This is a standard presentation, so welcome, Raul.
Thank you so much. First of all, it's nice to see you, and my thanks to our colleagues at Jefferies for having invited us again. I appreciate the opportunity. I'd like to tell you about Rigel and where we are. First, some important forward-looking statements here. This is also available on our website, so please feel free to read this. Let me tell you where Rigel is right now. It's a pretty exciting time for the company. We have, as you see on this summary slide here, our goal to grow our hematology and oncology business. I'd like to particularly focus on the commercial aspects of the business, where we have three approved products on the market: TAVALISSE for ITP, REZLIDHIA for mutant IDH1 relapse and refractory AML, and GAVRETO for RET fusion positive non-small cell lung cancer and thyroid cancer.
Together, this product makes a very potent commercial portfolio, and we've done very well with it, and I'd like to share that with you today. When you couple that strong commercial execution and strict financial discipline at the bottom left to right of the slide, what you have is a company that has reached the point where we are profitable. We are giving guidance to remain profitability, and what we want to do with those profits from the commercial business is a really important thing because it, in turn, will transform this company yet again. We'd like to invest them in really exciting development opportunities. R289, our dual IRAK1/4 inhibitor, is in a phase I b study for lower-risk MDS.
An exciting opportunity with tremendous medical need, where we think this product may have a unique role and may provide an additional alternative to available therapies that I think may really benefit these patients. It's probably the most exciting thing we've ever worked on at Rigel. In addition, we have olutasidenib, which is approved for mutant IDH1 AML, but our plans are to go beyond that and consider a trial in glioma that we're hoping to launch later this year. All of that, we continue to look externally for in-licensing and acquisition opportunities for products that are late stage, have solid data backing them up, which we think allows us to leverage our current infrastructure and capacity in hematology and oncology areas.
You put that together: a strong, growing, profitable commercial business, financial discipline, a development pipeline that is really exciting that will be transformative for the company, and we're able to fund ourselves through our own cash flow and looking externally for additional opportunities. It's a very exciting place for the company to be, and I'm happy to tell you about it. Let's start with this summary slide, which I'd love to share. Since coming out of COVID, as you see, the company's commercial business has grown quite nicely: 32% CAGR a year, and that's driven by growth in TAVALISSE, shown here in the deep green bars, but then incremental adds by REZLIDHIA starting in 2023 and GAVRETO starting in 2024. We acquired GAVRETO halfway through the year in 2024, and already it's having a substantial impact.
I'll come back to this, but we expect more of the same this year. Our guidance is for $185 -$192 million in net product sales this calendar year. That is continuing approximately 32% growth over this current year and, frankly, even beyond this. Really exciting about having this as a base business to build on. Here's a brief summary of Q1 of this year, which I think was an excellent Q1, our best ever. TAVALISSE continues to grow nicely: $28 million in sales, 35% growth over a year prior. Down at the bottom, REZLIDHIA, $6 million and 25% growth over a year, and that's still in its launch phase, but it's still growing nicely. Then GAVRETO, our most recent acquisition, we do not have a comparison, but Genentech, who was selling this product in the U.S., was selling $28 million annually.
That is about $7 million a quarter. As you see, in a short order, we've already exceeded that, and I can talk to you a little bit more about that. An exciting business in Q1. We're looking for continued growth from here for the balance of the year. Here's why we think this opportunity is so important for TAVALISSE. We continue to see demand growth. We continue to see new patient starts. The carryover, that is quarter to quarter. What we see patients is, once they've stabilized with TAVALISSE and their ITP is under control, they continue to stay on drug for quite a while. That's really beneficial because it allows you to build a business steadily quarter -over -quarter. We've also taken steps to streamline our distribution system, providing more efficiency and as well as easier access to patients.
On GAVRETO, every time you acquire a new product, you generally expect to see sales decline in the initial quarters as that transition happens. Delighted to say that we'd had an excellent transition for this product for Rigel. As a result, we saw no decline in sales, even in the first quarter where we had the product, and we've grown it ever since. That's a testament to the work that we did, the co-ordination with our partners, Blueprint and Genentech, in making that transition work, and frankly, just a lot of efforts in making sure every patient that was benefiting from GAVRETO continued to do so now that they're buying it through our distribution system. Demand continues, and we expect this to go forward.
REZLIDHIA, we continue to make patients and doctors aware of its benefits, and as a result, we think we continue to grow the product in relapsed refractory AML. It is the education and the sharing of that data that continues, and we're doing an excellent job of it. I'll show you a couple pieces of data in a minute about why we continue to be so excited about REZLIDHIA. Let's start with ITP and TAVALISSE. TAVALISSE is indicated for the treatment of adult chronic ITP in patients that have had an insufficient response to a prior therapy. That prior therapy is usually a steroid. That tends to be the first line, and then products like TAVALISSE are considered. There are about 81,000 patients in the U.S. suffering from ITP. First line is typically a steroid. That's about 20,000.
Then in second line and beyond, about 24,000 patients. That is where we are indicated for all of those nodes where a patient is considering a next line of therapy and treating their ITP. At launch, we were more used in the refractory lines, fourth, fifth line, and as the product has become an established part of the treatment paradigm, we are being used across the board: 2nd, 3rd, 4th, 5th , line. As a result, we are growing the business, and we are growing the patient stability with the product. What I mean by that is this: on the left-hand side, the earlier you use this product, 2nd and 3rd line, the better your results are. As doctors have become familiar and comfortable with this product, in the later lines, they moved it up naturally, and as a result, the results are even better.
Those patients once successful on the product tend to stay on it, and you see that on the right-hand side. The efficacy is a durable type of efficacy, and we're delighted to be used across all those lines, and having that durability allows us to really build a nice business here. Let me go on to REZLIDHIA and IDH1 relapse refractory AML. REZLIDHIA is indicated for adult patients with relapse refractory AML that have an IDH1 mutation. As you probably know, AML isn't just a god-awful disease. About 22,000 patients are diagnosed every year, and you have about 11,000 deaths a year, so quite a substantial number.
IDH mutations are about 6-9% of all overall AML cases, and by the time they get to the relapse and refractory setting, they're generally genotyped, so you know that they have this mutation, and you can access a product like REZLIDHIA in setting whether they started as fit or unfit patients. Here's what got us excited about this product. It's a clinical trial, primarily elderly people. That's who gets AML. A CR+CRh rate of 35%. That was slightly better than what was available prior, but what's even more impressive is the durability of that response: nearly 26 months of durability of that response. That's about three times better than what was available previously. That's an exciting advance in terms of this product and this indication.
Now we can say the response rates are maybe a little better equal to, but boy, if you have a response, you really hold it for a long time. If you look at the CR+CRh , CR rates, we have about 92% of our responders are CR responders, so pretty high quality. For those, it is 28 months. Really exciting data. If the doctors use the product and stay on it, you can get good responses and hold those responses for a fairly long time. That is a very sizable advance over what was previously available, and it is something that we are very proud of, and we are sharing this data, obviously, with clinicians as we launch this product. GAVRETO in RET fusion positive non-small cell lung cancer and thyroid cancer. It is indicated for those two things. I'll skip this chart. Here is what we are excited about this product.
GAVRETO is a RET inhibitor for RET fusion positive patients, and it has actually about a 50% market share, as you see on the right. However, about 25% of patients are treated with multikinase inhibitors and chemotherapeutics and immune checkpoint inhibitors. It happens that those treatment approaches are not very good. They're not as effective as the RET inhibitors are. Eating into that share, that 25% that you see in the gray bars, is our objective in growing this product by providing our GAVRETO to those patients and giving them a better treatment than they currently are receiving.
We were fortunate, soon after acquiring this product, that we were able to get, and you see here, the guidelines had changed to say that the preferred first-line treatment for RET-positive patients is a RET fusion inhibitor, and that even if a patient is succeeding or being treated with multikinase inhibitors or chemotherapeutics, they should switch to a RET inhibitor. Strong support from the community in terms of helping us get this type of product out to these patients and hopefully have a real benefit on these patients. We are excited about the opportunity here. The only once daily RET inhibitor available, highly durable responses, shown some results in brain mets, which I think are very supportive and a very well-established safety and tolerability profile. We are excited about this. It is still early stages for us.
We just acquired it in June of last year, so we've only had it for three quarters, and each of those quarters, we've grown the product and look to continue to grow this product nicely. A very useful addition to the portfolio. Outside the U.S., in the U.S. is our sole focus for ourselves. We've put partnerships in place for TAVALISSE in Europe with Grifols, Kyowa Kirin in Asia-Japan, and Medison in Canada and Israel. Our partners have gotten the product on the market in various territories and produced fairly nice revenues for us this past quarter, as you see here, from the various partnerships. Included in this is a one-time payment for approval in Korea from our partner Kyowa Kirin, about $3 million. In this is not just royalties, but also supply that we supply our partners for the product at a small markup.
In addition, we'll put a couple partnerships in place for REZLIDHIA, one with Kyowa Kirin in Asia-Japan and another one with Dr. Reddy's and across Latin American territory. Expanding in other countries beyond the U.S., but already a meaningful producer of our revenues. Let me move on to what I think is the most exciting piece of this presentation: the clinical development update. The clinical development pipeline has R289, an IRAK1/4 inhibitor, which we're looking at at low-risk MDS. There we have both fast track as well as orphan designation from FDA. Very good engagement with FDA on this product and this indication. Olutasidenib, we're looking at beyond relapsed refractory IDH1 mutant AML.
I'll share a little bit of our trials we've launched in other areas, as well as considering a glioma study, phase II study in glioma with this product, and I'll talk to you a little bit about that. We continue to look at in-license opportunities. There's quite a number of things out there. We're looking at things that are differentiated, that have data that we think is compelling in hematology or oncology, that have late-stage programs, that is, have registrational data in hand, have already perhaps filed an NDA, the NDA is approved and waiting to launch, or the product is on the market and we feel we can add value to the marketing of that product. They have to be synergistic with our current in-house capabilities.
This is a strategy of Rigel, one we've executed with two products now, quite successfully, and have been successful with the launch and execution of those products to now. We're excited about continuing that strategy because that, plus the development pipeline, especially R289 and low-risk MDS, has potential to really grow this business very substantially, and therefore its profitability and our ability to do even bigger trials and more important trials and larger indications over time. Let's move on to, oh, thank you. One area that I would quickly highlight for you is the various presentations at ASCO and EHA, focusing on oluta and focusing on GAVRETO PRAL in various settings, which I think continue to confirm the benefit of the product, those two products in those respective indications, as well as looking at a couple different assets of patients that we hadn't studied before.
The ASCO presentations have already occurred, and those are available, and then the EHA's presentations are up and coming, but I think a robust set of data across those two products at those two conferences. Let me move on to 289 in low-risk MDS. Here's what we're excited about this: tremendous value proposition. There are about 12,000 patients with lower-risk MDS that have previously been treated. That's who we're targeting for our current trial. We're looking at taking those patients who are transfusion dependent and getting them to attain transfusion independence. That's a paradigm, the endpoint that the FDA has been looking for, and therefore one that we are really excited about what we're doing with this area because we think we can have a meaningful impact on lower-risk MDS patients. The mechanism is novel.
No one else is working in lower-risk MDS with an IRAK1 and IRAK 4 inhibitor. In fact, I could say we're the only one actively developing an IRAK1 and IRAK 4 molecule overall, and 1 and 4 confers us substantial advantages. 1 and 4 inhibition is better than IRAK4 alone. We were able to more profoundly inhibit inflammatory cytokines, including in the bone marrow, which is our target in lower-risk MDS, and that's an exciting addition to the treatment approach in lower-risk MDS. IRAK1 and 4 inhibition blocks toll-like receptor signaling and IL-1 family of signaling, two key inflammatory pathways that if we're able to do that in the bone marrow, we should have a real benefit. We did a proof of concept study. We took normal healthy volunteers in a hospital setting. We gave them an LPS protein, and as a result, a cytokine storm occurs.
We are able to demonstrate that with this product, we are able to greatly diminish, and in a dose-dependent manner, that cytokine storm. That is an acute setting. We caused the insult. We solved the insult. If we could do that on a chronic basis, we may have a new approach to treating diseases such as lower-risk MDS, where the inflammatory cascade that is going on in the bone marrow is a key driver of the progression of lower-risk MDS. Completely new approach, and it has only been in the last really 10 years where it has been acknowledged and now commonly understood that inflammatory process is a key driver of this disease. We are excited to have a molecule that is active against two key signaling pathways because we think we could have a real benefit to these patients.
I'll show you in a minute why we still believe that there is a significant need for new treatments in this area. Frankly, I think we can provide such a treatment, and the opportunity is very profound, transformational for this company. As I mentioned earlier, we have fast track and orphan designation and early, but a very encouraging clinical profile. We presented some data at ASH that I'll quickly review for you today, but it's showing that the product may have real promise in treating lower-risk MDS and more to come. Here's the treatment landscape for lower-risk MDS. Initial therapies are typical ESAs and transfusions. Failing that, then they move into other areas such as Luspatercept, imetelstat, or RYTELO, and then failing those, they use hypomethylating agents, but not approved as yet.
We put little asterisks, little stars, blue stars in areas where we may proceed with this product. We have opportunities after HMAs, much smaller opportunity. The two stars, blue stars on the left are really large opportunities, and that's areas that we'd like to explore further, and I'll tell you what we're doing there. We're beginning to focus on treatment of transfusion-dependent lower-risk MDS patients where, frankly, there's just not enough here to treat these patients, and we think we could be a meaningful contributor to how these patients are treated. Let me tell you about the phase I B study that we're in the middle of or towards the end of at this point. It's a very typical dose escalation phase study, three plus three design. We started at a very low dose, dose level one.
We only did three patients there because we were comfortable that really that was just too low a dose, and then the more meaningful doses are dose level two and above. At the ASH meeting in 2024, we presented data on dose level 1,2,3 , and 4, and we since then have recruited dose level 5 and are now recruiting dose level and enrolling dose level 6. At the end of this year, we should have a good data set on all these dose groups, and we hope to share them at a medical conference at the end of this calendar year. Also, this year, what we hope to do is to pick two of those doses that look the most compelling and move them into a dose expansion phase.
This could be about up to 20 patients a dose, and we compare what the two doses look like now with more robust numbers. By the end of that expansion phase, we should have roughly 25 patients in each of those two doses where we can make some meaningful differentiation between the two and meaningful comment in terms of this is a real product here. That is coming shortly, and we will initiate those expansion phases later this calendar year. After that, we will launch a registration study, and we are going to consult with FDA in terms of what that might look like and obviously share with you what that might look like. Importantly, this is something that RYTELO, Luspatercept have done already, and we know what to do here. We are not reinventing the wheel here.
We know what we have to show, and that is transfusion independence with a safety profile that's acceptable. Given the mechanism, we're confident we can show that with this product. We're excited about that. You see here in the little blue box in the middle, we also want to try a smaller study to show earlier patients. Are we able to have a benefit in those that have only taken an ESA and are treatment naive to everything else and see what the benefit is on that earlier phase as well? I think that could be a very exciting additional opportunity for us. Data's coming at the end of this year on the dose escalation phase. We will announce that we've started a dose expansion phase and what the two doses there are.
We will have discussions with FDA in terms of what the plan is going forward to registration, and we'll launch this additional exploratory study in the post-DSA patients. It's pretty a lot of effort, a lot of excitement around this product, and we're incredibly excited about it because we think it has such a meaningful impact on this disease in various settings, and we have, importantly, the ability to fund this. You can't get a more exciting time for the company than this very thing. Let me share with you a few other things. Safety looks acceptable in most of the cases. AEs were diarrhea, fatigue, other things like that. We had grade 3, 4 AEs as well. There were about two of those of platelet count decreases, pneumonia, ALT increases. You see here data treatment emerging AEs.
The 500 QD looks pretty clean, and even the 750 looks pretty clean. I think you see in a footnote there we did have increases in ALT and AST that might be dose limiting at the 750 dose group. We are obviously taking that into account. In general, low incidence of grade three, four cytopenias and infections with the product. We think a manageable safety profile. The data looks exciting. This is data we shared at the ASH of last year, but I want to highlight the two in boxes, the 500 QD in green and the 750 QD in black. What we saw in each of those groups, there were five evaluable transfusion-dependent patients in each of those two doses, of which we had two responders. That is about a 40% response rate in those two patient populations. That is a pretty good response for this patient.
Considering especially that these were highly treatment refractory populations, that is, going back to this bar here, it was patients who generally had failed luspatercept. They had failed HMA. Really at the extreme right of this, very difficult to treat patients. Despite that, we were able to show good solid responses, 40% in those two dose groups. We're really delighted by that, and we're obviously hoping that we could achieve similarly or even better in future doses, especially if we go into earlier patients where they're more likely to succeed on this product. That's exciting. Here's a little bit of a summary of the four responders we had. There were four of them. Three of them were high transfusion burden patients. You see many of them elderly patients. What's remarkable here is the number of prior therapies that they had failed.
Three of them have failed luspatercept. They failed even experimental agents. You see fostamatinib there in one of the patients. Yet we were able to get them to good responses. One, even 52 weeks. This is the cutoff of last year, so we'll have more updated data later this year. Really impressive results and impressive increases in hemoglobin as well, 2.3-5 g per deciliter versus their baseline. You want to see that as well as transfusion independence achieved. Really pleased with the results of those earlier dose groups. We're looking for the same as we go into higher dose groups and selection of two of these dose groups to move forward with. Let me move on to olutasidenib in a couple of areas, but particularly glioma. Glioma continues to be one of the most challenging areas in treatment. Very difficult to treat these patients.
Many of them succumb. Historically, not much has worked. A couple of years ago at the ASCO meeting, vorasidenib showed very solid data, grade two, low-grade glioma that demonstrated that IDH1 inhibition may be really beneficial if you're able to cross the BBB, the blood-brain barrier. And our product is, there's this trial here that I cite, 26 patients with oluta in highly treatment refractory patients. And what we're able to show is that we had a couple of partial responses, 10 stable disease. That is, disease control rate of about half the patients. That's a really good result given how difficult to treat those patients were, showing also that the product does obviously in patients cross the BBB, and we may have success here. What we're doing here is two things. We've already launched this Connect target phase two clinical study.
The Connect organization is conducting an umbrella study across the U.S. studying high-grade glioma. What we've agreed to with them is that we would add olutasidenib as a targeted phase two study arm. If those patients have IDH1 mutations, they can enroll into this study and receive olutasidenib as a treatment in a maintenance setting. These are newly diagnosed patients, and we're giving the product with TMZ to start and then eventually just olutasidenib over the course of time. This study is now open for enrollment. In addition, we're planning to start a phase two study in glioma later on ourselves, and we'll share that information with you a little bit later this year.
In addition, we have put our collaboration with MD Anderson for olutasidenib in various other areas, including AML, looking at AML in first line as well as relapsed refractory, higher risk MDS, lower risk MDS, and CCUS, as well as transplant in the maintenance setting. Some pretty exciting opportunities there that are now all open for enrollment. Let me just quickly say some of the milestones we're looking to do: complete the dose escalation of R289 in lower-risk MDS, initiate the expansion phase study, interactions with FDA leading to a registrational program, and present the data at the end of this calendar year. With olutasidenib, initiate the phase two study in glioma and continue to support our collaborations with MD Anderson and Genentech. I'll pass on this R289 slide. It's available on our website for you to look at. Financially, we're in really good shape.
Here we have our quarterly results every year. Q1s are always a little bit more challenging, and you generally grow out of those strongly, and that is what we expect this calendar year. Cash about $77 million, and we at our quarterly call restated our financial outlook. We anticipate total revenue of $200 million to $210 million, comprised of net product sales of $185 millionto $192 million, as well as contract revenue of $15 million to $18 million. Continued strong growth, 30% plus over last year. Importantly, there you see on the bottom right, we continue to project positive net income this year. That is being profitable, but funding all the things that I have just told you about. Ability to fund our programs ourselves with our own means, and I think that is going to continue. That is our plan.
The value drivers for this year, TAVALISSE, GAVRETO, and REZLIDHIA, continue to work on adoption of those products and show strong year-over-year growth. I'll skip down, continued financial discipline, driving substantial cash flow to advance our development programs, particularly R289 in lower-risk MDS, but also in other areas such as that we're looking at even front earlier line, and then oluta in glioma as well. Continue to look at external opportunities. It's a very strong position that we're in this year. I think a growing strong commercial business that's generating profits and of scale now that we're able to count on those profits on a regular basis. Still continued financial discipline. We've really kept a tight lid on our expenses. We expect to spend more on the development side as we develop these programs.
An incredible opportunity to transform the company with 289 and lower-risk MDS. That opportunity is tremendous, and we're going to do everything possible to expedite those clinical trials and getting the product on the market for that indication. Again, really a fantastic place to be as a company with all the various components, commercial, development, financial, working together to really drive ours into the future. With that, I'd like to thank you for your interest.
Thank you, Raul.
Thank you.