Rigel Pharmaceuticals, Inc. (RIGL) Earnings Call Transcript

All right. Good afternoon, everyone. I'm Kalpit Patel, part of the biotech team here at B. Riley. Our next presenting company is Rigel Pharmaceuticals. I'm delighted to have with me the CEO of the company, Raul Rodriguez, Raul, welcome. Raul is going to give a quick overview, and then we'll have some time for Q&A at the end. Raul, the mic is yours.

Thank you so much, Kalpit. Thank you, Andy, and thank you to our colleagues at B. Riley for having invited me. I'm delighted to spend some time with you and tell you a little bit about Rigel. So forward-looking statements here are also available on our website for your review if you would please do that. Let me tell you the story of Rigel. It's a story where we're looking to build that we are actively building a Hem/Onc business, and we need to make this an incredibly attractive and positive impact from this business. And it's been really years in the making, but I am delighted to report that we've made some substantial strides in bringing this to fruition in the last 1.5 years or so. Let me tell you a little bit about TAVALISSE in ITP. This is our own internally discovered product, which we launched a few years ago in the U.S. for the treatment of ITP. I'll tell you more out there. But the highlights for TAVALISSE and ITP is this Q4 just completed from '22 was our best quarter ever in terms of numbers of bottles shipped to patients and clinics since launch. And that's built on a very good Q3, which was to that point, the best quarter we'd ever have in terms of sales for the product, which built on Q2 of this year -- of this past year, which was at that point, the best ever we've ever done. So it's been really a very good year in '22 for TAVALISSE growth in ITP, only driven by a slightly expanded sales force and really just availability of our clinicians now receptive, able to see our sales reps. And as a result, we really have been able to grow this product in a post-pandemic environment, not fully normal, but certainly substantially improved. We have also worked on making the access to our product much better by providing preferred status in the top 3 PBMs. And we received a bit of great news outside of the U.S., our partner Kissei received Japanese approval for chronic ITP, and this has triggered a $20 million milestone which we expect to receive in the first quarter of '23, this quarter. So that as the base, then last summer, we in-licensed REZLIDHIA, olutasidenib, which had been filed for relapsed/refractory AML. And we were delighted that about 6 weeks ago, we received approval for REZLIDHIA for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with patients with an IDH1 mutation. I'll tell you why we believe this could be the market-leading IDH1 inhibitor and supporting that. Also we made the product available in the third week of December after receiving approval in the first and announced this morning that we've received inclusion in the NCCN treatment guidelines for REZLIDHIA, so we're delighted by that. And importantly, I'll tell you a little about the synergy between this molecule and our base TAVALISSE molecule and how the 2 work well together and really build upon each other. I'll also tell you a little bit about our next molecule R289, which is an IRAK1 and 4 inhibitor. We're testing this in lower-risk MDS. Our first patients have been dosed here, and we're adding patients now and continue to add to the already handful of clinical sites in the U.S. that are enrolling patients. So I'll focus on those. I won't go into other detail on other programs because I think it's a very interesting story that I'd like to share with you. Let me start with TAVALISSE. So TAVALISSE in ITP is indicated for the treatment of adult patients with chronic immune thrombocytopenia, who had an insufficient response to a previous treatment. A previous treatment is almost always a steroid, usually prednisone, but sometimes dex. After that, they go on to other things. In the U.S., there is about 81,000 adult patients with chronic ITP, about 37,000, as you see here, are watchful waiting, that is they either have a milder form of the disease or in some transient remission. But then eventually, most of those need other agents. First line, as I mentioned, is typically a steroid, prednisone being the most common, and we are indicated for what is in the orange side here, about 24,000 patients in this second line or ladder, and a good deal of switching as patients need other agents they consider what to use. And we aim to make TAVALISSE part of the discussion at every one of these notes where you see these little errors. In first -- in the second-line category, sometimes Rituxan is used, sometimes class of agents called TPO mimetics are used. And our aim is to be used earlier and earlier, and I'll share you some of the data, which is the basis for the growth of the product as we move up line initially from a more refractory lines fourth or fifth. Now it's third lines and in some cases, second lines. So that's our objective overall. And the formularies that we were able to gain preferred status is really a tremendous health because it removes an obstacle towards reimbursement that existed earlier. And I think that's helped us as well in terms of how we rate the product available. Here's the data on this chart that is the reason we are so excited about TAVALISSE. The earlier you used the product, the better the results are and that's very good. So as we try to move up line, the performance of the product is better. This is not atypical in autoimmune diseases. ITP is an autoimmune disease where the body destroys its own circulating platelets. And so here, again, the early treat, the better the results you get. And if you get a response, you're able to keep it. On the right side of this slide, you're able to keep it for a good long time. So if you succeed, the chances are you can succeed for a very good long time, many weeks of usage and we've had patients over 10 years on TAVALISSE where their ITP is well managed with the product. So it's an exciting product, a differentiated product from everything else that is available and has really served as the basis for us to build a Hem/Onc business that now we are looking to expand further on. As I mentioned, outside of the U.S., we had relied on partners, really very good partners with expertise and commercial capabilities in their respective areas. In Europe, our partner is Grifols, where they have -- we've got an approval for the product, and have launched in all the large countries and are continuing to roll it out in some of the smaller countries in Europe. In the -- in Canada and Israel Medicine, our partner has approval there and products available. Most recently, we signed a deal with Knight in Latin America, where we will make the product available to patients with ITP in South America and Latin America. And as I mentioned, our partner, Kissei conducted its -- their own Phase III trial. That's a requirement for Japanese approval. So excellent results. Those are now public -- published and available. And the results really replicated and maybe a little even better than the U.S. data showing a tremendous benefit. So that product was approved in Japan, branding TAVALISSE there as well, and will be available to Japanese patients now this quarter. We're delighted by that progress. So that's our business. We had a very attractive business based on TAVALISSE. And now we're looking to add to that business and leverage that commercial infrastructure with REZLIDHIA, which we in-licensed from our partners Forma in the middle of last year, a very attractive product. And what made it even more attractive, and I'll show you the clinical data, is that we're already calling on the majority of hematologists, oncologists in the U.S. for TAVALISSE. It's a broad number of clinicians who treat ITP. And because of that, we can add this on to that infrastructure at a minimal cost. We've not had to add any additional individuals to help us launch and sell REZLIDHIA in the U.S. We have 54 territories, which cover all the major markets for both of these agents across the U.S. and a group of people in our commercial area that are incredibly experienced, especially in the Hem/Onc field. So really having that as a base allowed us tremendously, our market access team, for example, was jumped on the opportunity and is making it available for REZLIDHIA just like they did with TAVALISSE to ensure that access is achieved for both of these. So the 2 agents work very well for clinicians that we have built a relationship with for TAVALISSE. We will now introduce them to REZLIDHIA and to doctors who are very interested in learning more about REZLIDHIA and its data. We will take the opportunity to share information about TAVALISSE. So these 2 products, I think, will really help each other out in terms of how we launch and how we grow both of them, and they should work very synergistically. So we're delighted to have REZLIDHIA as part of our portfolio. Let me tell you a little bit about -- more about the product and the field of AML and what we're excited about it. The approval for REZLIDHIA is here, I indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia with a susceptible IDH1 mutation as detected by an FDA-approved test, a very good label exactly what we were looking for in terms of the approval. AML is really an unfortunate and terrible disease. It's a very aggressive, highly complex malignancy typically in older adults. About 20,000 patients in the U.S. are diagnosed every year with AML and unfortunately, about 11,500 of them . IDH mutations are about 6% to 9% of total AML and these patients, especially in the relapsed/refractory are very well identified and genotype so they can identify those patients that had this mutation and consider using a product like REZLIDHIA, a significant unmet need exists in these patients for products that are well tolerated and efficacious. Looking over here on the chart on the right, typical patient is diagnosed with AML and is categorized in 1 or 2 buckets of fit bucket, they tend to be younger, they tend to be able to expand intensive chemotherapy and the goal there is to hopefully get them to a transplant. In the unfit category, they really can't take the risk of intensive chemotherapy, so you treat them with venetoclax or venetoclax and HMAs or a combination of the 2. But they relapse, and that's where we're indicated for the green boxes at the bottom, which is about 1,000 patients in the U.S. So a total of about 1,800 patients with IDH positive mutation, but 1,000 -- a bit more than half are already in the relapsed/refractory setting. Our colleagues at Forma did a very nice Phase II trial where Cohort 1 as a monotherapy in relapsed/refractory patients, about 153 patients enrolled in that trial, but they also did a number of other things shown here in the gray Cohorts 2 to 8, looking at various different settings, for example, in treatment-naive patients Cohort 7 and 8, patients with a previous IDH1 inhibitor and call it 3 and 6, patients with -- who have done various combinations of prior therapies as well. In order to really explore the opportunity, but the focus really is Cohort 1 since that was the cohort that was intended for approval. The primary endpoint, CR/CRh rate and secondary endpoints, obviously, a variety of other things. I'll show you some of that data. This is the data that excited us about this product. The CR/CRh rate, which is a completely remission with partial hematologic recovery, was about 35% as you see here, the quality of that remission was really excellent. Most of those were CRs, complete remission. Only a few of those were CRhs, which is not as good. But as you see the quality of the CR/CRh rate was excellent. And what impressed us the most was the following. The median duration of that CR/CRh 25.9 months. That is about 3 -- more than 3x longer than the currently available therapy. That's an impressive improvement in the disease that is deadly and is difficult to resist. If you can provide 25.9 months duration of this response that is outstanding. And when we saw this data, as we did diligence on this product, we really felt that this was a product we could do very well with them and the data supported the utility of this product in this indication. As you see in the CR rate is about 32% and the median duration of that CR rate 28 months. That's outstanding. We're really excited about this data. And as we've shared the data with KOLs and other clinicians, now even though we've only had the product for a few months, this is the data that they find incredibly compelling, and we're excited to provide the product to them because I think if we can provide this benefit to these patients, I am so excited about that opportunity because I think it's a tremendous help to them. So this is the data that is part of our poster session that we shared at the ASH meeting and will be part of a publication that will be -- that is forthcoming in the near future. The safety profile was no surprises. This is a very typical profile of our product in this category. We're impressed with it. It's not any different than you would expect for a product in this patient population. And especially, there's something called differentiation syndrome, which is a class effect. The other IDH inhibitors also have this and it occurred in a similar rate with our product than theirs, and it's successfully managed by dose interruption supportive care such as steroids or diuretics. Clinicians seem to be well aware of this and able and confident that they can address this should it arise, and, like I said, it's common to all IDH1 and IDH2 inhibitors in the similar patient population. So in summary, the CR/CRh rate of 35%, an excellent result. And the duration of response of nearly 26 months is incredibly important, and I think the key differentiating feature of this product. 92% of those responders were CRs, complete remission with a median duration of 28 months in this case. We achieved transfusion independence in all subgroups, and it has a very well-characterized safety profile with no cardiac events leading to discontinuation which is an excellent result. So we're delighted to do this. A little bit about the market. I may have told you a few of these data, about 20,000 patients in the U.S. with IDH-positive -- with AML, 60-40 split in terms of fit, unfit. And we think about 1,000 patients have IDH-positive relapsed or refractory AML in the U.S., which, as I said, about the majority of patients who are IDH positive are already on the relapsed/refractory setting. Our -- as we've done some market research, delighted to share this finding really interesting. Health care providers are looking at for targeted therapies and specially therapies that they find efficacious in -- especially in this relapsed/refractory setting. And what they want is longer duration of responses, they fear that patients will relapse that they will have limited options available to them. And that's really what they're looking for. And particularly, a balance between the efficacy and toxicity of agents to allow them to remain on a product for longer terms, years really. So finding that I think we have an agent that very much fits that need that desire, promising new treatment, targeting IDH positive mutation, appropriate for patients who failed other therapies, good response rate, very good duration of response superior to currently available therapies and position us to be compared favorably against those. So I think it addresses many of the needs, desires of patients and health care providers in the relapsed/refractory setting in AML. So our job now, and this includes our sales, marketing, medical affairs, market access is to drive awareness for this product and share that data I just shared with you and provide access to them so that there isn't barriers to access them and make sure that their experience as they use REZLIDHIA is really excellent. In a way to have this be a product that they are happy to use, happy to provide to their patients who in turn are able to have a very long duration of benefit of it. So it's an excellent product to add to the portfolio. So let me move on in the last few minutes to our pipeline product, R289 and IRAK1 and 4 inhibitor, which we're studying for lower-risk MDS. It's a dual inhibitor, which inhibits a multitude of inflammatory signaling pathways, particularly the Toll-like receptor and IL-1 family of signaling, which are really central to many bases of many inflammatory diseases, including lower-risk MDS, which in many ways is an inflammatory disease of the bone marrow. What we like about an IRAK1 and 4 inhibitor relative to, say, 4 is that it is more broadly immunosuppressive of these inflammatory cytokines as you see here for a couple of these, we're able to suppress those with 4 much more effectively than well-studied IRAK4 inhibitor. What we've done with our molecule also is to test that, not just in assays that I just showed you, but in humans. This is a human proof-of-concept study where you take healthy volunteers, give them LPS protein. And the result is you get a cytokine storm, you get elevated TNF and IL-6, other inflammatory cytokines are elevated. And with our product, we're able to substantially reduce that. Now albeit it's an artificial, we created the and we solved , but if we can do this on a more chronic basis with chronic doses, we'll have a tremendous product on our hands. Low-risk MDS, as I mentioned, it has a basis in inflammatory cytokines, TNF, IL-6, et cetera, as well as the , which is a program that is common in this area. We are able to address both of those pathways. And we think we have a good chance in showing we're benefiting lower-risk MDS. So other agents are currently available. We think we can provide a benefit alongside them and we're beginning the study to demonstrate that. This is a study we started in Q4. This is a study looking -- it's a very standard design, the 3+3 design, where you start at a low dose and then you stair-step upward, as you show some safety, and we currently had started this. So we're in the lower cohorts now, and we hope to escalate over the course of this year along this pathway. And at some point, you pick a dose expansion dose and add additional patients to that. The primary study is safety, but we're certainly going to be monitoring secondary efficacy, of course, as you see listed here. So we're really excited about this opportunity. It's a perfect fit for who we address out in the field. And this is a product that also is differentiated, and we believe addresses a essential aspect of lower-risk MDS that inflammatory cytokine storm basically that occurs in the bone marrow. So let me finish. We have built what I think is a very attractive Hem/Onc portfolio based initially on TAVALISSE as we sold that product and made it available across many Hem/Oncs in the U.S., and then we're able to expand upon that with the addition of REZLIDHIA, in-licensed middle of the year, approval 5 years ago, and it's on the market today, which is an excellent fit and, I think, a product that could make it the market-leading agent in IDH-positive relapsed/refractory AML. The 2 together, I think, are highly synergistic and allows us to continue to build this both internally, additional studies for either of these agents as well as to continue to look externally for potential additional in-licenses or acquisitions or products that are complementary to this. We have additional capacity to sell Hem/Onc products in the U.S., and we're looking to continue to add it by our own making with TAVALISSE or REZLIDHIA or our IRAK1/4 inhibitor 289, externally. So we're looking very actively to build this portfolio. We integrate what I think is the best Hem/Onc commercial business in the U.S. for a small company, and we're off to a great start. So thank you for your attention. Kalpit, back to you.

Yes. Thanks, Raul, for that wonderful overview. I think we can squeeze in a few questions here before the next presentation. Obviously, Raul, you're no longer just an ITP company. You have many other interesting developments in other areas. And I'm getting actually more interest on those other areas. One question that I've noted is about the company's go-forward plan for REZLIDHIA, A lot of people have asked me, is this company going to get REZLIDHIA in the frontline treatment paradigm like how TIBSOVO is doing it, right, or other targeted AML agents are doing it? So I'm curious to hear your view there. And you also have a very promising median duration of CR/CRh. So there's some excitement there and hence, the interest in the frontline setting.

Absolutely. So we're looking at the frontline setting. We're looking at various other segments as well that potentially IDH1 inhibitor might be beneficial. So we are very interested. We think that the relapsed/refractory setting is a very good basis for introducing the product and establishing its utility, but we don't want to stop there. I think there's more opportunity in AML and various segments within AML, we're delighted that our colleagues at Forma did various clinical trials and smaller cohorts, of course, that I shared with you because all of those are intended to provide a way forward as well. So we're looking at the dose to see what the next step is. We haven't revealed that yet. We're giving a lot of thought and a lot of consultation with key opinion leaders to get their input on this. And we're excited because I think it merits substantially more investment on our own -- ourselves and also with the potential partners as we look outside the U.S.

Okay. Okay. Fair enough. And you pointed out the inclusion of REZLIDHIA to the NCCN guidelines earlier, maybe educate me here, but was REZLIDHIA included as a preferred IDH1 inhibitor if there is such a thing in the guidelines? Or do they not traditionally discriminate between the different IDH inhibitors?

They don't traditionally discriminate between them. And so we were -- said that this is included in the listing for the right indication, IDH-positive relapse or refractory along with TIBSOVO. So I think that's really what they provide. They don't rank order them, so to speak, in those, at least, not in the NCCN listing.

Okay. Fair enough. And sticking to the heme malignancy theme, I guess, when should we expect data for the IRAK1/4 inhibitor in lower-risk MDS? I know you have that box there generate initial data, but I'm curious to hear when we should expect it.