Rigel Pharmaceuticals, Inc.

Greetings and welcome to the Rigel Pharmaceuticals Financial Conference call for the second quarter of 2026. At this time, all participants are on a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce our first speaker, Ray Furey, Rigel's Executive Vice President, General Counsel, and Corporate Secretary. Thank you, Mr. Furey.

Welcome to our second quarter of 2026 financial results and business update conference call. The financial press release for the second quarter of 2026 was issued earlier today and can be viewed along with the slides for this presentation in the news events section of our investor relations site on bridal.com. As a reminder, during today's call, we may make forward-looking statements regarding our financial outlook and our plans and timing for commercial regulatory product development and other business activities. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. Description of those risks can be found Thank you. Thank you. At this time, I would like to turn the call over to our President and Chief Executive Officer Raul Rodriguez.

Raul? Thank you, Ray, and thank you all for joining us today. Also with me today are Dave Santos, our Chief Commercial Officer, and Dean Schorno, our Chief Financial Officer. I would also like to welcome Dr. Alison Hannah, our newly appointed Chief Medical Officer, who is with us today and will discuss our development pipeline. To begin, I will provide an overview of Rigel's business, our accomplishments for the second quarter, and the strategic initiatives that positions us for continued growth in the coming years. Moving to slide four, the second quarter was an excellent one and marked an important step in Rigel's transformation into a diversified commercial oncology and hematology company. During the quarter, we continued to grow our current products. We completed the in-license of Vepinu, or Veptidgestrin, adding a significant near-term growth driver. We delivered another quarter of strong profits, and we continued advancing R289 and lower-risk MDS in our dose expansion trial with a readout at year-end. We believe these actions position us original for sustainable near-term and long-term growth. On the slide, you see the strategic framework that has guided Rigel's transformation and will continue to drive our growth. Our strategy is centered on four core strategic objectives. Grow our commercial business, expand our product portfolio and pipeline through licensing or acquisition, advance our development pipeline in the clinic, and maintain financial discipline. Together, these four pillars support a durable, long-term growth strategy. Our May announcement of the exclusive global license of Beppinew demonstrates our execution of this strategy. It expands our portfolio with an important new commercial opportunity and furthers our long-term growth trajectory. Moving to slide five, Bepinu significantly expands Rigel's commercial oncology platform into breast cancer and provides the opportunity to leverage our commercial capabilities across this very substantially larger market. Bepinu is the first and only FDA-approved proteolysis-targeting chimera, or PROTAC, for the patients with second-line or later ER-positive, HER2-negative, advanced or metastatic breast cancer with an ESR1 mutation. There is a critical unmet need in this patient population, and we believe Vepinu is an important new treatment option. With the novel mechanism and differentiated data, we believe Vepinu has potential to become a market-leading treatment. When the transaction was closed in June, our team across the organization began actively preparing for the commercial launch, and we are on track for Vepinu to be available in mid-August. Dave and Alison will provide more information on our launch preparations and the clinical data supporting the FDA approval. Moving to slide six. Since 2020, we have transformed Rigel from a single product company with a limited development pipeline and significant cash burn into the profitable multi-product company with a promising pipeline that we are today. In 2026, we expect to grow a compound annual growth rate of approximately 35% since 2022, using the midpoint of our 2026 net product sales guidance, which excludes any contribution from Bethany. We view this performance as a foundation of our next phase of growth. Our in-license of Epinu marks the next major step in Rigel's evolution. We believe it has potential to become Rigel's largest commercial product and meaningfully drive growth through the end of the decade and beyond. Looking towards the 2030s, we plan to build on the momentum of our commercial portfolio. We will also continue to evaluate late stage in licensing or acquisition opportunities that address areas of significant need, offer substantial growth potential, and continue to further expand our portfolio. and subject to positive clinical data and regulatory approval, R289 could become a new treatment option for patients with lower risk MDS and potentially other indications. Several of the possible R289 indications represent potentially billion-dollar market opportunities. If successful, this could significantly expand our commercial portfolio in the 2030s and beyond. Together, these opportunities can drive sustained growth and long-term shareholder creation. with the potential to transform Rigel once again. With that, I will turn the call over to Dave to discuss our commercial business and revenue and our progress towards commercial availability. Dave.

Thank you, Raul. On slide eight, you'll see our three commercial products, Tavolis, Gavretto, and ResLydia. Moving to slide nine, which shows our product revenue for the second quarter of 2026. Thank you for joining us.

and more.

And finally, for ResLydia, we reported $8.9 billion in net product sales, an increase of 27% compared to the prior year period. During the quarter, we saw growing community use, consistent with our efforts to expand adoption in that setting. We believe emerging frontline venetoclax data may further reinforce the relevance of ResLydia in the post-venetoclax setting and improve adoption We believe that these efforts and data can be elements to continued ResLydia growth into the future. Overall, we're pleased with our second quarter results. While Vepinu will become our lead focus upon commercial availability, we remain committed to supporting Tavolis, ResLydia, and Gifredo. Moving to slide 10. We generated $11.7 million in revenues from collaborations in the second quarter, driven by the availability of Tavalise in global markets and a regulatory milestone payment for Iludicidinib. Our partners continue to pursue regulatory approvals for both Tavalise and ResLydia in new markets. In May, our partner Knight commercially launched Tavalise in Mexico, and they achieved regulatory approval of Tavalise in Brazil. with plans to commercially launch there in the second half of 2026. Access to our products is expanding outside the U.S. With that, I'll now turn attention to the newest addition to our commercial portfolio, Vepinu, I'm now on slide 12. Vepinu is FDA approved for the treatment of adults with ER positive, HER2 negative, ESR1 mutated, advanced or metastatic breast cancer as detected by an FDA authorized test with disease progression following at least one line of endocrine therapy. Moving to slide 13. We believe Vepinu has the potential to transform our commercial portfolio. Importantly, Vepinu is the first and only approved ProTac, a new class of targeted agents. It has a novel mechanism of action and potential to be an important new treatment option for patients. We believe our proven commercial and medical expertise and organization enable us to successfully commercialize Vepinu. We integrated both ResLydia and Gavretto into our portfolio over the last four years, and that experience served us well as we needed to quickly integrate Vepinu to ensure readiness in such a short amount of time. Lastly and importantly, we believe moving forward that Vepinu has the potential to become Rigel's largest revenue producer. On slide 14, I'll take you through the unique biology of proteolysis-targeting chimeras, or protacks, which are bifunctional small molecules that destroy specific disease-causing proteins rather than just inhibiting them. The Evapidu protack design consists of three parts. A targeting ligand that binds to the estrogen receptor, or ER, a recruiting ligand, and more. Thank you for joining us. The ubiquitin-tagged ER is then recognized and eliminated by the proteasome, the cell's natural waste disposal system. And because Vepinu bonds transiently and reversibly on both ends, it can repeat the process multiple times, allowing a single protag to degrade many ERs. Because of Vepinu's unique design and mechanism of action, it is the first in a novel pharmacologic class of heterobifunctional protein degraders, which is differentiated from other estrogen receptor agonists, which only bind to the estrogen receptors. Moving on to slide 15, I'd like to review the significant patient opportunity for Vepinu. There are an estimated 170,000 patients in the U.S. living with metastatic breast cancer, and approximately 70%, or 119,000 patients, have ER-positive HER2-negative disease. The standard of care typically includes endocrine therapy and a CDK4-6 inhibitor, and over time, up to 50% of patients may develop an ESR1 mutation. In Veritac2, all patients had received endocrine therapy and a CDK4-6 inhibitor, and 43% had an ESR1 mutation. So using approximately 40% as a benchmark, more than 47,000 ER-positive HER2-negative patients could have the ESR1 mutated disease. Based on our internal market research, We assume that approximately 60% of these patients are diagnosed and treated annually. Because ESR1 mutations generally emerge after exposure to endocrine therapy and CDK4-6 inhibitors, most of these patients are in the second line or later setting. This results in an estimated 20,000 U.S. patients diagnosed and treated annually with second line or later ER-positive and Her2-negative ESR1-mutated metastatic breast cancer. Overall, we believe this represents a U.S. market opportunity of more than $1 billion. Moving to slide 16, I wanted to provide some background on current treatments for second line and later ESR1-mutated metastatic breast cancer. First and importantly, in the blue portions of the bars, You can see how oral SIRDs have rapidly become the treatment of choice in the second line setting, garnering nearly 60% share than since they've been introduced. Even in the third line setting, oral SIRDs make up nearly 30% of treatment. This demonstrates how eager clinicians have been to find new options versus older treatments like fulvestrant, chemotherapy, and other therapies. That said, Those options still make up more than 40% of treatment in the second-line setting and most of the treatment in the third-line setting. The adoption of oral SIRDs has been the strongest in academic centers, where ESR1 testing and awareness of new therapies are higher. However, approximately 80% of metastatic breast cancer patients are treated in community practices, where oral SIRD adoption remains lower. That creates a meaningful opportunity to increase awareness and use of Vepinu as a new oral treatment option. Moving to slide 17, we believe that Vepinu has the potential to become a market-leading treatment. In addition to Vepinu being the first and only ProTac with a novel mechanism of action, there are three reasons we believe this. VeptiGestrin demonstrated impressive efficacy in the Phase III Veritac II clinical trial, with a significant improvement in median PFS, a 2.4-fold improvement, and meaningful responses. Alison will walk you through the data from the trial in a few minutes. Phytogesterone demonstrated tolerability in the Phase III Veritac II study with a manageable safety profile and low rates and severity of GI-related events, namely vomiting and diarrhea, which can be challenging for patients on other metastatic breast cancer treatments. Indeed, as a marker of being well-tolerated, just 3% of patients discontinued and only 2% required dose reductions. These are important differentiators in this market. Last, we believe that the real-world applicability of the patient population in Veritac2 is meaningful to clinicians. The standard of care for ER-positive, HER2-negative metastatic breast cancer patients is to use endocrine therapy and a CDK4-6 inhibitor. VEPDAG demonstrated efficacy, safety, and tolerability in exactly this setting in Veritac2, where 100% of patients received a CDK4-6 inhibitor and endocrine therapy as previous treatment for their disease. Based on these data, the NCCN, or National Comprehensive Cancer Network, added Veptogestrin to the NCCN clinical practice guidelines for breast cancer as a category 2A targeted therapy treatment option for HR-positive HER2-negative ESR1 mutation for recurrent unresectable or stage 4 disease. Overall, we see significant potential for Vepinib as a valuable new option in the treatment armamentarium for both academic and community physicians as they treat second-line and later ER-positive HER2-negative ESR1-mutated metastatic breast cancer. Let's turn to commercialization planning, which you'll see on slide 18. First, thanks to close coordination and the strong partnerships we have, we are on track to make Vepinu available in mid-August, which is ahead of schedule compared to our initial expectations. Second, we've prepared key stakeholders for commercial availability, including distributors, patient services providers, payers, and GPOs. and further, we engaged with breast cancer key opinion leaders and identified key accounts in advance of commercial availability based on our market research, launch forums and other activation initiatives. And third, our teams fully leveraged our experience to immediately deploy critical promotional activities. After the transaction closed, vetbenew.com went live. and importantly, our sales team was fully trained in record time and began enthusiastically driving awareness of Vepidu's approval and near-term commercial availability. In addition, Raja OneCare, our patient services hub, is now live and ready to serve healthcare providers and patients to ensure prompt access to Vepidu upon commercial availability. And on slide 19, you'll see our three-phase launch roadmap and examples of the Vepinu marketing materials. Following the transaction close, we immediately activated our now-approved campaign. We launched Vepinu.com, added Vepinu to the Rigel OneCare and medical information websites, and provided initial materials to our sales force. With commercial availability this month, we're launching the next phase of materials to support customer engagement and patient starts. These include a Veritac2 publication overview, dosing and administration guidance, a distribution guide, and patient resources. And in the fourth quarter, we expect to begin our branded campaign using an omnichannel approach to expand awareness and adoption among healthcare providers and patients. Our organization has moved quickly to put our patient services, the field team, and promotional resources in place as quickly as possible. We're proud of what the organization has accomplished since closing and are fully ready to make Vepinu available to patients and drive rapid awareness and adoption. My sincere thanks to the entire Rigel team for all their hard work and commitment. And with that, I'll turn the call over to Alison for a review of the data from the Phase III Veritac II clinical trial and ongoing development of Epidigestrin and to update you on our development pipeline. Alison.

Thank you, Dave. I'm very excited to join Nigel at this important stage in the company's evolution. Having served on Nigel's board since 2021, I've seen firsthand the strength of his team, the scientific rationale behind our programs, and the opportunity we have to advance meaningful new therapies for patients with hematological disorders and other cancers. I'm happy to tell you about the continued development of R289 and Rigel's broader clinical strategy, including the recent addition of vebdigestrin. With that, let me walk you through Rigel's plans to advance our development pipeline. First, I'd like to start with the clinical data from vebdigestrin, which underlies its approval by the FDA and gives us confidence in its potential to help patients. I'm now on slide 22, which shows the design of the VERITAC-2 clinical trial. It was a global phase three trial evaluating veptic estrant versus fulvastrant, a drug initially approved by the FDA in 2002 in patients with ER positive, HER2 negative, ESR1 mutated, advanced or metastatic breast cancer. Patients were at least 18 years old and had ER-positive HER2-negative advanced rheumatostatic breast cancer, and all patients had already received endocrine therapy in combination with a CDK4-6 inhibitor. Patients were permitted to receive up to one additional line of endocrine therapy, and they needed to have been on their most recent line of endocrine therapy for at least six months. They were not allowed to have had a prior SIRD, whether that was fulvastrant or elicestrant, and they could not have had prior cytotoxic chemotherapy for metastatic disease. Patients were randomized in a one-to-one fashion to receive either fulvastrant, given at its approved dosing, or vebdigestrant, 200 milligrams orally, once daily. The primary efficacy endpoint was progression-free survival by Blinded Independent Central Review. Initially, in those patients with ESR1 mutations, if positive, then we would subsequently test progression-free survival among all patients, the ITT population. Secondary endpoints included overall survival, clinical benefit rate, objective response rate, as well as adverse events and tolerability. Moving to slide 23, we show the primary endpoint PFS by Blinded Independent Central Review among the patients with the ESR1 mutations. Median PFS was 5.0 months for those patients receiving veb digestrant, where it was only 2.1 months for those patients receiving fulvastrant. This was very much in line with what we expected of how a fulvastrant control arm would perform in this population. The hazard ratio was 0.57 for a statistically significant p-value of less than 0.001. You can see the landmark analyses at six months progression-free survival approximately double the percentage of patients remaining progression-free at six months who are receiving levdigestrin compared to those patients receiving fulvastrin. Slide 24. shows important secondary endpoints, clinical benefit rate and objective response rate by blind and independent central review. In patients with ESR1 mutations, the clinical benefit rate more than doubled with vebdigestrant at 42% compared to 20% with fulvastrant. In terms of objective response rate, vebdigestrant more than quadrupled the ORR observed with fulvastrant. and a breast cancer population known to have a relatively low objective response rate. Only 4% of patients receiving single agent fulvastrin had an objective response compared to 18.6% of patients who received deptogestant. Turning to safety and tolerability on slide 25, grade three or higher treatment emergent adverse events occurred in 23% of patients receiving vebdigestrin and 18% of patients receiving fulvastrin. Treatment discontinuations and dose reductions due to adverse events were low with vebdigestrin at 3% and 2% respectively. The most common treatment of urgent adverse event was fatigue reported in 27% of patients receiving vebdigestrin. ALT and AST increases occurred in approximately 14% with grade three or four events in only 1%. Nausea occurred in 13% with no grade three or four cases. I'd note, you do not see diarrhea on this slide because it did not meet the 10% threshold to be included. Any grade diarrhea was only 6% for patients receiving septic estrogen. Although QT prolongation of any grade, was reported in the Veritac 2 trial, which led to its inclusion in the warning and precaution section of the US package insert. No clinical sequelae were reported. A dedicated QT substudy in 88 patients showed a mean QTCF increase from baseline of 11.1 milliseconds, with the upper bound of the 90% confidence interval below 20 and others. The efficacy and manageable safety profile demonstrated in VERITEC2 supported FDA approval of vebdigestrin for patients with second-line or later ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. As we think about studying vebdigestrin further On the left side of slide 26, you will see the ongoing studies for which Arvinas and Pfizer will continue to maintain responsibility. As a reminder, all of the studies listed are active, but no longer enrolling patients with the exception of the hepatic impairment study. These studies include the completion of the VERITAC-2 trial for its time to event and disposition endpoints, In addition, there are four studies focused on studying veb digestrant in combination with other agents. We believe these studies will provide additional safety and efficacy data that will be helpful as we evaluate future development opportunities. Now let's move on to our development focus areas. I'm on slide 27. Our hematology and oncology pipeline focus is around the clinical development of R289, our potent and selective dual IRAC1 and IRAC4 inhibitor in lower risk myelodysplastic syndrome, referred to as MDS, and potentially other indications. I'll spend time providing an update on R289 in a minute. On the right side of the slide, you can see we are evaluating olutacitinib beyond relapsed or refractory IDH1 mutated AML. in collaboration with academic partners. MD Anderson is evaluating Iludacitinib in multiple clinical studies in IDH1-mutated AML and other hematologic malignancies where IDH1 plays a role. Iludacitinib is also being evaluated as maintenance therapy in IDH1-mutation-positive high-grade glioma by the Connect Cancer Consortium. Lastly, we are partnering with Minalmatch for a planned study in first-line AML and MDS. We look forward to seeing the data that these studies generate in the future. Now I will discuss R289, our novel dual IRAC1 and IRAC4 inhibitor. You can review the R289 slides in full in our corporate presentation that's posted in the investor section of our website. I'll provide a brief update on the program today. I'm now on slide 29. I'd first like to remind you about the treatment landscape for lower risk MDS. Therapies used in the upfront setting include erythropoiesis stimulating agents, or ESA, if patients are eligible, or Luzpatracept. Luzpatracept and more recently Imatelstat are also approved for ESA failure, transfusion dependent, and other lower-risk MDS patients. Finally, hypomethylating agents, or HMAs, are also approved. However, the percentage of patients receiving transfusion independence is low. With eight-week transfusion independence rates approaching 40% with lispatracept and imetelstat, there is still a need for safe, effective therapies for transfusion and other dependent lower risk MDS patients that are relapsed or refractory or ineligible for ESAs. On slide 30 is the value proposition of R289 and lower risk MDS. There are about 12,000 previously treated lower risk MDS patients in the United States. There is a high unmet need for therapies, including transfusion-dependent patients. R289 has a novel mechanism of action as a dual IRAC1 and IRAC4 inhibitor. Blocking both IRAC1 and 4 may suppress marrow inflammation and leukemic stem progenitor cell function and restore normal hematopoiesis. Clinical proof of concept came from a healthy volunteer study in which R289 and Dr. Gautam Chowdhury. Dr. Gautam Chowdhury and Dr. Gautam Chowdhury and Dr. Gautam Chowdhury and Dr. for MDS, giving the molecule an expedited regulatory pathway, potential priority review, and seven years of market exclusivity upon approval. R289 has thus far demonstrated a promising clinical profile with both encouraging preliminary safety and efficacy data in our Phase 1B study. Now on slide 31, you can see the design of our multicenter open label phase 1B study in patients with relapsed or refractory lower risk MDS. The phase 1B study evaluates the safety, tolerability, PK, and preliminary efficacy of R289 in patients with lower risk MDS and is also designed to select a dose for future studies. In the dose expansion part of the study, which we are enrolling now, up to 40 transfusion dependent relapse refractory lower risk MDS patients will be randomized to receive R289 doses of either 500 milligrams once or 500 milligrams twice daily in order to select the recommended phase two dose for future clinical studies. On slide 32, you see highlights from the dose escalation phase data presented at ASH meeting in 2025. Again, I encourage you to review the R289 ASH 2025 data slides in full in our corporate presentation. R289 was generally well tolerated. Of the 18 evaluable patients reading doses of 500 milligrams daily or higher, six patients, or 33%, achieved red blood cell transfusion independence, or RBCTI, lasting for eight weeks or longer. In four patients, RBCTI lasted for more than 16 weeks, and for three patients, more than six months. The median duration of RBCTI was approximately 23 weeks, ranging from nine weeks to more than 24 months. Median time to onset of RBCTI was about two months. In summary, R289 was generally well tolerated. with an encouraging safety profile and promising efficacy in an elderly, heavily pretreated, transfusion-dependent, lower-risk MDS population. While this is a small dataset, we're encouraged by the dose-dependent positive results given the highly refractory nature of these patients. On slide 33 are the next steps for R289. In lower-risk MDS, we plan to complete enrollment of the dose escalation phase of the Phase 1b study and select the recommended Phase 2 dose for future studies in the second half of this year. We anticipate sharing top-line data from the dose expansion phase by the end of the year. Once the recommended Phase 2 dose has been selected, we will evaluate R289 in a cohort of less heavily pretreated patients who are relapsed or refractory to or ineligible for ESAs in the same study. Upon completion of the Phase 1B study, we plan to follow up with the FDA to discuss a potential registration trial. In addition, we are continuing to progress with our evaluation of R289 and other potential indications that align with its mechanism of action and plan to provide an update later this year. I'll now pass the call to Dean to discuss our financial results for the quarter. Dean?

Thank you, Alison. I'm on slide 35. We reported net product sales of $67 million for the second quarter, a growth of 14% year-over-year, including Tavolis net product sales of $47.4 million, a growth of 18% year-over-year, Gavrador net product sales of $10.7 million, a modest decline year-over-year, and Rez Lydia, net product sales of $8.9 million, a growth of 27% year over year. Our net product sales were recorded net of estimated discounts, chargebacks, rebates, returns, copay assistance and other allowances of $21.4 million. We also reported $11.7 million in contract revenues for the second quarter primarily consisting of $5.8 million of revenue from Kisei, which included a $4 million regulatory milestone payment in connection with the marketing authorization application submission for Lutacidinib in Japan and the delivery of drug supplies. and others. Our total revenues for the second quarter was $78.7 million. Moving to slide 36, for the second quarter of 2026, our cost of product sales was approximately $8.5 million. Total costs and expenses were $55.1 million. and the Board of Directors of the Board of Directors of the Board of Directors of We reported net income of $17.3 million for the second quarter, compared to net income of $59.6 million in the same period in 2025. As a reminder, the second quarter of 2025 included $40 million in non-cash revenue related to Roger's collaboration agreement with Lilly. We ended the quarter with cash, cash equivalents, and short-term investments of $95.3 million compared to $155 million as of the end of 2025. Turning to our financial outlook for 2026, we've raised and narrowed our guidance range and expect total revenues in the range of approximately $285 to $295 million. Our guidance range includes our expectation of approximately $255 to $265 million in net product sales, excluding Bepinu, and approximately $30 million in contract revenues. We also anticipate reported positive net income for the full year, while funding existing and new clinical development programs. On slide 37, I'll review the key transaction terms of our Bepinu licensing agreement. Roger paid the upfront payment of $70 million following the close of the transaction. Beyond that, there are $15 million in milestones owed to Arvinas and Pfizer tied to the successful completion of transition activities. Arvinas and Pfizer are also eligible to receive potential regulatory and commercial payments totaling up to $320 million. The tiered royalties on cumulative net sales owed to Arvinas and Pfizer range from the mid-teens to the mid-20s. Also, and as Alison mentioned, Pfizer and Arbenis remain responsible for their current ongoing development activities for Vemta-Digest Sprint. Roger will contribute up to $40 million over the next four years in support of these activities. With that, I'd like to turn the call back over to Raul. Raul? Thank you, Dean. Moving on to slide 38.

The first half of 2026 marked significant progress across each of our strategic priorities. Most notably, we closed the VepaNew transaction, adding a fourth FDA-approved product to our portfolio and creating an important new long-term growth opportunity. We remain on track for commercial availability in mid-August. Our priorities for the second half of the year are clear. Successfully launch VepaNew and grow our commercial portfolio. complete R289 dose expansion enrollment, select the recommended phase two dose, and share top line data. Evaluate additional indications for R289, and finally maintain financial discipline while delivering top line growth and positive net income. With a broader commercial portfolio, a promising pipeline, and a strong financial foundation, we believe Rigel is well positioned for its next phase of growth and long-term shareholder value creation. We appreciate your time today. And with that, I'll turn the call back to the operator for your questions. Operator.

Thank you. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up the handset before pressing the star keys. One moment, please, for the first question. Our first question comes from the line of Joe Pangenius with AC Wainwright. Please proceed with your question.

Hey, everybody. Good afternoon, and thanks for taking the question. So I wanted to go back to one of your comments on the commercial assets that you have here. Obviously, Vepinu is, as you said, the largest potential financial opportunity, but I wanted to focus on the comment that This would be the lead focus on availability, so obviously you can't have the accelerator pushed, I guess, 100% on all your assets. What's sort of on autopilot? What gives you the confidence to say it will be the lead focus and how that impacts or potentially impacts your efforts on Tavalisa and ResLydia?

Thank you, Joe.

I'll ask Dave to comment. That's a great question, Joe. Over the years, you know, we have gotten very, very good at really understanding what impacts our business, particularly with Tavalise and certainly more recently over the last four years with ResLydia. With Tavalise, I think we understand that market quite well. We know, you know, where there are potential new prescribers as well as existing prescribers. and I think you have to understand that the majority of that comes from the community and our team is going to be in those community offices. So what I mean by support in terms of Tavalise is we're calling on them, bringing a Vepinu message and we're making sure that they're completely supported in their desire to prescribe Tavalise. With ResLydia, one of the things we've really done well, the team has done a lot of work on this, even incorporated AI, as well as a lot of looking at diagnostic data is we've really helped to have the team target potentially when an IDH1 patient occurs, particularly in the community. We get a lot of these, what we call them our alerts for the team, and they can focus on that when the opportunity arises. We don't have to spend a whole bunch of time going around and talking about AML and ResLydia in the community when there's no patients there. That's not what we want to do. We want to selectively find when we think there's going to be an opportunity and present that message, and that'll continue. What we have here is an opportunity to go in, really talk about Bepinu a lot. The team has already been doing that, as I said, since close. and actually what's been interesting is they're getting more access to accounts because of that. And that enables them to support Tavoli, support ResLydia when there are patients available.

That's very, very helpful. I appreciate that color. And then maybe a question for Alison, if you don't mind, and welcome to the full-time position off of the board as well. With regard to R289 and the different strategic collaborations, is there one that may or may not be your personal favorite with other hemes or even the glioma indication based on the drug's mechanism of action or other factors that might contribute.

So thank you for the question. Is there one favorite of our corporate collaborations? We have the MD Anderson Alliance, which is moving forward very well with multiple clinical trials at this time. We have the CONNECT study. We have myelomat. But in terms of favorite collaboration, I dare say it would have to be MD Anderson. I have personally worked with the hematological division of MD Anderson for nearly 30 years. So I'm very familiar with all the important scientific collaborations that they can bring. And they are attacking hematological malignancies in various different subgroups. that I find very attractive, including a maintenance trial, an upfront trial. So honestly, if I had to pick one favorite, it would probably be the MD Anderson collaboration. But thank you for the question.

No, I appreciate that. So, you know, maybe not favorite because I don't want you to have a favorite child. No, I feel like I may have gotten into trouble. You have great infrastructure relationships there. So thanks for the questions and the answers. Thank you.

Thank you, Joe.

Thank you. Our next question comes from the line of Farzin Haku with Jefferies. Please proceed with your question.

Hi. Thank you for taking our questions. This is Amin Khan for Farzin. A couple of questions from us. First, you increased the upper bound of guidance by $5 million, which doesn't include Vipinu. The question is, what are you seeing to date for the commercial portfolio that are underpinning this assumption, and what's your expectation for the webinar launch this year?

Well, I'll ask Dave and I can comment. By the way, the change to the guidance, before I turn it over to Dave, was we increased the contract revenue from 20 to 30 range to approximately 30, as we've seen strong contract revenue come in in the first half of the year. We left intact the product sales rep guidance of 255 to 265. That sales guidance is only on Tavalis, Gavretto, and ResLydia. So I'll ask Dave to comment on Vepinu specifically, but we maintain our guidance on the other products.

Thanks, Raul. Yeah, in terms of guidance for Vepinu, we're not going to be issuing any guidance in the short term for Vepinu. Obviously, we don't have any sales yet coming in, and you'll see that after third quarter. So we'll update you as we, you know, to give you color and insights into how the Vepinu launch is progressing. but I'll just reiterate that we believe that Vepinu can become a market leading treatment in this second line ESR1 mutated space. We believe we have a product with a differentiated mechanism and it's a wholly different pharmacologic class being a hetero-bifunctional protein degrader and we have the proven efficacy that Alison have all reviewed, and particularly not only a very strong treatment effect in PFS, but also higher response rates, both from a partial response rate or overall response rate and a clinical benefit rate, which includes stable disease, which is extremely important in metastatic breast cancer. And we think we have a tolerable agent. And for all these reasons, you know, Frankly, even now, I think as we talk to customers, there's a lot of interest in the product. And I think the most frequent question we have is, when is the product going to be available? We get this pretty much from all corners of the field. So I think we're really looking forward to this product gaining traction in the near future. And at some point, we will be issuing guidance on it.

We'll have to wait a little bit until we get some time under our belt, so that we can feel comfortable with the trajectory of the thing. But I have to say, we're excited to see the product in the hands of clinicians and patients in the short order, and then providing some revenue by the end of the year, what we've accomplished this shortened year. But it's an exciting driver for us. We're happy with the performance of the other products. They're growing modestly. And this, we expect to be the real driver underlying our commercial business.

Thanks. That's very helpful. And just one clarification question on webinar market opportunity. Can you clarify the 1 billion figure you referenced? Does this represent the overall second line ESR1 mutated opportunity available for oral certs, or this is an estimate specifically for Vipinil potential peak cells?

That's the market opportunity. We're clear that that's, we think that the second line and later ESR1 mutated patient population is about 20,000, which correlates to about a billion dollars.

And it's higher than that depending on what assumptions you take on pricing, etc.

Thanks. Thank you, Parson.

Thank you. Our next question comes from the line of Kristen Kluska with Cancer Fitzgerald. Please proceed with your question.

Hi. This is Jenny on Kristen's line. Thank you so much for taking my question. I have two. While not giving any guidance on Vepinu at this time, realistically, when should we start to model in first sales and what factors should we take into consideration for cadence and penetration? And then second, could you also provide some color on the ongoing studies that Pfizer is conducting, particularly those evaluating Vepinu in combination regimes?

Sure. So in terms of the timing, we will be reporting the Q3 sales that we accomplished, but that'll be in November. We'll actually have those.

Now, this will be a shortened quarter.

At J.P. Morgan, we typically put out a press release before that call, that meeting, saying what our revenues were for the year, in which case we'll include Bepinu sales for 2024, sorry, 2025, 26 in total. So that'll be a quarter and about a little bit more than that. And at that point, we'll figure out what we're giving in terms of guidance, but we haven't decided that yet. But it may not include Bepinu at the time. on collaborations.

Certainly, I can provide where we have been in terms of public distribution of data. The vebdigestrin plus palbocyclib, the data was initially presented as ESMO breast cancer 2024. The vebdigestrin plus abemocyclib was presented in ASCO 2026. and finally the veptic gastroenteritis plus a termocyclib was also presented at that same meeting, ASCO 2026. The data for ribocyclib and samuracyclib have not yet been publicly presented, but we would anticipate seeing those data in the future, in the not too distant future.

Thank you so much. The importance of this data is that it'll provide context for clinicians using this product in combo. As you probably heard, the product has a tolerability profile that's quite attractive and therefore may be a good partner in terms of combining with other agents. Thank you, Kristen.

Thank you.

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

Thank you everyone for joining us today. We are pleased with our second quarter performance and really look forward to Vepinu becoming commercially available later this month in the middle of it as well as several other important milestones with R289 that we are expected to achieve this year. We appreciate your continued interest and support and we'll keep you updated throughout the year. Thank you and have a good evening.

You may disconnect your line at this time. Thank you for your participation.