Greetings, and welcome to Rigel Pharmaceuticals Financial Conference Call for the fourth quarter and year end 2022. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce your first speaker, Raymond Furey, Rigel's Executive Vice President, General Counsel, and Corporate Secretary. Thank you. You may begin. Hello. Welcome to our fourth quarter and year-end 2022 financial results and business update conference call. The financial press release for the fourth quarter and year-end 2022 was issued a short while ago and can be viewed along with the slides for this presentation in the News & Events section of our investor relations site on rigel.com. As a reminder, during today's call, we may make forward-looking statements regarding our financial outlook and our plans and timing for regulatory and product development. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent annual report on Form 10-K for the year ended December 31st, 2022 on file with the SEC. Any forward-looking statements are made only as of today's date. We undertake no obligation to update these forward-looking statements to reflect subsequent events or circumstances. At this time, I would like to turn the call over to our President and Chief Executive Officer, Raul Rodriguez. Raul. Thank you, Ray. Welcome to the team. Thank you everyone for joining today. Also with me today are Dave Santos, our Chief Commercial Officer, Dr. Wolfgang Dummer, our Chief Medical Officer, and Dean Schorno, our Chief Financial Officer. Beginning on slide 5. We are thrilled with the progress we made in growing our hematology oncology business in 2022, and we look forward to continuing this momentum in 2023. We are committed to driving sales growth for our first approved product, TAVALISSE in ITP. In the fourth quarter, we achieved our highest quarterly net product sales to date. Alongside our international partners, we are focusing on making sure TAVALISSE is available for adult patients with chronic ITP across the globe. Our partner, Kissei, recently took an important step towards achieving this goal with Japan's PMDA approval of TAVALISSE. We congratulate them on this achievement. In December 2022, our commercial business was transformed with the approval and launch of our second product, REZLIDHIA, for the treatment of relapsed or refractory acute myeloid leukemia. REZLIDHIA is an important treatment option for patients with relapsed or refractory AML, and we are keenly focused on the execution on the commercial launch. With two approved products, our robust hem-onc sales team and a highly experienced marketing and operations team, we are in a strong position to drive sales for both TAVALISSE and REZLIDHIA. Beyond our commercial focus, we are committed to growing our business through internal development programs, partnered programs, and in-licensed opportunities. Our IRAK1/4 R2 inhibitor, R289, continues to progress in a phase 1b study in patients with lower risk MDS. We are pleased to report that we have completed enrollment in the first cohort of this study. Additionally, we continue to evaluate fostamatinib and olutasidenib for follow-on opportunities beyond their currently approved indications. Alongside our partner, Eli Lilly, we are advancing R552, a RIPK1 inhibitor. We look forward to initiation of a phase IIA study in rheumatoid arthritis in the first half of 2023. Our colleagues at NIH are also continuing to evaluate fostamatinib in COVID-19 in the ACTIV-4 phase III clinical trial. Moving on to slide 6. I wanna spend some time talking about the important achievements we've garnered as we expanded our hematology oncology portfolio with REZLIDHIA. In just a few short months, we've went from announcing a license agreement with Forma Therapeutics to the FDA approval, then the launch of REZLIDHIA. Our ability to navigate this quick turnaround is a testament to our business development, commercial, and medical affairs teams, as well as Rigel's commitment to patients in this as a hem-onc company. On announcing the deal in August, our team began to working diligently to prepare for the commercialization of REZLIDHIA, and I am proud to say that despite the early approval in December, we were ready to execute on our critical priorities for launch. Shortly after the approval, we had the opportunity to engage and educate the medical community at the 2022 ASH meeting. We were able to share new longer-term data from the registrational phase II study of REZLIDHIA in relapse or refractory AML, highlighting its durable efficacy and well-characterized safety profile. In December, REZLIDHIA was made available in the U.S. by prescription and since then has been added to the NCCN guidelines for AML and highlighted in Blood Advances with the publication of the phase II registrational study. While pleased with the success we've had so far, we are focused on continuing execution of the REZLIDHIA commercial launch. With that, I'll turn the call over to Dave for an overview of the quarter. Dave? Thank you, Raul. Now, I'd like to take a few minutes to discuss our progress with REZLIDHIA in the first three months of launch, and then transition to our continued growth of TAVALISSE during our record Q4. On slide 8, you will see our FDA-approved indication, which is for adult patients with relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation as detected by an FDA-approved test. Moving to slide 9, the American Cancer Society estimates that more than 20,000 patients will be diagnosed with AML in 2023, and unfortunately, about 11,300 patients will die from the disease this year. In terms of the eligible relapsed or refractory IDH1-positive AML patients, our research showed that up to 60% of fit patients progress in two years, and for unfit patients, most are refractory or relapse within two years. With 6%-9% of patients IDH1 positive, that gives us a near-term opportunity to impact the lives of around 1,000 new mutant IDH1 patients in the relapsed or refractory AML setting each year. On slide 10, we believe REZLIDHIA has the potential to address many key patient and HCP needs in the relapsed refractory AML space. It is a promising new treatment targeting mutant IDH1 that has shown impressive durable responses in patients who have failed previous therapies. As more clinicians review the demographics of our relapsed refractory patient population in our pivotal cohort and put that together with a complete response rate of 32%, a CRCRH rate of 35%, and especially the median duration of CRCRH of longer than two years, they see the value of an agent like REZLIDHIA in their treatment armamentarium. Combining that efficacy with a well-characterized safety profile without the requirement for cardiac monitoring, it becomes even more compelling to adopt REZLIDHIA in their mutant IDH1 relapsed refractory AML patients. Overall, we continue to see exciting potential to become a market-leading treatment in mutant IDH1 relapsed refractory AML and are looking forward to continuing to execute the launch plan. Moving to slide 11, our commercial and medical affairs teams have done a great job executing our launch plans to quickly raise awareness among leukemia treaters, ensure quick product availability and access for patients, accelerate launch momentum through the publication of critically important third-party references, and continue educating our field team to hone our REZLIDHIA messaging. Immediately upon approval on December 1st, our website was up, and within the first few days of launch, we had several marketing and patient access materials available to customers online and through our field teams. It was perfect timing as our team was at the 64th annual American Society of Hematology meeting a week later on December 9th, with our booth prominently announcing approval and team members interacting with important customers who were in attendance. On December 22nd, just over a week after ASH ended, our team worked closely together to have product available to stock our distribution network before year-end. Finally, we were extremely pleased that over the holidays on December 30th, our distribution network shipped out our first 2 bottles to an account for an AML patient. It was a meaningful way for us to end 2022. On slide 12, you will see that we continued to make strong progress on the medical affairs front as we moved into the new year. On January 13th, we were delighted that the NCCN Clinical Practice Guidelines for AML were updated to include olutasidenib as a recommended targeted therapy for relapsed refractory disease with an IDH1 mutation. This quick, unanimous decision by this recognized panel of experts is critically important for formulary and prescribing decisions by payers, GPOs, and other key accounts and prescribers. We will continue to highlight this important recommendation in our messaging. Also in January, we were pleased to confirm coverage through our first paid claims for REZLIDHIA patients. We continued to work with key payer and GPO accounts as well as individual prescribers to ensure that they have everything they need to minimize any reimbursement hurdles and maximize patient access to REZLIDHIA. Last month, our launch momentum continued with the February first online publication in Blood Advances of the data from our pivotal phase II cohort entitled Olutasidenib Induces Durable Complete Remissions in Patients with Relapsed or Refractory IDH1 Mutated AML. The conclusion states that olutasidenib monotherapy induced durable remissions and transfusion independence among patients with relapsed or refractory mutant IDH1 AML with a well-characterized and manageable safety profile. The observed efficacy is clinically meaningful and represents a therapeutic advance in this molecularly defined patient population with a poor prognosis and limited treatment options. This publication, which will soon appear in print in a well-known and respected peer-reviewed journal, is another highly credible third-party reference for REZLIDHIA that will be important for years to come. Finally, just a few weeks ago, our entire commercial and medical affairs team met in person for our annual meeting. We had a highly productive meeting and continued to build on the team's foundational knowledge established upon approval. Our team left that meeting more prepared than ever to continue spreading awareness of REZLIDHIA and accelerate uptake as we move into our next phase of launch. I look forward to providing updates as we continue our REZLIDHIA launch journey. On to growing sales of TAVALISSE in ITP. I have a few brief comments on our TAVALISSE progress in Q4. On slide 14, you will see our FDA-approved indication, which is for adult patients with chronic immune thrombocytopenia, or CITP, who've had an insufficient response to a previous treatment. Moving to slide 15, I am thrilled to announce that we had our best TAVALISSE quarter ever in Q4, shipping 2,196 bottles to patients in clinics, representing 23% growth over Q4 of last year. This robust growth was again driven by more new patients starting TAVALISSE. I am happy to report that we had more new patient starts in 2022 than any other year since launch. For Q4, we achieved net sales of $21.9 million, representing a 25% increase or $4.3 million more than the same quarter last year. We are extremely pleased with how we ended 2022 and the solid year-over-year growth we are seeing in ITP sales. We will continue to focus on targeted clinicians to identify appropriate patients that can benefit from TAVALISSE to grow our new patient starts beyond the record levels we saw in 2022. Finally, on slide 16, I wanted to update you on how we are continuing to expand access for patients globally with TAVALISSE. In December, Kissei, our partner in Japan, announced PMDA approval for TAVALISSE for the treatment of chronic ITP. Rigel earned $20 million in a regulatory milestone with the approval. We remain committed to continuing to impact CITP patients around the globe with continued expansion of TAVALISSE's commercial footprint through our partners. Thanks for your attention, I will now turn the call over to Wolfgang to provide a brief update on our development progress. Wolfgang? Thank you, Dave. I will briefly summarize our other programs. Slide 18, let me start with lower risk MDS. Our phase IB study evaluating R289, Rigel's IRAK1/4 dual inhibitor in lower risk MDS, has completed enrolling the first cohort and has now dose escalated to enroll patients into the next cohort. So far, the drug was well-tolerated, and no adverse events of concern have been seen. As you recall, the study uses a 3x3 dose escalation design to establish the maximally tolerated dose before expanding a dose level to patients to obtain additional safety data as well as preliminary efficacy information. We believe R289 may represent a promising new approach to treating patients with lower risk MDS and look forward to investigating R289 further in this study. On slide 19, you can see the overview of our ongoing programs. As Raul mentioned, we are primarily focused on growing our hem-onc business. That starts with our internal development programs. I just took you through the progress with R289 in lower risk MDS on the previous slide. We're also evaluating other opportunities for fostamatinib and olutasidenib, building on their regulatory success. This includes evaluating ex-US partners to bring REZLIDHIA to AML patients around the globe. I'd also like to remind everyone that the phase II clinical trial of olutasidenib includes additional cohorts beyond the registrational relapsed or refractory AML cohort, and we look forward to continued analysis and applications from this trial. Supplementing these internal development efforts, we continually evaluate potential new assets to in-license that can leverage our hem-onc capabilities. More opportunistically, we continue to work with Eli Lilly to advance our R552, our RIP kinase inhibitor, towards a phase 2 study in rheumatoid arthritis and with the NIH as they continue enrollment in the ACTIV-4 phase 3 study evaluating fostamatinib as a treatment for COVID-19. That concludes my development summary, and I will turn the call over to Dean. Dean? Thank you, Wolfgang. I'm on slide 21. For the fourth quarter of 2022, we shipped 2,417 bottles of TAVALISSE to our specialty distributors, resulting in $31.5 million of gross product sales. 2,196 of those bottles were shipped to patients in clinics, while 221 bottles increased the levels remaining in our distribution channels at the end of the quarter. Following our commercial launch of REZLIDHIA on December 22, 2022, we shipped 64 bottles of REZLIDHIA to our specialty distributors, resulting in $1 million of gross product sales. 2 bottles of REZLIDHIA were shipped to patients and clinics, while 62 bottles remained in our distribution channels at the end of the quarter. We reported net product sales from TAVALISSE of $21.9 million in the fourth quarter of 2022, a 25% increase compared to the same period in 2021. We reported net product sales from REZLIDHIA of $900,000 in the fourth quarter of 2022. Our net product sales from TAVALISSE and REZLIDHIA were recorded net of estimated discounts, chargebacks, rebates, returns, co-pay assistance, and other allowances of $9.7 million. For the fourth quarter of 2022, our gross to net adjustment was approximately 30% and 15% of gross product sales, respectively, for TAVALISSE and REZLIDHIA. Before we move on from net product sales, let me review our expectations for the first quarter of 2023. Let me start with TAVALISSE. 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 bottles shipped to patients and clinics in the first quarter of this year as compared to the fourth quarter of 2022. We expect to see continued growth in bottles shipped to patients and clinics throughout the year. For REZLIDHIA, and as you know, we are still only a couple of months into our launch. As Dave highlighted, we're encouraged by the initial interactions that our field team is having with physicians who treat patients with AML. With these interactions, and as awareness of REZLIDHIA increases, we expect to see increasing penetration into this new market for Rigel as we add new patients and as the year progresses. We look forward to providing more specific updates in the future as our launch progresses. Incrementally, we currently expect our gross to net adjustment for the first quarter of 2023 to be approximately 30% for TAVALISSE and approximately 15% for REZLIDHIA. On to the next slide. In addition to net product sales, our contract revenues from collaborations were $26.5 million, our government contract re-revenue was $2 million in the fourth quarter of 2022. Contract revenues from collaborations consisted of $20 million in revenue from Kissei related to a milestone payment earned upon Japan's PMDA approval of TAVALISSE for the treatment of chronic ITP, $5.7 million in non-cash revenue from their collaboration agreement with Medison, $600,000 in royalty revenue from Grifols, and $200,000 in revenue related to our license agreements with Lilly. Moving on to cost and expenses. Our cost of product sales was approximately $342,000 for the fourth quarter of 2022. Our cost of product sales for the quarter were inclusive of a 15% royalty on our REZLIDHIA net product sales. Total cost and expenses were $49.2 million in the fourth quarter of 2022 versus $41.8 million for the same period in 2021. This expected increase in cost and expenses was primarily due to personnel-related costs and commercial expenses, along with higher research and development costs related to the IRAK1/4 inhibitor program. As we look towards 2023, we currently expect our total cost and expenses for the full year of 2023 to be approximately $160 million. Finally, we ended the quarter with cash equivalents, and short-term investments of $58.2 million. With that, I'd like to turn the call back over to Raul. Raul? Thank you, Dean. As we reviewed on this call, 2022 was a transformational year for Rigel, and we believe that this positions us very well for a year of execution in 2023. Our commercial organization is focused on accelerating TAVALISSE sales with our expanded sales force and increasing interactions. For REZLIDHIA, we are continuing our commercial launch and prioritizing physician awareness and adoption, as well as identifying ex-U.S. collaborators. To supplement our commercial initiatives and business growth, we look forward to continued progress across our development and partnered programs while evaluating new external assets to leverage our hemo capabilities. We are very excited about this and about our commercial and clinical initiatives in 2023. On a final note, I'd like to take a moment to recognize that our CMO Wolfgang's last stay at Rigel will be March 31st. Wolfgang, on behalf of our team, I'd like to thank you for your service and contributions to Rigel. Currently, we are conducting a search for a new CMO with hematology-oncology experience. With that, I'd like to thank you for your interest in our progress in the fourth quarter and throughout 2022. Operator, if we could open up the call for questions. Thank you. Ladies and gentlemen, at this time, we'll be conducting a question and answer session. If you'd like to ask a question, you may press star one on your telephone keypad. Confirmation tone will indicate your line is in the question queue. You may press star two 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. Our first question comes from the line of Yigal Nochomovitz with Citi. Please proceed with your question. Hi, team. This is Carly on for Yigal. Thanks so much for taking our questions. We have a few on REZLIDHIA. I guess first, can you talk a bit about how concentrated the prescriber base is here? Obviously, it's still very early, but are you able to comment on how many unique prescribers have actually written a script so far? Carly, thank you so much. I'll ask Dave to comment. Yeah. Carly, on the second part of your question, we're not going to talk today because it's in Q1. As you know, those are results from Q1 that we'll share on our Q1 call. We won't share specifics on prescribers. I will say that, you know, as we've talked about, there are about 1,000 AML prescribers that we're calling on as targets. About half of those are consistent with our TAVALISSE targets, about half of those are leukemia treaters who really are specialized in leukemia. Those are the people that can be more difficult to access, it's been a little bit more difficult for us, you know, challenging, especially since we've only been at this now since December. You know, we're making progress, and, we're confident that we will continue to grow awareness in that group. Okay, great. That's helpful. You disclosed the 64 bottles shipped during the fourth quarter. I guess, can you just talk a bit about how we should be thinking about inventory stocking dynamics during the first quarter and the second quarter of 2023? Carly, I can take a stab at that and ask Dean or Dave to comment as well. The 64 quarters, all but two of those were into the inventory, into the channel. you know, we have a better sense now a couple of months beyond that in terms of that. Where that will stabilize, we don't really know yet. New institutions are ordering product, it's still too early to say something definitively in terms of what a stable or even trend in inventories may end up. We do know that there has been usage from that inventory, but the dynamics are still a little bit unknown given how early it is for us. Any comments, Dave or Dean? Yeah. The only thing I would say, Carly, is, you know, our distribution network is, we have an SP that ships directly to patients, and then we have distributors that ship to our accounts. We have seen orders go out from our entire distribution network. The distributors who are shipping to hospitals and as well, the SP that is shipping to patients. Just one detail as we launch REZLIDHIA, is that TAVALISSE, one month's supply is one bottle. For REZLIDHIA, two weeks' supply is one bottle. As we need to translate those 64 bottles into 32 months worth of treatment. Okay, got it. Just our last question is, I think in the past you've talked a little bit about the potential frontline AML opportunity for REZLIDHIA. Can you talk about where you stand with that and thoughts on potential timing for a registrational study? Thank you, Carly. You know, REZLIDHIA has tremendous opportunities. We think that it's shown some of the best data, the best data in IDH, relapse refractory setting. That gives us a molecule that I think has a lot of opportunity within it. We are working diligently in understanding where we'd like to go with it. We're looking at various segments, both of AML, there's quite a number of segments there that are potential opportunities, as well as some things outside of AML even, 'cause there's opportunities there as well. These decisions, you know, take a fair amount of interactions with KOLs, potential clinical, investigators, and the FDA. That effort, that body of effort is underway. Maybe I can speak a little bit about the timing, or maybe you could say a few things when we might be ready to say, Wolfgang. Yeah. I would say this is definitely one of our considerations. I can share with you, as I mentioned earlier, that we are analyzing other cohorts from the, from the first study. Both this patient population, target patient population as well as a population that has been experienced with Venclexta in the past, have shown very consistent efficacy numbers. I don't wanna give you the actual numbers today because we are fully analyzing it and then present it at appropriate scientific meetings. I do think we have options, and the option that you just brought up is one of several. Carly, the only other thing to add to that in terms of timing, later this year, for sure, we'll come back to you in terms of what we'd like to do next. Okay, perfect. Thank you so much for taking our questions. Thank you, Carly. Our next question comes from the line of Eun Yang with Jefferies. Please proceed with your question. Thank you very much. A couple of questions. At the end of last year, you had about $58 million in cash. Cash you burn for this year seems running higher than that. Can you talk about how you fund operations for this year and beyond? That's the number one question. Second question is now with the two products on the market, do you have some sense of when you would be able to reach profitability? My last question is, you mentioned looking into kind of evaluating other opportunities for fostamatinib. Can you talk about what other opportunities are you considering? Thank you. Thank you, Eun. Let me ask Dean to address the first two, your questions. Maybe I'll address the third. Sure. Hi, Eun. I'll address both of your questions I think together here. We ended 2022 with $58 million of cash, as you noted. Incrementally in January, we received $20 million from Kissei. We're comfortable with our current cash position in the business that we've discussed today. With respect to the path to profitability, we really do as a company, it's a priority for our business to achieve cash flow break even. As you've seen over the last year, we really have, you know, made some focused efforts on cost efficiencies and leverage as we establish the heme/onc business that we described today. We are reducing our operating expense from about $176 million in 2022, the numbers we just reported, down to what we expect to be about $160 million this year. I would note that over $10 million of the operating expenses I just described are non-cash. They're stock comp and depreciation. As we look forward with respect to getting to break even, we haven't given guidance on our top line, so we can't be specific on when we'll get to break even. As we look at our revenue growth over time, we just reported fourth quarter run rate results of about $90 million, $90 million plus, and that's fourth quarter run rate. And that's really almost exclusively TAVALISSE. We've got, you know, the week of REZLIDHIA sales in there. Incrementally, as we look at growth in that top line in 2023, we expect continued growth in TAVALISSE. We expect to now have the REZLIDHIA revenues, net revenues for the full year. As we've seen over time, we continue to expect collaboration revenues. Those can be collaboration revenues from our existing partners like Lilly, Kissei, Grifols. They can also be collaboration revenues from new opportunities. A couple of examples of new opportunities would be the ex-U.S. rights for olutasidenib, REZLIDHIA, as well as, you know, potential partnerships for our IRAK1/4 program that Wolfgang described. Haven't been specific on the time that we'll get to break even, but we're certainly focused on it and pleased with the progress we've made over the year as we set up and launch into 2023. Thanks, Dean. It's worth noting as Dean said in his comments, what we're seeing in TAVALISSE so far this quarter has been very positive. Usually, we see a downward draft because of Q1. We're seeing a small increase actually in patients, bottles shipped to patients in clinics. Just to remind you, last quarter, Q4, was our best quarter since launch. Given that we are seeing some growth on top of that, Q1, oddly, Q1 is always challenging. This Q1 will be our best quarter since launch, not our best quarter, first quarter, our best quarter since launch. That's a very positive sign and a testament to some of the expansion and focus from our commercial team in increasing TAVALISSE sales despite Q1 headwinds. Your third question, Yun, was other opportunities for fostamatinib. We're looking at other opportunities. As you may see in the press release, we put a little bit of information on opportunity in graft versus host. We haven't done thorough and final diligence on that as the opportunity, but it is there 'cause the data seems quite compelling. That's one thing we might consider with fostam. We have to look at the totality of where we wanna invest our clinical dollars, they're not infinite, they're limited, between olutasidenib and fostamatinib. We're gonna make those decisions and then come back to you later this year with what we'd like to launch in terms of registrational trials for these two drugs. Yeah. Can I ask you one quick follow-up? Are you thinking about revitalizing the warm autoimmune hemolytic anemia indication? Yeah. You know. For TAVALISSE. Thank you for that question. We've had interactions with FDA and what I think would be necessary in that is a de novo trial once again. It might be a little smaller than our prior trial, but maybe not substantially less than that. Given that and given, frankly, other opportunities that we have in front of us with both fostamatinib, but also now with olutasidenib, quite sizable opportunities that those probably would be the priority rather than warm autoimmune hemolytic anemia. Thank you. Thank you, Eun. Our next question comes from the line of Do Kim with Piper Sandler. Please proceed with your question. Hi. Thanks for taking my questions. I was hoping to get any initial feedback or sense of physician enthusiasm for REZLIDHIA and their willingness to use the drug. If you've seen any kind of pushback by docs, having a preference for Tibsovo for any reason, anything anecdotal? Dean? I could give you a lot of anecdotes, Do. I've actually just been out with customers as recently as yesterday. Just flew back this morning. At the end of the day, here's a couple things for you. First of all, when people truly understand this data and, you know, if you look at the Blood Advances publication, things are in there that we haven't even begun to talk about commercially yet, which is the survival data. You know, if you look at the survival data of the responders. You see what the CRCRH responders do in terms of survival, that that's not yet reached. As a matter of fact, at 18 months, you have 78% of patients surviving. Those are the kinds of pieces that as we, you know, take this publication and put it in a new piece and begin to talk to clinicians about it, which we have begun doing just very recently since this was published, people become more, much more, kinda convinced that there is something here. I mean, we have been out there with a response rate, which is clearly a CR response rate, which is clearly high at 32%, right? The CRCRH rate is at 35%, and people can look at that and say, "Yeah, that's kinda what I get." When you go to the duration data, people have to recall and put that in context that these are relapsed refractory patients. When you, when you do that, and when we passionately talk about that, it can really have an impact. Yes, there are clinicians who say, "It's kinda me too. Response rates look the same," but you have to really dive into that duration. We think the two things that are really gonna help in the Blood Advances publication are to be able to talk about survival, number one. Number two, to be able to also address the fact that we had patients on the trial who were on venetoclax. Those are two things that are in the publication that are gonna just help augment our story. Lastly, though, you know, we've just gotten in January the NCCN guidelines edition, and we're gonna continue to do that. As a matter of fact, if you look at our website now, we have links to both the NCCN guidelines announcement and the Blood Advances publication. Those are really two critical things that I think will help move. So far, I would say, you know, depending on the clinician, and how much time we get with them, we can move them. I will also say that among the top leukemia treaters in the country, you just have to remember that this is a phase II study that was done at very few institutions in the U.S., so a lot of people haven't had a chance to kinda use this product. It came on all of a sudden. As a matter of fact, last night I was just talking about this with some clinicians. They weren't even aware that it was filed, and then all of a sudden it was approved in December. This is the kind of thing we feel very firmly though, that the more we raise awareness, especially among key leukemia treaters, the more adoption we're gonna get. Thanks, Dave. That's, that's great to hear. Another question for you, but on TAVALISSE. Congrats on accelerating these sales. Can you talk about what you're seeing is the driver of the sales growth? Is it getting the product on formularies, or is it your expanded sales force? Where is the estimated market share of TAVALISSE now, and have you gotten much penetration in the, in the earlier lines? If you look at the... I'll take that last part of your question first. If you look at our data, and we look at it through our patients that are on the product of TAVALISSE, we actually have a pretty good percentage of our patients on in second-line disease if we look at our patients through RIGEL ONECARE. It actually makes up more than a quarter of our patients right now. We do believe we're making progress in earlier lines of therapy. In terms of what's kinda driving new patients to the brand, it's all of the above. I mean, at the end of the day, you know, we have more folks out there, and they are very sharp in their messaging. They know that we are looking for new patients to start on TAVALISSE. Again, if you go to our website, you see lots of patient cases that we use a lot. Again, just seeing a lot of customers over the weekend, we're continuing to get interest in this drug, and people are really beginning to get it. I really do believe it's all of the above. We, you know. Certainly access isn't hurting. By the way, we had more commercial starts last year than we've had before. We believe that's a direct result of the work we've done to not only do the contracting we've talked about, but also raise awareness of the access that patients have to the drug. You know, as Dean and Raul mentioned, we're looking at a Q1 here, where normally, things slow down a bit due to the reimbursement hurdles, and your whole goal is to start more new patients and get over that. We believe we're, you know, making progress toward that as we're sitting here in the first part of March. It's all of those things, though, and it's taken some time, but I just give it to, you know, our sales team that's out there every day, searching for new patients and painting that picture for clinicians and they're really making a difference. And our market access team has really worked so hard to ensure that patients, especially commercial patients, have access to the drug. Wonderful. Congrats on the progress and thanks for taking my questions. Thank you, Doug. Our next question comes from the line of Kristen Kluska with Cantor Fitzgerald. Please proceed with your question. Hi, good afternoon. Thanks for taking our questions. We've received some inbound interest on the cGVHD program following the data you had earlier this year. The question is, what factors are you considering as to whether you may look to conduct further studies in this patient population? What do you view as the potential market opportunity? I'll take a stab at that and ask Wolfgang to comment as well. Thank you, Kristen. We're looking at the whole variety of things you look at when you're looking at potential new indication for your drug. That includes, you know, the patient population, the indication, the competitive landscape presently, the competitive landscape anticipated by the time you complete your study and file for approval, as well as, you know, the fit to the current pricing and things like that. There's quite a number of things to consider when you do that, in addition to obviously interest from KOLs and possible sites to do that, as well as FDA feedback on your thoughts on it. Sometimes they have their own views on how things should be studied, as you know. it's a complicated decisions, frankly, in terms of doing a study. We are actively evaluating that opportunity overall. Wolfgang, on the specifics of it, anything else you'd like to add? Yeah, maybe just, since you have seen the paper and obviously read the paper, you looked at the numbers. Of course, the first thing we do is we look at these numbers and compare them with other compounds that are available right now, approved compounds. You will have seen that the numbers look pretty good. It's that the overall response rate over a year is high, certainly favorable to currently approved drugs. We will have to work with FDA to see what a registrational trial could look like. What's the sample size? What's the exact design? That will, you know, have an impact on timelines and how quickly can we do that. Also on cost and how much, how expensive is it going to be. From a market opportunity, we do see a lot of potential. This could be a sizable opportunity in the not too distant future as far as we can tell right now. I think that says it well. Okay. Thank you for that. Appreciate it. Outside of the Eli Lilly partnership, what are the key things you're looking out for in 2023 related to some of your partnered programs, including your ex-U.S. partners? Yeah. As you know, I'll handle that. With regards to TAVALISSE, good progress. The product now available or soon to be available commercially in Japan. They got the approval at the end, very end of the year and have to get through pricing, which they're working on now. Look forward to that. It is available in Europe, all the major countries in Europe, as well as Canada, Israel. I think in terms of partnerships, we are making very good progress with TAVALISSE. We are having discussions with olutasidenib. As you know, as part of the license, we have global rights to olutasidenib, and the opportunities are attractive ex-U.S. as well. We're in discussions with potential partners regarding that. Also not just in terms of what the economics might be, but also what their contributions clinically might be. As you said, there's various segments in AML that are of interest, and possibly their contributions in regards to those rather than just financial are very much of interest to us. The IRAK program, we have global rights to that program. Having a partner in place that can also help us explore the opportunity in heme onc indications, is of tremendous interest. It's a very attractive program that we're now generating data that we think will be helpful in terms of setting a partnership in place. We're looking forward to those new partnerships. Progress with our Lilly RIP kinase collaboration with the systemic program entering a phase IIA study in rheumatoid arthritis. We think it's a great indication. It's a very sizable indication, one with continued need for new treatments. We're excited about their testing R552 in a phase IIA study in rheumatoid arthritis and launching in the next handful of months. Because we'll get meaningful data and data that could serve as cross comparators to other agents currently available and things in development, which may show this product to be a very attractive product in rheumatoid arthritis. We're excited about that. They also have a CNS program associated with that hopefully they'll in the near future, move into preclinical development and then into humans. Very good progress with current collaborations. Very good progress with currently marketed products, and looking forward to putting a couple more in place. Thank you. Thank you, Kristen. Our next question comes from the line of Gary Nachman with BMO Capital Markets. Please proceed with your question. Thanks. Good afternoon. A few more for me on REZLIDHIA. How easy is it for physicians to use a diagnostic test for an IDH1 mutation in AML patients? Is that common practice? No issues there in identifying these patients? What has access been like so far for REZLIDHIA? How much are you minimizing reimbursement hurdles? You mentioned that in your prepared remarks. How is the sales force being allocated between REZLIDHIA and TAVALISSE? Maybe just a little bit more on that. What else can you do to further penetrate the leukemia specialist for REZLIDHIA? You mentioned that there are some challenges there. Sure. Dev, I'll ask you. I made a list of about. I'll ask you to take those, and if you miss one, I'll remind you. Yeah. I'll take the last one first, Gary. I think first of all, it's a matter of time. You know, some of these institutions and some of these leukemia treaters, you know, it takes a while to make appointments, get in there, see them, et cetera. You've got whole departments. You've got not only the MDs, you've got, you know, your nurse practitioners, PAs, fellows that you need to see. You know, we're working all of those angles in terms of getting in to see leukemia treaters. But we also have, you know, other field team members out there. They work together across commercial and medical affairs. Our MSLs are out there, partnering with our field sales reps. If they know clinicians, they are able to introduce those clinicians to the territory business manager and vice versa. It's just, you know, taking us some time, but we're working all the angles to ensure that we get to get in contact with as many of these leukemia specialists as possible. In terms of reimbursement, yeah, I mentioned that we've had paid claims. Our market access team, our payer field team, has been out there doing many, many interactions with different payers and PBMs in presenting the clinical data. Overall, things have been very positive. We've received a number of, you know, kind of indications that they are going to cover with a prior auth to our label, which is exactly what we want. You know, we've had a number of patients get referred in to our RIGEL ONECARE who have been able to secure reimbursement. Overall, I would say that has been a lot of work across a lot of customers, resulting in continued wins on that front. You know, I've really heard very little from customers about an issue with getting reimbursement for. It's still early, but getting reimbursement for REZLIDHIA at this time. The team has just done an exceptional job. I think, you know, the other thing that's gonna happen here is, you know, you do have the people who have touched this brand among KOLs and have seen really remarkable results and really believe in this re-believe in olutasidenib. You know, we are seeing educational programs out there where clinicians are telling their peers about olutasidenib or REZLIDHIA. We're going to obviously do more of that as we move forward. We haven't even established our peer-to-peer education yet. We're working on that right now. We've got a lot of work to do, but I am not, I am very confident around our ability to raise awareness. What we do know is it's, it's not... This isn't a fluke. This is a the drug. I think it's a winner, and it's just about getting the word out there to the people who see leukemia. I don't know if there's something else- A diagnostic test. Oh, oh, that's- How readily is that done? Yeah. That's, I think that is, that's not an issue at all, Gary. I mean, clinicians can order it from any number. They may have it in the institution. They may go through a third party. I think more than that, it's the results and what they do with the results, right? You know, clearly in the, in the academic setting, they may be able to get results quicker. It's more in the front line this is applicable in that, you know, they may need to wait to treat. That's, that's the issue. A lot of clinicians don't do that, which is why we, believe we have an opportunity. A lot of clinicians, particularly in the community, just move forward with a regimen, and then that leaves the relapse refractory setting open to choosing an IDH1 inhibitor if they're IDH1 positive. You know, I think from a testing standpoint, you know, we'll continue to talk about it and, you know, I'm not saying there's 100% that's going on out there right now, but it's high. It's a high rate of testing, and I think in a relapse refractory setting, we'll just continue to reinforce that, you know, olutasidenib is the drug of choice in mutant IDH1 relapse refractory patients. Okay, great. All that color was helpful. And then just on 289. What will you be looking for in the overall phase IB data in low risk MDS patients, and when will that data be available? Are we gonna see anything, any interim data, or are you gonna wait for all the cohorts? What have you learned from cohort 1 moving into cohort 2? Maybe a little bit on that. At what point would you consider maybe licensing opportunities for this asset? Thank you. I'll handle the last piece. Maybe you handle the other, Mukund. Yeah, I start with the first dose cohort. First of all, at this stage of the life cycle of this compound, we look for safety. As I told you, the drug was well tolerated. There were really no AEs of any interest. Now we're going to the next cohort, which, you know, the first cohort is a really low dose with a PK profile, where we wouldn't really expect a big pharmacodynamic or efficacy effect yet. Cohort 2 is approaching that range a little bit closer. That will be the next three patients. Remember, all of these patients continue to be treated, and this is an open label study. As the data evolve, we look at cohort two, takes 28 days to say it's safe to escalate to the next cohort. Those patients also continue. I'd say, you know, look at three months, you can get a rough handle of whether there's a major signal in there. Might be something in cohort 2, might be something in cohort 3. Once we look at, you know, some of the safety and clinical activity endpoints like transfusion independence, remission, overall response rates, things like that, or hematologic improvement, we will expand a dose and add more patients. You know, I mean, you can, you know, think for yourself how many patients for how long do you want in order to discuss with a partner whether there's a signal there. I would say probably several patients for 3-6 months, depending on what the data looks. We would be in a pretty good position to say we have something in our hands. It's, I think in the lower dose groups, we will have some data from those. Clearly, it might be more safety. As we get into the three or four dose groups, that's where more likely we'll see some signs of efficacy after 3- 6 months worth of dosing. That's really what partners are probably looking at. Not only is it safe, but also is there some signs that this is having a benefit in this area. It's, Gary, to answer your question, it's hard to say because we don't know which of these we're gonna need to expand at + 3, and that enrollment. Enrollment's going well, that's a good sign overall. When we decide to do that expansion in the higher dose, one of the higher dose groups is not certain. We'll have to look at the data 'cause it is a, kind of a data-driven design of the study. We and the partners wanna see the same potential partners wanna see exactly the same thing. It's an exciting opportunity for this product. It's certainly a mechanism that is unique. It's well adapted, this mechanism to treating an inflammatory condition such as low risk MDS. We're excited about the prospect of this. Okay, great. Thank you. Thank you. Our next question comes from the line of Joe Pantginis with H.C. Wainwright & Co. Please proceed with your question. Hey, everybody. Good afternoon. Thanks for taking the question. My first question, a little more macro. I'd like to balance Dean's guidance for costs for 2023 of around $160 million, if I heard you correctly, and your overall cost management, and if we can infer that the commercial side of the business and the sales force is essentially right-sized at this particular moment in time. Yeah. What I think, Dave can answer the right sizing of that and if there's any other comments on the guidance on the $160 from you. Yes. I think we are, we have the people we need and the resources we need to drive both brands, both, you know, across the commercial team from operations to market access to marketing and sales. Yeah. I. Got it. I think, Joe, we've talked for some time now about just the leverage and efficiency in the whole commercial organization, not just the sales team, but the whole field team. I think you're seeing that in our ability to launch REZLIDHIA as we did and all the efforts that Raul described. We're seeing that leverage in that $160 million expected OpEx for 2023. You know, the 160 is a good number for us. We had a restructuring last year. We let go some of our earlier colleagues in earlier areas. We also took some real rigor, too, in terms of managing our cost so that it allows us to do what we need to do in a more focused manner. I think it was a good practice to do that, and I think look forward to continued growth in the top line, both from products and also from partnerships. kind of a flat to downward trending expense line from relative to last year, so in the not too distant future to get to that break-even point. Okay, that's helpful. Diving down a little further into the TAVALISSE franchise, I guess, first, I didn't see it on the slides or hear the number, I'm sorry if I missed it though, with regard to what the current refill rate is. You know, especially with this new number that you've put out here, it's definitely at least the way we've been looking at it and the way you guys have been describing it, you know, an early proxy, hopefully for the post-COVID pounding the pavement as you guys have been describing it. First, you know, the refill rate and what are the competitive headwinds that you're seeing right now, potentially as you know, go push into the earlier lines as well as, you know, any sort of blocking and tackling you can talk about with Grifols and other territories as they look to expand into different geographies? Dave, can you comment on the refill rate and, post-COVID conditions? Yeah. I mean, Joe, we have not seen any change in our persistency. We have really focused on, you know, bringing new patients to the brand. The team does continue to work with clinicians who are prescribing in their offices to ensure that they know to, you know, things like, you know, bring the dose up to 150 to make sure you get that efficacy, make sure you keep them on the product. We're doing all of that, we haven't seen a change in persistency. Our growth is being because more new patients are on the brand. You know, we just would like to keep it where it is, and we haven't seen any sign of it changing. I hope that helps. Post-COVID in terms of access and so on. Yeah. From a, from a post-COVID situation, yeah, our team continues. You know, I think this is part of those institutions. Sometimes it can be more difficult still to get into those institutions than the office buildings. Yeah, I think we're seeing more appointments, more opportunities to interact with clinicians and especially more live conferences. I think that's been a great opportunity for all of our field teams to be able to interact with customers. I think it all helps. Okay. Thank you, guys. Thank you, Joe. Our next question comes from the line of Kalpit Patel with B. Riley. Please proceed with your question. Good afternoon. This is Andy Fletcher on for Kalpit. Thank you for taking questions. Regarding the data investigator-sponsored trial in GVHD that you just published data on, how do you perceive the competitiveness of these results compared to other emerging agents such as Sanofi's REZUROCK or Syndax's axatilimab? As a follow-up, I know that you're still considering development of this asset. Is this something you think you would consider potentially developing in-house or maybe through a partnership? Thank you. Take a stab at that, Wolfgang, and I can as well. Yeah. I think I responded to a similar question earlier. If you compare the numbers of overall response rates in the Foster Matten paper, with approved compounds, you said REZUROCK, for example. Syndax has some preliminary data out there. It looks like it's certainly in the ballpark. The sample size is limited, so we don't wanna over interpret the numbers, but we feel they're competitive, and we do sense some, also some substantial investigator enthusiasm around the data. I would say it certainly looks competitive at this point, but it's still also early in this patient population. Dave, you wanted... Can you comment as well? Yeah. Andy, I think what I wanted to say is that we have done some research since obviously the study came out and was published. You know, we've tested this. It's not a large N, but clinicians, you know. That's the thing about GVHD, even though there are approved products, even if you look at the NCCN guidelines, you know, what the NCCN encourages is clinical trial. They really, while, you know, one of the agents has category one evidence, they don't have one preferred over the other. We look at this, you know, if we, if we do pursue an angle, or this as a development area, that this is a space that, you know, there is no clear kind of leader in GVHD. You could. Again, I encourage you to look at the NCCN guidelines, for hematopoietic, transplant, and you will see that in GVHD, a number of agents are listed, both approved and not approved. Yeah. To keep in mind, you know, we are looking at this as an opportunity. We haven't made a decision to proceed with it at this point or, you know. Like I said earlier, we do have a limited amount of money to spend on new registrational trials for these two agents. We have to look at all of those opportunities and place our bets where we think gives us the greatest return and near-term returns specifically. Thanks. I appreciate the additional color. Thank you, Andy. There are no further questions in the queue. I'd like to hand the call back to Mr. Rodriguez for closing remarks. Thank you, operator. Thank you for your questions and your interest in Rigel. It was a tremendous year in 2022. Both challenging, but I think a year that was our best year in terms of where we started the year and where we ended the year. I think we really transformed the company with growth in TAVALISSE, really gaining substantial traction, and then addition of REZLIDHIA to this highly complementary product, positioning us well really for this year in 2023. We're, we're executing on that, and that's our commitment to you that we will continue to grow both of these products, look for other opportunities within these two assets, that are exciting, that I think will again transform the company and continue to look externally in terms of opportunities. There are quite a number of things there as well that we have interest in. I think, 2023 will be a great year for us. Thank you for your commitment to us. We aim to deliver. Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation. You may disconnect your lines at this time, and have a wonderful day.