of those opportunities are places where TAVALISSE could help these patients, about 24,000 patients in second line and older and later. Initially, when we launched the product, and this is what gets to what, where the growth is coming from. When we launched the product, we were used primarily in highly refractory patients, fourth and fifth line, the smaller buckets on this chart at the bottom there. Over time, as we continue to tell the story and share the data of TAVALISSE in these patients, doctors have grown more confident in the use of the product and have moved it more and more upline into second and third line, such that we reported last year that 70% plus of our patients are in second and third line.
Really a tremendous achievement, and it shows that doctors are learning about the product, using the product, perhaps in later lines, showing some success, and then moving it upstream into second and third line. That's where the majority of the patients are. Now, we're primarily in third line and less so in second line, and there's the opportunity: continue to move it up into third line, but especially into second line, and that's what we're working on getting done. So exciting because most of the patients are in second and third line. But in addition to that, that's where the product works the best. As you see here on the left, the product works the best when you use it earlier on. The earlier you use it, the better the results.
We're seeing responses of 94% on second line, 80-some% in third line, and then it drops down quite a bit, you see there. That is, the earlier you use it, the less treatment refractory the patient is, the better the results will be, Doctor, and the data supports that. So we want to get into those earlier lines because every patient we get there is very likely to succeed, and because they're very likely to succeed, they'll stay on the product very long. As you see on the other side of this chart, the durability of the benefit is really very long-lasting. If you get a response, you're likely to keep it. That's very valuable for us. It's very valuable for these patients as well.
So we've made tremendous progress since we launched the product in getting it to be used upfront, in giving doctors the confidence that it would work there, and then their own experience, such that doctors who use it in second or third line now use it in the next second and third line patient with confidence that they'll have a benefit. So we've been able to grow the product substantially by continuing to do that, and there's still room to grow, as I said, getting into more, even more second-line patients. We've grown patient starts on a quarterly basis in a very consistent manner, as you see here. And the CAGR here in terms of new patient growth, quite nice. We look for this to continue.
You know, the pandemic caused patients to stay at home a lot, not look for new treatments, in fact, make do with inadequate treatments. We had to pull our reps out of the field, so our ability to detail the product was limited. In 2022 and 2023, patients are doing exactly the opposite. They're going out and actively looking for new patients, new treatments. And we have introduced the product to doctors, and they're actively using it because we're able to be out in the field providing information to them that's very valuable, and that's what's driven new patient starts. The consequence of what I just told you is this: every quarter in 2023 was the best quarter since launch for TAVALISSE, every quarter. Really a tremendous performance. You see there in the orange bars, we reached nearly $26 million in sales in Q4.
Really a very great achievement, and the dynamics, we look to continue in this area with continued growth, continued patient looking for new treatments, and now increasing doctor confidence in the product, especially in those earlier lines. So very good performance, and we look for this to continue in 2024 as well. Let me shift over to REZLIDHIA. REZLIDHIA is a product we in-licensed in about a year and a half ago. We were able to get an early approval, three months early, in December of 2022. We launched it the last week or just before the holidays in 2022. So really, the first full year of launch was 2023.
The product is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia, AML, with a susceptible IDH1 mutation as detected by an FDA-approved test. So it's an IDH1 inhibitor product and can treat relapsed or refractory patients, as you see listed here, with AML. This is what attracted us about this product. The complete CR rate was about 35%. Very good response rates. But the most impressive piece of data was the durability of that response, nearly 26 months. As you may know, AML is a very aggressive disease. Every year in the U.S., about 20,000 patients are diagnosed with AML. About 11,000 or slightly more than that, 11,000, succumb to the disease. So more than half succumb to it on a yearly basis.
It really is a terrible diagnosis, and to be able to provide patients with a response and the ability to hold that response for over two years, to us, it was an impressive result, one that we thought we really want to provide this product to patients, because this is really a fantastic result. Also, second bullet point here, 92% of our responders were actually CRs, not CRHs. That is a complete response, almost all of them. And for those patients, 28 months of durability. That is really a great performance for this product, and we, we were delighted to be able to in-license it. We were delighted to be able to provide it to patients and doctors. The FDA was very collaborative. They approved it three months earlier to allow us to do exactly that. So we're delighted by that.
Transfusion independence was also achieved in a well-characterized safety profile with no cardiac monitoring, which we think is, very important. What we did last year. So we had a product with really excellent clinical data. We got it the approval. Our current sales organization at the time was selling TAVALISSE to community hem-oncs, and continues to do so. But in the middle of the year, to supplement that, we created an institutional business team, a sales force of about seven people, eight people, to address academic centers, providing information to academic centers about REZLIDHIA and its data. And you may know, when you introduce a new product, particularly in a relapse refractory setting, academic centers are the first to adopt that product and use it. And over time, as it becomes more established, the community's doctors begin to use it as well.
The market is divided about equally, community-based hem-oncs who use this product, treat the AML, and then academic doctors who treat AML. So with this new sales force, we were able to address both of those segments successfully. Our key drivers of growth in 2023 was this institutional sales organization and those institutional doctors. They're the ones that most quickly adopted this product, are adopting this product, and we still are not fully penetrated by any means, so it's still very much in the launch phase. And once we continue to grow here in the academic settings, we will continue to promote this in the clinical setting, in the communities, and then drive growth there as well in a in a biphasic type of manner. So we do this by speaker programs. We had very strong presence at hematology and leukemia meetings.
So we were at a big booth at the ASH meeting, a booth at ASCO as well. And what we're working on is increasing awareness of REZLIDHIA and its data, 'cause that is really what's the compelling story of the data through this team. But not only the right data, clinically, the right team, but also other scientific publications that allow us to talk about the product. One question we get very frequently, for example, was, "Does your product work post-venetoclax?" Venetoclax is typically used in the frontline setting, and the question is, does yours work in patients who haven't succeeded there, who are, have relapsed from venetoclax, venetoclax? And the answer is yes, it worked quite well. So we've been able to provide that data and other segment data that is important for doctors to understand and to consider using this product.
We're continuing to work in generating real-world data. Out in the field, patients who are on this study, we're following some of those to guide us in terms of how they're being treated and their success, so then in turn, we can share that with clinicians. That's very valuable data as we move forward, and in future studies, you'll see that. So we're quite active in providing a lot of scientific information to these clinicians to enable them to make a decision to use this product. So great data, great product, great team to promote this product to both institutions and community, and great scientific backup to it. So very good performance that has led to really an excellent launch. And in particular, Q4, where we grew the product 45% over the prior quarter to $3.9 million.
Total since launch, about $11 million, a little more, and we're looking for this product to be a key growth driver of our sales going forward. So we're, we're really delighted by this. Let me tell you a little bit about the second part to the story, how we're going to grow in the future and what our plans are there. I'll start on the right side of this, in-licensing. We, like REZLIDHIA, we're looking to do further in-licensing and acquisitions of products, specifically products in hemat area or closely related area, things like transplant rejection, for example, some other solid tumors that are used by these clinicians we already address. We're looking for these to be late-stage opportunities, that is, having registrational data in hand or having registrational and then, and file the NDA, or the NDA has already been approved, or we're waiting for a launch.
It has to be synergistic with what we do already have in-house, 'cause we have a really great infrastructure in terms of sales reps, marketing, medical affairs, market access, all these things, and we want to leverage it over a wider base of products and sales. That's what we're looking to do, just like what we did with REZLIDHIA. Moving to the other side, the left side of this slide, we're looking at to put in place collaborations for REZLIDHIA that address IDH mutant cancers, including AML, MDS, and glioma. I'll show you in a second a couple examples that we did in the fourth quarter to do that. We're looking to further evaluate our IRAK1/4 program, our molecule R289, in lower-risk MDS, and I'll share a little bit of information there as well.
Let me start with the alliance we put in place in Q4 with MD Anderson. As many of you know, MD Anderson is the premier cancer treatment center in the U.S., and frankly, the world. They have a very large patient population of patients in various cancers, but specifically AML. They pride themselves not in providing the standard of care today, but in fact, defining the standard of care of the future. When we met with them about REZLIDHIA, they were excited to work with us 'cause they believe REZLIDHIA could be the molecule that defines the standard of care in IDH mutant patients in the future, and they want to help us do that. We already have excellent data in relapsed refractory AML, as I shared with you, but we'd like to work on first-line or newly diagnosed patients in AML.
One of the trials we're looking to do with them is in first-line AML. We're also interested in high-risk MDS, where there's significant opportunity for IDH1 mutant patients, and they're going to conduct a trial in that population. Also, as monotherapy in lower-risk MDS, and finally, in maintenance therapy in post-transplant patients, four different trials that they will conduct. Because they have a large patient population, they're able to execute against all of four of these trials simultaneously. They have enough IDH1 mutant patients that we will be able to enroll this in quick manner. They're also excited to provide this information once they have it, to the market and to other clinicians, to help them consider how best to treat their patients and help define the future standard of care with IDH1 mutant patients.
It's a very exciting collaboration. For us, it's cost-efficient, $15 million over five years for four separate trials. Excellent economics to that. We have to provide them some funding and obviously drug material, which we have plenty. But it's also time-efficient, and that's perhaps even more important. Because this is an organization that's already there, they have the infrastructure, the capabilities to execute across all of these, they'll be able to generate data much faster than if we were going to, going out and trying to start these four trials on our own. The time frames to do that is expedited, and for us, that's critical, 'cause this, data in each of these areas is important.
Itself, they might be registrational, but more likely, they're likely will set us up for doing a registrational trial ourselves, and we'd like to begin working on planning that soon, but this data would support such an effort. So we're excited to have this launch. Glad to have MD Anderson as our partner. They're the biggest, they're the best in this area, and we're awfully proud of it. Let me move to glioma, and I'll come back to what we're doing here. But just to give you some background in glioma, you know, we're in this, in this business to really save lives for people and create new opportunities to, for them to live and, and live happy lives. And glioma is one of these deadly cancers that is absolutely horrible.
Horrible, and nothing has really worked and improved the lives of these patients in the last 50 years since we've had this war on cancer. We've not succeeded. Very deadly, 20,000 cases in the U.S. every year. 70% of patients with grade 2 and grade 3 are IDH1 patients. 5%-7% with grade 4 are IDH1 mutant patients. So this is a fairly prevalent mutation in these patients. As I said, the standard of care, surgery, radiation, chemotherapy, not very effective at all. Significant unmet need, and in fact, I'll come back, touch this, this a little bit. In some populations, the five-year survival is less than 10%. five-year survival, less than 10%. That is, more than 90% of the people succumb within five years, who have a diagnosis of glioma, high-grade glioma.
On the right side here, our colleagues at Forma, from whom we licensed olutasidenib, did this very nice trial. 26 patients in relapse/refractory, highly treated, treatment-experienced patients with olutasidenib, 150 milligrams, the-- that's the standard dose. No DLTs and a pretty good disease control rate. So for a very poor, poorly off patient population, that's actually a really good outcome. Well-tolerated as well, and obviously, it crosses the BBB, which you need to have to treat this type of disease. Let me go on to particularly the pediatric and adolescents and young adults, where, if anything, it's actually far worse. These patients are not well treated at all with the current therapies, and like I said, five-year survival in this gray bar, less than 10%. It's really, really quite sad.
So what we've done here is we put a collaboration in place with the CONNECT Consortium. CONNECT is a consortium that's doing this Targeted Therapy trial. This is a molecularly guided phase II umbrella trial in glioma. They have sites open across the U.S. and enrolling active patients in glioma, trying to get new treatments for patients with glioma. And they were excited to work with us because they are excited to have a very attractive IDH mutant product, olutasidenib, as part of that. So as part of this, we're going to put Oluta into their ongoing trial, and if you're an IDH1 patient, you will enroll in this trial and be able to have potential benefit from this product. So this is newly diagnosed patients. They go through radiotherapy first, and then they enter this trial.
So it's earlier patients than that earlier phase II trial that I shared with you just a minute ago. And we think the results, hopefully, are very positive, 'cause certainly the market needs that. It's a four-year collaboration, and it's gonna cost us $3 million. Again, very cost-efficient to get this done. And more importantly, time-efficient. If we wanted to start a trial like this, it would take us a fair amount of time to do this, get the sites up and running, IRB approvals, all that thing. It takes a lot of effort and a lot of time. This is already there. We're simply gonna tap into it with our product. That's very attractive, and so we can get data much faster here than we could if we did it on our own. So it's an exciting collaboration for us.
The design of the trial looks something like this. It's 60 patients, like I said, newly diagnosed patients. They go through radiation first, and then they come into this trial, and we're gonna treat them with olutasidenib and TMZ, the typical agent, for a year and follow them, and then a subsequent year with just olutasidenib. And we're looking at progression-free survival as the primary outcome. Again, this is an open-label study, so when we get enough patients in this trial and the data's compelling, we'll be able to look and share this data with you to show you what is a potential opportunity here. Glioma is not a small opportunity. It's a major opportunity, and it's a major unmet need. IDH1 mutations are an important and it plays an important role in these, in this glioma.
Hopefully, we can have something here that really dramatically changes the lives of these patients. Let me go on with our next opportunity in lower-risk MDS, our IRAK1/4, with our molecule 289. Low-risk MDS is a clonal disorder, leading to dysplasia and ineffective hematopoiesis in the bone marrow. Effectively, it's inflammation of the bone marrow, and this leads to various things, including AML and death. First-line therapy is typically transfusions and erythropoietic agents. Second line, HMAs, luspatercept, a couple other agents are used there. But frequently, these lose responses, and that's where there's not a good treatment available. There's no good therapies in the post-second line setting for lower-risk MDS. We're working in a phase II trial that looks like this, a phase I-B trial that will become a phase II-A trial.
It's a dose escalation, three-by-three design, very standard design. The first two doses, dose cohorts, Cohort I, Cohort II, are fully enrolled. Those were more for safety, probably not effective doses as yet. Cohort III and Cohort IV are where we hope to see some efficacy signals in addition to continued safety. So we're enrolling Cohort III. We'll then enroll Cohort IV, and our goal is to share this information by the end of this calendar year, perhaps at the ASH meeting. So it's exciting because this could be a novel new treatment to treat patients who have failed those other agents. We hope to get to a dose expansion phase or select a dose for that, and then with positive data here, so consider doing a registration trial ourselves in lower-risk MDS.
So later this year, we look forward to sharing this information, but it's exciting and definitely an area of substantial medical need. Let me just round out the discussion a little bit by updating you on our RIP kinase inhibitor in immune and CNS diseases with our partner, Lilly. On the immune disease side, the lead molecule is a molecule called R552, or now Lilly's renamed it LY3871801, harder to pronounce. It's a highly selective, highly potent RIP1 inhibitor. We completed successful phase one study, which demonstrated really what we view as best in class relative to competition. And now Lilly has initiated a phase II -A trial in rheumatoid arthritis, moderate to severe active rheumatoid arthritis. And so this trial is enrolling.
We look to have interim data in this trial as a next step, and we'll look forward to sharing that with you. On the CNS side, different molecules. We gave to Lilly a basket of molecules that cross the BBB for CNS diseases. They're looking at that. They're gonna take steps to evaluate which one they're gonna put into the clinic next, and then do so. So it's delightful to have progress in this program. I think it has tremendous opportunity on the immune side, RA, but then success in RA maybe leads to other immune diseases that are of interest. And on the CNS side, where there's tremendous medical need, a great opportunity as well. So look forward to data from this collaboration. Let me move on to our financials.
Really a very good year, as I said, and very good quarter. Our total revenue for the quarter was $35.7 million, mostly product sales, nearly $30 million, as you see here, TAVALISSE being the lead there. And every quarter last year was a great quarter, as you see here from the bars on the right-hand side, driven by TAVALISSE, but substantial contribution now from REZLIDHIA as well. A key point, as we've worked on increasing the sales of these products and our collaboration revenue, we've worked hard on maintaining financial discipline last year, such that, as you see on the bottom there, we started the year last year with $58 million. We ended the year with about $57 million, so not a lot of cash consumed, in other words. That is, our top line is mostly paying for all our expenses.
Not fully, but getting there. And that's a key objective for us, to reach a form of financial break even in the future, and yet still fund all the things that I've discussed with you in terms of developing the pipeline further, and we've done so in a very cost-effective, time-effective manner, as you've learned today. So we look forward to continuing that next year. Here's what we're looking to accomplish in 2024: Continue to grow the sales of REZLIDHIA and TAVALISSE, continue to discuss the data there with TAVALISSE, specifically in earlier lines of therapy, which we think will expand the confidence, the knowledge of these doctors, and they'll become more established in its use in the frontline settings or second- and third-line settings.
With REZLIDHIA , share the really attractive data that we have and continue to generate additional real-world data to allow us to discuss the product more fully with doctors. Still focused on the academic centers, but beginning hopefully some growth in the community side as well. And continued financial discipline. It's a... You know, we intend to live within our means, but continue to invest in our products so that we are not yet self-funding, but at some point in the future, we'll reach that. And continue to invest in our programs. You've heard what we're working on doing in AML, MDS, with our partnership with MD Anderson, with glioma, a huge and exciting opportunity with our partnership with the CONNECT team.
But we'll continue to evaluate clinical opportunities, registrational opportunities for these areas, for REZLIDHIA—REZLIDHIA, and perhaps also put additional alliances in place in other areas where we think we could do so cost-effectively and time efficiently. Continue to look at opportunities for fostamatinib and enroll and generate data for our R289 phase I-B and low-risk MDS. And a very active part of what we've done here at JP Morgan, thank you again for having us, is to be able to have discussions on potential in-licenses and acquisitions. This is a key focus for us. REZLIDHIA is the start, the first molecule where we were able to do that, certainly not the last.
We're looking at other in-license and acquisition opportunities that fit within our portfolio and continue to drive the top line of the product of our sales, so that in the future, it's far larger than I shared with you today. And hopefully, we'll have data in the near future on the phase II-A from our partner, Eli Lilly. So with that, I'd like to thank you for doing it. I think it was a good JP Morgan for us. I could speak to that. Many, many meetings and the disposition, the demeanor of the people we met with was much more positive than I think last year or the year before, or the year before that. So I think it was a great meeting. So again, thank you for everything.
Thank you.
Thank you.
Thank you, Raul.
Go ahead.
We'll do some Q&A now. If anyone in the audience has any questions, if you could put your hand up, we'll have a mic handed over to you. A gentleman over there.
Thanks. So for REZLIDHIA, can you just talk, like... So you've got some good CRs, but I'm still trying to understand where exactly does it go, and what is it displacing when people start to use it?
So in the relapse refractory setting, let me take a step back. When you're first diagnosed with AML, the standard of care, and this is in the unfit population, the standard of care is venetoclax and azacitidine today. That's what you get, and you may get genotyped, or you may not initially. If you are genotyped, you're discovered to have an IDH1 mutation. At that point, you've already started treatment, and so you continue venetoclax. Venetoclax is a pretty effective treatment in the first line, but people relapse from that very predictably over time. And so in the second-line setting is, what do you do there?...There's a currently approved agent named TIBSOVO. They were approved prior to us. They are also an IDH1 mutant molecule, and that's who we're competing for that relapsed refractory setting.
There's other agents in there. There's some cases where they are approved with TIBSOVO in the first-line setting. So some doctors use it in the first-line setting, reserve venetoclax or venetoclax for the refractory line, in which case we're competing with those at venetoclax in the relapsed refractory setting. So that's the competition in the relapsed refractory setting, but that's what they currently use. Our goal is to make doctors aware of REZLIDHIA and its data in that setting 'cause we think it's quite compelling.
If someone uses the other IDH inhibitor first, either in first line or in second line first-
Very good question.
Can you use yours, or will it no longer have an effect?
We've gotten two key questions. One is, "Does your product work post-Ven? 'Cause that's what I'm using as a standard of care." The second one is exactly what you have—you just asked: "Does your product work post-ivo or ivosidenib?" The answer is also yes. Our product is very different than theirs. Structurally, it's a different molecule altogether, and we've shown that we work even when that product has failed. That's a very useful bit of information 'cause in academic setting, some of them are adopting ivosidenib in the first line.
Then for TAVALISSE, as you noted earlier in the presentation, you're trying to move from, of course, a process of from fifth line up towards second line. How far along are you in that, and how-
Yeah
... how much of the sales are, you know, fifth or fourth line versus second or third line, and, like-
Uh-
So, like, what does the peak sales get to?
Yeah. We haven't given guidance to peak sales, but I'll tell you the answer to the other questions. A bit over 70% of our patients are in second and third line. So we are and recall the slide, 75% of patients in the market are second and third line. We're a little bit short of that, but getting close. However, we're mostly third line and not as much second line, and second line is bigger than third line in the slide I shared with you earlier. So there's opportunity to move from third line to second line, and that's a typical progression. A doctor gives us a patient in fifth or fourth line. Sometimes they succeed. The success rate is less, as I shared.
But when they do, then eventually they give you a third-line patient, and when you succeed there, then they consider giving you a second-line patient. So that's the progression or the scaling that happens in that field. But there's opportunity 'cause I don't think we're nearly as highly represented in the second line as there are patients in second line. And there are about 11,000 patients of the 24,000 that are in second line and beyond. 11,000 of those are in that second-line setting, so there's room to grow there. And the confidence the doctor has will allow us to get to that.
And then final question, then for the TAVALISSE, what's the duration of treatment now, as you've moved up-
Yeah
... towards third and second line?
You know, at fourth month, we have 55% retake at the fourth month. The reason we cite the fourth month is that, the label says, "Doctor, use this for 3 months. If it hasn't succeeded, then stop using it." They usually stop before that. But when you have the fourth-month refill, we're confident all of those patients are succeeding, otherwise they wouldn't be taking this product. So we cite that number as 55% of patients who start have their fourth-month refill. Our objective, what we expect that number to, is to rise over time. As we get more patients staying on longer and they're earlier-line patients, we expect that to increase. As yet, we haven't seen that yet, but it's getting there. So we'll provide an update on that data maybe sometime this year, later this year.
Thank you for your questions. Very good questions.
Thank you. Could you also elaborate more about your recently announced collaborations with MD Anderson and CONNECT, and how do these fit, you know, into your pipeline strategy? And are there any other indications you're most excited to explore for REZLIDHIA?
Yeah. So, MD Anderson, as I said, really the premier cancer institution in the U.S. and certainly one of the premier institutions in the world. And a very engaged collaboration with us. It's a strategic alliance. They're going to study our product in a range of different trials: first-line AML, MDS, high-risk MDS, low-risk MDS, and then post-transplant patients as a maintenance therapy. And those are all really attractive segments for us. And, you know, we wanna make this the standard of care with IDH1 patients in all of those segments. We have excellent data in relapsed refractory already. Our intent is to create comparable data in these other, in the areas: first line AML, MDS, high-risk, low-risk MDS, as well as post-transplant. And really, the collaboration is intended to be doing that and doing that simultaneously.
It's a very nice collaboration. They're excited to work with us. They think very highly of the product, clearly. They obviously can work on lots of other things, but they very much wanted to work with us and this molecule, and likewise, we wanted to work with the best.
Can you help us understand the commercial and medical capabilities you've built, specific to, you know, hem-oncs and competitive advantages they bring? And how can these capabilities be leveraged to expand your portfolio beyond your current products-
Sure.
- pipeline?
So, you know, it's very interesting. So with REZLIDHIA as an example, you know, why would someone license REZLIDHIA to Rigel? Not top of mind, right? I'll tell you why. The key presentation we did to them was on our capabilities on the commercial medical side, the range of different people that we had in those areas, the quality of those people, and frankly, what we did with TAVALISSE. Once we did that presentation, they were convinced we could sell this product. For them, olutasidenib was their baby. They discovered it, they moved it forward. You're like giving your firstborn child to some other party and hope they do well with them.
And we were able to convince them that we shared their commitment to the product, that their product was an important—would be, and is, an important product to us, and that we had the capabilities across all those commercial medical areas to do really well and continue to invest in the product to explore its full potential. And we're living up to that commitment. We're using those resources to do so for this product, all those different functional areas, and we're looking how we advance this product, broadly speaking. And I think that's a very nice pitch for someone else that has a late-stage hem-onc or related opportunity, 'cause we could do the same for their product.
If I could make a plug, if there are any listening out there, and you have a late-stage product, and you're considering building a whole commercial infrastructure to launch your product, this is a more efficient cost-wise, time-wise, risk-wise way of doing it with Rigel rather than doing it yourself. We'll give you an upfront payment. We'll give you milestones. We'll give you royalties. I assure you, from a cash position, from a P&L position, this is a far better alternative than building that huge infrastructure for a single product that, you know, may be delayed or all sorts of issues with it. We have that infrastructure in place, and we'd like to leverage it across many other products, and we have the bandwidth to do so in all the functions, including our two sales forces, one community-focused, one institutional, academic-focused.
And we'd like to very much do that for other products 'cause we think we could bring these. The world of commercializing in hem-onc doesn't need more infrastructure. It needs more product flow, and that's where we come in.
Can you give us a sense of timing for the readout in R289, your Rigel's IRAK1/4 inhibitor trial in the lower-risk MDS, and what would you view as a successful readout?
So, we're enrolling the two cohorts, the higher-dose cohorts, that we think there's a good chance of efficacy, and that's the 750 milligram and then the 1,000 milligram cohorts. And there, we're looking for safety. That's important to continue that. But importantly, we're looking for transfusion independence as a key marker there. And these patients are coming in, many of them transfusion-dependent, and we're hoping to improve that. So that would probably be the most important. Other biomarkers that you see there, you know, platelet counts, red blood cell counts, et cetera, are key other metrics that we're looking at. But if we're able to improve transfusion independence, that's a great achievement, and that sets us up well for a subsequent registrational trial.
That's great. Any other questions from the audience? If none, we can conclude this session, but a huge thanks to Rigel Pharmaceuticals, and thank you, Raul.
Thank you. Appreciate it.