Earnings Call Transcript - RIGL Q2 2025

Raymond J. Furey, Executive Vice President, General Counsel and Corporate Secretary

Welcome to our second quarter 2025 financial results and business update conference call. The financial press release for the second quarter of 2025 was issued a short while ago and can be viewed along with the slides for this presentation in the News and Events section of our Investor Relations site on rigel.com. As a reminder, during today's call, we may make forward-looking statements regarding our financial outlook and our plans and timing for regulatory and product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent annual report on Form 10-K for the year ended December 31, 2024, and subsequent filings with the SEC, including our Q2 quarterly report on Form 10-Q on file with the SEC. Any forward-looking statements are made only as of today's date, and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances. At this time, I'd like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez. Raul?

Raul R. Rodriguez, President and CEO

Thank you, Ray, and thank you, everyone, for joining us today. Also with me today are Dave Santos, our Chief Commercial Officer; Lisa Rojkjaer, our Chief Medical Officer; and Dean Schorno, our Chief Financial Officer. Beginning on Slide 4, I will provide an overview of Rigel's accomplishments across the business and our financial results for the second quarter of 2025. Let me start by saying that this was a really great quarter for Rigel. We continue to make significant progress on the execution of our corporate strategy. For those not familiar with Rigel, our focus is on growing our hematology and oncology business through commercial execution, advancing our pipeline, product in-licensing and acquisition, and financial discipline. With this in mind, in the second quarter, we achieved net product sales of more than $58 million, an increase of 76% year-over-year and our best quarter ever. This all-time high was driven by our growing commercial portfolio and increased sales across all our commercial products. Dave will provide a more detailed update on our three products and their second quarter contributions later on in the call. Total revenue for the second quarter was $101.7 million, including $42.7 million in contract revenues from collaborations. As I discussed during our May call, we notified Lilly that we would not exercise our right to share in future development expenses for ocadusertib, Rigel's RIPK1 inhibitor previously known as R552. As a result, we recognized $40 million in noncash revenue in the second quarter. Dean will discuss the accounting of this in his remarks. Now let's talk about our development opportunities. We are excited about the potential of our development pipeline and our ability to fund the clinical development of R289 and olutasidenib. R289, our novel and selective dual IRAK1/4 inhibitor is currently being evaluated in a Phase 1b clinical study in patients with relapsed or refractory lower-risk MDS. We completed enrollment in the dose escalation part of the study in July and expect to share updated data from the study later on this year. Lisa will walk us through the latest updates on our development pipeline. While we're focused on our internal development, we're also excited about the potential of ocadusertib, a potent oral and selective inhibitor of RIPK1 and Lilly's efforts to advance this molecule. In parallel with growing our commercial business and expanding our development pipeline, we remain committed to pursuing additional in-licensing deals or acquisitions of assets that fit our capabilities commercially and our product focus, such as we've already done successfully with both REZLIDHIA and GAVRETO. Underscoring this effort is an emphasis on maintaining financial discipline while making the clinical development investments. This has resulted in both top line and bottom line growth and allowed us to generate $59.6 million in net income and to increase our cash balance to more than $108 million in the second quarter. Moving on to Slide 5. You'll see the growth of our net product sales year-over-year. We have consistently delivered top line growth as evidenced by the 32% compound annual growth rate or CAGR from 2021 to 2024. Year-to-date, in 2025, we have generated $102.5 million in net product sales. This is nearly the same net sales that we generated for the full year of 2023, and so a tremendous start to this year. We are now raising our total revenue guidance in 2025 to between $270 million and $280 million from the previous range of $200 million and $210 million, which includes net product sales of $210 million to $220 million, an increase from the prior range of $185 million to $192 million. This new outlook reflects anticipated growth of 45% to 52% compared to 2024, exceeding the roughly 30% growth rate that we delivered over the last few years. Rigel is in a unique position as a self-sustaining company with the added benefit of a promising pipeline of assets. We remain focused on the execution of our corporate strategy and continuing our progress throughout 2025 and beyond. Now with that, I will turn the call over to Dave to provide more information on our commercial business for you. Dave?

David A. Santos, Chief Commercial Officer

Thank you, Raul. On Slide 7, you'll see our three commercial products, TAVALISSE, GAVRETO, and REZLIDHIA. Moving to Slide 8. We are thrilled to report another excellent quarter from our commercial portfolio, marked by strong year-over-year growth and an all-time high in revenues in the second quarter of 2025. You can see on the slide how our quarterly and annual net product sales have increased since 2021. We have grown each quarter's sales over the previous year, and that growth continues. In the second quarter of 2024, we reported $33.5 million. And now for the second quarter of 2025, we generated $58.9 million. Our second quarter results reflect accelerated demand through improved patient affordability in 2025, augmented by favorable gross-to-net dynamics, which drove a 76% increase year-over-year. Our commercial team has been dedicated to execution, driving continued momentum for TAVALISSE, raising awareness for GAVRETO after a successful transition into our portfolio and improving demand for REZLIDHIA. Slide 9 shows a summary of our commercial performance by product. First, on TAVALISSE. I'm pleased to report another record quarter in which we generated $40.1 million in net product sales, an increase of 52% compared to the second quarter of 2024. This growth was driven by continued strong new patient demand with another consecutive quarterly record high and increased carryover demand from new patients that started therapy in prior quarters. For GAVRETO, we delivered $11.8 million in net product sales in Q2. As a reminder, in the second quarter of 2024, we recorded $1.9 million of revenue as GAVRETO just became commercially available from Rigel in late June of 2024. On a sequential basis, we saw 32% revenue growth versus the first quarter of 2025 as we continue to see an increase in new patients and carryover demand. We are focused on driving awareness of GAVRETO and ensuring patients are educated on the latest treatment guidelines that recommend the use of a RET inhibitor in the frontline setting. And lastly, for REZLIDHIA, we reported $7 million in net product sales, an increase of 36% compared to the prior year period, reflecting demand growth. We continue to focus on educating healthcare providers about the potential benefits of REZLIDHIA for patients with relapsed to refractory IDH1 mutant AML. Driving awareness of the efficacy data for REZLIDHIA in the post-venetoclax setting, which we believe is important to physicians, continues to be a key priority for us. We also believe we have compelling data for the earlier use of REZLIDHIA in mutant IDH1 patients who relapse or are refractory to frontline therapy. To that end, at ASCO in June, we presented data for patients who received REZLIDHIA after either one to two lines of therapy or three or more lines of prior therapy. Patients in the one to two prior regimens group showed a higher overall response rate and longer median overall survival than those who had three or more prior lines of therapy, providing a rationale for initiating treatment with REZLIDHIA earlier in the relapsed or refractory treatment paradigm. This supporting data shows why we believe we have significant opportunities to grow REZLIDHIA in relapsed or refractory IDH1 mutant AML. Overall, we're very pleased with our commercial performance in the second quarter, and I would like to express our sincere thanks to the entire team for their outstanding performance in Q2. Moving to Slide 10. We continue to work on expanding access to our products in markets outside of the U.S. TAVALISSE is commercially available in Japan, in Europe under the brand name TAVLESSE, and in Canada and Israel via our partners, Kissei, Grifols, and Medison. In addition, our partners continue to pursue regulatory approvals for TAVALISSE in new markets. Most recently, in early July, Kissei's licensing partner, JW Pharmaceutical Corporation, launched TAVALISSE in South Korea. For REZLIDHIA, in 2024, we expanded our relationship with Kissei to include several countries in Asia for all potential indications, and we entered into an exclusive license agreement with Dr. Reddy's for all potential indications throughout Dr. Reddy's territory. We are pleased that access to our products is expanding outside the U.S., and we continue to explore other opportunities for partnerships to bring our products to markets around the globe. I will now pass the call over to Lisa to provide an update on our development pipeline. Lisa?

Lisa Rojkjaer, Chief Medical Officer

Thanks, Dave. I will now provide an overview of our pipeline progress and plans for the remainder of the year. I'm on Slide 12. Our hematology and oncology pipeline strategy is focused on the clinical development of R289, our novel dual IRAK1 and IRAK4 inhibitor in lower-risk myelodysplastic syndrome, or MDS, and the expansion of olutasidenib beyond relapsed or refractory IDH1 mutated AML into other cancers with IDH1 mutations such as recurrent glioma. Beginning with R289, our Phase 1b study in patients with relapsed or refractory lower-risk MDS is progressing well and enrollment in the dose escalation part of the study was completed in July. We plan to share updated dose escalation data later this year. We remain on track to initiate the dose expansion part of the study in the second half of the year, which will be a randomized comparison of two doses of R289 in order to select the recommended Phase 2 dose for future studies. For olutasidenib, we believe it has potential in several cancers where mutated IDH1 plays a role. Regarding our partners, olutasidenib is being evaluated as maintenance therapy in IDH1 mutation-positive glioma by the CONNECT Cancer Consortium and in IDH1 mutation-positive AML and low and high-risk MDS by MD Anderson. We remain open to additional opportunities or collaborations to evaluate olutasidenib in IDH1 mutated cancers. Rigel also remains focused on evaluating potential acquisition and in-licensing opportunities that strategically fit our hematology and oncology portfolio and infrastructure. We're focused on evaluating differentiated assets in hematology, oncology, or related areas that are late-stage programs. Now, I'll spend a few moments on R289, our dual IRAK1 and IRAK4 inhibitor. On Slide 14, I'd like to spend a few minutes reviewing the value proposition of R289 in lower-risk MDS. There are about 12,000 previously treated lower-risk MDS patients in the U.S. There's a high unmet need for therapies in this disease area, particularly for transfusion-dependent patients. Disregulation of inflammatory signaling is key to the pathogenesis of lower-risk MDS and IRAK1 and 4 mediate this process. Blocking both IRAK1 and 4 may suppress marrow inflammation and leukemic stem and progenitor cell function and restore normal hematopoiesis. R835, the active moiety of R289, blocks toll-like receptor and IL-1 receptor signaling in vitro and was active in various preclinical models of inflammation. Clinical proof of concept of this anti-inflammatory effect came from a healthy volunteer study in which R835 markedly suppressed LPS-induced cytokine release compared to placebo. As a reminder, R289, which is currently being evaluated in the clinic, is the oral prodrug that is rapidly converted to R835 in the gut. R289 has both Fast Track and Orphan drug designations from the FDA, giving the molecule an expedited regulatory pathway, potential priority review, and seven years of market exclusivity upon approval. Both of these designations underscore the agency's interest in this rare disease, the unmet need of the patient population, and the FDA's willingness to collaborate with Rigel in the development of R289. In addition, R289 has thus far demonstrated a promising clinical profile in a Phase 1b study. The initial dose escalation data that were presented at last year's ASH Annual Meeting demonstrated promising preliminary safety and clinical activity in elderly, heavily pretreated patients with relapsed or refractory lower-risk MDS. While I'm here, I wanted to mention that we noted that with the recent data cut, there was a change in status for one patient previously reported with a minor response, that is a reduction in the number of red cell transfusions by more than 50% compared to baseline. We discovered that this patient had received additional red cell transfusions that were not entered into the database at the time of the initial analysis. Thus, this patient is no longer considered a responder. I'll discuss the study design in a moment. On Slide 15, I'd like to update you on several key milestones for the program that we're focused on this year. First, as mentioned, we completed enrollment in the dose escalation part of our ongoing Phase 1b study in July. We remain on track to initiate the dose expansion phase in the second half of this year, potentially within the third quarter. We recently engaged with the FDA to discuss the dose expansion phase and to seek preliminary input on a potential path to registration. We're aligned with the FDA on the dose expansion part of the study, and we'll provide more details on the registrational path following completion of the Phase 1b study and once we've aligned with the agency on the design of our pivotal study. And lastly, we look forward to sharing updated data from the study later in the year. On the next slide, I'll review the study design. This is our multicenter open-label Phase 1b study in patients with relapsed/refractory lower-risk MDS that are either transfusion-dependent or have symptomatic anemia. Initial data from the study was presented at ASH in late 2024. The study aims to evaluate the safety, PK, and preliminary efficacy of R289 in this patient population as well as selected dose for future studies. It includes a dose escalation part utilizing a modified 3+3 design evaluating six dose regimens of R289 and a dose expansion phase, which will compare two doses of R289 head-to-head in order to select the recommended Phase II dose. Once this occurs, we'll open up a cohort of patients to explore upfront dosing of R289 in patients that are relapsed, refractory to, or ineligible for ESAs. On Slide 17, I'd like to talk about the treatment landscape for lower-risk MDS. MDS is a clonal disorder of hematopoietic stem cells, leading to dysplasia and ineffective hematopoiesis. The main consequences for patients are anemia and transfusion dependence, which adversely impact quality of life. In addition, infections, iron overload from transfusions, and subsequent organ dysfunction all negatively impact the patient. Therapies used in the upfront setting include erythropoiesis stimulating agents, or ESAs, if patients are eligible or luspatercept. Luspatercept and more recently, imetelstat, are also approved for ESA failure transfusion-dependent lower-risk MDS patients. Finally, hypomethylating agents or HMAs are also approved. However, the percentage of patients achieving transfusion independence is low. With 8-week transfusion independence rates approaching 40% with luspatercept and imetelstat, there's still a need for safe, effective therapies for transfusion-dependent lower-risk MDS patients that are relapsed/refractory to or ineligible for ESAs. Now, I'll shift focus to our strategic collaborations. As I've mentioned, we have collaborations in place with CONNECT and MD Anderson to evaluate olutasidenib in other cancers harboring IDH1 mutations. I'm now on Slide 19. CONNECT is a global pediatric neuro-oncology consortium that we entered into a collaboration with last year. In CONNECT's TarGeT trial, a molecularly guided Phase 2 umbrella clinical trial for high-grade glioma, the Rigel-sponsored arm of the study called TarGeT-D will evaluate a post-radiotherapy maintenance regimen of olutasidenib in combination with temozolomide, followed by olutasidenib monotherapy in newly diagnosed patients between 12 and 39 years of age with IDH1 mutation positive high-grade glioma. This study is open for enrollment. In addition to this collaboration with CONNECT, we continue to look at other opportunities to expand our studies of IDH1 mutated cancers through our own studies or collaborative partners, including a potential Rigel-led Phase 2 glioma study. We, along with CONNECT, are excited about olutasidenib's potential to provide a much-needed new treatment option to this underserved patient population with significant unmet need. On Slide 20, we summarize our strategic alliance with the MD Anderson Cancer Center to advance olutasidenib more broadly into AML, MDS, and beyond. All four studies within this collaboration are open for enrollment, and we look forward to sharing updates in the future. Now, I'll pass the call to Dean to discuss our partnered program with Eli Lilly and our financial results for the quarter. Dean?

Dean L. Schorno, Chief Financial Officer

Thank you, Lisa. I'm on Slide 22. Before I review our financial results for the quarter, I want to provide a brief update on our collaboration with Lilly and the related impact to our financial statements during the quarter. The RIPK1 inhibitor programs are progressing well, and we're excited about the program's potential. Ocadusertib, the non-CNS penetrant RIPK1 inhibitor, previously referred to as R552, is currently being studied in an adaptive Phase 2a/2b clinical trial in up to 380 patients with active moderate to severe rheumatoid arthritis. Enrollment in the Phase 2a study is ongoing. The preclinical CNS penetrant RIPK1 inhibitor program is also progressing toward lead candidate nomination. As Raul mentioned, we notified Lilly that we will not exercise our opt-in right related to the development and commercialization of olutasidenib. As a result, we recognized $40 million in collaboration revenue in the second quarter. This is noncash and related to the release of the remaining cost share liability that was on our balance sheet. Note that under the terms of our collaboration agreement, Rigel will continue to be entitled to receive milestone and tiered royalty payments on future net sales. Moving on to our financials. I'm on Slide 24. We reported net product sales of $58.9 million for the second quarter, a growth of 76% year-over-year, including TAVALISSE net product sales of $40.1 million, a growth of 52% year-over-year. GAVRETO net product sales of $11.8 million. As a reminder, GAVRETO became commercially available from Rigel in late June of 2024, and we reported $1.9 million of revenue for the second quarter of 2024. Lastly, we reported REZLIDHIA net product sales of $7 million, a growth of 36% year-over-year. Our net product sales were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance, and other allowances of $20.7 million. We also reported $42.7 million in contract revenues from our collaborations for the second quarter, primarily consisting of the $40 million of noncash revenue from Lilly as well as contributions from Grifols, Kissei, and Medison related to delivery of drug supply and earn royalties, bringing our total revenues for the second quarter to $101.7 million. Moving to Slide 25 and down the income statement to cost and expenses. Our cost of product sales were approximately $4.5 million for the second quarter of 2025. Total cost and expenses were $40.6 million compared to $36.4 million for the same period of 2024. The increase in costs and expenses was mainly due to higher cost of product sales, increased research and development costs driven by the timing of clinical activities related to olutasidenib and R289, and higher personnel-related costs and stock-based compensation expense. We reported net income of $59.6 million for the second quarter compared to a net loss of $1 million in the same period in 2024. We ended the quarter with cash, cash equivalents, and short-term investments of $108.4 million compared to $77.3 million as of the end of 2024. Turning to our financial outlook for 2025. We're raising our total revenue guidance to approximately $270 million to $280 million, an increase from our prior range of $200 million to $210 million. This includes updated net product sales expectations of approximately $210 million to $220 million, an increase from the prior range of $185 million to $192 million and contract revenues from collaborations of approximately $60 million, an increase from the prior range of $15 million to $18 million. The updated total revenues and contract revenues from collaborations expectations are inclusive of the $40 million in noncash contract revenue related to Rigel's agreement with Lilly. In addition, we continue to anticipate that we will report positive net income for the full year 2025, while funding existing and new clinical development programs. To wrap up my section, we look forward to continued financial discipline for the remainder of 2025 and beyond. With that, I'd like to turn the call back over to Raul. Raul?

Raul R. Rodriguez, President and CEO

Thank you, Dean. And moving on to Slide 26. To reiterate, we have made significant advancements over the last several years in expanding our hematology and oncology business. We have consistently delivered meaningful top line growth, enabling us to fund our business and strategic priorities. We have now raised our net product sales expectations for 2025 and now expect to generate 45% to 52% year-over-year growth, an increase from the roughly 30% growth that we delivered in the prior four years. Moving on to Slide 27. For the remainder of the year, we continue to focus on increasing sales of our three commercial products and delivering on our revenue guidance. We are committed to advancing our Phase 1b clinical study evaluating R289 for the treatment of patients with lower-risk MDS. We plan to share updated data by year-end and potentially initiate the dose expansion phase of the study in the third quarter. For olutasidenib, we plan to continue progress to initiate a Rigel-sponsored Phase 2 study in recurrent glioma while supporting our strategic collaborations with the CONNECT organization as well as MD Anderson. We will also continue to look for opportunities to expand our product portfolio through in-license and/or acquisition of synergistic late-stage assets. With our anticipated strong revenue growth and continued financial discipline, Rigel is well positioned for the near term and for the long term. In closing on Slide 28, Rigel has delivered a strong first half of 2025, and we are focused on continuing that momentum throughout the remainder of the year. Our proven strategy has built Rigel into a profitable, growing, and sustainable business. And with that, I'd like to thank you for your interest, and we will now open the call to your questions. Back to you, operator.

Operator, Operator

And your first question comes from Pantginis with H.C. Wainwright.

Joseph Pantginis, Analyst

So it really means great growth, and good management of GAVRETO and REZLIDHIA. Regarding TAVALISSE, it has experienced a significant increase, particularly with the 52% growth. You mentioned that this is driven by new patient demand and an increase in carryover. Could you provide the percentage contributions to this growth?

Raul R. Rodriguez, President and CEO

Dave, can you comment on that? Thank you. Joe, thank you for the question.

David A. Santos, Chief Commercial Officer

Yes. Joe, great question. And I will say that particularly in the first half of the year, we did have more new patient starts than ever before. So, our percentage of our growth due to new patient starts was higher. And I think you heard me say in my prepared remarks that, that was accelerated by improved patient affordability in 2025.

Joseph Pantginis, Analyst

No, that's great. I'm just curious about the level of surprise you had regarding the growth and affordability compared to a potential bear case suggesting that TAVALISSE has reached a steady state.

David A. Santos, Chief Commercial Officer

We have been planning to continue growing TAVALISSE with a strong focus on new patient growth. This year, the elimination of the coverage gap due to the Inflation Reduction Act in 2025 has been significant for us. Previously, patients often faced difficulties accessing their medications due to coverage gaps, especially at the start of the year. However, with the introduction of a $2,000 annual out-of-pocket cap and the option to smooth out those payments throughout the year, patients can more easily access TAVALISSE. We were well-prepared to meet this change at the beginning of the year, maintaining our focus on new patient starts. While it's unclear if the improved affordability has exceeded our expectations, the team's execution has been outstanding. Additionally, our portfolio of oral therapies has overall benefited from the enhanced affordability in 2025, which has also positively impacted our gross-to-net dynamics.

Raul R. Rodriguez, President and CEO

It's a combination of several factors. We were aware of this situation going into the year and were well-prepared to address it. It was essential to anticipate the changes and to have a plan in place. I believe we executed very well in the first half of the year, and many patients continued into the following quarters. What used to be a challenging Q1 has benefited from the IRA, leading to more patients accessing medications that they may not have received before due to the changes. Overall, this is a positive development.

Operator, Operator

And your next question comes from Yigal Nochomovitz with Citigroup.

Yigal Dov Nochomovitz, Analyst

Congrats on the impressive progress both commercially and with the pipeline. I'm interested in your comment about the 32% compound annual growth rate from 2021 to 2024 and the significant rise to between 45% and 52%. Can you clarify if this expectation applies not only to this year but also through 2026 and beyond? Are we entering a new growth trajectory? How would you describe that inflection point when considering the long-term performance of the business?

Raul R. Rodriguez, President and CEO

Yes, I can address that, and I'll also ask Dave to provide his thoughts. We've had an excellent start to the year, and several factors have contributed to the positive changes we've seen. David mentioned a few key developments from earlier this year that contributed to our growth. The underlying business has been performing well, particularly TAVALISSE, which has seen a 32% year-on-year growth and has been a strong performer since its market introduction. A combination of factors has driven this increase in sales this year. While we haven't provided guidance beyond this year, we do anticipate continued growth in the business and have confidence that our products offer significant value to patients. With the fact that these products are oral, we can ensure that more patients benefit from them. We are very optimistic about what lies ahead. Overall, we've had a fantastic first half of the year, our best to date, and we expect these positive dynamics to remain stable as we move forward.

David A. Santos, Chief Commercial Officer

Yes, Raul, I would just like to emphasize that we have a growing business. We are highly focused on providing patients with the opportunity to try TAVALISSE, REZLIDHIA, or GAVRETO, depending on the type of patient the clinician is treating. We strive to ensure we efficiently target these opportunities. Our ability to increase revenues with minimal additional costs across our three-product portfolio is evident, and that is exactly what we are working on. We are identifying and pursuing our impactful opportunities with great focus. Therefore, we definitely intend to continue increasing new patient starts and demand as we move forward.

Raul R. Rodriguez, President and CEO

You also note the leverage in the business. You have a stable, good quality commercial organization that really has delivered in the past. And now you add additional products to it, and you see the economic benefit of that.

Yigal Dov Nochomovitz, Analyst

I have a few additional questions regarding glioma and the oluta development. Can you elaborate on the Phase 2 design? How do you plan to conduct that study, and what would be the appropriate comparator arm? Additionally, concerning your work with CONNECT and the TarGet-D trial, if the results are favorable, how do you intend to utilize that data? Could it be used for submission in the pediatric segment, or would another company-sponsored study be necessary to bring that pediatric segment to market?

Raul R. Rodriguez, President and CEO

I'll ask Lisa to comment on those two.

Lisa Rojkjaer, Chief Medical Officer

Thank you, Raul, and thank you for the question, Yigal. Regarding our plans for glioma, we will provide more details about the study design in recurrent glioma later this year when we are ready. For the CONNECT study, that's a good question as well. We still need to have further discussions regarding CONNECT and potentially with the agency about supporting a filing. We haven't initiated that yet, and I do not expect that we will conduct an additional study in that area.

Operator, Operator

And your next question comes from Farzin Haque with Jefferies.

Unidentified Analyst, Analyst

This is Amin on for Farzin. Congrats on the quarter. A couple of questions from us. Well, based on what you're seeing so far in 3Q in numbers of bottles shipped and the IRA impact, how does that shape your thinking around the guidance going forward? And are there any anticipated headwinds or tailwinds specifically around TAVALISSE sales and GAVRETO ramp-up at this point? And I have a follow-on.

Raul R. Rodriguez, President and CEO

Thank you, Farzin. I'll ask Dave to comment on that.

David A. Santos, Chief Commercial Officer

Yes, we experienced a 20% revenue growth in the six months just completed compared to the previous six months. Our guidance indicates that at the midpoint, we still expect double-digit revenue growth, with the upper end projected at around 15%. We anticipate continued growth. Regarding the improved affordability dynamics earlier this year, the coverage gap was significant when patients were just starting their medications and facing the donut hole experience. However, as we enter the second half of the year, we expect fewer patients to encounter that situation, so I believe the impact will be less pronounced. I hope that clarifies things.

Unidentified Analyst, Analyst

Yes, very helpful. And how much impact are you seeing on the gross to net for the three drugs with the Part D?

Dean L. Schorno, Chief Financial Officer

We haven't provided specific details on the gross to net. I can say that there are several factors affecting it. We made some changes to our distribution channels last year, which have had a positive effect. The product mix also plays a role in gross to net, and as Dave mentioned, there is some benefit from the IRA adjustments. Looking ahead, the mix and the programs we implement will influence gross to net as well. While we haven't detailed the individual products, we anticipate that the favorable gross to net trends we've observed over the past couple of quarters will continue.

Operator, Operator

And your next question comes from Kristen Kluska with Cantor Fitzgerald.

Unidentified Analyst, Analyst

This is Ion on Kristen's line. I understand that the main objective in treating lower-risk MDS is to reduce or eliminate the need for transfusions. What feedback have you received from physicians regarding the extent of transfusion reduction or independence that is deemed clinically significant in this context?

Lisa Rojkjaer, Chief Medical Officer

Yes, I could take that. I mean, you know that as I mentioned in my prepared remarks, the approvals of luspatercept and imetelstat were based on a transfusion 8-week transfusion independence rate of around 38% to 40% for both agents. So, there's around 60% of patients are still not benefiting. So, I think that there's still room for improvement in this area. And with hypomethylating agents that were approved around 25 years ago, it's really not much better. So, lots of room to improve. So, I don't know that the physicians are I think anything above this is people would be looking forward to. And also, considering those agents, there are also associated toxicities and a bit of an inconvenience with the route of administration. So, I think aside from the activity there, there's also room for improvement in administration.

Operator, Operator

And there are no further questions at this time. I would like to turn the floor back to Mr. Raul Rodriguez for closing comments. Thank you.

Raul R. Rodriguez, President and CEO

Thank you for joining us on this call and for your interest in Rigel. In the first half of this year, we have delivered strong results and are very proud of our achievements in both our commercial operations and the financial health of the company, which is stronger than ever. Additionally, we've made significant progress with our product portfolio. I want to express my gratitude to the employees of Rigel for their dedication to our goals. This has been a major advancement for us in the first half of the year, and we are excited to keep this momentum going. Take care.

Operator, Operator

This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation.