Q1 2024 Rigel Pharmaceuticals Inc Earnings Call

Operator: Greetings and welcome to Rigel Pharmaceuticals' financial conference call for the first quarter of 2024. At this time, all participants are in a listen-only mode. A brief question and answer session will follow the formal presentation. If anyone today 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. You may now begin.

Greetings and welcome to Rigel Pharmaceuticals Financial conference call for the first quarter 'twenty 'twenty four.

Operator: At this time all participants are in a listen only mode a.

Operator: A brief question answer session will follow the formal presentation.

Operator: If anyone today should require operator assistance during the conference. Please press star zero on your telephone keypad.

Operator: As a reminder, this conference is being recorded.

Raymond J. Furey: It is now my pleasure to introduce our first speaker Ray Fury, Rachel's Executive Vice President General Counsel and corporate Secretary. Thank.

Raymond J. Furey: Thank you Mr. Ferry you may now begin.

Raymond J. Furey: Thank you. Welcome to our first quarter 2024 financial results and business update conference call. The financial press release for the first quarter of 2024 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 Ryder.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.

Raymond J. Furey: Thank you welcome to our first quarter 2024 financial results and business update conference call.

Raymond J. Furey: National Press release for the first quarter 2024 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.

Raymond J. Furey: Hi.

Raymond J. Furey: 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.

Raymond J. Furey: These statements are subject to risks and uncertainty that may.

Raymond J. Furey: Cause actual results differ from our forecast.

Raymond J. Furey: These statements are subject to risks and uncertainty 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-end of December 31, 2023, and subsequent filings with the SEC, including our Quarter 1 quarterly report on Form 10-Q on file with the SEC. Any forward-looking statements are made only as of today, and we undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances. At this time, I would like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez. Thank you, Ray.

Raymond J. Furey: Description of these risks can be found in our most recent annual report on Form 10-K for the year ended December 31, 23, and subsequent filings with the SEC sooner quarter. Once quarterly report on Form 10-Q filed with the SEC.

Raul R. Rodriguez: 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.

Speaker Change: At this time I would like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez Ramos.

Raul R. Rodriguez: Thank you, Ray, and thank you, everyone, for joining me today. With me today are Dave Santos, our Chief Commercial Officer, and Dean Schorno, our Chief Financial Officer. Additionally, I'd like to introduce Lisa Royker, our new Chief Medical Officer. Lisa joined us in March and brings over 20 years of clinical development, regulatory, and medical affairs experience to Rigel. We are thrilled to have her on the team. Now, beginning slide four.

Raul R. Rodriguez: Thank you Ray and thank you everyone for joining today.

Raul R. Rodriguez: With me today are Dave <unk>, our Chief commercial officer, and Dean <unk>, our Chief Financial Officer. Additionally.

Raul R. Rodriguez: Additionally, I'd like to introduce Lisa ROIC here, our new Chief Medical Officer.

Raul R. Rodriguez: Lisa joined US in March and brings over 20 years of clinical development regulatory and medical affairs experienced Durango, we are thrilled to have her on the team.

Raul R. Rodriguez: Now beginning on slide four.

Raul R. Rodriguez: We continue to grow our hematology and oncology business in the first quarter of the year, positioning us well for the remainder of 2024 and beyond. We started 2024 with strong commercial demand for our two marketed products, Tavalisin ITP, and Reslydia in Mutant IDH1 Relapsor Refractory AML, with demand for bottles for each of these two products reaching a new quarterly high since their launch. This is particularly impressive since the first quarter of the year is typically one where our industry faces headwinds due to insurance co-pays and resets and the medical doughnut hole. The decline in net product sales from the prior quarter is primarily due to a decrease in Tablilis bottles remaining in our distribution channel or inventory.

Raul R. Rodriguez: We continue to grow our hematology and oncology business in the first quarter of and your positioning positioning us well for the remainder of 2024 and beyond we started 2024 with strong commercial demand for our two marketed products have a lease in RTP and red linear I D. H, one relapsed or refractory AML with the <unk>.

Raul R. Rodriguez: Bottles for each of these two products reached a new quarterly highs since their launch.

Raul R. Rodriguez: This is particularly impressive since the first quarter of the year is typically one where our industry faces headwinds due to insurance co pays and resets and the Medicare Donut hole.

Raul R. Rodriguez: The decline in net product sales from the prior quarter is primarily due to a decrease in total these bottles remaining in our distribution channel or inventory.

Raul R. Rodriguez: In addition, we are also expanding our commercial product portfolio with the recent acquisition of GABRETTO, an FDA-approved therapy for the treatment of red fusion positive metastatic non-small cell lung cancer and advanced or metastatic thyroid cancer. Gavreto offers a valuable targeted treatment option for lung cancer patients with red fusion positive disease. Navreda will provide us with top-line growth as well as leverage our existing commercial and medical affairs infrastructure. We remain on track to complete the transition of this asset in July of this year.

Raul R. Rodriguez: In addition, we are also expanding our commercial product portfolio with the recent acquisition of <unk>, an FDA approved therapy for the treatment of ret fusion positive metastatic non small cell lung cancer and advanced or metastatic thyroid cancer.

Raul R. Rodriguez: <unk> offers a valuable targeted treatment option for non small cell lung cancer patients with ret fusion positive disease.

Raul R. Rodriguez: Yeah, Brennan will provide us with top line growth as well as leverage our existing commercial and medical affairs infrastructure. We remain on track to complete the transition of this asset in July of this year.

Raul R. Rodriguez: In parallel, we're advancing our development programs, including the evaluation of Rizalidia in a broad range of IDH1 mutant cancers with our strategic partners, MD Anderson Cancer Center and Connect. These alliances greatly enhance our ability to further evaluate Resilidia's potential in a cost and time-efficient manner.

Raul R. Rodriguez: In parallel we're advancing our development programs, including the evaluation of Paris linear in a broad range of <unk> mutant cancers with our strategic partners M D Anderson cancer Center and connect.

Raul R. Rodriguez: These alliances greatly enhance our ability to further evaluate <unk> potential in a cost and time efficient manner.

Raul R. Rodriguez: As we grow our commercial product portfolio and prioritize prudent clinical development, we are well positioned to advance our business and work towards financial breakeven. Before I turn the call over to Dave, I'll provide a summary of our previously announced acquisition of U.S. rights to Gabretto on slide five. We are working diligently to ensure a smooth transition of Gabaretto into our commercial product portfolio, which we expect to complete in July. There are strong synergies between this product and our existing portfolio, infrastructure, and expertise.

Raul R. Rodriguez: As we grow our commercial product portfolio and prioritized prudent clinical development, we are well positioned to advance our business and work towards financial breakeven.

Raul R. Rodriguez: Before I turn the call over to Dave I'll provide a summary of our previously announced acquisition of U S rights to <unk>.

Raul R. Rodriguez: On slide five.

Raul R. Rodriguez: We are working diligently to ensure a smooth transition of care right now into our commercial product portfolio, which we expect to complete in July.

Raul R. Rodriguez: There are strong synergies between this product and our existing portfolio infrastructure and expertise. We believe we have the right people and systems in place to bring this product to physicians and their patients.

Raul R. Rodriguez: We believe we have the right people and systems in place to bring this product to physicians and their patients. Gabretto is a once-daily oral RET inhibitor with an established foothold in the U.S. market, having generated $28 million in U.S. net product sales in 2023. Further, with patents that have issued or are expected to issue with statutory expiration dates between 2036 and 2041, we are well positioned to make GABRETTO available for years to come.

Raul R. Rodriguez: Yeah, Brett always is a once daily oral ret inhibitor with an established foothold in the U S market, having generated $28 million in U S. Net product sales in 2020 threes.

Raul R. Rodriguez: Further with patents that are issued are expected to issue when statutory expiration dates between 2036 and 2041, we are well positioned to make that brought all available for years to come.

Raul R. Rodriguez: In exchange for U.S. rights to Gabrielo, we will pay our partner, Blueprint, a purchase price of $15 million, $10 million of which is payable upon the first commercial sale and $5 million of which is payable upon the first anniversary of the closing date. The deal also includes potential future regulatory and commercial milestone payments to Blueprint, as well as tiered royalties on net sales of CADRETO. We believe this puts Rigel in a favorable position to begin capturing value from this program in the near term. Now, I will turn the call over to Dave to provide updates on our commercial product portfolio. Dave? Thank you, Raymond.

Raul R. Rodriguez: In exchange for U S rights to kept rental we will pay our partner blueprint a purchase price of $15 million 10 million of which is payable upon first commercial sale and 5 million of which is payable upon the first anniversary of the closing date.

Dave: The deal also includes potential future of regulatory and commercial milestone payments to blueprint as well as tiered royalties on net sales of that Brett.

Dave: We believe this puts rigel in a favorable position to begin capturing value from this program in the near term.

Raul R. Rodriguez: No I will turn the call over to Dave to provide updates on our commercial product portfolio.

Dave: Thank you Raul.

David A. Santos: First, on to growing demand for Tobilis and ITP. I have a few brief comments on our continued momentum with Tavalese and QY. On slide 7, you will see our FDA-approved indication, which is for adult patients with chronic immune thrombocytopenia, or CITP, who have had an insufficient response to a previous treatment. Moving to slide 8, I'm happy to report that in Q1, Tabliliz achieved its sixth consecutive quarterly record high for bottles shipped to patients in clinics.

Dave: First on to growing demand probably use an I T P.

David A. Santos: I have a few brief comments on our continued momentum with top lease in Q1.

David A. Santos: On slide seven you will see our F. D. A approved indication which is for adult patients with chronic immune thrombocytopenia or C. I T. P who had an insufficient response to a previous treatment.

David A. Santos: Moving to slide eight I'm happy to report that in Q1, probably use achieved its sixth consecutive quarterly record high for bottles shipped to patients and clinics.

David A. Santos: Over those six quarters, we have increased Togliatti's quarterly demand volume by 23 percent, and Q1 2024 demand grew 10% over the same period last year. We are pleased that our team has continued to produce double-digit, year-over-year growth starting our sixth full year after approval. Total bottles sold in Q1 were 290 bottles less than our bottles shipped to patients and clinics as our distribution channel reduced inventory. Dean will discuss this later in our presentation. This resulted in Tavalisse net sales of $21.1 million for Q1.

David A. Santos: It was six quarters, we have increased probably quarterly demand volume by 23%.

David A. Santos: And Q1, 'twenty 'twenty four demand grew 10% over the same period last year.

David A. Santos: We are pleased that our team has continued to produce double digit year over year growth starting our sixth full year after approval.

David A. Santos: Total bottles sold in Q1 were 290 barrels less than our bottles shipped to patients and clinics as our distribution channel and reduced inventory.

David A. Santos: Jim will discuss this later in our presentation.

David A. Santos: This resulted in <unk> net sales of $21 1 million for Q1.

David A. Santos: On slide nine, the driver of our continued demand growth with Tabolisse is our new patient start. The graph on the left shows that since 2021, after we emerged from the pandemic, our new patient starts have continued to improve each year. In Q1, we achieved the highest first quarter new patient start since launch.

David A. Santos: On slide nine the driver of our continued demand growth with top police is our new patient starts.

David A. Santos: The graph on the left shows that since 2021. After we emerge from the pandemic are new patient starts have continued to improve each year.

David A. Santos: In Q1, we achieved the highest first quarter new patient starts since launch with.

David A. Santos: We generated this new patient start growth through continued focus on expanding the breadth and depth of prescribers, ensuring strong coverage and reimbursement with greater than 95% commercial coverage, and constantly reinforcing the clinical efficacy and safety of Tavalese through our own clinical trials. I want to thank our entire team for their continued focus and execution to impact more CITP patients with TABLY. We are very pleased with the consistent growth in new patient starts and how that has continued to drive our demand both in Q1 and as we move forward through 2024. Moving to slide 10, now I'd like to take a few minutes to discuss our strong quarter in growing res lidius.

David A. Santos: We generated this new patient start growth through continued focus on expanding the breadth and depth of prescribers.

David A. Santos: Ensuring strong coverage and reimbursement with greater than 95% commercial coverage and constantly reinforcing the clinical efficacy and safety of <unk> with our customers.

David A. Santos: I want to thank our entire team for their continued focus and execution to impact more in CIC patients with top beliefs.

David A. Santos: We are very pleased with the consistent growth in new patient starts and how that has continued to drive our demand both in Q1 and as we move forward through 2024.

David A. Santos: On slide 11, you will see our FDA-approved indication for Reslydia, which is for adult patients with relapsed or refractory acute myeloid leukemia who have a susceptible IDH1 mutation as detected by an FDA-approved test. Moving to slide 12, we shipped 326 bottles of Reslydia to patients and clinics in Q1, representing strong 17% growth versus Q4 of 2023 and nearly tripling the demand generated a year ago in Q1, our first full quarter of launch.

David A. Santos: Moving to slide 10, now I'd like to take a few minutes to discuss our strong quarter growing rents linear sets.

David A. Santos: On slide 11, Youll see our FDA approved indication for bracelet, yet, which is for adult patients with relapsed or refractory acute myeloid leukemia with the susceptible I D. H one mutation as detected by an FDA approved test.

David A. Santos: Moving to slide 12, we shipped 326 bottles in Brentwood, yet to patients and clinics in Q1, representing strong 17% growth versus Q4 of 2023 and nearly tripling the demand generated a year ago in Q1, our first full quarter of launch.

David A. Santos: We sold 390 bottles of Reslydia into our distribution channel, resulting in $4.9 million in net sales in Q1 2024. This was 26% above what we sold in Q4 and more than triple the net sales of the same period last year.

David A. Santos: We sold 390 bottles of Rensselaer into our distribution channel, resulting in $4 $9 million in Q1 net to 2024 net sales.

David A. Santos: This was 26% above what we sold in Q4 and more than triple the net sales of the same period last year.

David A. Santos: We are very encouraged by the momentum we are now building with Rensselaer. On slide 13, I wanted to update you on how our Res Lydia institutional business continues to be the driver of our growth. 84% of our total bottles shipped to patients and clinics were generated from use in institutional accounts.

David A. Santos: We are very encouraged by the momentum we are now building with the Reds Lady yet.

David A. Santos: On slide 13, I wanted to update you on how our rents linear institutional business continues to be the driver of our growth.

David A. Santos: 84% of our total bottles shipped to patients and clinics were generated from use in institutional accounts.

David A. Santos: Our breadth and depth of use in institutions continues to grow as more academic leukemia treaters are becoming more aware of Reslydia's data in relapsed refractory mutant IDH1-AML. As we've discussed on prior calls, we believe we have an opportunity to grow ResLydia use further in the community, as in that segment of our business, quarterly demand has remained stable. We did see a highly encouraging trend in Q1, as the community drove more than one quarter of our new patients' starts.

David A. Santos: Our breadth and depth of use in institutions continues to grow as more academic leukemia treaters are becoming more aware of rez Linnaeus data in relapsed refractory mute 90, H one a M L.

David A. Santos: As we've discussed on prior calls we believe we have an opportunity to grow risk Lady at US further in the community and in that segment of our business quarterly demand has remained stable.

David A. Santos: We did see a highly encouraging trend in Q1 as the community drove more than one quarter of our new patient starts.

David A. Santos: This signals that community leukemia treaters are also becoming aware of Reslydia and are trying it in their mutant IDH1 AML relapsed or refractory patients. However, we believe a significant opportunity remains to grow Reslydia use among community AML treaters, particularly because of their adoption of venetoclax-based regimens for their newly diagnosed patients. We feel ResLydia's data in post-banetoclax patients will be particularly compelling to them. I want to thank our entire team for their hard work in growing awareness of Ryslydia both in academic institutions and community practice. They have worked closely across functions as one United Teeth to broaden Reslidious' impact on mutin andy H1 relapse refractory AML.

David A. Santos: This signals that community leukemia, Treaters are also becoming aware of rents Lady yet and they're trying it in their mute 90, H, one AML relapsed or refractory patients.

David A. Santos: We believe a significant opportunity remains to grow rents Lady you use among community AML treaters, particularly because their adoption of <unk> based regimens for their newly diagnosed patients.

David A. Santos: We feel rez Linnaeus data imposed banana clacks patients would be particularly compelling Tibet.

David A. Santos: I want to thank our entire team for their hard work in growing awareness of risk linear both in academic institutions and community practices.

David A. Santos: They have worked closely across functions as one United team to broaden rents Lady has impact on mutant and each one relapsed refractory AML patients.

David A. Santos: Moving to slide 14, I wanted to provide an update on our commercialization plans for Devreda. On slide 15, I'll begin by reviewing the FDA-approved indications for Givretto, which include the treatment of adult patients with metastatic Rett fusion-positive non-small cell lung cancer, as well as adult and pediatric patients 12 years of age or older with advanced Rett fusion-positive thyroid cancer who require systemic therapy and who are radioactive Moving to slide 16, I want to reiterate why we believe Giveretto is an important strategic addition as the third FDA-approved oral targeted therapy in our Rigel commercial portfolio. As you'll recall from Raul's remarks, Givretta generated nearly $28 million in U.S. net sales last year.

David A. Santos: Moving to slide 14, I wanted to provide an update on our commercialization plans for <unk>.

David A. Santos: On slide 15, I'll begin by reviewing the FDA approved indications forgive ran out which include the treatment of adult patients with metastatic ret fusion positive non small cell lung cancer as well as the adult and pediatric patients 12 years of age or older with advanced Ret fusion positive thyroid cancer.

David A. Santos: This requires systemic therapy, and who are radioactive iodine refractory.

David A. Santos: Moving to slide 16, I want to reiterate why we believe you have red Oak is an important strategic addition, as the third FDA approved oral targeted therapy in our roadshow commercial portfolio.

David A. Santos: As Youll recall from relatives remarks give red are generated nearly $28 million in U S. Net sales last year. So this is an excellent opportunity for us to continue providing meaningful therapy to ret fusion positive patients with non small cell lung cancer and advanced thyroid Kid.

David A. Santos: So this is an excellent opportunity for us to continue providing meaningful therapy to RET-fusion positive patients with non-small cell lung cancer and advanced thyroid cancer. We believe this compelling Govretto opportunity suits our business well for a few reasons. Number one, it enables us to immediately and efficiently move into a large solid tumor market where most clinicians are already testing patients and immediately recognize Rett as a biomarker associated with FDA-approved therapy.

David A. Santos: Sir.

David A. Santos: We believe this compelling gunvor auto opportunity seats, our business well for a few reasons number one it enables us to immediately and efficiently move into a large solid tumor market, where most clinicians are already testing patients and immediately recognize rent as a biomarker.

David A. Santos: Associated with FDA approved therapies.

David A. Santos: So we anticipate that the rent market will continue to expand as more ret fusion positive non small cell lung cancer and advanced thyroid patients are identified.

David A. Santos: So we anticipate that the RET market will continue to expand as more RET fusion positive non-small cell lung cancer and advanced thyroid patients are identified. Number two, we believe we have built strong access capabilities that we can fully leverage to ensure current and newly prescribed patients have access to Gavretto. Our efficient and customer-friendly distribution network with Tavolese and Residia will soon be ready to accommodate Gavretto, as will our Rigel OneCare patient services hub that has established a reputation for being highly responsive to patients and providers.

David A. Santos: Number two we believe we have built strong access capabilities that we can fully leverage to ensure current and newly prescribed patients have access to get Brad out are efficient and customer friendly distribution network with top leaf some rent side, yet we will soon be ready to accommodate get read out.

David A. Santos: Well, our rigel, one care patient services hub that has established a reputation for being highly responsive to patients and providers.

David A. Santos: We also have a track record of ensuring strong coverage and reimbursement for oral targeted therapies in difficult-to-treat diseases, which we plan to continue with Everett. And, number three, this opportunity makes perfect sense for us because it is a highly complementary one to both the commercial and medical affairs teams we have in place to call on both academic centers and community oncology practices. With our IGO footprint already in these accounts, we'll be able to be even more efficient with our time and resources as we discuss multiple products within these.

David A. Santos: We also have a track record of ensuring strong coverage and reimbursement for oral targeted therapies in difficult to.

David A. Santos: To treat diseases that we plan to continue with <unk>.

David A. Santos: And number three this opportunity makes perfect sense for us because it is a highly complementary one to both the commercial and medical affairs teams, we have in place to call on both academic centers and community oncology practices.

David A. Santos: Without rigel footprint already in these accounts will be able to be even more efficient with our time and resources as we discussed multiple products within these accounts.

David A. Santos: On the right side of the slide, I wanted to highlight our biggest opportunity with Gevretto, and that is in non-small cell lung cancer. As you recall, approximately 1-2% of the 194,000 non-small cell lung cancer patients each year will test positive for the RET fusion, translating to approximately 3,000 RET fusion positive non-small cell lung cancer patients. The graphics show research done last year on the first line therapies that were used in rep fusion positive patients who were eligible for treatment.

David A. Santos: On the right side of the slide I wanted to highlight our biggest opportunity with Jeff read out and that is in non small cell lung cancer as youll recall, approximately 1% to 2% of the 194000 non small cell lung cancer patients each year will test positive for the ret fusion translating to approximately.

David A. Santos: <unk> 3000, ret fusion fusion positive non small cell lung cancer patients this year.

David A. Santos: The graphic shows research done last year on the first line therapies that we're used in ret fusion positive patients who were eligible for treatment three.

David A. Santos: Three-quarters of the patients were treated with one of the two FDA-approved Rett inhibitors, with Gevretto used in about a fifth of patients prescribed Rett. Importantly, there is still approximately a quarter of the market being treated by chemotherapy with or without an immune checkpoint inhibitor or multi-kinase inhibitor. We view this quarter of patients as a growth opportunity for RET inhibitors and Giveretto. Slide 17 reviews what we believe are the four key drivers for continued growth as we begin our commercialization journey with Gebretto. The first driver is patient identification.

David A. Santos: Three quarters of the patients were treated with one of the two F. D. A approved ret inhibitors with gift rata used in about a fifth of patients prescribed the ret inhibitor <unk>.

David A. Santos: Importantly, there is still approximately a corner of the market being treated by chemotherapy with or without an immune checkpoint inhibitor or multi kinase inhibitor. We view this quarter patients as the growth opportunity for ret inhibitors and give read out.

David A. Santos: Okay.

David A. Santos: Slide 17 reviews, what we believe are the four key drivers for continued growth as we began our commercialization journey with camera it out there.

David A. Santos: The first driver is patient identification.

David A. Santos: It is important that as many as possible of the 3,000 potential RETFusion-positive non-small cell lung cancer patients are identified each year. Fortunately, even if clinicians aren't specifically looking for RETFusion-positive patients when they do test, about 90% of them immediately recognize the RET biomarker as being associated with an FDA-approved therapy. Also, in research conducted last year, about 80 percent of non-small cell lung cancer patients are being tested, and that rate is improving. When clinicians don't test, it is more likely due to not having adequate tissue available, in addition to inadequate tissue being the top barrier for testing.

David A. Santos: It is important that as many as possible of the 3000 potential ret fusion positive non small cell lung cancer patients are identified each year.

David A. Santos: Fortunately, even if clinicians aren't specifically looking for ret fusion positive patients when they do test about 90% of them immediately recognized the rat biomarker as being associated with an FDA approved therapy.

David A. Santos: Also in research conducted last year about 80% of non small cell lung cancer patients are being tested and that rate is improving when clinicians don't test. It is more likely due to not having adequate tissue available.

David A. Santos: And in addition to inadequate tissue being the top area for testing.

David A. Santos: A significant portion of HCPs are concerned about delaying treatment while waiting for test results. However, we believe that, especially with the recent data and adjuvant approvals of targeted therapies for biomarkers such as EGFR and ALK in early stage lung cancer. Biomarker testing to identify appropriate tests for patients will expand even further in non-small cell lung cancer. Both patient and HCP education on biomarker testing and the importance of targeted therapies in non-small cell lung cancer are growing, and that's a lane clinician's concern about the lane.

David A. Santos: A significant portion of Hcp's are concerned about delaying treatment, while waiting for test results.

David A. Santos: We believe that especially with the recent data and adjuvant approvals of targeted therapies for biomarkers, such as Egfr and out in early stage lung cancer.

David A. Santos: Biomarker testing to identify appropriate test patients will expand even further in non small cell lung cancer.

David A. Santos: With patient and HCP education on biomarker testing and the importance of targeted therapies in non small cell lung cancer are growing and that's a laying because clinicians concerns about delaying treatment.

David A. Santos: Secondly, and more importantly for Givretto, optimizing the choice of therapy in those identified patients who are treatment eligible is an impactable growth opportunity for us. Most oncologists have yet to try Givretto on the front line, and the biggest reason for that is comfort and familiarity with other drugs.

David A. Santos: Secondly, and more importantly for get read out optimizing the choice of therapy in those identified patients who are treatment eligible is an impactful growth opportunity for us most of oncologists have yet to try and get red oak in the frontline and the biggest reason for that is comfort and familiarity with.

David A. Santos: Other drugs from the prior slide the use of chemotherapy with or without immune checkpoint inhibitors and multi kinase inhibitors represents about one quarter of the use in the first line treatment of ret fusion positive patients by growing awareness of <unk> efficacy.

David A. Santos: From the prior slide, the use of chemotherapy with or without immune checkpoint inhibitors and multikinase inhibitors represents about one quarter of the use in the first line treatment of RET fusion positive patients. By growing awareness of Gibretto's efficacy, safety, and once-daily oral dosing, we believe we can grow future use of Gibretto among current non-users. And importantly, as more clinicians are educated about testing and the impact of targeted therapies in lung cancer.

David A. Santos: Safety and once daily oral dosing, we believe we can grow future use of <unk> among current non users.

David A. Santos: And importantly, as more clinicians are educated about testing and the impact of targeted therapies in lung cancer. We believe the number of clinicians who are concerned about delaying treatment and therefore initially treat with a non targeted treatment will decrease resulting in more ret fusion.

David A. Santos: We believe the number of clinicians who are concerned about delaying treatment and therefore initially treating with a non-targeted treatment will decrease, resulting in more RET-fusion positive non-small cell lung cancer patients currently treated with chemotherapy-based regimens or other agents moving to RET-targeted therapy like Evreta.

David A. Santos: Positive non small cell lung cancer patients currently treated with chemotherapy based regimens or other agents moving to rest targeted therapy like I've read out.

David A. Santos: Third, we believe that Gevretto will continue to grow due to its high response rates, long duration of response, and convenient once-daily dosage. Lisa will discuss these and other impressive Gevretto efficacy data in her presentation. These important drivers of persistency should continue to grow our carryover business each month as patients refill their prescriptions. And finally, as we have discussed, as we leverage our strengths in coverage, reimbursement, and patient services with Rigel OneCare, we believe we can gain loyal Gavretto users from clinicians who view out-of-pocket costs and difficulty obtaining reimbursement as barriers to the use of RET inhibitors.

David A. Santos: Third we believe that gave Renato will continue to grow due to its high response rates long duration of response and convenient once daily dosing Lisa will discuss these and other impressive give red oak efficacy data in her presentation.

David A. Santos: These important drivers of persistency should continue to grow our carryover business each month as patients refill their prescriptions.

David A. Santos: And finally, as we have discussed as we leverage our strengths and coverage reimbursement and patient services with fragile one care. We believe we can gain loyal give rental users from clinicians who you out on pay pop patient out of pocket cost and difficulty obtaining reimbursement as barriers for that.

David A. Santos: Use of Ret inhibitors in.

David A. Santos: In summary, we are well positioned to continue growing Gamaretto through positive momentum in these four key drivers. As shown on slide 18, we have made continued progress in working closely with Genentech and Blueprint to ensure both current and newly prescribed patients continue to have access to Gevretto without interruption. Rigel OneCare is preparing to work with providers to assist in transitioning patients from the existing Genentech Network and Access Programs to the Rigel Network and Rigel OneCare Patient Program, ensuring patients experience no interruption to therapy.

David A. Santos: In summary, we are well positioned to continue growing that red oak through positive momentum in these four key drivers.

David A. Santos: On Slide 18, we have made continued progress in working closely with Genentech and blueprint to ensure both current and newly prescribed patients continue to have access to give reno without interruption.

David A. Santos: Rigel, one care is preparing to work with providers to assist in transitioning patients from the existing Genentech network and access programs to the Rigel network and Roger one care patient programs, ensuring patients experienced no interruption to therapy.

David A. Santos: Our distribution network ensures patient and provider choice in where their prescription is filled, and we will have RIGEL OneCare staff fully dedicated to GiveRETA to ensure the highest-level of access support and customer service. I am pleased to report that everything is on track for Rigel to begin supplying patients and clinics with Gibretto in July. And to wrap up Giretto on slide 19, I just wanted to update our high-level timeline of our plans for the rest of the year.

David A. Santos: Our distribution network ensures patient and provider choice in where their prescription is filled and we will have rigel care staff fully dedicated to give read out to ensure the highest level access support and customer service I am pleased to report that everything is on track for rigel to begin supply.

David A. Santos: Patients in clinics with give read out in July.

David A. Santos: And to wrap up cabrito with slide 19, I just wanted to update our high level timeline of our plans for the rest of the year.

David A. Santos: Our market access team made excellent progress in preparing our distribution network for the addition of Gevretto in Q1, and everything is on track for this quarter to prepare Rigel OneCare and our field teams for the transition. We anticipate that in July, we will begin shipping Gevretto to patients and clinics, and Rigel OneCare will transition the majority of current and newly prescribed Gevretto patients. Our field teams will simultaneously begin discussing Gabretto with customers, with a focus on the accounts that have current patients on Gabretto.

David A. Santos: Our market access team made excellent progress in preparing our distribution network for the addition of you have read out in Q1 and everything is on track for this quarter to prepare rigel, one care and our field teams for the transition.

David A. Santos: We anticipate that in July we will begin shipping I've read out to patients and clinics and Rigel, one care will transition the majority of current and newly prescribed patients.

David A. Santos: Our field teams will simultaneously begin discussing caporetto with customers with a focus on the accounts that have current patients odd get read out.

David A. Santos: Then, in Q4, we will continue expanding our breadth of prescribers by calling on users and non-prescribers, particularly in the community setting. It'll be an exciting year bringing Gevretto into our portfolio of oral targeted therapies, and I look forward to continuing to update you on our progress as the year moves ahead. Now, I'd also like to say how thrilled we are to have our new Chief Medical Officer with us, and I'll now turn the call over to her for an update on our development activities. Welcome, Lisa.

David A. Santos: Then in Q4, we will continue expanding our breadth of prescribers by calling on users and non users, particularly in the community setting.

Lisa: There'll be an exciting year for you and give red oak into our portfolio of oral targeted therapies and I look forward to continuing to update you on our progress as the year moves ahead.

David A. Santos: Now I'd also like to say how thrilled we are to have our new chief Medical officer with Us and I'll now turn the call over to her for an update on our development activities welcome Lisa.

Lisa Royker: Thank you Dave, and good afternoon everyone. I'm excited to have joined Rigel just a couple of months ago at an important inflection point for the company as we expand our hematology and oncology portfolio. First, I'd like to begin by underscoring how precision medicine approaches to lung cancer are positively impacting patient outcomes, including those patients with rat fusion. And why, from the clinical perspective, we are excited about Gabretto

Lisa: Thank you, Dave and good afternoon, everyone I'm excited to have joined Rigel, just a couple of months ago at an important inflection point for the company as we expand our hematology and oncology portfolio.

Lisa Royker: First I'd like to begin by underscoring how precision medicine approaches to lung cancer are positively impacting patient outcomes, including those patients with ret fusions and why from a clinical perspective, we are excited about got brought up.

Lisa Royker: On slide 21, RET fusions are present in approximately 2% of all non-small cell lung cancers, representing approximately 3,000 new patients per year in the U.S., and in around 20% of papillary thyroid cancers, for around 1,000 new cases per year. Testing for RET fusions is an essential part of the pre-treatment evaluation of non-small cell lung capacity. In fact, clinical practice guidelines recommend the use of targeted therapies as first-line treatment for eligible patients with metastatic non-small cell lung cancer harboring actionable genetic variants such as RETFUSION.

Lisa Royker: On slide 21, where applications are present in approximately 2% of all non small cell lung cancers, representing approximately 3000, new patients per year in the U S. And then around 20% of papillary thyroid cancers for around 10000, new cases per year.

Lisa Royker: Testing for Ret Fusions is an essential part of the pre treatment evaluation of non small cell lung cancer. In fact clinical practice guidelines recommend the use of targeted therapies as first line treatment for eligible patients with metastatic non small cell lung cancer harboring actionable genetic variance such as ret fusions.

Lisa Royker: Prior to the advent of RET-targeted therapy, patients with advanced RET-fusion-positive non-small-cell lung cancer received a platinum-based chemotherapy regimen. With overall response rates in the 50% range and median progression-free survival of six to eight months, the use of non-selective multikinase inhibitors with anti-RET activity has shown only modest efficacy and high rates of treatment-related toxicity. Because ratfusion-positive non-small lung cancers exhibit low PDL1 expression, immune checkpoint inhibitors have demonstrated only limited efficacy here, with overall response rates less than 10% and progression-free survival in the range of two to three months. Gabretto is an oral, highly potent, selective RET inhibitor with once-daily dosing that is FDA approved for RET fusion positive non-small cell lung cancer or thyroid cancer as first-line or subsequent-line therapy.

Lisa Royker: Prior to the advent of targeted therapy patients with advanced Ret fusion positive non small cell lung cancer received platinum based chemotherapy regimens.

Lisa Royker: Overall response rates in the 50% range and median progression free survival of six to eight months.

Lisa Royker: Use of non selective multi kinase inhibitors with anti ret activity has shown only modest efficacy at high rates of treatment related toxicity.

Lisa Royker: Because ret fusion positive non small cell lung cancers exhibit low PDL, one expression immune checkpoint inhibitors have demonstrated only limited efficacy here with overall response rates less than 10% and progression free survival in the range of two to three months.

Lisa Royker: Yeah, Brad though is in the oral highly potent selective ret inhibitor with once daily dosing that is FDA approved for ret fusion positive non small cell lung cancer or thyroid cancer as first line or subsequent lines of therapy.

Lisa Royker: On the next slide, I will review updated clinical data from the Phase 1 to Arrow study, which led to the approval. Slide 22 summarizes updated clinical results from the AERO studies with the data cutoff date of March 2022. This Phase 1-2 Multi-Center Open-Label Dose Escalation and Expansion Study was conducted at 71 sites in 13 countries with an original data cut-off date of May 2020. In phase one, pralsetinib at a dose of 400 milligrams daily was determined to be the recommended phase two dose.

Lisa Royker: On the next slide I'll review will review updated clinical data from the phase one two arrow study, which led to the approvals.

Lisa Royker: Slide 22 summarizes updated clinical results from the Arrow study once the data cutoff date of March 2022.

Lisa Royker: This phase one two multicenter open label dose escalation and expansion study was conducted at 71 sites in 13 countries with an original data cutoff date of May 2020.

Lisa Royker: In phase one <unk> at a dose of 400 milligrams daily was determined to be the recommended phase two dose and.

Lisa Royker: In phase 2, the safety and efficacy of Prosetinib 400 mg daily were evaluated in patients with RET fusion positive advanced non-small cell lung cancer, thyroid cancer, and other RET fusion positive solid tumors. The primary endpoint was overall response rate.

Lisa Royker: In phase two the safety and efficacy of <unk> 400 milligrams daily was evaluated in patients with ret fusion positive advanced non small cell lung cancer thyroid cancer and other ret fusion positive solid tumors.

Lisa Royker: In the lung cancer subgroup, clinical activity was observed irrespective of prior therapy. The overall response rate in 130 patients with previous platinum-based chemotherapy was 63%, and 74 to 80% in 107 treatment-na patients, with tumor shrinkage observed in all previously untreated patients. In the overall subset of 260 non-small cell lung cancer patients, median duration of response, one of the key secondary endpoints, was 19.1 months. Procentinib was generally well-tolerated with predominantly low-grade toxicity, with only 10% discontinuing therapy due to treatment-related adverse events. In the subgroup of 22 patients with rat fusion positive thyroid cancer, 91% of previously treated patients achieved a response.

Lisa Royker: Primary endpoint was overall response rate.

Lisa Royker: Isn't the lung cancer subgroups clinical activity was observed irrespective of prior therapy.

Lisa Royker: <unk> response rate and a 130 patients with previous platinum based chemotherapy was 63% and 74% to 80% and 107 treatment naive patients with tumor shrinkage observed in all previously untreated patients.

Lisa Royker: And the overall subset of 260, non small cell lung cancer patients median duration of response one of the key secondary endpoint was $19 one months.

Lisa Royker: That number was generally well tolerated with predominant predominantly low grade toxicity with only 10% discontinuing therapy due to treatment related adverse events.

Lisa Royker: In the subgroup of 22 patients with Ret fusion positive thyroid cancer, 91% of previously treated patients achieved a response.

Lisa Royker: And finally, in the subgroup of 23 patients with RETFUSION-positive solid tumors, the overall response was 57%. These results underscore the benefit of utilizing RET-targeted therapy with prosetinib in the first or later lines of treatment for patients with RET-fusion positive non-small cell lung and thyroid cancer. Moving to slide 23, patients with rat fusion positive non-small cell lung cancer have a high rate of brain metastases, which are present in 25% of patients at the time of diagnosis, and approximately 50% of patients will develop brain metastases over the course of their lifetime. In the AERO study, the intracranial response rate for 15 patients with brain metastases was 53%, and complete responses were seen in three patients. Overall, the median duration of response was 11.5 months.

Lisa Royker: And finally in the subgroups of 23 patients with Ret fusion positive solid tumors. The overall response was 57%.

Lisa Royker: These results underscore the benefit of utilizing ret targeted therapy with <unk> first our later lines of treatment for patients with ret fusion positive non small cell lung and thyroid cancer.

Lisa Royker: Moving to slide 23 patients with ret fusion positive non small cell lung cancer have a high rate of brain metastases, which are present in 25% of patients at the time of diagnosis and approximately 50% of patients will develop brain metastases over the course of their lifetime.

Lisa Royker: And the Arrow study the intracranial response rate for 15 patients with brain metastases was 53% and complete responses were seen in three patients.

Lisa Royker: Overall, the median duration of response was 11 five months.

Lisa Royker: On slide 24, based on these data, we believe that prosthetinib has a differentiated value property. It's the only once-daily oral RET inhibitor approved for patients with non-small cell lung and thyroid cancer with a RET gene fusion. When considering the spectrum of prior treatment approaches we previously reviewed, pralsetinib is associated with favorable response rates and durable activity, regardless of prior treatment history. Procentinib has also demonstrated promising intracranial activity in patients with brain metastases, and it has an established safety profile with manageable adverse events and a low discontinuation rate. Finally, Prosetinib is a recommended treatment option for patients with RETFusion-positive non-small cell lung cancer and advanced thyroid cancer.

Lisa Royker: On slide 24 based on these data we believe that <unk> has a differentiated value proposition.

Lisa Royker: It's the only once daily oral ret inhibitor approved for patients with non small cell lung and thyroid cancer with Ret gene fusions.

Lisa Royker: When considering the spectrum with prior three treatment approaches. We previously reviewed process that is associated with favorable response rates and durable activity regardless of prior treatment history.

Lisa Royker: <unk> has also demonstrated promising intracranial activity in patients with brain metastases and has an established safety profile with manageable adverse events and a low discontinuation rate.

Lisa Royker: Finally, pros setting up as a recommended treatment option for patients with ret fusion positive non small cell lung cancer and thyroid cancer.

Lisa Royker: So to summarize, we believe that Pralsetinib is a differentiated target treatment option for patients, and we look forward to fully integrating the product into our portfolios. I would now like to provide an update on our development programs and clinical research collaborations, which foster continued growth of our HMOG pipeline. Moving to slide 26, we shift focus to our strategy to continue expanding our hematology and oncology pipeline. First, we are focused on advancing our IDH1 inhibitor elutacidinib into new clinical indications. We believe lytacidinib has potential in a number of cancers where mutated IDH1 plays a role, such as additional AML segments, myel dysplastic syndrome, or MDS, and glioma, either as monotherapy or in combination.

Lisa Royker: So to summarize we believes that <unk> has a differentiated targeted treatment option for patients and we look forward to fully integrating products into our portfolio.

Lisa Royker: I would now like to provide an update on our development programs and clinical research collaborations, which foster continued growth of our hemo pipeline.

Lisa Royker: Moving to slide 26, we shift focus to our strategy to continue expanding our hematology and oncology pipeline.

Lisa Royker: First we are focused on advancing our I D. H one inhibitor all the looser sitting up into new clinical indications, we believe Elisa Sydney has potential in a number of cancers, where mutated I D. H. One plays the role such as additional AML segments, Myelodysplastic syndrome, or Mds and <unk>.

Lisa Royker: Either as a monotherapy or in combination.

Lisa Royker: To further evaluate lutecidinib in these indications, we have entered into strategic development collaborations with the MD Anderson Cancer Center and the Connect Consortium. We're also advancing R-289, our novel IRAC1-4 inhibitor, in patients with lower-risk MDS. Enrollment continues in our Phase 1B trial, and we expect to have preliminary data from the first part of this trial later this year. In addition, we remain focused on evaluating potential opportunities to in-license or acquire products that would be a strategic fit for our portfolio.

Lisa Royker: To further evaluate to looser Sidner then these indications we've entered into strategic development collaborations with the MD Anderson cancer Center and the <unk> consortium.

Lisa Royker: We're also advancing our 289 our novel Iraq, one four inhibitor in patients with lower risk Mds enrollment continues into our phase one b trial, and we expect to have preliminary data from the first part of this trial later this year.

Lisa Royker: In addition, we remain focused on evaluating potential opportunities to in license or acquire products that would be a strategic fit for our portfolio. We.

Lisa Royker: We are looking for differentiated products in hematology, oncology, or related areas; products that are late stage, possibly with registrational data, soon to have registrational data, or more advanced, and products that can leverage our hematology and oncology infrastructure. As demonstrated with our acquisitions of Alutacitinib and Pravacitinib, our goal is to continue to find assets that are a strategic fit with our organization, pipeline, and ability to export.

Lisa Royker: We are looking for differentiated products in hematology oncology or related areas.

Lisa Royker: Folks that are late stage, possibly with Registrational data soon to have Registrational data are more advanced and products that can leverage our hematology and oncology infrastructure.

Lisa Royker: As demonstrated with our acquisitions of elusive sitting up in processing the.

Lisa Royker: Our goal is to continue to find assets that are a strategic fit with our organization pipeline and ability to execute.

Lisa Royker: First, we're very pleased to have started a development collaboration with the MD Anderson Cancer Center to advance elutacidin more broadly into AML, MDS, and beyond. Through our partnership, we are planning to evaluate lutecidinib in combination with other agents in first-line IDH1-mutated AML and higher-risk MDS. We also plan to evaluate elutucidinib as a monotherapy in lower-risk MDS and CCUS, a condition associated with an increased risk of developing MDS, and in the post-transplant maintenance setting. That's four potential clinical trials on the horizon with up to $15 million paid over five years. We expect these trials to position us to conduct a subsequent registrational trial or clinical trial.

Lisa Royker: First we're very pleased to have started the development collaboration with the MD Anderson cancer Center to advance a looser sit in that more broadly into AML Mds and beyond.

Lisa Royker: Through our partnership we are planning to evaluate to looser sit in that in combination with other agents in first line I D. H, one mutated AML and higher risk Mds. We also plan to evaluate Alicia sit in that as a monotherapy in lower risk Mds and Cc U S. A condition associated with an increased risk of developing M. D. S.

Lisa Royker: And in the post transplant maintenance setting.

Lisa Royker: That's for a potential clinical trials on the horizon with up to $50 million paid over five years. We expect these trials to position us to conduct a subsequent registrational trial or trials.

Lisa Royker: We look forward to working with MD Anderson and providing updates as our collaboration progresses. Moving to slide 28, another important development collaboration we have is with the Connect Consortium to conduct a Phase II trial in patients with IDH1-mutated glioma. Gliomas account for around 30% of CNS tumors in children, adolescents, and young adults, with approximately one-third of these being high-grade gliomas, translating to approximately 800 to 1,000 new cases each year in the U.S. High-grade gliomas are a leading cause of cancer-related death in adolescents and young adults. Despite available therapies, the five-year survival of this population is less than 10%. IDH1 mutations are found in approximately 6% of pediatric patients and up to 36% of high-grade gliomas in adolescents and young adults.

Lisa Royker: We look forward to working with MD, Anderson and providing updates as her collaboration progresses.

Lisa Royker: Yeah.

Lisa Royker: Moving to slide 28, another important development collaboration we have is with the connect consortium to conduct a phase two trial in patients Society H mutated I'd each one mutated helmer.

Lisa Royker: We all must account for around 30% of CNS tumors in children adolescents and young adults with approximately one third of these being high grade Gliomas translating to approximately 800 to 1000, new cases, each year in the U S.

Lisa Royker: High grade Gliomas are a leading cause of cancer related deaths in adolescents and young adults.

Lisa Royker: Spite available therapies, the five year survival in this population is less than 10%.

Lisa Royker: I D. H one mutations are found in approximately 6% of pediatrics and up to 36% of high grade Gliomas in adolescence and young adults are.

Lisa Royker: Based on these data, we believe that elutucicidinib has potential in this indication, and elutacinib will be included in CONNECT's TARGET-D trial, a molecularly guided phase 2 umbrella clinical trial for high-grade gliomas. The Phase 2 Connect Open Label study intends to enroll approximately 60 patients. In the Rigel-responded arm, adolescents and young patients that are 39 years old and younger, with newly diagnosed IDH1 mutation positive high-grade glioma, will receive maintenance therapy with allutacidnib in combination with tamazolamide for the first year after radiotherapy, followed by lutecidinidine monotherapy for the second year.

Lisa Royker: The safety and preliminary activity of single agent, who is just sitting up in a cohort of 26 patients with relapsed or refractory high grade I D. H one gauge simply illness were recently reported.

Lisa Royker: Based on these data we believe that a looser Sydney has potential in the syndication and the looser Sydney will be included in connects target D trial, a Molecularly guide it phase two umbrella clinical trials for high grade glioma.

Lisa Royker: The phase two connect the open label study intends to enroll approximately 60 patients and the Rigel sponsored arm adolescence and young patients that are 39 years old and younger with newly diagnosed I D. H, one mutation positive high grade glioma.

Lisa Royker: <unk> maintenance therapy with the looser said that in combination with <unk> for the first year after radiotherapy.

Lisa Royker: Followed by Elisa citizens mono therapy for the second year.

Lisa Royker: The primary objectives are to evaluate the safety and tolerability of elutucidinib with and without temozolomide and progression-free survival. We anticipate the trial to initiate this summer. We will provide funding of up to $3 million in study materials over the four-year collaboration.

Lisa Royker: The primary objectives are to evaluate the safety and Tolerability of Elisa sit in the with and without tenants overnight and progression free survival, we anticipate the trial to initiate this summer.

Lisa Royker: We will provide funding of up to $3 million in study material over the four year collaboration.

Dean L. Schorno: We, along with Connect, are excited about elutacidinib's potential to provide a much-needed new treatment option to this underserved patient population. And finally, on slide 29, I'd like to tell you about our novel dual IRAP1-4 inhibitor R289, which we are evaluating in a Phase 1b trial in patients with lower-risk MDS. This is another area of high unmet need in a primarily elderly patient population facing progressive cytopenias, particularly anemia, resulting in transfusion dependency and increased risk of infections and the risk of progression to acute leukemia. The therapeutic strategy for MDS depends upon the patient's MDS risk classification.

Lisa Royker: We along with connect are excited about the looser sit and the potential to provide a much needed new treatment option to this underserved patient population.

Dean L. Schorno: And finally on slide 29, I'd like to tell you about our novel dual IRA one four inhibitor are 289, which we are evaluating in a phase one b trial in patients with lower risk Mds.

Dean L. Schorno: This is another area of high unmet need and are primarily elderly patient populations facing progressive cytopenia, particularly anemia, resulting in transfusion dependency and increased risk of infections and the risk of progression to acute leukemia.

Dean L. Schorno: The therapeutic strategy for M. D S depends upon the patient <unk> classification.

Dean L. Schorno: For lower-risk MDS patients, first-line treatment options include the use of red cell transfusions, erythroid-stimulating agents, lispatercept, and lenalidomide for those with a deletion 5q abnormality. In second and later lines of therapy, durable responses are difficult to attain, and toxicity becomes more of an issue. There are currently no approved therapies for lower-risk MDS patients that have failed hypomethylating agents.

Dean L. Schorno: For lower risk Mds patients first line treatment options include the use of Red cell transfusions, erythroid stimulating agents lists powder subs and leave a little money for those sorts of deletions five Q abnormality and.

Dean L. Schorno: And second and later lines of therapy durable responses are difficult to attain.

Dean L. Schorno: So city becomes more of an issue.

Dean L. Schorno: There are currently no approved therapies for lower risk Mds patients that had failed hypo methylated agents. We believe that our 289 has the potential to address the unmet needs in this patient population.

Dean L. Schorno: We believe that R289 has the potential to address the unmet needs of this patient population. Moving to slide 30, I'd like to highlight why we are excited about R289. Dysregulation of the immune and inflammatory signaling pathways is associated with MDS, with chronic stimulation of both the toll-like and IL-1 receptor pathways involving IRAC1 and IRAC4, leading to a pro-inflammatory marrow environment and cytopenia. The activation of IRAC1 and 4 was recently reported to also occur independently of this signaling pathway, leading to persistent inhibition of hematopoietic cell differentiation, and that co-targeting both is required to fully suppress inflammation, leukemic stem cell progenitor function, and restore hematopoiesis and MDS.

Dean L. Schorno: Moving to slide 30, I would like to highlight why we are excited about our 289.

Dean L. Schorno: Dysregulation of the immune and inflammatory signaling pathways associated with M. D S with chronic stimulation of both the toll like and IL, one receptor pathways involving Iraq, one and Iraq for leading to a pro inflammatory marrow environment Cytopenia.

Dean L. Schorno: The activation of Iraq, London for recently reported to also occur independently of this signaling pathway, leading to persistent inhibition of hematopoietic cell differentiation and that co targeting both is required to fully suppress inflammation leukemic stem cell progenitor function and restore human health.

Dean L. Schorno: Out of Polices and M D S.

Dean L. Schorno: Clinically, IRAC-4 inhibitors and MDS and AML have thus far shown only modest activity supporting this concept, and in Preclinical and Healthy Volunteer Studies, R835, a dual IRAC1,4 inhibitor, suppressed pro-inflammatory cytokine production. R-289, an oral prodrug that is rapidly converted to R-835, was well tolerated with once and twice daily dosing and is now being evaluated in a Phase 1B Slide 31 shows the design of our ongoing open-label, multi-centered phase 1B study of R289 in patients with relapse refractory, lower risk MDS, which has a dose escalation phase with the standard 3 plus 3 design and a dose expansion phase for confirmatory safety.

Dean L. Schorno: Clinically Iraq for inhibitors in Mds and AML has thus far shown only modest activity supporting this concept and <unk>.

Dean L. Schorno: Preclinical and healthy volunteer studies are 835 dual Iraq, one four inhibitor suppressed pro inflammatory cytokine production.

Dean L. Schorno: Our 289, an oral pro drug that is rapidly converted to our 835 was well tolerated with once and twice daily dosing and is now being evaluated in a phase <unk> study in lower risk Mds.

Dean L. Schorno: Slide 31 shows the design of our ongoing open label Multicenter Phase <unk> study of <unk> 89 in patients with relapsed refractory lower risk Mds, which has the dose escalation phase with the standard three plus three design and the dose expansion phase for confirmatory safety.

Dean L. Schorno: The primary endpoints for this trial are safety and selection of the recommended dose for expansion, and secondary endpoints include response rates and PK. Based on emerging data from the study, we have recently included two additional dose levels with a twice daily dosing regimen. The study continues to progress well. We have completed enrollment in the third cohort, and we anticipate presenting preliminary data from the first part of the trial later this year. Lastly, on slide 32, our RIPK1 inhibitor programs are progressing well with our partner, Lilly.

Dean L. Schorno: The primary endpoint for this trial are safety and selection of the recommended dose for expansion and secondary end points include response rates and Teekay.

Dean L. Schorno: Based on emerging data from this study we have recently included two additional dose levels with twice daily dosing regimens.

Dean L. Schorno: <unk> continues to progress well, we completed enrollment in the third cohort and we anticipate presenting preliminary data from the first part of the trial later this year.

Dean L. Schorno: Lastly, on slide 32, our rent K, one inhibitor programs are progressing well with our partner Lilly.

Dean L. Schorno: RIK-K1 is implicated in a broad range of inflammatory cellular processes and plays a key role in tumor necrosis factor signaling. OCADU Sertib, our non-CNS penetrant RIPK1 inhibitor, previously referred to as R552 or LY3871801, is currently being studied in an adaptive phase 2A, 2B clinical trial in up to 380 patients with active, moderate to severe Phase IIa enrollment of approximately 100 patients is advancing well, with preliminary analysis of the Phase IIa results anticipated by the end of the year.

Dean L. Schorno: Cable one is implicated in the broad range of inflammatory cellular processes and plays a key role in tumor necrosis factor signaling.

Dean L. Schorno: Okay, Sir to our non CNS penetrant K, one inhibitor previously referred to as our five five to our L. Y 38718, or one is currently being studied in an adaptive phase two a two b clinical trial in up to 380 patients with active moderate to severe rheumatoid arthritis.

Dean L. Schorno: Yes.

Dean L. Schorno: Phase two of enrollment of approximately 100 patients is advancing well with preliminary analysis of the phase Iia results anticipated by the end of the year.

Dean L. Schorno: Our preclinical CNS Penetrant Rip K1 Inhibitor Program is also progressing for lead candidate nomination. We are excited about the progress of our programs and their broad potential in RA and other immune and CNS diseases. To conclude, I'm excited to have joined Rigel at this time of progress and expansion in our development program. I look forward to contributing to the growth of our hematology and oncology portfolio.

Dean L. Schorno: Our preclinical CNS penetrant Rip K one inhibitor program is also progressing towards lead candidate nomination.

Dean L. Schorno: We are excited about the progress of our programs and their broad potential in our a and other immune and CNS diseases.

Dean L. Schorno: To conclude I'm excited to have joined Rigel at this time of progress and expansion in our development programs I look forward to contributing to the growth of our hematology and oncology portfolio I will now turn the call over to Dave.

Dean L. Schorno: Thank you, Lisa. I'm on slide 34. For the first quarter of 2024, we shipped 2,193 bottles of Tavolis to our specialty distributors, resulting in $21.1 million in net product sales. 2,483 bottles of Tavolis were shipped to patients and clinics, while 290 bottles decreased the levels remaining in their distribution channels at the end of the quarter. For the first quarter of 2024, we shipped 390 bottles of Roselidia to our specialty distributors, resulting in $4.9 million in net product sales.

Dean L. Schorno: Thank you Lisa I'm on slide 34 for the first quarter of 2024, we shipped 2193 bottles of travel reach to our specialty distributors, resulting in $21 $1 million and net product sales 2483 balls with travel east were shipped to patients and critics.

Dean L. Schorno: 290 bottles decreased to levels remaining in our distribution channels at the end of the quarter for.

Dean L. Schorno: For the first quarter of 2024, we shipped 390, Bozarth media to our specialty distributors, resulting in $4 $9 million from net product sales of 326 bottles.

Dean L. Schorno: 326 bottles of Rosalidia were shipped to patients and clinics, while 64 bottles increased to levels remaining in our distribution channels at the end of the quarter. We reported net product sales of tablilis of $21.1 million in the first quarter of 2024, a 5% decrease compared to the same period in 2023, resulting from a decrease in bottles remaining on our distribution shelves of 10 and a quarter. I will describe this in a bit more detail on the next slide.

Dean L. Schorno: Were shipped to patients and clinics or 64 bottles increase the levels remain.

Dean L. Schorno: Distribution channels and in the quarter we.

Dean L. Schorno: We reported net product sales in Tahoe east of $21 $1 million in the first quarter of 2024, 5% decrease compared to the same period in 2023, resulting from the decrease in bottles remaining in our distribution channels and in the corner.

Dean L. Schorno: I will describe this in a bit more detail on the next slide.

Dean L. Schorno: We reported net product sales from Roslidia of $4.9 million in the first quarter of 2024, compared to $1.5 million in the same period in 2023. As a reminder, Brasilinia was launched in the United States in December of 2022. Our net product sales from Tableau East and Roselidia were recorded in the net of estimated discounts, chargebacks, rebates, returns, copay assistance, and other allowances of $12.4 million. For the first quarter of 2024, our gross-to-net adjustment for Tableau East and Roselidia was approximately 34% and 24% of gross product sales, respectively.

Dean L. Schorno: Reported net product sales from <unk>, maybe a $4 $9 million in the first quarter of 2024 compared to $1 $5 million in the same period in 2023 as.

Dean L. Schorno: As a reminder, Brazil, India was launched in United States in December of 2022.

Dean L. Schorno: Net product sales from <unk> linear were recorded net of estimated discounts charge backs rebates returns co pay assistance and other allowances of $12 $4 million for the first quarter of 2024, our gross to net adjustment for top where Houston was radio was approximately 34% and 24%.

Dean L. Schorno: Product sales respectively.

Dean L. Schorno: Before we move on from Net Product Sales, let me review our expectations for the second quarter of 2024. We're pleased with the strength of our business and expect to see continued growth in bottles, ships, patients, and clinics for both Tavolese and Roselidia.

Dean L. Schorno: If we move on from net product sales, let me review our expectations for the second quarter of 2024.

Dean L. Schorno: We're pleased with the strength of our business and I expect to see continued growth in bottles shipped to patients and clinics for both travel reach radio we expect our gross to net adjustments in the second quarter of 2024 to be approximately 35% for total knees and approximately 26% from original Lydia.

Dean L. Schorno: We expect our gross to net adjustment in the second quarter of 2024 to be approximately 35% for Tavolese and approximately 26% for Roselidia. On slide 35, before I move on to a review of our financials for the quarter, I want to provide a brief review of the dynamics of the sequential decrease in net product sales we saw during the quarter. Starting with the orange bars, in the fourth quarter of 2023, we saw 2,463 bottles shipped to patients and clinics. This is our key demand metric, and it highlighted our highest demand volume since launch.

Dean L. Schorno: On slide 35, before I move on to a review of our financials for the corner I want to provide a brief review of the dynamics of the sequential decrease in net product sales we saw during the quarter starting with the orange bars in the fourth quarter of 2023, we saw in 2000, and 463 bottles shipped to patients and clinics.

Dean L. Schorno: This is our key demand metrics and Dave highlighted our highest volume since March.

Dean L. Schorno: Incrementally, we saw a significant decrease and a significant increase in bottles made in a distribution channel of 208 bottles. This resulted in total bottles for the fourth quarter of 2023 of 2,671 bottles, which generated $25.7 million of net product sales. Now to discuss the green bars.

Dean L. Schorno: Incrementally we saw a significant decrease significant increase in bottles remaining distribution channel of 208 vials.

Dean L. Schorno: And in total bottles for the fourth quarter of 2023 of 2000, and 671 bottles, which generated $25 $7 million of net product sales.

Dean L. Schorno: To discuss the green bars in the first quarter of 2024, we saw in 2000 and 483 bottles shipped to patients at clinics. This small increase is despite the typical first quarter industry challenges associated with the resetting of co pays and the Medicare Donut hole to weigh in both new prescriptions and refills in both ways.

Dean L. Schorno: In the first quarter of 2024, we saw 2,483 bottles shift to patients and clinics. This small increase is despite the typical first quarter industry challenges associated with the reset and of co-pays and the Medicare donut hole to laying both new prescriptions and refills that both we and our industry experience each year. You'll note in the thin green bar that this small increase in demand volume resulted in a sequential increase in net product sales of $200,000.

Dean L. Schorno: And our industry experienced each year.

Dean L. Schorno: The thin green bar.

Dean L. Schorno: All increase in demand volume resulted in a sequential increase in net product sales of $200000.

Dean L. Schorno: The bigger impact in this sequential reduction in net product sales came from the reduction of inventory levels at our distributors. The reduction from 1,374 bottles of inventory to our distributors in Q4 of 2023 down to 1,084 bottles at the end of Q1 of 2024 contributed to a sequential decline in our debt product sales of $4.8 million, the thick red bar in this graph. Inventory levels at our distributors are variable, but we do expect them to generally increase over time as our business grows.

Dean L. Schorno: It's a bigger impact on the sequential reduction in net product sales came from the reduction of inventory levels at our distributors.

Dean L. Schorno: Reduction from $1374 of inventory at our distributors in Q4 of 2023 calendar 1084 bottles at the end of Q1 of 2024 contributed to a sequential decline in our net product sales of $4 $8 million footprint Barton This graphic inventory.

Dean L. Schorno: Levels that our distributors are variable and we do expect them to generally increase over time as our business grows.

Dean L. Schorno: To illustrate the effect of change in inventory levels on our net revenues, let me provide an example. Well, we have said that we expect to see continued growth in bottle shipment to patients and clinics for some time and that our inventory levels are variable. If we assume that both inventory levels and demand volume are flat as compared to the first quarter of 2024, we would expect to see quarter-over-quarter growth of approximately 12% for the second quarter of 2024. This is calculated with our current wholesale price and an anticipated gross to net adjustment. Again, this calculation is intended to be illustrative only. On to the next slide.

Dean L. Schorno: To illustrate the effective change in inventory levels on a net revenues, let me provide an example or <unk>.

Dean L. Schorno: We've said that we expect to see continued growth in bottles shipped to patients and clinics.

Dean L. Schorno: And then our inventory levels are variable.

Dean L. Schorno: We assume that both inventory levels and demand volume or flat as compared to the first quarter of 2024, we would expect to see quarter over quarter growth of approximately 12% for the second quarter of 2024.

Dean L. Schorno: This is calculated with our current wholesale price and anticipate gross to net adjustment.

Dean L. Schorno: Jim This calculation is intended to be illustrative.

Dean L. Schorno: In addition to net product sales, our contract revenues from collaborations were $3.5 million in the first quarter of 2024. These revenues consisted of $2.3 million from Keysight, $1.1 million from Griffles, and $100,000 from MediSign. Moving on to cost and expenses, our cost of product sales was approximately $2 million for the first quarter of 2024. Total cost and expenses were $36.5 million, compared to $38.8 million in the same period of 2023.

Dean L. Schorno: Either the next slide.

Dean L. Schorno: In addition to net product sales our contract revenues from collaborations were $3 $5 million in the first quarter of 2024.

Dean L. Schorno: Tracked revenues from collaboration consisted of $2 $3 million and she said $1.1 million from granite falls in $100000 from that aside.

Dean L. Schorno: Moving on to cost and expenses our cost of product sales was approximately $2 million for the first quarter of 2024.

Dean L. Schorno: The decrease in costs and expenses was primarily due to decreased research and development costs due to the timing of clinical trial activities related to the ARRAC1-4 inhibitor program, as well as the timing of trial completion activities related to two phase three clinical trials of fostamatinib in patients with COVID-19 and warm-body hemolytic anemia. In addition, the decrease was also due to lower consulting and third-party services as well as lower facility-related costs. These decreases were partially offset by higher stock-based compensation expenses, mainly from performance-based awards.

Dean L. Schorno: Total costs and expenses were $36 $5 million compared to $38 $8 million in the same period for 2023.

Dean L. Schorno: The decrease in costs and expenses was primarily due to decreased research and development costs due to the timing of clinical trial activities related to direct <unk> four inhibitor program as well as the timing of trial completion activities related to the two phase III clinical trials of fast imatinib in patients with COVID-19.

Dean L. Schorno: In warm autoimmune hemolytic anemia.

Dean L. Schorno: In addition, the decrease was also due to lower consulting and third party services as well as lower facility related costs.

Dean L. Schorno: Decreases were partially offset by higher stock based compensation expenses, mainly from performance based awards. We ended the quarter with cash cash equivalents and short term investments of 49 $6 million, we look to maintain our focus and disciplined financial approach and its future.

Dean L. Schorno: We ended the quarter with cash, cash equivalents, and short-term investments at $49.6 million. We look to maintain our focus and disciplined financial approach in the future. Lastly, in April, we entered into an amendment to our credit agreement with MidCap Financial. As part of the amendment, we extended the maturity date and interest-only period by one year. Our principal repayment period now starts in Q4 of... 2025 and extends for 24 months. With that, I'd like to turn the call back over to Raul. Thank you, Dean.

Dean L. Schorno: Lastly in April we entered into an amendment to our credit agreement with Midcap financial as part of the amendment, we extended the maturity date, an interest only period by one year, our principal repayment period now starts in Q4.

Raul: 2025 and expense for 24 months with that I'd like to turn the call back over to Raul Pro.

Raul R. Rodriguez: Thank you, Dean. Looking ahead to the remainder of 2024, we are focused on continuing to grow sales of Reslydia and Tavalis while adding Gravretto to our commercial operations in July of this year. With the help of our strategic collaborators, we look forward to initiating additional allusion-sensitive clinical studies, and we will evaluate other opportunities for expanding the development of our product. We will also enroll and generate preliminary data from our Phase 1B clinical trial of R289 in lower-risk MDS.

Raul: Thank you Dean looking ahead to the remainder of 'twenty 'twenty four we are focused on continuing to grow sales of raws Lydia anti bodies, while adding <unk> to our commercial operations in July of this year.

Raul R. Rodriguez: With the help of our strategic collaborators, we look forward to initiating additional clinical.

Raul R. Rodriguez: Clinical studies, and we will evaluate other opportunities for expanding the development of our products.

Raul R. Rodriguez: We will also enrolling generated preliminary data from our phase <unk> clinical trial of arc to ignore in lower risk Mds and lastly, we will continue we will actively pursue additional in licensing deals and acquisitions similar to our strategy with spreads where they are in great Britain.

Raul R. Rodriguez: And lastly, we will continue to actively pursue additional in-licensing deals and acquisitions, similar to our strategy with Reslydia and Gabretto. As we execute on our strategy to grow our hematology and oncology business, we remain committed to working towards financial break-even and making Rigel a self-sustaining company. With that, I thank you for your interest in our progress in the first quarter, and now we will open the call to your questions.

Raul R. Rodriguez: And as we execute on our strategy to grow our hematology and oncology business, we remain committed to working towards financial breakeven and making rigel is self sustaining company.

Raul R. Rodriguez: With that I. Thank you for your interest in our progress in the first quarter and now we will open the call to your questions.

Raul R. Rodriguez: Operator.

Operator: Thank you. If you'd 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. If you'd like to withdraw your question from the queue, you may press star 2. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key.

Speaker Change: Thank you.

Raul R. Rodriguez: If you'd like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue if.

Operator: If you'd like to withdraw your question from the queue. You May press star two for participants using speaker equipment. It may be necessary to pick up your handset before pressing the Turkey.

Operator: One moment, please, for the first question. Thank you, and our first question is from the line of Yigal Nochomovitz with Citigroup. Please proceed with your question.

Operator: One moment please for the first question.

Yigal Dov Nochomovitz: Thank you and our first question is from the line of Jack All my comments with Citigroup.

Yigal Dov Nochomovitz: Please proceed with your question.

Operator: Yeah.

Yigal Dov Nochomovitz: Hi, thank you very much for taking the question. On the cash guidance, you're burning about $8 million a quarter. You mention getting to break-even and also investing in licensing activities. Could you just help us walk through the path to getting to break-even as far as the existing burn and the revenue picture as well as the investment in the portfolio? Thank you.

Yigal Dov Nochomovitz: Oh, hi, Thank you very much for taking the question on the cash guidance, you're burning about $8 million a quarter you mentioning getting to break even and also investing in and lessons learned in licensing activities could you just help us walk through the path to getting to breakeven as far as the existing burn.

Yigal Dov Nochomovitz: And the revenue picture as well as the investment in the portfolio. Thank you.

Raul R. Rodriguez: Thanks Yigal. I'll ask Steve to comment on that, and I'll add to that. Sure. Hi Yigal.

Speaker Change: Thank you for your golf I'll ask Dean to comment on that no add onto that sure hi, Yigal. So so as it relates to the current quarter and from a cash burn perspective, I'd encourage you to look back a couple of quarters and then as some sort of general comments as we look forward, we haven't given top line guidance.

Steve (Last Name Unknown): Hi Yigal. So as it relates to the current quarter, and from a cash burn perspective, I'd encourage you to look back on a couple of quarters, and then some general comments as we look forward. We haven't given top-line guidance. In our last quarterly call in March, we did describe our expectations for 2024 OPEX. So that's available.

Steve (Last Name Unknown): In the in our last quarterly call in March we did describe our expectations for.

Steve (Last Name Unknown): For 2024 Opex. So that's that's available with respect to Q1 I would note a couple of things one is the dynamic of the net sales that I've described so we did have.

Steve (Last Name Unknown): With respect to Q1, I would note a couple of things. One is the dynamic of the net sales that I described. So we did have the inventory reduction, which impacted net sales and also impacted our cash flows as a result of that. Incrementally, I would note that we paid $2 million, and this is in our queue; we paid $2 million on the MD Anderson collaboration. So from a cash flow perspective, there are a variety of elements going into that burn that you described.

Steve (Last Name Unknown): The inventory reduction, which which impacted net sales also impacted our <unk>.

Steve (Last Name Unknown): Or our cash flows as a result of that.

Steve (Last Name Unknown): Incrementally I would note that we paid $2 million and this is this is in our two we paid $2 million on the MD Anderson collaboration so from a cash flow perspective, theres a variety of elements going into that burn that you described.

Steve (Last Name Unknown): With respect to our future point of financial breakeven, and that continues to be a focus of the business, we do expect to see revenues increase. We look to launch Gabretto and start to recognize revenues in the third quarter. With that, we've described that we believe that there is less than $10 million of SG&A and clinical spend with respect to Gabretto, and so we believe that that will become rapidly accretive. All that said, we believe we're on a path to financial breakeven. We just haven't provided the guidance to say exactly when that will occur.

Steve (Last Name Unknown): With respect to our future point of financial breakeven and that continues to be a focus of the business. We do expect to see see revenues increase we look to launched Alvarado and start to recognize revenues in the third quarter with that we've described that we believe.

Steve (Last Name Unknown): That there is less than $10 million of SG&A and clinical spend with respect to GAAP Red Oak. So we believe that that will become rapidly accretive all of that said, we believe we're on a path to financial breakeven. We just haven't provided that guidance too to say exactly when that will occur.

Speaker Change: Thank you okay. Thanks.

Yigal Dov Nochomovitz: Okay, thanks. And then switching to a clinical science question, it's interesting regarding brain activity for Gervetto as well as your interest in gliomas for Olatucidinib. I'm just curious, could you comment on the, you know, if you have details on the brain plasma ratio, whether you have information on that for both of those drugs; I'm just curious how brain penetrant are they?

Steve (Last Name Unknown): And then switching to a clinical science question.

Yigal Dov Nochomovitz: Interesting regarding the the brain activity for a week of Red Oak as well as your interest in glioma for Oh.

Yigal Dov Nochomovitz: I'll, let sue said, they're not sitting there I'm just curious could you comment on the.

Yigal Dov Nochomovitz: If you have details on the brain plasma ratio, whether you have information on that for both of those drugs just curious how how brain penetrant or are they.

Yigal Dov Nochomovitz: Each.

Raul R. Rodriguez: Yeah, you know, Yigal. Thank you for the question. I think it's very helpful.

Yigal Dov Nochomovitz: Yeah.

Speaker Change: Thank you for the question, but I think it's it it's very helpful. Clearly it cross the blood brain barrier, which is critical and we've been able to show in the clinical studies for get rid of as Lisa discussed as well as we also know that our older sitting here also crosses the BBB and so we're excited about opportunity a try both of those molecule.

Raul R. Rodriguez: Clearly, they cross the blood-brain barrier, which is critical. And we've been able to show in the clinical studies for Gavreto, as Lisa discussed, as well as we also know that olutacinib also crosses the BBB. And so we're excited about the opportunity to try both of those molecules in this area and, obviously, generating the data on Gavreto already based on the AERO study, which is very helpful. Anything else, Lisa?

Raul R. Rodriguez: And.

Lisa Royker: In this area and obviously generating the data I've got Brito.

Raul R. Rodriguez: Already based on the Arrow study, which is very helpful anything else Lisa.

Lisa Royker: I would say that the actual ratios that you're asking about, though, are But we know that there's a therapeutic...

Lisa Royker: I would say that see actual ratios that you're asking about though arent.

Lisa Royker: That hasnt been determined.

Lisa Royker: Yeah.

Lisa Royker: But we know that there's a therapeutic effect on both in relevant studies. One already with the AERO study on brain meds. And then we did publish, and Lisa referenced this, ELUDA, a smaller study that showed a benefit in patients that were highly refractory.

Lisa Royker: But we know that there's a therapeutic effect on both absolute and relevant studies one already with the Arrow study in the brain Mets and then we did publish and Lisa referenced this on Malouda a smaller study that showed a benefit in patients that were highly refractory.

Yigal Dov Nochomovitz: Got it, okay, thanks. Thank you, Yigal. Our next question is from the line of Kristen Kluska with Candor Fitzgerald. Please proceed with your question. Hi, everyone. Thanks for taking the question.

Speaker Change: Got it okay. Thanks.

Lisa Royker: Rob.

Kristen Brianne Kluska: Our next question is from the line of Kristen Kluska with Cantor Fitzgerald. Please proceed with your question. Hi everyone, thanks for taking the questions.

Kristen Brianne Kluska: Our next question is from the line of Kristen <unk> with Cantor Fitzgerald. Please proceed.

Kristen Brianne Kluska: With your questions.

Kristen Brianne Kluska: Hi, everyone. Thanks for taking the question maybe just to follow up on the last one and ask in a different way you know can you talk about how you're going to balance the current pipeline where each of these assets in itself could potentially be evaluated in other indications and then also the continued appetite.

Kristen Brianne Kluska: For more of the bolt on deals.

Kristen Brianne Kluska: Fit your pipeline and maybe another way to ask it is like where do you see the company maybe in two years from now.

Raul R. Rodriguez: Yeah, let me take a crack at that, if I may. Thank you for the question, Chris. I appreciate that. So, you know, we're excited to have Tavalisse, and Tavalisse continues to grow very nicely. And the demand for bottles was, again, a new quarterly high. And that's really the fundamental basis of that excitement in terms of the growth of the product. Inventories go up and down on a quarterly basis. They were huge last quarter, I mean, in Q4 and even in Q3 of last year, in the other way.

Speaker Change: Yeah, Let me take a crack at that if I may. Thank you for the question Chris I. Appreciate that so you know we're so did you have a total lease until the lease continues to grow very nicely and the demand bottles were again, a new quarterly high and that's really the fundamental basis. So bad excitement in terms of the growth of the product inventories go up.

Raul R. Rodriguez: And don't know what a quarterly basis. They were huge last quarter in Q4 than it had been in Q3 of last year.

Raul R. Rodriguez: And Reslydia, we're excited about the launch of the product. It's really just underway in many ways, and it's still being introduced to clinicians, and we think there's a good opportunity there as well. And with the addition of Gavretto, again, an oral targeted therapy, having three products in the bag where our sales organizations, institutional and community, can make tremendous headway with all of those, so we look for the top line to continue to grow very nicely.

Raul R. Rodriguez: In the other way and whereas with you. We're excited because of the launch of the product is it's really just underway in many ways and it's still being introduced to our clinicians and we think there's good opportunity there as well and with the addition of got rid of again, a oral targeted therapy, having three products in the <unk>.

Raul R. Rodriguez: Where are our sales organizations institutional and community can make tremendous headway with all of those so we look for the top line to continue to grow very nicely. We also can look for the opex to be growing but relatively more much more modestly than the top line that was two things and we gave some guidance has been.

Raul R. Rodriguez: We also can look for OPEX to be growing, but relatively much more modestly than the top line. Those were two things, and we gave some guidance, as Dean said, last quarter in terms of our view of the year that still holds.

Raul R. Rodriguez: You said less last quarter in terms of our view of the year that still holds and so put those together, we see us being able to generate sufficient resources to be able to execute unpolitical trials ourselves and we're looking at various opportunities, particularly with our ludo in areas like O M. B a M L.

Operator: And so, put those together, we see us being able to generate sufficient resources to be able to execute on clinical trials ourselves, and we're looking at various opportunities, particularly with Aluda in areas like AML and glioma, which are very exciting in terms of the things that we could do ourselves. We're delighted to have Lisa with us now and her experience in this very area to be able to help us evaluate, design, and then launch studies in this area in future years based on increased cash flows from the ongoing business.

Operator: In glioma, which are very exciting in terms of the things that we could do ourselves. We're delighted to have Lisa with Estelle and her experience and this very area to be able to help us evaluate decide and then launch studies in this area in the in future years based on our increased cash flows from the ongoing business we have.

Operator: We also want to continue to grow the business, and the addition of each of these two products, Reslydia and then Gabretto, in sequence, have been very, very useful in terms of growing the top line and, importantly, fully leveraging the infrastructure that we have in place. It's really an excellent oncology-oriented and ability to sell into both institutions and community-based clinicians is tremendous, and we've been able to leverage the organization with fairly small increments in terms of infrastructure growth to be able to do that.

Operator: Also want to continue to grow the business.

Operator: And the addition of each of these two products, whereas Lydia and Democrat Brito and sequence had been very very useful in terms of growing the topline and importantly fully leveraging.

Operator: The the infrastructure that we have in place, it's really an excellent oncology oriented and ability to sell into both institutions and community base clinicians I think is tremendous and we've been able to leverage the organization with fairly small increments in terms of infrastructure.

Operator: Growth.

Operator: To be able to do that the results of that is that were all that much further along in terms of reaching that financial breakeven and then subsequently generating cash to do more and more clinical studies on our own Registrational studies and more in a continued acquisitions or in licensing of other products.

Operator: The result of that is that we're all that much further along in terms of reaching that financial break-even and then subsequently generating cash to do more, more clinical studies on our own, registrational studies, and more continued acquisitions or in licenses of other products. So that's how we see the business growing in the next few years, two years for sure and beyond that. I think it's very exciting to be able to have a growing business, exciting trials that we may launch that address major areas in AML and glioma, say, and then continuing to look externally for additional products to add on that do so without having to increase our infrastructure very much, if at all.

Operator: So that's how we see the business growing in the next few years two years for sure and then beyond that I think it's very exciting to be able to have a growing a growing base business.

Operator: Exciting trials that we may launch that are addressing major areas in AML, but you're almost saying and then continuing to look externally for additional products to add on that that do so without having to increase our infrastructure very much if at all.

Speaker Change: Thank you.

Speaker Change: Thank you Chris.

Farben Heike: As a reminder, if you'd like to ask a question today, you may press star 1 on your telephone keypad. Our next question is from the line of Farben Heike with Jeffreys, please answer your question.

Operator: As a reminder, if you'd like to ask a question today you May press star one from your telephone keypad.

Speaker Change: Our next question is from the line of Farhan I cant with Jefferies. Please proceed with your question.

Farben Heike: Thank you for taking our questions. So for TAPLs, based on the distribution Channels inventory in one queue, how should we think about this for the rest of the year? And how variable is it? Like you just showed the numbers for the four queue levels, but is it really variable across quarters?

Farben Heike: Thank you for taking my question, so far definitely based on the distribution channels and venturing into one how should we think about.

Farben Heike: This for the rest of the year and how variable is it like you just showed the numbers for Q level, but is it really been able across the quarters.

David A. Santos: Yeah, I'll ask Dave to comment on that, and then we can point you to another place where you can look at the variability of that.

Farben Heike: Yeah, I'll ask Dave to comment on that and then we can point you to another place you can look at the variability of that.

David A. Santos: Yeah, it's a question about kind of the variability of inventory through the quarters. And I will say Q1 was a bit unique in terms of, again, that's why Dean explained the drawdown of inventory of 290 bottles. We do believe that, you know, we have inventory because it's sitting in either our distributors, which distribute to our direct accounts, or SPs, which distribute to patients. And, you know, they purchase from us, then they sell out to those two portions of the network, and what's left is the inventory.

Dave: Yes, it's it I understand your question as well.

David A. Santos: It's kind of the variability of inventory through the quarters and I will say Q1 was a bit unique in terms of again, that's why Dean explained the drawdown of inventory of 290 bottles. We do believe that you know we have we have inventory because it's sitting in either our disc.

David A. Santos: <unk>, which distributed to our direct accounts or S p's, which distribute to patients and are you know they purchase from US and then they sell out to those two portion.

David A. Santos: Of the network and what's left is the inventory and so you know they did purchase a little bit more in Q4, but I think the key is that in Q1.

David A. Santos: And so, you know, they did purchase a little bit more in Q4, but I think the key is that in Q1, that kind of went down. But as Dean kind of demonstrated in his example, even if we don't build any inventory this quarter and we stay flat on demand, we're expecting double-digit growth versus last year in terms of net sales. So, we wouldn't expect continued significant variability, but this does happen, particularly with, you know, Q4 around the holidays, moving into Q1.

David A. Santos: That that kind of went down but as dean kind of demonstrated in his example, even if we don't build any inventory this quarter and we stay flat on demand, we're expecting double digit growth versus last year in terms of net sales. So are we we wouldn't expect.

David A. Santos: <unk> significant variability, but this does happen, particularly with that are you know Q4 around the holidays moving into Q1 and.

David A. Santos: And also, as Dean mentioned, you usually start out the quarter with a little bit lower demand, and I think that was reflected in the purchases that happened early in the quarter. And then we ended the quarter with very high demand, which is why we increased our demand quarter over quarter. So, I think there's a number of variables that contributed to this drawdown, in particular this quarter, but we don't see any significant variability up or down as we move forward, and I would invite Raul Rodriguez to provide any more clarity on that, but that's my view.

David A. Santos: And also as Dean mentioned, you know you start out the quarter with usually a little bit lower demand.

David A. Santos: And I think that was reflected in the purchases that happened early in the quarter and then we ended the quarter with very high demand, which is why we increased our demand quarter over quarter. So I think there's a number of variables that contributed to this drawdown in particular this quarter, but we don't see any significant.

David A. Santos: Variability up or down as we move forward.

Raul R. Rodriguez: Yeah, and I would even by Brown work each day at <unk>.

Raul R. Rodriguez: Provide any more clarity on that but that's my view I.

Raul R. Rodriguez: Yeah, I think we have seen in some cases highly large numbers. In fact, this drawdown wasn't the largest. We had a larger one in early 21, for example.

Raul R. Rodriguez: I think we have seen in some time.

Raul R. Rodriguez: Cases highly.

Raul R. Rodriguez: Larger numbers that back. This this brought on resin and the largest we've had a larger one in early 'twenty. One for example, so it does vary substantially I think b what is consistent though in the longer term the inventory our inventory levels grow as the business grows and that is.

Raul R. Rodriguez: So it does vary substantially. I think what is consistent, though, in the longer term, inventory levels grow as the business grows. And that is consistent. It's not in any specific quarter or any one quarter, and we see oscillations on both sides. It's just that the overall trajectory is a growth trajectory when the business is growing. Taveliz is growing. I can share some prior quarter numbers as well, if you wish. In our corporate deck, we include a nice little table that shows the inventory changes on a quarterly basis, going back as early as 2021.

Raul R. Rodriguez: <unk> could stop in any specific quarter or any one quarter and we see oscillations in both sides. It's just the overall trajectory is a growth trajectory when the business is growing it's all the leases growth.

Raul R. Rodriguez: Yeah.

Speaker Change: Got it okay.

Raul R. Rodriguez: Here are some some priority prior quarter numbers as well if if you wish you could.

Raul R. Rodriguez: Corporate deck, we include a nice little table.

Raul R. Rodriguez: Table that has inventory changes on a quarterly basis going back to us as early as 2021.

Farben Heike: And then, for Reslydia, he had a nice uptake, so I was wondering what proportion of the cells were from new patients versus the existing patients? And then, what needs to be done to better compete with Servier's Tibsovo in de novo?

Speaker Change: Got it helpful. And then forest media you had a nice uptick so I'm wondering what proportion of the sales were from new patients versus the existing patients and then what needs to be done to better compete with the <unk>.

Farben Heike: We are deep summer in de Novo patients.

Farben Heike: Yeah.

David A. Santos: Go ahead, David. Sure. Actually, if you look at total demand bottles, the percentages I showed you are still pretty strongly toward institutions. And similarly, our demand bottles are strongly from patients who have previously started. And that's because, as you know, you only have three months to get business from the patients who started in Q1. And actually, we did have a number of patients start in March. So those would only have had a small number of bottles.

Speaker Change: Good day.

Speaker Change: Sure actually if you look at total demand bottles are the percentages I showed us is pretty still strongly toward institutions and similarly, our demand bottles are strongly from patients who previously started and that's because as you know them you know you only.

David A. Santos: Have a max three months to get our business from the patients who started in Q1 and actually we did have a number of patient starts and in in March. So those would have only had a small number of bottles. So I.

David A. Santos: So I don't have the exact percentage, but it's around the percentage of, I'd say, around 20 or so percent of the bottles were in new patients in Q1. And so we think that's an excellent sign, obviously, that more new patients started in Q1. That clearly drove sales.

David: I don't have the exact percentage, but it's around the percentage of I'd say around 20, or so percent of the bottles are.

David A. Santos: We're where are in new patients in Q1, and so we think that's an excellent sign obviously that are either new patients more new patients started in Q1 that clearly drove the sales, but I think what you're also seeing is that carryover growing from last year.

David A. Santos: But I think what you're also seeing is that carryover from last year. And secondly, in terms of, I wouldn't say we're competing. I would just say that we are really trying to differentiate elutacidinib in mutant IDH1 relapsed refractory disease because we feel we have a very long duration of response. That's getting out there. And in particular, when you look at the subset of patients who've had previous venetoclax, we believe we have a great story to tell there in terms of response rates and duration of response.

David A. Santos: And then secondly in terms of I wouldn't say, we're competing I would just say that we are really trying to differentiate our leadership may have been viewed 90, H one relapsed refractory disease, we feel we have a very long duration of response, that's getting out there and.

David A. Santos: In particular, when you look at the subset of patients who had previous banana clacks. We believe we have a great story to tell there in terms of response rates and duration of response. So at the end of the day you know those are the pieces you know when when when you when you're able to do.

David A. Santos: So at the end of the day, those are the pieces. When you're able to talk about the duration of response that we have in the relapsed refractory setting and then talk about that in a venetoclax-treated population, you have a consistent response rate and duration, that becomes very compelling to clinicians. Because I think, as you're probably aware, venetoclax continues to grow in use, particularly in first-line AML. Thank you very much.

David A. Santos: Talk about the duration of response that we have in the relapsed refractory setting and then talk about that in a venetic clacks pop treated population you have a consistent response rate and duration.

David A. Santos: That that becomes very compelling to clinicians because I think as you're probably aware banana class continues to grow us, particularly in first line AML.

David A. Santos: Yeah.

Operator: Thank you very much. Any other questions?

Speaker Change: Thank you any.

Speaker Change: Any other question.

Speaker Change: Thank you.

Speaker Change: Thank you.

Raul R. Rodriguez: There are no further questions at this time. I would like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Operator: There are no further questions at this time I would like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Operator: In closing, I'd like to thank everyone on this call and for your continued interest in Rigel and our progress. And, as always, I would like to thank our employees for their commitment to improving the lives of patients because every single day does count. We look forward to updating you on our progress in future calls. And, with that, I wish you a great day.

Raul R. Rodriguez: Thank you in closing I'd like to thank everyone on this call and for your continued interest in Rigel, and our and our progress and as always I'd like to thank our employees for their commitment to improving the lives of patients because every single day it does count.

Operator: Look forward to updating you on our progress in future calls or would that have a great day.

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

Speaker Change: This concludes today's teleconference. You may disconnect your lines at this time. Thank you.

Operator: You for your participation.

Operator: Yes.