Q4 2023 Rigel Pharmaceuticals Inc Earnings Call

Greetings and welcome to Rigel Pharmaceuticals Financial conference call for the fourth quarter and full year 2023.

Unknown Executive: The full year 2023. At this time, all participants are in a listen-only mode.

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

Unknown Executive: A brief question and answer session will follow the formal presentation. If anyone should require the operator's 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 you to our first speaker, Ray Furey, Raul's Executive Vice President, General Counsel, and Corporate Secretary. Thank you, Mr. Furey.

A brief question and answer session will follow the formal presentation.

If anyone should require operator assistance during the conference. Please press star zero on your telephone keypad as a reminder, this conference is being recorded.

Rafe Theory: It is now my pleasure to introduce you to our first speaker Rafe theory, right, We will executive Vice President General Counsel and corporate Secretary. Thank you missed your theory you may begin.

Raymond J. Furey: You may begin. Welcome to our fourth quarter and year-end 2023 financial results and business update conference call. A financial press release for the fourth quarter and year end 2023 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. Please visit our website at www.ragel.com. As a reminder, during today's call, we may make forward-looking statements regarding our financial outlook and our plans and timing for regulatory and product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent annual report on Fallen Pancake for the year ended December 31st, 2023 on file, www.larryweaver.com. At this time, I would like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez.

Rafe Theory: Welcome to our fourth quarter and year end 2023 financial results and business update conference call.

Speaker Change: The press release for the fourth quarter and year end 2023 was issued a short while ago.

Speaker Change: We viewed along with the slides for this presentation and the news.

Speaker Change: And events section of our Investor Relations site.

Speaker Change: Right.

Speaker Change: As a reminder, <unk> call, we may make forward looking statements regarding our financial outlook.

Speaker Change: Our plans and timing for regulatory and product development.

Speaker Change: They are subject to risks and uncertainties that may cause actual results to differ those for now.

Speaker Change: A description of these risks can be found on our most recent annual report for the year.

Speaker Change: <unk> ended December 31 2023.

Speaker Change: So with the SEC any forward looking statements are made only as of today's date and we undertake no obligation to update those 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 R. Rodriguez: Thank you, Ray, and thank you, everyone, for joining me today. Also with me today are Dave Santos, our Chief Commercial Officer; Francois DiTrupani, our Senior Vice President of Medical Affairs; Joel Asaga, our Executive Vice President of Corporate Development; and Dean Schorno, our Chief Financial Officer. We have an exciting presentation today, and we will provide substantial information on Grabetto, our most recent addition to our portfolio. Because of this, this presentation will run for approximately 40 to 45 minutes, to be followed by Q&A. Let me begin on slide four.

Speaker Change: Great.

Speaker Change: Thank you Ray and thank you everyone for joining today.

Speaker Change: Also with me today are Dave <unk>, our Chief Commercial Officer, Francois Digital Party, our senior Vice President Medical Affairs, Joel the stagger, our executive Vice President corporate development and deep Jordan, our Chief Financial Officer.

Speaker Change: We have an exciting presentation today.

Speaker Change: He will provide substantial information on Roberto are most.

Speaker Change: In addition to our portfolio because of this this presentation, we're growing approximately 40 to 45 minutes to be followed by Q&A.

Raul R. Rodriguez: We are thrilled with the significant progress we made in growing our hematology and oncology business in 2023 and in the early part of 2024. We look forward to maintaining this momentum throughout the remainder of the year. Our two marketed therapies, Tavalisin ITP and Reslydia and Mutant IDH1 Relapse or Refractory AML, saw record sales in 2023 of $104 million, a 36% growth over 2022. This is an outstanding performance for both products, and this growth can be attributed to the execution of our initiatives by our commercial and medical affairs teams, and frankly, across the entire organization. We are focused on continuing this growth to drive growth for these two important treatments. Most recently, we expanded our commercial product portfolio with the acquisition of Gabaretto.

Speaker Change: Let me begin on slide four we are thrilled with the significant progress we've made in growing our hematology and oncology business in 2023 and in the early part of 2024.

Speaker Change: We look forward to maintaining this momentum throughout the remainder of the year.

Speaker Change: Our two marketed therapies, <unk> and red linear in Newton I D. H, one relapsed refractory AML saw record sales in 2023 of 104 million.

Speaker Change: 36% growth over 2022 visits.

Speaker Change: This is an outstanding performance for both products and this drove can be attributed to the execution of our initiatives by our commercial and medical affairs teams and frankly across the entire organization we.

Speaker Change: We are focused on continuing this growth to drive growth for these two important treatments.

Speaker Change: Most recently, we expanded our commercial product portfolio with the acquisition of Red Oak.

Speaker Change: Hum.

Raul R. Rodriguez: An FDA-approved therapy for the treatment of red fusion positive metastatic non-small cell lung cancer and advanced or metastatic thyroid cancer. Gavretta is a compelling addition to our portfolio, representing a valuable, targeted treatment option for non-small cell lung cancer patients with red fusion positive disease. This acquisition is part of the execution of our corporate strategy.

Speaker Change: And FDA approved therapy for the treatment of Ret fusion positive metastatic non small cell lung cancer and advanced or metastatic thyroid cancer, you have read or was a compelling addition to our portfolio representing a valuable targeted treatment option for non small cell lung cancer patients with ret fusion positive disease.

Speaker Change: This acquisition is part of the execution of our corporate strategy.

Raul R. Rodriguez: Leveraging our existing commercial and medical affairs infrastructure and providing top-line growth. We will have Dave and Francois speak more about this product later on in today's call. In addition to our commercial efforts, we are continuing to advance our development programs with two recent and important strategic alliances, advancing our goal of evaluating Reslydia in a broad range of IDH1 mutant cancers, including AML, MDS, and glioma. These alliances with MD Anderson and Connect greatly enhance our ability to further evaluate Reslydia's potential in a cost-efficient and time-efficient manner. We'll touch more on these plans later on in this call.

Speaker Change: Bridging our existing commercial and medical affairs infrastructure and providing top line growth.

Speaker Change: We will have Dave and Francois speak more about this product later on today's call.

Speaker Change: In addition to our commercial efforts, we are continuing to advance our development programs with two recent and important strategic alliances advancing our goal of evaluating red linear and a broad range of I D H ones mutant cancers, including AML Mds and glioma.

Speaker Change: Licenses with M D Anderson and connect greatly enhance our ability to further evaluate <unk> potential in a cost efficient and time efficient manner. We.

Speaker Change: We will touch more on these planes later on this call in addition, or tweak knowing our Iraq, one and four inhibitor is advancing in a phase one b study of lower risk Mds.

Raul R. Rodriguez: In addition, R289, our IRAC1 and 4 inhibitor, is advancing in a phase 1B study of lower risk MDS. With the growth of Tel Avis and ResLydia sales and the addition of Gap Grado, which we expect to start recognizing revenue in the third quarter of 2024, as well as our cost efficient and disciplined approach to clinical development, we are well positioned to continue growing our business and to reach financial break Now, let me give you an overview of the acquisition of Granvereto and why we're so excited to add this product to our portfolio. But first, let me say that we are delighted to have acquired the U.S. Rights Group at Bredo and, more importantly, to continue making this treatment available to patients in need. What makes this acquisition so compelling to us are the synergies between this product and our existing portfolio, infrastructure, and expertise.

Speaker Change: With the growth of Toby's Edwards relating to sales and the addition of kept Brito, which we expect to be start recognizing revenue in the third quarter of 2024 as well as our cost efficient and disciplined approach to clinical development, we are well positioned to continue growing our business and to reach financial breakeven.

Speaker Change: Now let me give you an overview of the acquisition of Baghdad up grabbed Red Oak and why we're so excited to add this product to our portfolio.

Speaker Change: First let me say that we are delighted to have according to U S. Reits look at bread aisle and more importantly to continue making the treatment available to patients in need.

Speaker Change: It makes this acquisition is so compelling to us are the synergies between this product into our existing portfolio infrastructure and expertise.

Raul R. Rodriguez: We believe we have the right people and the right systems in place to bring this product to patients and their physicians. Gaviretta is a once-daily oral RET inhibitor with an established foothold in the U.S. market and generated $28 million in U.S. net product sales in 2023. Further, with patents that are issued or expected to issue with a statutory expiration date between 2036 and 2041, we are well positioned to make Apparato available for years to come. In exchange for U.S. rights to Gabriela, we will pay our partner, Blueprint, a purchase price of $15 million, $10 million of which will be payable upon the first commercial sale, and $5 million, which will be payable upon the first anniversary of the closing

Speaker Change: We believe we have the right people and the right systems in place to bring this product to patients and their physicians.

Speaker Change: I've read a as a once daily oral ret inhibitor with an established a foothold in the U S market and having generated 28 million in U S. Net product sales in 2023.

Speaker Change: Further with patents that are issued or expected to issue with a statutory expiration dates between 2036 and 2041, we are well positioned to make that Brett available for years to come.

Speaker Change: In exchange for U S. Reits do get better we will pay our partner blueprint a purchase price of $15 million 10 million of which will be payable upon first commercial sale.

Speaker Change: 5 million, which will be payable upon the first anniversary of the closing date.

Raul R. Rodriguez: The deal also includes potential future regulatory and commercial milestone payments to Blueprint, as well as tiered royalties on net sales of Gabretto. We believe these are very good economics for Rigel and put us in a great position to begin recognizing product sales in the third quarter of 2024 and to begin capturing the value from this program in the near term. With that, I'll turn the call over to Dave and then Francois to talk more about Gabaretto and the opportunity it presents. Dave?

Speaker Change: <unk> also includes potential future regulatory and commercial milestone payments to blueprint as well as tiered royalties on net sales of caporetto.

Speaker Change: We believe these are very good economics for Rigel and put us in a great position to begin recognizing product sales in the third quarter of 'twenty 'twenty four it should be getting capturing the value from this program in the near term.

Speaker Change: With that I'll turn the call over to Dave <unk> to talk more about cat retro and the opportunity it presents.

David A. Santos: Thank you, Raul. On slide 6, I'll begin by reviewing the FDA-approved indications for dibretto, which include the treatment of adult patients with metastatic ret fusion positive non-small cell lung cancer, as well as adult and pediatric patients 12 years of age or older with advanced ret fusion positive thyroid cancer who require systemic therapy and who are in radioactive iodine refraction. Moving to slide 7.

Thank you Raul.

Dave: On slide six I'll begin by reviewing the FDA approved indications forgive Reno, 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 the bats, ret fusion positive thyroid cancer, who.

Dave: Systemic therapy, and Horton right radioactive iodine refractory.

Dave: Moving to slide seven.

David A. Santos: I want to expand on Raul's opening remarks and why we believe Givretto is a strategic addition as the third FDA-approved oral-targeted therapy in our Rigel commercial portfolio. On the left, as Raul mentioned, Gabretto generated nearly $28 million in U.S. net sales last year. Those sales grew more than 21% above recorded sales of almost $23 million in 2022. So this is clearly an important opportunity to continue providing meaningful therapy to RETFusion-positive patients with non-small cell lung cancer and advanced thyroid cancer. We believe this compelling Gabretto opportunity fits our business well for a few reasons. First and foremost, it enables us to immediately and efficiently move into a large, solid tumor market where a lot of time and effort have already been invested to maximize both the importance of testing for actionable targets and the awareness of therapies specific to those targets.

Dave: I wanted to expand on round for opening remarks, and why we believe get read out is a strategic asset.

Dave: Third M D. A approved oral targeted therapy, and a rigel commercial portfolio.

Dave: On the left as Raul mentioned give rather generated nearly $28 million in U S. Net sales last year.

Dave: Those sales grew more than 21% above reported sales by almost $23 million in 2022.

Dave: So this is clearly an important opportunity to continue providing meaningful therapy to ret fusion positive patients with non small cell lung cancer and advanced thyroid cancer.

Dave: We believe this compelling you brito opportunity fits our business well for a few reasons.

First and foremost it enables us to immediately and efficiently move into a large solid tumor market, where a lot of time and effort have already been invested to maximize both the importance of testing for actionable targets and the awareness of therapy specific to those targets. Indeed most club.

David A. Santos: Indeed, most clinicians are already testing patients and immediately recognize RETS as a biomarker associated with an FDA-approved therapy. Therefore, we anticipate that the Rett market will continue to expand as more Rett fusion positive non-small cell lung cancer and advanced thyroid patients are identified. Secondly, we believe we have built strong access capabilities that we can immediately leverage to ensure current and newly prescribed patients have access to GiveRedOut. We have an efficient distribution network with Tavalis and Roslidia that will soon be ready to accommodate Gavreto, combined with our Rigel OneCare patient services hub that has established a reputation for being highly responsive to patients and providers.

Dave: Issues are already testing patients and immediately recognize red as a biomarker associated with an FDA approved therapy.

Dave: So we anticipate that the rec market will continue to expand as more ret fusion positive non small cell lung cancer and advanced I rode patients alright indentified.

Secondly, we believe we have built strong access capabilities that we can immediately memory to ensure current and newly prescribed patients have access to get read out.

Dave: We have an efficient distribution network with probably sadrists linear that will soon be ready to accommodate get read out combined with our rights of wound care patient services hub that has established a reputation for being highly responsive to patients and providers.

David A. Santos: And importantly, we have a track record of ensuring strong coverage and reimbursement for oral targeted therapies in difficult-to-treat diseases that we plan to continue with GiveRedO. Lastly, this opportunity makes perfect sense for us because it is highly complementary to both the commercial and medical affairs field teams we have in place, who call on both academic centers and community oncology practices. With our Rigel footprint already in these accounts, we will be able to be even more efficient with our time and resources, as we discuss multiple products within On slide eight, I'll provide a brief market overview of our biggest opportunity, non-small cell lung cancer. You will see on the left that approximately 235,000 lung cancer patients will be diagnosed. And of those, 80 to 85 percent, or approximately 194,000, will be non-small cell lung cancer.

And importantly, we have a track record of ensuring strong coverage and reimbursement for oral targeted therapies in difficult to treat diseases that we plan to continue to give right now.

Dave: Lastly, this opportunity makes perfect sense for us because it is highly complementary to both the commercial and medical affairs field teams, we have in place who call on both academic centers and community oncology practices.

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

Dave: On slide eight I'll provide a brief market overview of our biggest opportunity non small cell lung cancer.

You will see on the left that approximately 235000 lung cancer patients will be diagnosed this year and of those 80% to 85% or approximately 194000 will be non small cell lung cancer patients.

Francois DiTrupani: Approximately one to two percent of those 194,000 non-small cell lung cancer patients will test positive for the RET fusion, giving us a total incidence of approximately 3,000 RET fusion positive non-small cell lung cancer patients visited. On the right side of the slide, the graph shows research done last year on the first-line therapies that were used in RET fusion positive patients who were eligible for treatment. As you can see, about three-quarters of the patients were treated with one of the two FDA-approved RET inhibitors, with Gevretto used in about a fifth of patients prescribed an RET inhibitor. Additionally, you will see that there is still approximately a quarter of the market being treated with chemotherapy with or without an immune checkpoint inhibitor or a multikinase inhibitor.

Dave: Approximately 1% to 2%, there's 194000 non small cell lung cancer patients will test positive for the ret fusion, giving us a total incidents of approximately 3000 ret fusion positive non small cell lung cancer patients this year.

Dave: On the right side of the slide the graph shows research done last year on the first line therapies that were used in ret fusion positive patients who were eligible for treatment.

Dave: As you can see about three quarters of the patients were treated with one of the two F. D. A approved ret inhibitors with give Reno used in about a fifth of patients prescribed a ret inhibitor.

Dave: Importantly, you'll see that there is still approximately a quarter of the market being treated by chemotherapy with or without an immune checkpoint inhibitor or a multi kinase inhibitor.

Francois DiTrupani: We view this quarter of patients as a growth opportunity for RET inhibitors and Gabretto because, as you will hear from Francois, those therapies are suboptimal in the treatment of RET fusion positive non-spots allergen. With that background, let me turn it over to Francois to share more about the RET biomarker, its role in non-small cell lung cancer, and the profound impact that RETO can have on RET Francois.

Dave: We've used this quarter of patients as a growth opportunity for ret inhibitors and cabretta.

Dave: Because as you will hear from Francois those therapies are suboptimal in the treatment of ret fusion positive non small cell lung cancer patients.

Dave: With that background, let me turn it over to Francois to share more about the rest biomarker its role in non small cell lung cancer and the profound impact get red Oak can have on ret fusion positive non small cell lung cancer patients Francois.

Francois DiTrupani: Thank you, Dave. Let me give you a brief overview of the role of red fusion in solid tumors, with a specific focus on non-small cell lung cancer and the clinical data with PAL-CT. On slide 10, I will summarize why rat-altered stomach tumors have been underserved historically. RET is a non-oncogenic driver in many cancers and can lead to tumor growth and proliferation across a variety of different tumors. Two primary mechanisms have been identified, fusion and activating mutation.

Francois: Thank you Dave Let me give you a brief overview on the walnut pricing fusion in solid tumors with a specific focus on non small cell lung cancer and the clinical data that we see.

Francois: On slide 10 I will.

Francois: Summarize why rent other tests, how many tumors have been underserved you're starting to see.

Francois: Branches are known oncogenic driver in many cancers and can lead to trim up growth and penetration across a variety of different tumors to primary and make an easement BD densify fusion and activating mutation.

Francois DiTrupani: In red fusions, which are relevant for non-small cell cancer and papillary thyroid cancer owing to aberrant DNA repair processes, the red gene is fused to another unrelated gene. Red fusions have been identified in approximately 1-2% of patients with non-small cell lung cancer, representing approximately 3,000 new patients a year in the United States. Incidence of right fusion positive non-small cell cancer is higher in adenocarcinoma, in patients with a minimal smoking history, in younger patients, and in diagnoses. No differences are observed between genders.

In west fusion, which aren't even for non small cell lung cancer, and papillary thyroid cancer, owing to aberrant DNA repair processes, the wrenching excuse to another and on Atg.

Francois: Registrations have been identifying approximately one 2% of patients with non small cell lung cancer.

Francois: Approximately 3000, new patients a year in the United States.

Francois: Incidents of French fusion positive non small cell lung cancer is higher in adenocarcinoma and fisheries for many more smoking history in younger patient and Jack knows no difference at all.

Francois: Between genders.

Francois DiTrupani: Red positive fusion is also reported in 20% of papillary thyroid cancer, representing approximately 1,000 new cases a year in the United States. Historically, there is a great medical need, as non-selective therapies in rat-positive non-small cell cancer have shown poor outcomes with an overall response rate inferior to 30%, are associated with drug-related toxicity, and a high rate of dose reduction in up to 75% of patients. Moving to slide 11, early clinical trials in red fusion-positive non-small cell cancer evaluated multi-kinase inhibitors, including cabozantinib, bandetanib, lambatinib, or sorafenib. They have shown some degree of anti-red activity in the preclinical stage. However, these agents showed modest clinical activity with response rates ranging from 0 to 28%, short median progression for survival, and high rates of treatment-related toxicity resulting from their non-red kinase inhibition. Although PD-1 and PD-L1 expression can be elevated in some patients with an oncogenic driver such as RET, preliminary data suggest that immunotherapy is less effective in patients with RET-driven non-small cell cancer, showing a 6% overall response rate and progression for survival of 2.1 months.

Francois: I suppose diffusion is also reported in 20% of capillary styrene cancer, representing approximately 1000, new cases, a year in the United States.

Historically, there was a great medical need as nonselective chop easy right as opposed to cheap non small cell lung cancer have shrunk poor outcome with an overall response rate.

Francois: 3%.

Speaker Change: Appreciate you doing drug related toxicity.

Speaker Change: I read some of those reductions.

Speaker Change: 75% of patients.

Speaker Change: Moving to slide 11.

Speaker Change: Clinical trials in Ret fusion positive non small cell lung cancer evaluating multi kinase inhibitors, including Cabozantinib and Disney Lamborghini Seraphine and that's shown some degree of anti right G V. G in the preclinical setting.

By way of her these ancient showed modest connectivity. We for instance, as rate response rates ranging from zero to 28% shows median progression free survival and higher rates on treatment or an agent persistency, resulting from them no rent kinase inhibition.

Although PD, one and PDL one expression can be alleviated in SUNFISH and my final question and drivers such as Red.

Speaker Change: Preliminary data suggest that immunotherapy, that's effective and visionary breads, driven non small cell lung cancer, showing 6% overall response rate and progression free survival at two one months.

Francois DiTrupani: Furthermore, practice guidelines state that contraindications for treatment with PD-1, PD-L1 inhibitors in patients with advanced or metastatic non-small cell cancer may include the presence of oncogenes such as EGFR, ELK, and RET, which may predict a lack of benefit. Therefore, the same practice guidelines recommend that targeted therapy with the oncogenic driver should take precedence over treatment with an immune checkpoint inhibitor. Owing to the low activity and toxicity concerns with both multikinase inhibitors and immunotherapies, treatment paradigm for advanced red fusion positive disease has historically been centered around platinum-based chemotherapy, which exhibits a response rate in the 40 to 50% range and provision for survival of six to eight months, further highlighting the need for more effective and selective therapy. While chemotherapy has long been the gold standard in metastatic non-small cell lung cancer, the landscape has shifted over the past two decades to the use of therapies targeting specific driver mutations, and the FDA has approved several therapies for biomarkers for non-small cell lung cancer in the past 10 to 15 years.

Speaker Change: Furthermore, practice guidelines state that contra indication for treatment with PD, one PDL, one inhibitors ambition with advanced or metastatic non small cell lung cancer may include that presents a phone call genes, such as Egfr, and alk and rats, which mean predicts a lack of business.

Therefore, the same practice guidelines recommend that target the top young cushioning driver shouldn't take precedence over treatment with an immune checkpoint inhibitor.

Speaker Change: Moving to the low activity and toxicity concerns.

Speaker Change: Multi kinase inhibitors and immunotherapy.

Speaker Change: Treatment paradigm for advance ret fusion positive disease.

Speaker Change: Three key center around platinum based chemo types.

Speaker Change: He would be the response rates in the 40% to 50% range and progression free survival of six to eight months further highlighting the need for more I think that she and selected chops.

Speaker Change: Why chemotherapy has long been the go to stand out in metastatic non small cell lung cancer landscape has shifted over the past two decades. So if you use a therapy targeting specific driver mutation and you have D. As opposed to several onetime diesel biomarkers non small cell lung cancer in the past 10 15 years.

Francois DiTrupani: Palsetinib is an oral tyrosine kinase inhibitor that selectively and potently targets oncogenic red fusions and mutations, including mutations associated with resistance to multikinase inhibitors, and has shown high selectivity for red over other tyrosine kinase, while Cetinib is 81-fold more selective for RET than VGFR2 and 24 more selective for Preclinical studies of palisetinib have also shown blood-brain barrier penetration and activity against intracranial tumors.

Speaker Change: Yeah.

But since you need is an all time at tyrosine kinase inhibitor and selectively and Potently targets unfortunate crisis, fusions and mutations including mutation associated refreshes extends to meet your guidance you'd be terms and that's shown ice selectivity for rides order powers in Chinese.

Speaker Change: Pardon <unk> 81 fold more selective for right then V. G F L. Two and Twentyfold more select cheap forest than Jack one in biochemical assays.

Speaker Change: Preclinical studies of our Ascension Eaton has also shown blood brain barrier penetration and activity against intra cranial tumors.

Francois DiTrupani: Finally, practice guidelines also recommend targeted therapies as first-line treatment for eligible patients with metastatic non-small cell cancer with actionable genetic variants. Let's now turn our attention on slide 13 to the clinical results from the study that led to the approval of palsatinib in both red fusion positive non-small cell end cancer and red fusion advanced or metastatic thyroid cancer. I must note that the data highlighted on this slide represents a more recent data cut, and therefore the results presented here, while consistent, may be slightly different than those in the prescribing information for price. The ARWA study is a Phase I-II, multi-center, open-label, dose-escalation and expansion study.

Speaker Change: Finally practice guidelines or sort of all come in targeted therapies as first line treatment for each patient with metastatic non small cell lung cancer, we have actionable genetic variance.

Speaker Change: Let's turn our attention on side 14, so the clinical results from the study that led to the approval potentially in both French fusion positive non small cell lung cancer and ret fusion had been some intensity salary cuts.

Speaker Change: I must note that the data highlighted on this slide represent a more recent dip pens and that foreign reserves presented here when consistent maybe slightly different than the one in the prescribing information in pulp prices.

Speaker Change: Yeah, our studies the phase one two multi center open label dose escalation and expansion study.

Francois DiTrupani: Phase 1 portion of the study, at a primary endpoint of maximum tolerated dose, recommended dose for phase two, and safety. Phase II portion of the study, at co-primary endpoints of overall response rate and safety. Key secondary endpoints were duration of response, clinical benefit rates, disease control rates, progression for survival, and overall survival. From phase one, the investigators concluded that paracetamines are generally well-tolerated at doses up to 400 mg QDD.

Speaker Change: Phase one portion of the study.

Speaker Change: The primary endpoint of maximum tolerated dose recommended dose for phase III and safety.

Speaker Change: Phase II portion of the study a co primary endpoint of overall response rate and safety.

Speaker Change: Key secondary endpoints with duration of response clinical benefit rate disease control rate progression free survival and overall survival.

Speaker Change: From the phase one Jim as he gives us concluded that I am thinking of Genuity western rates, you're not doing this to 400 milligrams QD.

Francois DiTrupani: Therefore, 400 mg QD was determined as the maximum tolerated dose and recommended dose for phase 2 based on safety, PK, and anti-tumor activity. In the non-small cell cancer subset, overall responses were recorded in 63% of the 130 patients with previous platinum-based chemotherapy and in 70-80% of the 107 treatment-nave patients. Tumor shrinkage was observed in 100% of treatment nave patients and 97% of prior platinum-based chemotherapy with baseline and post-baseline measurable disease.

Speaker Change: Therefore find whether it be granting treaty what does that mean at the maximum tolerated dose and recommended dose for the phase two based on 50 D G and antitumor activities.

Speaker Change: The non small cell lung cancer subset of all responses were recording and 63% of the 100 infatuation with previews of platinum based chemotherapy and in seven seats waiting your percent of the 107 in treatment nave patients.

Speaker Change: Tumor shrinkage was observed in 100% of treatment naive and 97% of prior platinum based chemotherapy with baseline and post baseline measurement of disease.

Francois DiTrupani: Overall, in the subset of non-small cell cancer patients, median duration of response, one of the key secondary endpoints in the ARO trial, was durable at 19.1 months, ranging from 14.5 to 27.3 months. In the safety population of 281 patients, median treatment duration was 15 months with a median relative dose intensity of 86.1%. Palsatinib was generally well-tolerated, with predominantly grade 1-2 adverse events. 10% of patients discontinued Palsatinib due to treatment-related adverse events in the Ryan Fusion Positive thyroid cancer subset, while Cetinib continues to show efficacy and a manageable safety profile. 20 out of 22 patients with previously-treated red fusion-positive thyroid cancer achieved a response.

Speaker Change: Overall in a subset of non small cell lung cancer submission median duration of response one of the key secondary endpoints in the Allentown with Trimble at 1941 months ranging from $14 five to 27.3 months.

Speaker Change: In the safety population of 281 patients median treatment duration was 15 months with a median range you've dose intensity of 86, 1%.

Speaker Change: <unk> was generally well tolerated.

Speaker Change: I mean, that's the grade one two adverse events 10 per cent a patient discontinued <unk> due to treatment related adverse events.

Speaker Change: No rights fusion plus your teeth salaried conceptual sense.

Speaker Change: Since you named continues to show efficacy and a manageable safety profile.

Speaker Change: 20 out of the 22 patients previously treated with intrusion pretty cheap thyroid cancer and human response.

Francois DiTrupani: Finally, in the 23 patients evaluable for efficacy from the right fusion positive solid tumor subset, patients older than thyroid or non-sporty cellulite cancer and including colorectal pancreatic cancer patients, for example, the overall response rate was 57%, and the disease control rate was 83%. On slide 14, you can see that the development of CNS metastasis is common, with nearly half of non-small cell cancer patients developing And it is a poor prognosis factor in patients with red fusion positive non-small cell cancer. In a study by Drellon et al., 25% of patients had brain metastasis at the time of diagnosis. Non-selective therapies such as multikinase inhibitors have shown low intracranial response rates with short median progression for survival and overall survival, respectively, at 2.1 months and 3.9 months. Patients with untreated CNS metastasis were permitted in the hour study if not associated with progressive neurological symptoms.

Speaker Change: Finally, you know twenty-three patiently, but at one point if you can see from the rent infusion because it just solid tumor subsets.

Speaker Change: Shouldn't order then tirade on non small cell lung cancer, and including colorectal and pancreatic cancer patients. For example, Johann response rate was 57% and the disease control rate was 83%.

Speaker Change: On Slide 14, you can see that the development of CNS metastases coopman with nearly half of non small cell lung cancer patients developing brain metastases during their lifetime and he's a poor prognosis factor in patient with transfusion pushing to keep non small cell lung cancer.

Speaker Change: You know certainly by drilling you know 25% of patients had brain metastases at the time of technologies.

Speaker Change: Nonselective choppy such as multi kinase inhibitors have shown low intra cranial response rates.

Speaker Change: Schultz median progression free survival in Ohio, or somebody from respectively, a 2.1 month and three nine months.

And shouldn't we send treating CNS metastases.

Speaker Change: Mentioned in the hours study, if not associate you'd be overseas in order to support sometimes.

Speaker Change: As I indicated to you earlier preclinical studies are probably thinking ive shown blood brain barrier penetration and activity against them trying cranial tumors.

Francois DiTrupani: As I have indicated to you earlier, preclinical studies of trisetinib have shown blood-brain barrier penetration and activity against intracranial tumors. In the present study, trisetinib showed intracranial activity in patients with RETF, fusion positive non-small cell cancer, and measurable baseline by metastasis, with a 53% overall response rate, including the inducement of intracranial complete response in three out of 15 patients, all 20% of the cohort, and a median duration of response of 11.5 months. Moving to slide 15, falcitinib is the only oral once-daily therapy that selectively and potently inhibits rat alteration, and has demonstrated high rates of durable response regardless of treatment history, with response rates in the range of 74 to 80% for treatment-nave patients and 63% for previously treated non-small cell and cancer patients. While Centinib is clinically proven to cross the blood-brain barrier and has demonstrated intracranial activity, it has an established safety profile with manageable adverse events and a low discontinuation rate.

Speaker Change: In the present study party city named shown intra cranial activity ambition, we French.

Speaker Change: <unk> positive non small cell lung cancer and missionary about baseline brain metastases with a 53% overall response rate, including the inducement of N track. When you complete response in three out of 15 fishing, all 20% of the calls and a median duration of response of 11.5 months.

Speaker Change: Moving to slide 15.

Speaker Change: <unk> is the only or one they need jobs.

Speaker Change: Collectively and importantly, you need the right transformation as demonstrated I rates of durable response, regardless of treatment is to me.

Speaker Change: For instance rates in the range of 74% to 80% for treatment naive patients and 63% for previously treated non small cell lung cancer patient.

Speaker Change: Our attention is clinically proven to cross the blood brain barrier and as demonstrated in triclinium activities.

Speaker Change: That's an established safety profile with manageable adverse events and no discontinuation rates.

Speaker Change: Sydney does not carry a warning and point question, Paul could you point mutation in non small cell lung cancer population, where the incidence of cardiovascular comorbidities is approximately 20% to 40%.

Speaker Change: Finally.

Speaker Change: Since your name is recommended by practice guidelines as a treatment option for certain patients we find person team at Bernstein cancer, and Wentworth Chief maintenance, taking on sports center cancer and carrier category to a preferred recommendations as far as <unk> talked before I suppose you've made dusty comes once in cancer.

Francois DiTrupani: Palsatinib does not carry a warning and precaution for QT prolongation in non-small cell cancer populations, where the incidence of cardiovascular comorbidities is approximately 20 to 40%. Finally, Pralsetinib is recommended by practice guidelines as a treatment option for certain patients with red positive advanced thyroid cancer and red positive metastatic non-small cell cancer and has a category 2A preferred recommendation as first-line therapy for red positive metastatic non- In conclusion, all those elements lead us to firmly believe that pralsetinib has a differentiated value proposition. With that, I will turn the call back to Dave to talk about the commercial plans for pralsetinib. Thank you, Francois.

Speaker Change: In conclusion, all of those elements lead us to believe that Sydney as a differentiated value proposition, we thought we'd start off at a call it back to Dave to talk about the commercial plans for <unk>.

Dave: Thank you Francois.

Dave: Now that we've covered both the opportunity and the clinical overview, Brett non small cell lung cancer and get read out.

Dave: I wanted to provide a brief overview of the red Oak commercialization plans and timeline as we move through an exciting 2024.

Dave: I'll also briefly review our Q4 results showing continued momentum with our two other oral targeted therapies tallis address Lydia.

David A. Santos: Now that we've covered both the opportunity and the clinical overview of RETS, non-small cell lung cancer, and Guvretto, I wanted to provide a brief overview of the Guvretto commercialization plans and timeline as we move through an exciting 2024. I'll also briefly review our Q4 results showing continued success with our two other oral-targeted therapies, tablilis, and reslipid. Moving to slide 17, I want to provide a little more detail on why we believe our capabilities are especially suited to this great opportunity with Gibretta. First, we have an efficient distribution network for Tavalese and Reslydia that swiftly and dependably delivers our products to accounts and patients overnight. Our network can readily accommodate Gibretto accounts.

Dave: Moving to slide 17, I want to provide a little more detail on why we believe our capabilities are especially suited to this great opportunity with getting right up.

Dave: First we have an efficient distribution network for <unk> and Reds linear that swiftly independently delivers our products to accounts in patients overnight.

Dave: Our network can readily accommodate get righto accounts in patients.

Dave: Second our Rigel, one care patient services hub has over seven years of experience working with patients providers and payers and our team. There will also be fully ready to provide the outstanding services to give red oak patients and customers.

David A. Santos: Second, our Rigel OneCare Patient Services Hub has over seven years of experience working with patients, providers, and payers, and our team there will also be fully ready to provide those outstanding services to Gabretto patients and customers. And lastly, our access team has strong existing relationships with payers and networks, which we will continue to leverage to ensure the same high levels of coverage and reimbursement that led to the 97% commercial coverage we achieved with Top Up. Specifically, on slide 18, we have already begun the process of working closely with Genentech and Blueprint to ensure both current and newly prescribed patients continue to have access to Gibretto without interruption. Rigel OneCare will work with providers to assist in moving patients from the existing Genentech network and access programs to the Rigel network and Rigel OneCare patient program.

Dave: And lastly, our access team has strong existing relationships with payers that networks, which we will continue to leverage to ensure the same high levels of coverage and reimbursement that have led to our 97% commercial coverage, we have achieved with top police.

Dave: Specifically on slide 18, we have already begun the process of working closely with Genentech and blueprint to ensure both current and newly prescribed patients continue to have access to get Brito without interruption.

Dave: Rigel, one care will work with providers to mean to assist in moving patients from the existing tenant Tech network and access programs to the Rigel network and Rigel, one care patient programs, ensuring a seamless transition for patients.

Dave: Our distribution network ensures patient and provider choice in where their prescription is filled and we will have Roger one care staff fully dedicated to give rep to ensure the highest level access support and customer service.

David A. Santos: Ensuring a seamless transition for patients. Our distribution network ensures patient and provider choice in where their prescription is filled, and we will have Rigel OneCare staff fully dedicated to Gevretta to ensure the highest level of access support and customer support. We anticipate beginning the transition in Q2 and completing the transfer of all patients in Q3. Slide 19 reviews what we believe are the four key drivers for continued growth as we begin our commercialization journey with GevRev. The first step is patient identification.

Dave: We anticipate beginning the transition in Q2 and completing the transfer of all patients in Q3.

Dave: Slide 19 reviews, what we believe are the four key drivers for continued growth as we begin our commercialization journey with gift wrap.

Dave: The first is patient identification.

Dave: It is important that as many as possible of those 3000 potential ret fusion positive non small cell lung cancer patients identified each year.

Dave: Fortunately, even if inclinations arent, specifically looking for ret fusion positive patients when they do test about 90% of them immediately recognized the ret biomarker as being associated with an FDA approved therapy.

David A. Santos: It is important that as many as possible of those 3,000 potential RET fusion-positive non-spell cell linkage patients are identified. Fortunately, even if clinicians aren't specifically looking for Rett fusion-positive patients when they do test, about 90% of them immediately recognize the Rett biomarker as being associated with an FDA-approved therapy. Also, in research conducted last year, about 80% of non-small cell lung cancer patients are being tested. And that is the same in both academic and community settings.

Dave: Also in the research conducted last year about 80% of non small cell lung cancer patients are being tested and that is the same in both the academic and community settings. When clinicians don't test, it's more likely due to not having adequate tissue available.

Dave: So again, we do not anticipate a need to educate clinicians about the importance of rat for testing.

David A. Santos: When clinicians don't test, it's more likely due to not having adequate tissue available. So again, we do not anticipate a need to educate clinicians about the importance of RET or tests. Awareness is high, and that will continue to drive patient identification of RET fusion-positive non-small cell-like tissue. Secondly, and more importantly for Devretto, choice of therapy in those identified patients who are treatment eligible is an impactable growth opportunity for us. Most oncologists have yet to try Gevretto on the front line.

Dave: Awareness is high and that will continue to drive patient identification of ret fusion positive non small cell lung cancer patients.

Dave: Secondly, and more importantly for Red Arrow choice of therapy, and those identified patients who are treatment eligible isn't impactful growth opportunity for us.

Dave: Most oncologists have yet to try get read out in the front line and the biggest reason for that is comfort and familiarity with other drugs.

Dave: As you heard from my opening comments and from Francoise presentation, the use of chemotherapy with or without an immune checkpoint inhibitor and multi kinase inhibitors represents about one quarter of the use in the first line treatment.

David A. Santos: And the biggest reason for that is comfort and familiarity with other drugs. As you heard from my opening comments and from Francois' presentation, the use of chemotherapy with or without an immune checkpoint inhibitor and multikinase inhibitors represents about one quarter of the use in the first-line treatment of RETFusion-positive patients. By growing awareness of Gavretto's efficacy, safety, and once-daily oral dosing, we believe we can grow future use of Gavretto among current non-users. Third, we believe that Gavretto will continue to grow due to its long duration of response and convenient once-daily dosage. These drivers of persistency should continue to drive 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 users of Gevretto from clinicians who view out-of-pocket costs and difficulty obtaining reimbursement as barriers to the use of Retin-H.

Dave: Ret fusion positive patients.

Dave: By growing awareness of Gav Red is efficacy safety and once daily oral dosing. We believe we can grow future use of get read out among current 90 users.

Third we believe that give red oak will continue to grow due to its long duration of response and convenient once daily dosing.

Dave: These drivers of persistency should continue to drive our care yogurt business each month as patients refill their prescriptions.

Dave: And finally, as we have discussed as we leverage our strengths and coverage reimbursement and patient services with Roger one care. We believe we can gain loyal users of give red oak from clinicians, who view out of pocket cost and difficulty obtaining reimbursement as barriers for that use.

David A. Santos: In summary, we are well positioned to continue growing Gabretto through positive momentum in these four key drivers. And to wrap up our prepared remarks on Gibretto, with slide 20, I wanted to provide a high-level timeline of the plans for the rest of the year. Through this month, we'll be preparing our distribution network for the addition of Givereto, and then beginning next quarter, Rigel OneCare will begin implementing a plan to transition current and newly prescribed Givereto patients. We will also begin preparing our field. In Q3, we expect to begin distributing Gabretto and promoting it to customers, with a focus on current use.

Dave: Ret inhibitors.

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

And to wrap up our prepared remarks hard and get read out with slide 20, I wanted to provide a high level timeline of the plans for the rest of the year.

Dave: Through this month, we'll be preparing our distribution network for the addition of gay Brad at that beginning next quarter Rigel wouldn't care will begin implementing a plan to transition current and newly prescribed gave right on patients. We will also begin preparing our field teams in.

Dave: In Q3, we expect to begin distributing give red oak and promoting it to customers with a focus on current users than in Q4, we will continue expanding our breadth of prescribers by calling on non users in both the academic and community settings. It.

David A. Santos: Then, in Q4, we will continue expanding our breadth of prescribers by calling on non-users in both academic and community settings. It will be an exciting year, bringing Gavreto into our portfolio of oral targeted therapies, and I look forward to updating you on our progress as the year progresses. Moving to slide 21, just a few brief comments on our continued growth of Tavalis and our progress with Reslydia in the first full year of law. On slide 22, you will see that 2023 was a strong year of portfolio growth, as our quarterly U.S. net product sales grew from $24 million in the first quarter to $29 million in the fourth quarter. That consistent quarter-over-quarter growth enabled us to generate total net product sales of nearly $104 million for the full year, $28 million more than in 2022, representing an impressive 36% growth. Tavalese, the main driver of this growth, generated approximately $94 million in net sales, up 24% over the prior year.

Dave: It will be an exciting year, bringing red oak into our portfolio of oral targeted therapies and I look forward to updating you on our progress as the year moves ahead.

Moving to slide 21, just a few brief comments on our continued growth of top of lease and our progress with Fred's linear in the first full year of watch.

Dave: On Slide 22, you will see that 2023 was a strong year of portfolio growth as our quarterly U S. Net product sales grew from $24 million in the first quarter to $29 million in the fourth quarter.

Dave: That consistent quarter over quarter growth enabled us to generate total net product sales of nearly $104 million for the full year $28 million more than 2022, representing an impressive 36% growth rate.

Dave: <unk> believes the main driver of this growth generated approximately $94 million in net sales up 24% over the prior year.

David A. Santos: That growth was driven by our continued focus on generating new patient starch, which reached the highest daily average of the year in Q4. We believe this momentum with new patient starts will continue to fuel growth at Tavalese in 2024 and beyond. ResLydia also contributed to our top line in a meaningful way, generating $10.6 million in net product sales. We are growing both breadth and depth of adoption among academic AML treaters. And for 2024, we see a great opportunity to increase awareness and adoption of Reslydia in the community. Overall, we are thrilled that we surpassed $100 million in U.S. net product sales in 2023, and we look forward to building on this momentum in 2024 and beyond. I look forward to updating you again on our progress next quarter. And with that, I'd like to thank you for your attention, and I will now turn the call back over to Raul to provide a brief update on our development progress. Raul?

Dave: That growth was driven by our continued focus on generating new patient starts which reached the highest daily average of the year in Q4.

Dave: We believe this momentum with new patient starts will continue to fuel growth at top of lease in 2024 and beyond.

Dave: Whereas it's Lydia also contributed to our top line in a meaningful way generating $10 $6 million in net product sales.

Dave: We are growing breadth and depth of adoption among academic AML treaters and for 'twenty 'twenty four we see a great opportunity to increase awareness and adoption of rest Lydia in the community setting.

Dave: Overall, we are thrilled that we surpassed $100 million of U S. Net product sales in 2023, and we look forward to building on this momentum in 2024 and beyond.

Dave: I look forward to updating you again on our progress next quarter and with that I'd like to thank you for your attention and I will now turn the call back over to Ralph to provide a brief update on our development progress.

Raul R. Rodriguez: Thank you, Dave. I will now summarize our pipeline expansion plans and provide updates on our other development programs, beginning on slide 24. Beyond the growth of our three approved products and their indications, here's how we're going to grow our hematology and oncology business. There are two major ways.

Ralph: Thank you, Dave I will now summarize our pipeline expansion plans and provide updates on our other development programs beginning on slide 24.

Ralph: Beyond the growth of our three approved products and their indications here's how we're going to grow our hematology and oncology business.

Ralph: Two major ways first on the rig and we will continue to in license or acquire or possible, possibly acquire companies with products that meet our criteria.

Raul R. Rodriguez: First, on the right, we will continue to in-license or acquire or possibly acquire companies with products that meet our criteria. We are looking for differentiated products in hematology or oncology or related areas, products that are in late stage. What this means is that with registrational data, or with soon-to-have registrational data, or more advanced, that fit into our hematology and oncology infrastructure. Rigel, as a transaction partner, presents a more attractive alternative to a company with such a product versus building an entire commercial infrastructure in Genova.

Ralph: We're looking for differentiated products in hematology or oncology or related areas or products that are late stage.

Ralph: What this means is with registrational data or with zoom to have registrational data or more advance that fits into our hematology and oncology infrastructure.

Ralph: Rigel is a transaction partner presents a more attractive alternative to a company with such a product versus building an entire commercial infrastructure in de Novo too.

Ralph: Two companies have already made this decision with our two recently acquired products, we have the ability to do this for other products in the hematology and oncology space and we are actively pursuing this approach we encourage companies to reach out to us if they have such an opportunity.

Raul R. Rodriguez: Two companies have already made this decision with our two recently acquired products. We have the ability to do this for other products in the hematology and oncology space, and we are actively pursuing this approach. We encourage companies to reach out to us if they have such an opportunity. On the left side of this slide is how we're going to grow our current products with new data and, particularly, new indications. From our current product portfolio, we believe olosutinib has potential in numerous cancers where mutant IDH1 plays a role.

Ralph: On the left side of this slide is how we're going to grow our current products with new supportive data and particularly with new indications.

Ralph: From our current product portfolio, we believe has potential in numerous cancers, where mutant I D. H one plays a role they see additional segments in AML in glioma and an M. D S. As promising indications for all this wouldn't have.

As mentioned earlier in this call we've entered into strategic development alliances with M. D. Anderson and connect to further evaluate the certifications and I'll touch more on these agreements in the next slides.

Ralph: Lastly, our two ignoring our Iraq wanted before inhibitor is continuing to enroll its phase one b trial, we hope that this program demonstrates the potential of our choice, but to provide patients who have failed other agents with a much needed treatment option. We expect to have preliminary data from the first part of this trial late this year.

Raul R. Rodriguez: We see additional segments in AML, in Glioma, and in MDS as promising indications for olosutinib. As mentioned earlier in this call, we've entered into strategic development alliances with MD Anderson and Connect to further evaluate these indications. I'll touch more on these agreements in the next slide. And lastly, R289, our IRAC1 and 4 inhibitor, is continuing to enroll in its Phase 1B trial. We hope that this program demonstrates the potential of R289 to provide patients who have failed other agents with a much-needed treatment outcome. We expect to have preliminary data from the first part of this trial late this year. With that, let me turn to slide 25 to review the strategic efforts with MD Anderson. As many of you know, MD Anderson is a premier cancer center and treatment center in the U.S., and, frankly, the world. They have a very large population of patients with various cancers, including AML, as well as the infrastructure and capabilities to run studies quickly. They pride themselves not on providing the standard of care of today but rather defining the standard of care of the future.

Ralph: With that let me turn to slide 25 to review the strategic efforts with MD Anderson.

Yeah.

Ralph: As many of you know M. D. Anderson is a premier cancer center treatments that are in the U S and frankly the world.

Ralph: They have a very large population of patients in various cancers, including AML as well as the infrastructure and capabilities to run studies quickly.

Pride themselves not in providing the standard of care of today, but rather defining the standard of care of the future and they share with us a strong conviction in the potential of oldest wouldn't it.

Ralph: There are four patient populations that we end up in the industry and are particularly excited about for all of a sudden we are planning to evaluate a lizard them in first line AML.

Ralph: In high risk Mds in combination with other agents. We're also going to conduct a trial in seacoast and lower risk Mds, and one and maintenance therapy in post transplant patients.

Ralph: That's for potential clinical trials being conducted in a cost efficient manner with up to $15 million paid over five years.

Ralph: This is also very time, Mr. Fisher as they're able to generate data quickly in these various opportunities.

Ralph: We expect these trials to set us up for conducting a registrational trial subsequently.

Raul R. Rodriguez: And they share with us a strong conviction in the potential of all those who... There are four patient populations that we at MD Anderson are particularly excited about for illicidinib. We are planning to evaluate illicidinib in first-line AML, in high-risk MDS, in combination with other agents. We're also going to conduct a trial in CCUS and lower-risk MDS, and one in maintenance therapy and post-transplant therapy. That's four potential clinical trials being conducted in a cost-efficient manner with up to $15 million paid over five years. This is also very time efficient, as they are able to generate data quickly in these various opportunities.

Ralph: And we're very proud to have empty understood as a partner.

Ralph: Moving on to slide 26.

He is a tough cancer that has very limited treatment options that are efficacious. There are approximately 20000 cases of glaucoma in the U S every year.

Ralph: Probably 70% of grade two and grade three patients and 5% to 7% upgrade for patients our I D. H one positive.

Ralph: This is a fairly prevalent mutation in these patients and there is high unmet need for effective treatment options.

Ralph: On the right side of the slide we showed data from a trial evaluating well it shouldn't have been twenty-six relapsed or refractory highly treatment experienced patients with them.

Raul R. Rodriguez: We expect these trials to set us up for conducting a registrational trial later on, and we're very proud to have MD Anderson as a partner. Moving on to slide 26, glioma is a tough cancer that has very limited treatment options that are effective. There are approximately 20,000 cases of glioma in the US every year. Approximately 70% of grade 2 and grade 3 patients and 5% to 7% of grade 4 patients are IDH1 positive.

Ralph: In this trial no dose limiting toxicities were observed and all it shouldn't have demonstrated a meaningful disease control rate a very good outcome for a very poor prognosis patient population.

Ralph: Moving on to Slide 27, we are excited for our collaboration with connect <unk>.

Ralph: Jim to evaluate all this wouldn't have been patients with glaucoma connect as a consortium that is currently conducting a phase two umbro and trilingual yellow and we are adding all the sued them to this trial to evaluate its safety and efficacy in newly diagnosed pediatric and young adult patients with I D. H, one reaching positive high grade glioma.

Raul R. Rodriguez: This is a fairly prevalent mutation in these patients, and there is a high unmet need for effective treatment options. On the right side of this slide, we show data from a trial evaluating, or the student evading 26 relapse or refractory, highly treatment experienced patients with glioma. In this trial, no dose-limiting toxicities were observed, and olasutinib demonstrated a meaningful disease control rate, a very good outcome for a very poor prognosis patient population.

Ralph: We were providing funding of up to $3 million and study materials over a four year period for the collaboration.

Ralph: Again, a very cost efficient and timely efficient approach.

Ralph: We're very excited about all the student has the potential to provide a much needed treatment option for these patients with such a poor prognosis.

Ralph: With that let me reiterate that we are very excited with the progress we've made across all of our development programs and we look forward to continuing to invest these programs with that I'll turn the call over to Dean for a financial update.

Raul R. Rodriguez: Moving on to slide 27, we are excited about our collaboration with Connect Consortium to evaluate olosudenib in patients with glioma. Connect is a consortium that is currently conducting a phase two umbrella trial in glioma, and we are adding olosudenib to this trial to evaluate its safety and efficacy in newly diagnosed pediatric and young adult patients with IDH1 mutant positive high-grade glioma.

Dean: Thank you Rommel I'm on slide 29, and I begin to review our typical financial highlights for the quarter I'd first like to highlight and we reported net income of $737000 for the fourth quarter of 2020 for your Motor. My review. This was accomplished in part through increasing net product sales, including royalties.

Dean: Revenues periodic drug supply purchases from our international distribution partners and continued disciplined operating expense management across our business. We're pleased with the financial leverage that we're seeing and have been able to successfully grow sales of <unk> at launch for some videos and both the community and academic settings within this.

Raul R. Rodriguez: We will be providing funding of up to $3 million and study materials over a four-year period for the collaboration. Again, a very cost-efficient and time-efficient approach. We are very excited about all the students' potential to provide a much-needed treatment option for these patients with such a poor prognosis. With that said, let me reiterate that we are very excited with the progress we've made across our development programs, and we look forward to continuing to advance these programs. With that, I'll turn the call over to Dean for a financial update. Dean?

Dean: Cost structure.

Speaker Change: I'll now provide our detailed highlights.

Speaker Change: For the fourth quarter of 2023, we shipped 2000, and 671 bottles and tabori ease to our specialty distributors, resulting in $36 $9 million of gross product sales 2000, and 463 positive top elyse shipped to patients and clinics, while 208 bottles increase the levels remaining at or distribution channel.

Speaker Change: At the end of the quarter.

Dean L. Schorno: Thank you, Raul. I'm on slide 29. As I begin to review our typical financial highlights for the quarter, I'd first like to highlight that we reported net income of $737,000 for the fourth quarter of 2023. You'll note in my review that this was accomplished in part through increasing net product sales, including royalty revenue. Periodic Drug Supply Purchases from our International Distribution Partners and Continued Disciplined Operating Expense Management across our business. We're pleased with the financial leverage that we're seeing and have been able to successfully grow sales of Tavolis and launch Reslydia in both the community and academic settings within this cost structure. And that provides our detailed highlights.

Speaker Change: For the fourth quarter of 2023, we shipped 308000 versus maybe yet to our specialty distributors, resulting in $5 million of gross product sales 278, Bob's original idea are shipped to patients and clinics, while 30 bottles increase the levels remained in our distribution channel and in the quarter.

Speaker Change: We reported net product sales from <unk> of $25 $7 million in the fourth quarter of 2023% to 17% increase compared to the same period in 2022.

Speaker Change: We reported net product sales from our survey to yet a $3 $9 million in the fourth quarter of 2000 Twenty's race.

Speaker Change: Our net product sales from Cobham Eastern Pennsylvania are recorded net of estimated discounts charge backs rebates returns co pay assistance and other allowances of $12 $3 million for the fourth quarter of 2023, our gross to net adjustment for top of recent Wrestlemania was approximate 34.

Dean L. Schorno: For the fourth quarter of 2023, we shipped 2,671 bottles of Tavolese to our specialty distributors, resulting in $36.9 million in gross product sales. Additionally, 2,463 bottles of Tavolese were shipped to patients and clinics, while 208 bottles increased the levels remaining in our distribution channels at the end of the quarter. For the fourth quarter of 2023, we shipped 308 bottles of Virzalidia to our specialty distributors, resulting in $5 million in gross product sales. 278 bottles of Roslydia were shipped to patients and clinics, while 30 bottles increased the levels remaining in our distribution channels at the end of the quarter. We reported net product sales from Tavolisse at $25.7 million in the fourth quarter of 2023, a 17% increase compared to the same period in 2022. We reported net product sales from Roslydia at $3.9 million in the fourth quarter of 2023.

Speaker Change: <unk> and 21, 9% of gross product sales respectively.

Speaker Change: Before I move on from net product sales, let me review our expectations for the first quarter of 2024, let me start with Tom always despite the typical first quarter reimbursement issues confronting our industry such as the resetting of co pays and the Medicare Donut hole, except expect to see a small increase in bottles shipped to patients and clinics.

Speaker Change: In the first quarter of this year.

Speaker Change: Compared to the fourth quarter of 2023.

Speaker Change: Expect to see continued broken bottles shipped to patients and quite extra hours a year.

First linear we expect to see continued strength in our bottles shipped to patients and cracks in the first quarter of 2024.

Speaker Change: I would highlight that we saw an increase in bottles remaining in our distribution channels.

Speaker Change: Third and fourth quarters of 2023 of 139 and <unk>.

Speaker Change: Nate bottles for top or east respectively.

Speaker Change: These increases we expect to see a drawdown of inventory levels in the first quarter of 2024 with a total lease and linear inventory levels levels are variable and outside of our control.

Speaker Change: Incrementally, we expect our gross to net adjustment in the first quarter of 2024 to be approximately 33% for top movies and approximately 27% for linear.

Dean L. Schorno: Our net product sales from Tavolese and Rizzolidia were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance, and other allowances of $12.3 million. For the fourth quarter of 2023, our gross-to-net adjustment for Tavolese and Rizzolidia was approximately 30.4% and 21.9% of gross product sales, respectively. Before we move on from net product sales, let me review our expectations for the first quarter of 2024. Let me start with Tavoli.

Speaker Change: Mainly as an important reminder, we do not expect to start recognizing revenue from that Brad or until the third quarter of 2000, and the third quarter of this year, we look forward to providing further updates as the year progresses.

Speaker Change: To the next slide.

Speaker Change: In addition to net product sales in the fourth quarter of 2023, our contract revenues from collaborations of approximately $6 $2 million and our government contract revenues were approximately $100000 contract revenues from collaboration consisted of approximately $1.1 million of royalty revenue.

Dean L. Schorno: Despite the typical first quarter reimbursement issues confronting our industry, such as the resetting of co-pays and the Medicare donut hole, we expect to see a small increase in bottle ship to patients and clinics in the first quarter of this year as compared to the fourth quarter of 2023. We expect to see continued growth in bottle ship to patients and clinics throughout the year. For Ms. Lydia, we expect to see continued strength in our bottle shift to patients and clinics in the first quarter of 2024. I would highlight that we saw increases in bottles remaining in our distribution channels at the end of the third and fourth quarters of 2023 of 139 and 208 bottles for Tavois, respectively. Given these increases, we expect to see a drawdown of these inventory levels in the first quarter of 2024. However, both the Tavalis and Reslydia inventory levels are volatile and outside of our control.

Speaker Change: <unk> made $5 $1 million from periodic drug supply purchases from our international distribution partners.

Speaker Change: Moving on to costs and expenses, our cost of products sales rose approximately $3 $8 million for the fourth quarter of 2023.

Speaker Change: Total costs and expenses were $33 $8 million in the fourth quarter of 2023, compared with $49 $2 million in the same period in 2022.

Speaker Change: Decrease in costs and expenses was partly due to decreased research and development costs due to the timing of trial completion activities related to the phase III clinical trials of fast about nib and patients with COVID-19, and warm autoimmune hemolytic anemia, as well as the timing of trial activities related to our Iraq <unk> four inhibitor.

Speaker Change: Programs. In addition, the decrease was also due to lower facility related costs and a milestone payment to form a therapeutics recorded an in process R&D included within cost and expenses in the fourth quarter 2022.

Dean L. Schorno: Incrementally, we expect our growth to net adjustment in the first quarter of 2024 to be approximately 33% for Tavolis and approximately 27% for Izolidia. Finally, as an important reminder, we do not expect to start recognizing revenue from Gabretto until the third quarter of this year. We look forward to providing further updates as the year progresses. Moving on to the next slide.

Speaker Change: As we move into 2024, we currently expect our total costs and expenses for the full year of 2024 to increase by a typical annual increases in compensation and other business costs, along with increases in our cost of goods sold as our business continues to expand incrementally we look forward to progressing.

Speaker Change: Our strategic collaboration with MD Anderson at connect and the very cost effective manner. We previously reported.

Dean L. Schorno: In addition to net product sales, in the fourth quarter of 2023, our contract revenues from collaborations were approximately $6.2 million, and our government contract revenues were approximately $100,000. Contract revenues from collaborations consisted of approximately $1.1 million of royalty revenue and approximately $5.1 million from periodic drug supply purchases from our international distribution partners. Moving on to cost and expenses, our cost of product sales was approximately $3.8 million for the fourth quarter of 2020.

Speaker Change: Incremental to this costs these costs.

Speaker Change: Plan to complete the transition of the cab rider asset to Rigel and expect to incur certain.

Speaker Change: Specifically as certain costs, specifically associated with this new product.

Speaker Change: We continue to review opportunities for this asset and related costs. We currently expect our SG&A costs, along with our clinical development costs, consisting of an expected drug interaction studies to be less than $10 million for 2024, we look forward to providing further updates in the future.

Speaker Change: Finally, we ended the fourth quarter of 2023 with cash cash equivalents and short term investments of $56 $9 million, we look to maintain our focus and disciplined financial approach into the future with that I'd like to turn the call back over to Ralph.

Dean L. Schorno: Total cost and expenses were $33.8 million in the fourth quarter of 2023, compared with $49.2 million in the same period of 2022. The decrease in cost and expenses was partly due to decreased research and development costs due to the timing of trial completion activities related to the Phase III clinical trials of fostamatinib in patients with COVID-19 and warm autoimmune hemolytic anemia, as well as the timing of trial activities related to our IRAC1.4 inhibitor. In addition, the decrease was also due to lower facility-related costs and a milestone payment to Forma Therapeutics, recorded as in-process R&D, included within costs and expenses in the fourth quarter of 2022. As we move into 2024, we currently expect our total costs and expenses for the full year of 2024 to increase by typical annual increases in compensation and other business costs, along with increases in our cost of goods sold as our business continues to expand.

Speaker Change: Judy.

Ralph: So we're very proud of the progress we've made in 2023 and in the early part of 'twenty, 'twenty, four and expanding our hematology and oncology business.

Ralph: As we look ahead for the remainder of 'twenty 'twenty, four where folks are focused on continuing to grow our sales of lithium until the lease.

Ralph: Broadening awareness and adoption of our prescriber base further.

Ralph: Further we are acutely focused on focused on transitioning grabbed that red oak to our commercial operations. We look forward to initiation of additional clinical studies alongside our partners M D Anderson and connect.

Ralph: And we will continue to evaluate other opportunities for expanding the development of our products and we will enroll and generated preliminary data from our phase wouldn't be in which weight died in low risk Mds.

Ralph: We are actively pursuing additional in license deals or acquisitions looking to do similar to our approach. We've used we've got brito and red lithium.

With the growth of our commercial products or.

Ralph: Cost efficient approach to clinical development and financial discipline, we remain focused on working towards financial breakeven, making rigel the source of stable company.

Speaker Change: With that I'd like to thank you for your interest in our progress in the fourth quarter and we will now open the call to your questions.

Dean L. Schorno: Incrementally, we look forward to progressing our strategic collaborations with MD Anderson and Connect in the very cost-effective manner that we've previously reported. Incremental to these costs, we plan to complete the transition of the Gabaretto asset to Rigel and expect to incur certain, www.yigalnochomovitz.com. Finally, we ended the fourth quarter of 2023 with cash, cash equivalents, and short-term investments of $56.9 million. We look to maintain our focus and disciplined financial approach into the future. With that, I'd like to turn the call back over to Raul. Raul

Speaker Change: Operator.

Speaker Change: Thank you.

Speaker Change: You would 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.

Speaker Change: You May press star two if he would like to remove your question from the queue.

Speaker Change: For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys.

Speaker Change: Enrollment please while we poll for questions.

Speaker Change: Okay.

Thank you. Our first question comes from the line of Yigal <unk> with Citigroup. Please proceed with your question.

Yigal: Oh, Hi, Raul and team. Thank you for taking the questions.

Yigal: I have coupons of Red Oak I understand that some of these approvals are currently accelerated approvals on and there were some post marketing requirements specifically for the <unk>.

Raul R. Rodriguez: Thank you, Dean. Now, we're very proud of the progress we made in 2023 and in the early part of 2024 in expanding our hematology and oncology business. As we look ahead towards the remainder of 2024, we're focused on continuing to grow our sales of Ritalinia and Tavalese by broadening the awareness and adoption of our prescriber base. In addition, we are keenly focused on transitioning Grabaretto into our commercial operation.

The ret fusion positive thyroid cancer, there was the arrow trial in the Tampa St trial, there were some additional data that the FDA was expecting and then for ret fusion lung cancer I believe there was some additional work being done with the accelerate lung trial can you just provide any up.

Yigal: States as to what the status of those studies are and whether they're continuing or whether you need them anymore.

Speaker Change: Longer thank you.

Speaker Change: Thank you Hugo I, Oh, that's a S Watson answer at all but a lot of them at the end.

Speaker Change: Yeah, So I can't be really to be definitive date on the accelerate study ended up history says you know what I'm, saying right is the randomized open label controlled phase III study of <unk> versus kind of careful in first line treatment of fusion first human testing on sports Center concept and that'd be street, the non randomized open label.

Raul R. Rodriguez: We look forward to initiating additional holistic clinical studies alongside our partners, MD Anderson and Connect, and we will continue to evaluate other opportunities for expanding the development of our products. And we will enroll and generate preliminary data from our Phase 1B study in 289 patients with low-risk MDS. We are actively pursuing additional in-license deals and acquisitions, looking to do similar to our approach we've used with Gabretto and Resilidio.

Speaker Change: Agnostic phase II platform trials that doors in water, but he didn't warrant exchange and fisheries suite, you mind thyroid cancer. So given blueprint medicines lack of Bluebird is trial and fostering a true the company has decided to discontinue global development and wind done wind down activities and she basically to begin in the first quartile.

Raul R. Rodriguez: With the growth of our commercial products, a cost-efficient approach to clinical development, and financial discipline, we remain focused on working towards financial break-even and making Rigel a self-sustaining company. With that, I'd like to thank you for your interest in our progress in the fourth quarter, and we will now open the call to your questions. Operator.

Speaker Change: 'twenty 'twenty, four and that's saying actually I mean, both studies actually the history and you know like I said it might actually learn a rideshare, we'd be looking at analyzing the data when available.

Speaker Change: Maybe I add in the non small cell lung cancer in the U S. We have a full approval and the requirements are a drug drug interaction studies. So some minor work.

Speaker Change: Celebrate the study was not necessary for U S approval or maintenance of U S approval since we have a full approval in thyroid cancer. It was conditional as you've noted and we are in discussions with FDA in terms of maintaining that Ah indication of what's going to be necessary for that we'll be sharing that wouldn't be up some.

Unknown Executive: Thank you. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue.

Unknown Executive: You may press star 2 if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. One moment, please, while we poll for questions. Thank you. Our first question comes from the line of Yigal Nochomovitz with Citigroup. Please proceed with your question. Hi, Raul and team. Thank you for taking the questions. I have a few on Govretto.

Speaker Change: Loses to that those discussions.

Speaker Change:

Speaker Change: Okay. Thanks, and then could you just expand a little bit with respect to the synergies on the existing sales infrastructure, both on the reps as well as the medical affairs, given that you're extending into the solid tumor world.

Yigal Dov Nochomovitz: I understand that some of these approvals are currently accelerated approvals, and there were some post-marketing requirements specifically for RETFusion positive thyroid cancer. There was the ARROW trial and the Tapestry trial. There were some additional data that the FDA was expecting. And then for RETFusion lung cancer, I believe there was some additional work being done with the AccelerRET lung trial. Can you just provide any updates as to what the status of those studies is and whether they are continuing or whether you need them anymore or no longer do? Thank you, Yigal. I'll ask Francois to answer, and I'll pile on at the end.

Speaker Change: Beyond beyond the hematology, a world where do you see the synergies with the current infrastructure for Gov retro.

Speaker Change: Thank you David sure absolutely I'd love to answer that question do you call them first of all you know just from an experience standpoint on our team.

David: If we looked at our field team and there's 80% of them have solid tumor experience and there's 80%. The experience level is nearly 10 years in solid tumors. So we have extraordinary experience on our field team and then if you look at lung more than half of our team had lung cancer experience with an average in there.

Francois DiTrupani: Yes, I can give a little bit of an update on the ACCELERATE study and TAPIST-3. As you know, ACCELERATE is a randomized, open-label, controlled, phase-3 study of paracetamol versus standard of care for first-line treatment of white fusion-positive hematocytic non-sport salient cancer. And TAPIST-3 is the non-randomized, open-label, agnostic phase-2 platform trial that does enroll, actually, I mean, or that did enroll, actually, in patients with solid tumor and thyroid cancer. So, given Blueprint Medicine's lack of global infrastructure, the company has decided to discontinue global development and wind down activities anticipated to begin in the first quarter of 2024. That said, actually, I mean, for both studies, actually, TAPIST-3 and, you know, ACCELERATE actually learned, RIGEL will be looking at and analyzing the data when available. Let me add, for non-small cell lung cancer in the U.S., we have full approval, and the only requirements are a drug-drug interaction study, so some minor work. The accelerated study was not necessary for U.S. approval or maintenance of U.S. approval since we have full approval.

David: Half of.

David: The field team, which includes medical affairs.

David: Of about four and a half years. So we want to exploit that experienced very strongly because they're calling on the same accounts and I'm I'm I want to make sure everybody understands that you know they're in the community oncology setting.

David: <unk> treat them docs treat a.

David: Lung cancer or quite a bit and so now we have a product. We can go in in a large tumor type, albeit with a very targeted aged but have have a discussion about a product that's very very relevant to their practice. Each day and then of course, we will have the opportunity to talk about top lease at Wrestlemania too with this AML treaters.

David: In the academic centers.

David: We obviously will need to call on lung specific treaters in those academic centers, but that what makes it. So efficient is we're already in those centers and so you know sending a one of our at institutional reps into an app.

David: That makes center with one product is not as efficient and sending them in to cover two departments with two products and so those are some of the synergies from a field execution standpoint, but I will say you know we have invested a lot of our resources in making sure we have a really great access.

Raul R. Rodriguez: In thyroid cancer, it was conditional, as you noted, and we are in discussions with FDA in terms of maintaining that indication and what's going to be necessary for that, and we'll be sharing that when we have some conclusions from those discussions. Okay, thanks. And then can you just expand a little bit with respect to the synergies on the existing sales infrastructure, both for the reps as well as for the medical affairs, given that you're expanding into the solid tumor world beyond the hematology world? Where do you see the synergies with the current infrastructure for Govretta? Thank you. David?

David: Services for patients and providers and the more we can put it into our distribution network and leverage our what rigel, one care our patient services hub, the better will be for that in that synergy I think it is something we really plan to.

David: Capitalize that leverage as we move into this market.

Speaker Change: Got it thank you very much.

Speaker Change: Thank you Joe.

David A. Santos: Sure, absolutely. I'd love to answer that question, Yigal. First of all, you know, just from an experience standpoint on our team, if we looked at our field team, 80% of them have solid tumor experience, and of those 80%, the experience level is nearly 10 years for solid tumors. So we have extraordinary experience on our field team. And then if you look at lung cancer, more than half of our team has lung cancer experience, with an average in that half of the field team, which includes medical affairs, of about four and a half years.

Speaker Change: Thank you. Our next question comes from the line of Kristine <unk> with Cantor Fitzgerald. Please proceed with your question.

Kristine: Hi, everyone good afternoon, and congrats on it.

Very good for your portfolio.

Kristine: I wanted to comment on some of your drivers for growth one of the.

Kristine: Barriers you said.

Kristine: And every equity with other drugs, so I I know.

Speaker Change: That's helpful.

Speaker Change: Does that impact how big.

Speaker Change: Uh huh.

Speaker Change: A lot of their adoption.

David A. Santos: So we want to exploit that experience very strongly because they're calling on the same accounts. And I want to make sure everybody understands that, you know, they're in the community oncology setting, and doctors treat lung cancer quite a bit. And so now we have a product we can go in with a large tumor type, albeit with a very targeted agent, but have a discussion about a product that's very, very relevant to their practice each day. And then, of course, we'll have the opportunity to talk about Tavalese and Reslevia-2 with those AML treatments. In the academic centers, we obviously will need to call on lung-specific treaters in those academic centers, but what makes it so efficient is we're already in those centers. And so, you know, sending one of our institutional reps into an academic center with one product is not as efficient as sending them in to cover two departments with two products.

Speaker Change: And then on that no.

What would you believe your stock.

Speaker Change: Oh wait.

Speaker Change: Alright.

Speaker Change: But the other job.

Speaker Change: I'll ask Dave to comment on that sure absolutely Christine I I think you know when when you look at that barrier, we look at that as a great opportunity for us.

Speaker Change: Genentech.

Dave: And blueprint did a great job along with other companies in the AR targeted space in lung cancer, raising awareness of testing raising awareness of that when you do have a biomarker with an actionable.

Dave: Drugs that are in actual biomarker with an FDA approved product you should be moving there and that's what all the experts are saying over and over yet a pretty significant portion still like to stay with that chemotherapy with or without a checkpoint inhibitor and use other products and so you know we do.

David A. Santos: And so those are some of the synergies from a field execution standpoint, but I will say, you know, we have invested a lot of resources in making sure we have really great access services for patients and providers, and the more we can put into our distribution network and leverage our Rigel OneCare patient services hub, the better we'll be for that. And that synergy, I think, is something we really plan to capitalize on and leverage as we move into this part of the program. I got it.

You that its an opportunity. We think this market is continuing to move towards more testing more identification of these biomarkers and and more.

Dave: Use of targeted agents versus chemotherapy and checkpoint inhibitors in the first line and that's what why we think it's an efficient call for US you know we will we were actually quite glad that this product has been on the market along with other targeted therapies as you know in K Ras.

Kristen Brianne Kluska: Thank you very much. Thank you, Yigal. Thank you. Our next question comes from the line of Kristen Kluska with Cancer Fitzgerald. Please proceed with your question. Hi everyone.

Dave: That's now a you know a big discussion topic, among clinicians who treat a lung cancer all of this noise out there just it requires us to focus they've message on red Oak and the more people hear about Caporetto I think the more usage will get and we believe we can get our fair share.

Kristen Brianne Kluska: Good afternoon and congratulations on this acquisition. Very good for your portfolio. So I wanted to comment on some of your key drivers for growth. One of the barriers for usage you noted was discomfort and familiarity with other drugs. So I know Blueprint has had some experience here with Genentech. Have they seen, are a lot of their adoptions naive, or is it switched?

Dave: The ret inhibitor space.

David A. Santos: And then on that note, I guess what you believe your team is going to do to help switch some of these patients in light of their familiarity with other drugs? I'll ask Dave to comment on that. Sure, absolutely, Christine.

Dave: So you know.

Dave: That's why we believe it's a great opportunity for us.

Dave: <unk> just being a smaller company, we have the ability to focus on it.

Dave: And.

Dave: It'll be something that we are you know are very important to us.

David A. Santos: I think, you know, when you look at that barrier, we look at that as a great opportunity for us. Genentech and Blueprint did a great job, along with other companies in the targeted space in lung cancer, raising awareness of testing, and raising awareness that when you do have a biomarker with an actionable drug, or an actionable biomarker with an FDA-approved product, you should be moving there. And that's what all the experts are saying over and over.

Dave: Not saying that it's not important to those other companies, but but obviously, we think it could be a driver for us and so.

Dave: That's why we believe you know.

Dave: With the right direction, and the right tools and and you know a really smart investment in this place we can grow with the market.

Speaker Change: Thanks, So much and then on top of it can you comment on how you're seeing the breakdown between the different lines. There because I know 2023 was a record year for you. When you say part of that was driven by the earlier lines and.

David A. Santos: Yet, a pretty significant portion still like to stay with chemotherapy with or without a checkpoint inhibitor and use other products. And so, you know, we view that as an opportunity. We think this market is continuing to move toward more testing, more identification of these biomarkers, and more use of targeted agents versus chemotherapy and checkpoint inhibitors in the first line. And that's why we think it's an efficient call for us. You know, we're actually quite glad that this product has been on the market, along with other targeted therapies, as you know, in KRAS. That's now, you know, a big discussion topic among clinicians who treat lung cancer. All of this noise out there just requires us to focus the message on Gavretto.

And greater.

Speaker Change: Thanks again.

Speaker Change: Yeah. Thanks for that question actually seen we we M. We have updated our data that we shared from Roger one care and it's pretty similar I will say that in Q4, we had a little bit more business in the second and third line setting that we did that we shared.

Speaker Change: Previously with you. So I think that's moving in the right direction, where we're continuing to focus on patients.

Speaker Change: You know who are post steroids or post just won a tipo agents and I think it's working more and more clinicians continue to use probably.

Speaker Change: The good thing about those earlier lines as the response rates are better and response positive responses. It leads to a greater desire to use the product yet again, so that's actually.

David A. Santos: And the more people hear about Gavretto, I think the more usage we'll get, and we believe we can get our fair share of the RET inhibitor space. So, you know, that's why we believe it's a great opportunity for us. Just being a smaller company, we have the ability to focus on it. And it'll be something that is very important to us. Not saying that it's not important to those other companies, but obviously, we think it could be a driver for us. And so that's why we believe, you know, with the right direction, the right tools, and, you know, a really smart investment in this place, we can grow with the market. Thanks so much.

Speaker Change: In a virtuous circle there.

Yeah.

Speaker Change: Thank you Christian.

Speaker Change: Thank you.

Speaker Change: Our next question comes from the line of Cal P Patel with B Riley Securities. Please proceed with your question.

Speaker Change: Good afternoon, thanks for taking the question.

Speaker Change: Maybe one question on.

Brightcove.

Speaker Change: Nation today in the real World do.

Speaker Change: Do we have any color on where the utilization is it mostly a treatment naive patients.

Speaker Change: Or is it is it mostly in previously treated patients for lung cancer and how do you anticipate that they want to shift over time.

Kristen Brianne Kluska: And then on Tavaleve, can you comment on how you're seeing the breakdown between different lines of therapy? I know 2023 was a record year for you; would you say part of that was driven by some earlier line usage and greater compliance as a result of that? Thanks again.

Speaker Change: You know we have uses in both cap. It we you know at least in the market research we previewed.

Speaker Change: There is huge in the first line as I showed you in the data, but there's also usage in second life.

David A. Santos: Yeah, thanks for that question, Christine. We have updated our data that we shared from Miragea OneCare, and it's pretty similar. I will say that in Q4, we had a little bit more business in the second and third line setting than we did in the first line setting, which we shared previously with you, so I think that's moving in the right direction. We're continuing to focus on patients, you know, who are post-steroids or post just one TIPO agent, and I think it's working. More and more clinicians continue to use Tavalease.

Speaker Change: We do know that patients don't generally get two ret inhibitors. They get one and then you know if you start on our ret inhibitor and the frontline you'll move to chemotherapy in the second.

Speaker Change: With or without an immune checkpoint inhibitor or vice versa, and so, but obviously with some patient drop out as you move from first slide the second life, it's critical that patients get treated at the earliest opportunity and so that's our focus there is use in later lines, but where.

David A. Santos: The good thing about those earlier lines is that response rates are better, and positive responses lead to a greater desire to use the product yet again, so that's actually a virtuous circle there. Thank you. Thank you, Kristen.

We're much more focused on looking at what our opportunity is through the first mindset.

Speaker Change: Okay got it and can you maybe help us understand the gap between.

Kalpit R. Patel: Thank you. Our next question comes from the line of Kalpit Patel with Be Riley Securities. Please proceed with your question. Good afternoon.

The sale of your drug versus together ret inhibitor.

Speaker Change: It looks like they were both perhaps launched around the same time, but the sales of.

Kalpit R. Patel: Thanks for taking the questions. Maybe one question on Gavrilo's utilization today in the real world. Do we have any color on where the utilization is? Is it mostly treatment naive patients? Or is it mostly in previously treated patients for lung cancer?

Speaker Change: The competitor have kind of taken off.

Speaker Change: So at least relative to yours.

Speaker Change: Yeah, I'll make a few comments on that cap. It. The first thing is is Ah you know.

Speaker Change: <unk> was launched second to market and I think you know as I said.

David A. Santos: And how do you anticipate that to shift over time? You know, we have uses for both CalPIT and RP. We, you know, at least in the market research we've reviewed, there is use in the first line, as I showed you in the data, but there's also usage in the second line. We do know that patients don't generally get two RET inhibitors; they get one. And then, you know, if you start on an RET inhibitor in the front line, you'll move to chemotherapy in the second phase, with or without an immune checkpoint inhibitor, or vice versa.

Speaker Change: Said comfort and familiarity in this place means a lot and second to market Ah Ah is is a more challenging situation and that's part of it and it's not only taking it to market.

Speaker Change:

Speaker Change: With approval, it's been second market with data as well as subsequent to that and so you know I think clinicians just generally think first the first product. They came to market and are very comfortable and familiarity are there and familiar with it and to you know I think that's.

David A. Santos: And so, but obviously, with some patient dropout as you move from first line to second line, it's critical that patients get treated at the earliest opportunity. And so that's our focus. There is use in later lines, but we're much more focused on looking at what our opportunity is in the first line.

Speaker Change: Just an awareness issue that will continue to assess and pursue but you know I think more importantly for US. We are focused on the we are very focused on the patients who are not getting our ret inhibitor and the first one.

Kalpit R. Patel: Okay, got it. And can you maybe help us understand the gap between, you know, the sales of your drug versus the other inhibitor? It looks like they were both perhaps launched around the same time, but the sales of the competitor have taken off significantly, so at least relative to yours.

Speaker Change: Because we think that's where we can make a difference in discussing with clinicians are the advantages of a ret inhibitor, particularly.

Speaker Change: And specifically get read out.

David A. Santos: Yeah, I'll make a few comments on that, Kalpit. The first thing is, is, you know, Gevretto was launched second to market, and I think, you know, as I said, comfort and familiarity in this place means a lot, and second to market is a more challenging situation, and that's part of it. And it's not only second to market with approval, it's been second to market with data as well, subsequent to that. And so, you know, I think clinicians just generally think first of the first product that came to market and are very comfortable and familiar with it, and so, you know, I think that's just an awareness issue that we'll continue to assess and pursue, but, you know, I think more importantly for us, we are focused on the, we are very focused on the patients who are not getting a Rett inhibitor in the first line, because we think that's where we can make a difference in discussing with clinicians the advantages of a Rett inhibitor, particularly, and specifically, Gevretto.

Speaker Change: They have come up with is that as Dave said in his presentation relative mission is touching breaks are high awareness of red and the importance of it as treatment is high and so now we have to introduce this product and its data to have it be a choice for these doctors and many doctors are non users of Caribbean, 80%. So there's a lot of opportunity there.

Speaker Change: To grow this brand.

Okay got it and one last question and apologies if you already mentioned that sort of thing.

Speaker Change: How much of an SG&A change should we expect I know you said, there's some overlap in there.

Speaker Change: The community centers, where you can maybe cross selling your products Hum, but what about any increases in.

Speaker Change: Reps for academic centers.

Yeah. So you know well, we're looking at that still and as Dave said on the community side, we're already seeing that most of these doctors already on the institutional side, we're still evaluating that the institutional side, there's different individuals' would treat lung cancer versus AML. For example, so that's something that the revaluation there may be some ads.

David A. Santos: The good thing about CALPIT is that, as Dave said in his presentation, Rett inhibition is, testing rates are high, awareness of Rett and the importance of it as treatment is high, and so now we have to introduce this product and its data to have it be a choice for these doctors, and many doctors are non-users of Grevetto, 80%, so there's a lot of opportunity there to grow this brand.

Speaker Change: Throughout the organization now with brief products relative to one not that long ago. So there will be some increases and some head counts across the board a bit but not very many frankly, we expect it to be minor in terms of those additions and an all in we expect the incremental debt red oak costs.

Raul R. Rodriguez: Okay, got it. And one last question, and apologies if you already mentioned this earlier, but how much of a SG&A change should we expect? I know you said that there's some overlap in the community centers where you can maybe cross-sell your products.

Speaker Change: For SG&A, along with critical development of the drug interaction study, they're all referred to to be less than $10 million for 2024 on top of it.

Speaker Change: Okay perfect. Thank you very much for taking the question.

Kalpit R. Patel: But what about any increases in reps for academic centers? Yeah, so, you know, we'll, we're looking at that still. And as Dave said, on the community side, we're already seeing most of these doctors already. On the institutional side, we're still evaluating that. On the institutional side, there are different individuals who treat lung cancer versus AML, for example.

Speaker Change: Thank you Kelvin.

Speaker Change: Thank you there are no further questions at this time I'd like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Raul R. Rodriguez: Thank you for your questions and your interest in Rigel. This past year in 'twenty, three and the start of 'twenty four it's been an exciting year and exciting start to 2024, we look forward to continue to keep you updated on our progress I think it's going to be our best year, yet and look forward to sharing that with you take care.

David A. Santos: So that's something under evaluation. And there may be some ads just throughout the organization now with three products relative to one not that long ago. So there will be some increases in some headcounts across the board a bit. But not very many, frankly; we expect them to be minor in terms of those additions, for SG&A along with clinical development of the drug interaction study that Raul referred to, to be less than $10 million for 2024 CalPERS.

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

Speaker Change: [music].

Kalpit R. Patel: Okay, perfect. Thank you very much for taking the question. Thank you, Kalpit. Thank you. There are no further questions at this time. I'd like to turn the floor back over to Mr. Raul Rodriguez for closing comments.

Raul R. Rodriguez: Thank you for your questions and your interest in Rigel this past year, 2003 and the start of 2024. It's been an exciting year and an exciting start to 2024. We look forward to continuing to keep you updated on our progress. I think it's going to be our best year yet and look forward to sharing that with you.

Unknown Executive: Take care. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation. The Bulletproof Executive 2013, BF-WATCH TV 2021, BF-WATCH TV 2021 BF-WATCH TV 2021 BF-WATCH TV 2021