Welcome, everyone, to the Piper Sandler Healthcare Conference. My name is Ashleigh Acker, a Biotech Analyst on Allison Bratzel's team here at Piper. It's my pleasure to introduce our next presenting company, Rigel, CFO, Dean Schorno. Welcome, Dean.
Great. Thank you. And I'd like to thank Piper Sandler for having us at their conference this year, as well as you for your interest in Rigel. As I get started here today, I'm going to be making some forward-looking statements. I'd encourage you to look at our investor site at rigel.com, where you can find our SEC reports, as well as a complete corporate deck. So I'll be moving fairly quickly through this today. I'm excited today to talk about our growing hematology and oncology business. And the business I described to you today is really some strong commercial execution, some really great pipeline opportunities I'll describe. In-license and product acquisition has been a core to what we've been doing, as well as financial discipline. So as I describe this, we're very pleased with the progress of the company, but we want to be larger.
We want to scale the business, have more commercial products, larger commercial products. And we think there's real opportunity from a pipeline development perspective to have really transformational products in the future. And I'll be describing that today. From a US net product sales growth, we've had really nice growth, 65% year-over-year growth, up to $64.1 million in Q4, leading to $166 million through Q3. And in Q3, the $64 million is greater than our 2021 revenue. So we've seen very nice revenue growth. From a commercial performance perspective, diving into the products specifically, we've got the ITP product, really TAVALISSE, the foundation of our business, $44.7 million, a 70% year-over-year growth. GAVRETO, which we acquired from Blueprint Medicines, which was previously sold by Genentech, was about $7 million per quarter in Genentech's hands. Over the last year, we've grown that to over $11 million.
Strong growth, strong leverage in our commercial as well as MSL operations. From a REZLIDHIA perspective, continued strong growth at 50% year-over-year. Briefly on the products, ITP is the indication for TAVALISSE. It's indicated for adult chronic ITP, for patients who've had an insufficient response to a previous treatment, and that's almost always steroids. From a market perspective, there's about 81,000 patients in the U.S. who suffer from chronic ITP. At any given time, and patients are cycling through these therapies, at any given time, there's about 37,000 patients who are just being watched with stable disease. About 20,000 patients are on steroids, often a high-dose steroid, which isn't really a sustainable long-term therapy. Then there's about 24,000 patients who are second line or later. When we launched, we were primarily used in that fourth and fifth line.
Over time, we've increasingly been utilized in that second and third line, where you see there's more patients, a real opportunity for us. The other thing to note as we move into the second and third lines, as the chart on the left illustrates, is in the second line, getting to 30,000 or 50,000 platelets is 78% and 94% response rate. So very high response rates as we move further up in the line of therapy. The byproduct of that, again, there's larger patient populations, but you've also got the durability benefit that you see on the right-hand side, so important to our business. From a REZLIDHIA perspective, REZLIDHIA is indicated for IDH1 positive AML patients. As we all know, AML is a terrible disease. About 22,000 patients will be diagnosed in the U.S. 11,000 of those patients will succumb to the disease.
IDH1 mutations are seen in about 6%-9% of the population, and it's well identified. So these patients, it's an opportune situation where they know that they have IDH1 positive disease. As we look at the clinical trial highlights, and really why we were interested in in-licensing the global rights from Forma Therapeutics, which was later acquired by Novo Nordisk, is that this elderly patient population really fit nicely into our commercial organization. And what really impressed us was the CR/CRH rate of 35%, and most notably the 25.9 months of duration of response. So as we look across the other available therapies for patients, that's really a differentiating feature that was important to us. Also notable, 92% of the CR/CRH responders were complete CR responders. Moving on to GAVRETO.
GAVRETO is indicated for RET fusion-positive non-small cell lung cancer, as well as advanced and metastatic RET fusion-positive thyroid cancer. The opportunity here, again, great synergy with our sales and marketing organization, our MSL team. And on the right side, you really see the market dynamics. So we have a large competitor who launched first, has a larger stake in the RET fusion-positive therapeutic market than we do. We're at about 15%. So there's opportunities there for our commercial organization. But really, what's most notable is the 25% of patients who are still receiving chemotherapy and checkpoint inhibitors, as well as MKIs, multi-kinase inhibitors. There's real opportunity here. And I'll describe a change in the practice guideline that really enhances that opportunity. Pralsetinib, or GAVRETO, was really an intriguing product for us to acquire the U.S. rights, as I said, from Blueprint Medicines.
It's a once-daily oral, high response rates, strong safety and tolerability profile, and then at the bottom is the practice guidelines. They shifted at the beginning of this year to say that if a physician has initiated a patient on chemotherapy or a multikinase inhibitor, that they should, if they determine that the patient is RET fusion positive, should shift therapies to a RET fusion positive product like GAVRETO. From a commercial global perspective, we've got great collaboration partners throughout the world, with Grifols in Europe, selling TAVALISSE, Kissei in Japan, and most recently, South Korea, and then Medison in Canada, as well as Israel. We've got opportunities also with respect to Mexico with Knight, where they've received approval for TAVALISSE. With respect to REZLIDHIA, we've partnered with Kissei for Japan and Asia, as well as Dr. Reddy's in Latin America.
From a clinical development perspective, really an exciting part of our business. And starting on the right, from an in-license product acquisition perspective, I've described REZLIDHIA and GAVRETO and the value that that's created. We're looking to continue that expansion commercially to leverage our organization. We're looking for differentiated assets in hematology, oncology, and related areas. Late-stage programs, and these are programs where the registrational data is available, it's on file, the registration's been filed, or it's a product that's already on the market. So lots of opportunity there. I'll touch briefly on our important IRAK1/4 inhibitor program, where we'll have a presentation, an oral presentation at ASH this Sunday, as well as some of the strategic collaborations that we have with olutasidenib across a variety of opportunities. Our IRAK1/4 program is currently in lower risk MDS.
From a treatment landscape perspective, there's lots of opportunities in lower risk MDS for advancement of the treatment paradigm. Really briefly, first line is typically an ESA. Post-ESA failure, luspatercept, and most recently, imetelstat are utilized. These are products that work 38%-40% of the time. And then hypomethylating agents, HMAs, are used in the later lines, in the refractory lines. These work 18%-20% of the time. So there's real opportunity here for us to impact that truly refractory population on the far right, the post-luspatercept failure opportunities, but also moving all the way up to post-ESA. So large opportunity and really transformational opportunity for Rigel. From a value proposition perspective, big unmet medical need, 12,200 patients, and I've described kind of the current therapeutic options available to these patients.
From a mechanism of action, the dysregulated inflammatory signaling and the impact that our IRAK1/4 asset has on that is meaningful. We've done a clinical proof of concept with a healthy volunteer population. We've introduced LPS, and then we've seen the cytokine reduction across a variety of the key cytokines. The FDA is supportive of what we're doing in that we have fast-track designation as well as orphan designation. And then from an encouraging clinical profile, I'll describe on the next slide what we've presented to date from a data perspective and what you can expect to see at ASH on Sunday. On the left side, we've got the dose escalation phase. We've now completed enrollment in the dose escalation phase, which is dose levels one through six. At ASH last year, we presented data on the first four dose levels.
On Sunday, we'll present incremental data on dose levels five and six. We've also, in October, enrolled our first patient in the dose expansion phase, which is a 500 mg QD and a 500 mg BID dose level. We'll be moving those forward. We're in the dose escalation phase. We had up to six patients. Now we'll have up to 20 incremental patients. That's really meaningful to the business in that we'll start to have upwards of 20-plus patients to see results from. Once we choose that dose, and the blue box in the bottom here is we'll do a post-ESA, kind of that early-stage study where we'll look at treatment-naive low-risk MDS, again, post-ESA failures. What are the next steps? We'll have the data cut through October 28th. We'll present that at the oral presentation on Sunday at ASH.
We'll complete enrollment of the dose expansion phase that I described, select a recommended dose in the back half of next year, and then work with the FDA on a registrational path forward. From a strategic collaboration perspective and an advancement of olutasidenib, we've got three key collaboration partners. We've got MD Anderson, clearly a leader in the field. They're looking across monotherapy as well as combination therapy and just a variety of IDH1 positive indications that are important from frontline AML to lower risk MDS, higher risk MDS, CMML, as well as MPN, as well as some post-transplant maintenance therapy. So really an important partner for us. Advancing olutasidenib in glioma, we're partnering with the CONNECT organization and doing work in high-grade gliomas. And this is an important study that will look at temozolomide in combination with olutasidenib.
IDH1 positive disease is known through recent work to have an impact in glioma. We think this is an opportunity for us. Finally, with respect to our collaborations, we've set up a relationship with MyeloMATCH, which is an NIH NCI-sponsored cooperative, and we'll be evaluating frontline newly diagnosed AML and MDS with them and the impact of olutasidenib across a variety of combination therapies. As I said, we'll have the ASH oral presentation on Sunday for IRAK1/4, and there's four poster presentations for olutasidenib. Notably, one of the posters has a post-venetoclax treatment data that will be reviewed. We have a RIPK1 program with Lilly that we've partnered that they're in a phase 2A in rheumatoid arthritis. Exciting partner. We developed the SYK mechanism, which was the foundation of TAVALISSE in-house, IRAK1/4, which we've talked about, as well as this RIPK1 opportunity.
Lilly's a great partner, potential for milestones, royalties in the future on this program. From a financials perspective, we've talked about the meaningful revenue growth. There's $5.4 million of that ex-U.S. partner collaboration. That's a meaningful contributor to our business also. Financial results, a bit of an eye chart here, but I'd note that through the three months, through the Q3, net income was about $28 million. Through three quarters, we've been profitable each of the quarters. Our cash balance is $137 million now. We've increased our cash balances by $60 million, which will allow us to fund these transformational opportunities like the IRAK program that I described. We also recently increased our guidance to $285 million-$290 million total revenue. The net product sales are $225 million-$230 million. Collaboration revenues at about $60 million.
Really strong foundation to all of the opportunities I've described. To wrap things up, strong U.S. net product sales growth, 32% compound annual growth rate through 2024, but then we're seeing this uptick, and our guidance has 55%-59% year-over-year growth. Finally, and just to sum things up, we'll look to continue. When we entered 2025, here's what our goals were, and I think we've been successful, growing product sales across the three products, advancing our development pipeline. Stay tuned for the update on Sunday and then the dose expansion phase data into next year. We're still looking for in-license opportunities, and we've got a nice financial foundation under all of this. Appreciate your time today, and we're always available for questions. And again, thanks for having us to the conference.