Information on our rigel.com site where you can see our SEC filings. You can see this slide deck, but you can also see a broader corporate slide deck that has much more information. I encourage you to take a look at that. Really excited today to tell you about our growing hematology and oncology business. Really pleased with where we're at from a business perspective, but we want to be larger. We want to be larger with respect to more products. We want to be larger with respect to the products we have, and we've got some great development opportunities I'll tell you about today, to walk you through this. As we talk about the business, we've got three commercially launched products. One is TAVALISSE. It's indicated in ITP. That was developed by Rigel.
We have REZLIDHIA in relapsed/refractory mIDH1-positive AML, as well as GAVRETO, which is for RET fusion-positive non-small cell lung cancer and thyroid cancer. Both of those assets we in-licensed or acquired. That's part of our strategy to grow the business. I'll describe a bit about that and the leverage and the commercial execution around that. From a development perspective, a really two-pronged approach here. We've got some great assets in development. We have an IRAK1/4 dual inhibitor that we have a phase Ib in lower-risk MDS. Incrementally, we've got opportunities with olutasidenib , our REZLIDHIA asset, through both strategic partnerships and collaborations, as well as through potential Rigel-led studies. Finally, from an in-license and product acquisition perspective, I'll describe a little bit about the success we've had with REZLIDHIA and GAVRETO. We'd like to do more. I'll describe some of the type of acquisitions and opportunities we're looking for.
From a financial discipline perspective, operating expenses is well managed with our growing revenues, the guidance we, the guidance raise we had, generating net income and significant cash. We're in a really strong position across all of these pillars. As we look at the U.S. net product sales, and I'll break this down a little bit, 76% year-over-year growth, Q2 of 2024 to Q2 of 2025. You'll see the $102.5 million through Q2 of 2025 is essentially the number we had in all of 2023 at $104 million. Starting with TAVALISSE, a brief overview. TAVALISSE, and this is our label, is indicated for adults with chronic ITP who've had an insufficient response to a previous therapy. That previous therapy is almost always, always steroids. From a market opportunity, about 81,000 patients with chronic ITP in the U.S. The patients are cycling through the categories I described.
About 37,000 at any given time are in watchful waiting with stable disease. 20,000 are in first line, which is often almost always, a steroid, a high-dose steroid that's not a sustainable therapy. Then about 24,000 of those patients are in the second through fifth line. When we launched TAVALISSE, we were used primarily in that fourth and fifth line. We've moved up along the way. It's important for a couple of reasons. One is that the number of patients in the earlier lines are much higher than in the later lines. Incrementally, as this chart shows, in the second line, the response rates are in the 80% - 90% range. As you go down the patient journey, and these patients typically have had ITP for a longer period of time, could be a more sick population, you get to 40 %- 50% efficacy.
Early lines of therapy is really beneficial to patients. Once the drug is effective, you see on the right-hand side that the response is very durable and patients can be on TAVALISSE for years. Moving on to REZLIDHIA, which is indicated for IDH1-positive AML. This was an asset that we in-licensed from the global rights from Forma Therapeutics a couple of years ago now. As we looked at the opportunity and what excited us about the opportunity to have this product is just the opportunity in AML. It's a terrible disease, as we all know. 22,000 patients will be diagnosed in the U.S. Unfortunately, about 11,000 of those patients will succumb to the disease. IDH1-positive patients are well-characterized, well-identified, about 6 %- 9% of the population. Forma had done a phase II trial. They had done the registration. We then completed the registration and commercialized it.
What the data showed was in a population, an elderly population, the second bullet's really the key here, and that's that the CR+CRh rate was 35%. Very strong response rates. Importantly, it was about 26 months of durable response, which was an improvement in anything in the market at the time. 92% of those responses were complete responses, and the median duration was longer, 28 months there. A really, really strong product opportunity. We then acquired the rights to GAVRETO, mid-2024. Really, our first full quarter was in Q3 of 2024. This was a product that we acquired the U.S. rights from Blueprint Medicines. It was previously distributed by Genentech, and they were turning the product to Blueprint. The label for this product is it's indicated in RET fusion-positive non-small cell lung cancer, as well as thyroid cancer.
As we look at the market opportunity here, it moves us into solid tumors. It leverages our patient access programs, our commercial organizations, our MSL organizations like REZLIDHIA. We've got nice leverage across the business. On the right side really shows where the opportunity is, though. When we look at the overall marketplace for RET fusion-positive non-small cell lung cancer patients, about 75% of the patients are treated with a RET fusion-positive therapy. There's still 25% of the patients who are treated with multi-kinase inhibitors and chemotherapy plus checkpoint inhibitors. That's really a suboptimal therapy. There's an opportunity for these patients. There's an opportunity for Rigel that I'll tell you about. As we looked at pralsetinib, which is GAVRETO, it's a once-daily oral, high and durable response rates. Safety and tolerability is strong.
The practice guidelines at the bottom were actually modified in January to state that if a physician has a patient on chemotherapy or the multi-kinase inhibitors, and they then determine that the patient is RET fusion-positive, they should switch therapies to a RET fusion-positive therapy. That's really an opportunity for Rigel and part of the success that I'll describe to you. As we look at the commercial performance, the result of those efforts I just described, we've got the significant year-over-year growth I described. 52% year-over-year growth for TAVALISSE. Very meaningful. $11.8 million of Q2 net revenues for GAVRETO. In Genentech's hands, in 2024, they were selling about $7 million per quarter of products. We not only avoided that dip that would typically happen when you acquire a new product, but we've been able to grow it on a quarter-over-quarter basis based on the activities I described.
REZLIDHIA continuing to grow in a strong way at 36%. All of these are contributing meaningfully to the top line, as we'll see. As we look across the global access, TAVALISSE is available, broadly. Medison in Canada and Israel, Grifols throughout much of Europe, and Kissei in Japan and certain Asian countries. Down right here, you see the collaboration revenues about $2.6 million. We're seeing nice revenues, nice revenue growth from our ex-U.S. collaborators. We're working with Knight in Mexico and Latin America to expand the availability of TAVALISSE. We're also working with Kissei as well as Dr. Reddy’s to expand the availability of REZLIDHIA where we have global rights. Moving to our development programs, I'll start on the right side with the in-license and product acquisition opportunities. I described the success we've had with REZLIDHIA as well as GAVRETO.
We think there's more opportunity for our field sales force to have more products and us to impact patient lives in a broader way. We're looking for differentiated assets in hematology, oncology, or related areas. We're looking for late-stage programs. Late-stage programs could be that the registrational data is ready, that the NDA's been filed, the NDA's been approved, or the drug has been launched and is on the market. We're actively looking for those opportunities because we can really get leverage out of our commercial MSL and our patient services aspects of the business. Many of these, all of these new products have been very synergistic to our capabilities. Moving on importantly to our IRAK1/4 i nhibitor program. This is the lower-risk MDS landscape. This is a clonal disorder, and this is a patient population that still can benefit from increased therapies across the space as I described.
From a first-line perspective, ESAs, luspatercept, and lenalidomide are used for those patients with Del(5q) deletions. The opportunity for Rigel, as I described the work we're doing in lower-risk MDS, is really in these next couple of columns. There's post-ESA and ESA-ineligible patients, and they're receiving luspatercept as well as most recently a metal stat. 38 %- 40% response rates in this population. You then get into the relapsed refractory disease, and you get to HMAs where it's 18 %- 20% response rate. There's tremendous opportunities for these patients and a continued unmet medical need. As we look at the potential for our R289 program, we've talked about the medical need, 12,000 plus patients with lower-risk MDS.
The mechanism of action and the dysregulation of the inflammatory signaling that we've shown in a first-in-human study as well as in our phase Ib program, is a compelling and novel mechanism of action. We did a proof of study, an LPS challenge where we induced a cytokine storm, and we showed that IRAK1/4 in combination would be able to mitigate that cytokine storm, which we believe will have a significant impact on lower-risk MDS. From a regulatory perspective, we have FDA support as demonstrated through their fast-track designation and the orphan drug designation. I'll describe the clinical profile and the clinical benefit we saw and we presented at ASH in 2024. Here's the phase Ib study. What we have on the left side is dose level one through six. We started 250 mg QD
We most recently completed enrollment with our last patient in the dose level six of 500 mg BID . That was in July. We're now done with the enrollment of this dose escalation phase. At ASH last year, we presented the intermediate data for dose level one through four. We expect later this year to complete and present the majority of the data across all six of these dose levels. This is an important milestone for the business. We then will work on the dose expansion phase. We've recently met with the FDA, and we've got alignment with the FDA in how we'll choose the dose level A and B. We'll do the dose expansion up to 20 patients. We'll go ahead and get that started in advance of the end of the year when we present this full data set.
We agreed with the FDA that the primary decision point will be around the safety and exposures. We'll look across this data, look at safety and exposure, and we'll get started with that dose escalation phase in the upcoming months. It could be as early as later this month and into October. Very excited about getting that program started. As we think about the data over the next, you know, through the end of next year, when we move from having six patients in a dose to 26, up to 26 patients with the dose expansion, that becomes a really meaningful data set to look at the safety, the PK, as well as potential efficacy. We're excited about that, and we're excited to present this dose escalation phase later this year. Moving on to the data that we saw in the phase Ib study, it was well tolerated.
Notably, there were no cytopenias and infection rates were low. What we did see at dose levels at 500 mg QD and 750 mg QD is we saw that the concentrations were high above the 50% level that we saw in that LPS challenge. Importantly, the red blood cell transfusion independence occurred in 3 out of 10 of the evaluable patients. Really meaningful for a very refractory population. Physicians are very encouraged by the fact that 30% of patients, again, in this refractory population, had response rates. The patients, in fact, 77% of them previously had luspatercept and 73% had HMA. In that landscape slide I described, they're very far to the right. Really encouraging data. From an incremental opportunity perspective with REZLIDHIA and olutasidenib, there's opportunities in glioma that we're exploring both through strategic partnerships and in consideration with our own programs. Very high unmet need.
With the approval of vorasidenib in grade 2 glioma, it showed that there's a potential for IDH1 inhibition to play a role in glioma of a huge unmet need. Our colleagues at Forma had done a study in glioma that's highlighted on the bottom here across 26 patients, encouraging clinical data with two partial responses in grade 3/4 . The later stage glioma, 40% with stable disease and a 48% disease control rate. Really encouraging, promising data in glioma with the olutasidenib. How do we move that forward? We have a collaboration with CONNECT, which is doing a high-grade glioma study across a basket of potential therapeutics. Olutasidenib is included in that study in combination with temozolomide. That study is open for enrollment. We'll look to see data there. We're also in the process of considering opportunities for Rigel to initiate our own studies.
We'll provide updates in the future on that. We have strategic collaborations across other IDH1 opportunities with MD Anderson in both combination therapies and AML, high-risk MDS, CMML, advanced MPN, as well as in monotherapy and CCUS, MDS and also post-transplant maintenance. What are the milestones for R289? Very important milestones. Completion of the dose escalation part of the study I described. Initiate dosing that expansion phase, those up to 20 patients in the two cohorts. Interactions with the FDA regarding registrational path. We've started those conversations, and those will continue as we go through the dose expansion phase. We'll present the dose escalation phase later at a medical meeting or by year end. Then expand in the olutasidenib opportunities we described. We have a Lilly collaboration in a RIPK1 program. This was a program internally developed at Rigel.
We partnered with Lilly, a great partner, and they're moving forward with an immune-mediated disease, phase IIa in rheumatoid arthritis. Lots of opportunity here in psoriasis, IBD, and other indications. They also have a basket of assets from Rigel in CNS diseases that can, as they move that forward, impact those disease states. Great opportunity here. There's milestones and royalty potential. Lilly is a great partner for us here. From a financial perspective, nice growth in the business. $58.9 million of net product sales, $42.7 million of collaboration revenue in Q2. $40 million of that was a one-time non-cash revenue as a result of the lapse of a commitment from Rigel to have to fund some of the Lilly co-development. That was a one-time, but $2.7 million was from our base business.
As we look at the financials, a bit of an eye chart here, but what you see in the six months ended is you see $71 million of GAAP net income. Again, $40 million of that is from Lilly. So call it $31 million that's from our base business. Our cash grew by $31 million. We're in a very nice position from a financial perspective and creating tremendous leverage in the business to invest in the R289 programs and others into the future. We raised our guidance to $270 million- $280 million. Again, that has the $40 million built into it. What's it look like from a growth perspective? You're seeing in the lighter green shades, you're seeing that our strategy to bring in new products as well as to grow our existing products in the dark green. TAVALISSE is contributing very nicely to this growth in our business.
32% CAGR over the last four years, around 50% in the last year. What are the value drivers? Growing our sales through our existing products as well as adding new products, advancing our development programs, lower-risk MDS, the most immediate and very large transformational opportunity for Rigel , as well as opportunities with the olutasidenib. We're actively looking for those next REZLIDHIA, GAVRETO-like transactions because it's beneficial to our business, beneficial to patients, and we'll wrap around all of that to continued financial discipline. I'd like to thank everyone for your involvement today, and we're always available for questions. Please do reach out to us, and thank you again.
Yeah, no problem. I want to take an opportunity to thank Dean and Rigel for an excellent presentation. As Dean mentioned, we don't have time for questions, but if you do want to follow up, we encourage you to do so after the session at the conference. I'm sure you can find Dean in the hallway. Go catch up then. All right. Thank you again, everyone. Appreciate it.