Rigel Pharmaceuticals Inc. (New) H.C. Wainwright 28th Annual Global Investment Conference

Don, welcome. Thank you. I'm going to stand up and present this morning.

Thank you, H.C. Wainwright, for having us to the conference this year and for all of you for your interest in Rigel. As I get started today, I just want to remind you I'll be making some forward-looking statements. I'd encourage you to look at our rigel.com site where you can find our full SEC reporting, as well as the complete corporate deck. I'm going to move through fairly quickly today. Again, I'd encourage you to take a look at these materials as there's lots of good news at Rigel. As we think about Rigel, for some time now, we've talked about our transformational growth strategy, really four elements, and these elements all work together.

We've got growing our commercial business, and before the VEPPANU transaction that I'll describe in a little bit more detail, we had three commercial products. Nice growth in the commercial products, and really a foundation to the rest of the business I'll describe. We had aspirations and continue to have aspirations for in-licensing and business development transactions. VEPPANU is a big step in that journey for us. Advancing the development pipeline, a robust pipeline, really the foundation being our R289 IRAK1/4 program that I'll describe in low-risk MDS, but incremental opportunities beyond that. And then financial discipline. Wrapped around all of this is a financial structure that has us over the last eight quarters being profitable each and every quarter. With those profits, we've had cash generation. We were able to pay the $70 million upfront for VEPPANU with our own cash. So really a solid financial foundation.

The big news over the last quarter is the VEPPANU transaction, where we closed in mid-June. 60 days later, approximately August 13, we announced the availability of VEPPANU. And now we're about a month into that availability and well into our launch phase. So exciting news for Rigel. This transformational growth strategy and accelerated growth. Earlier this year, we presented this slide that showed in 2020, Rigel was a one-product company with a limited pipeline. At the end of 2025, three products, an encouraging pipeline with R289, and a very stable financial footing. And then we were looking to 2030s where we'll really see transformational growth opportunities. We've executed at least in part on one of these, and that's adding to our commercial portfolio with VEPPANU. But we've also got the R289 program I'll describe, which is truly a very large market opportunity that we're excited about.

Again, with financial strength wrapped around it. Growing our commercial business in Q2, we had 14% year-over-year growth in our net revenues up to $67 million. Our base business, our historic base business, exclusive of VEPPANU, is really performing nicely. VEPPANU is a big add to this. From a global perspective, we have great collaboration partners with respect to both TAVALISSE and REZLIDHIA. TAVALISSE, we have Grifols, Kissei, and Medison that are really generating in the second quarter, we generated $11.7 million of collaboration revenues. Our partner, Knight, in Latin America is making great strides in making product available, as well as our partners with respect to REZLIDHIA, both Kissei and Dr. Reddy's in Japan, Asia, and with Dr. Reddy's Latin America and other geographies are making great strides in making REZLIDHIA available to patients outside the U.S.

In licensing and business development, that second element, VEPPANU is really the foundation to the next phase of that growth. VEPPANU is indicated in ER-positive, HER2 negative, estrogen receptor-mutated advanced or metastatic breast cancer following at least one line of endocrine therapy. So a label, and I will describe the market opportunity here, but significant market opportunity. This really does have the potential to transform our portfolio. It is the first and only approved PROTAC, a new class of targeted agents. That is foundationally a very important element. I will describe the novel and unique mechanism of action and how that is differentiated from other therapies in the market. Our commercial teams, our medical teams, our market access teams, and really across the entirety of the organization, the G&A functions, very well situated to leverage all of those assets and create a successful launch for VEPPANU.

What we have said is that this can be the largest asset in our portfolio. We think that this is a true growth driver of the commercial business. Key to VEPPANU's differentiation from others is that this is a PROTAC. It is a proteolysis targeting chimera. It has a heterobifunctional design. This unique structure is important as we look to differentiate in the marketplace. One end of the PROTAC molecule binds to the ER receptor. The other end of targets that E3 ligase complex recruits ubiquitin proteins, which are then recognized by the proteasome and destroyed. That is really the cell's natural waste destruction system. What is unique with VEPPANU is that it bonds transiently, and therefore a single VEPPANU molecule can degrade multiple ERs, and this catalytic process is important differentiation. Significant unmet medical need. There are about 170,000, mostly women, who have metastatic breast cancer in the United States.

The largest segment is the ER positive, HER2 negative, about 70% of those patients. Standard of care therapy for these patients is endocrine therapy and a CDK4/6 inhibitor. Approximately, we estimate 40% of those patients will develop an ESR1 mutation. Of those patients, we believe that around 60% of them will be identified through genetic testing and treated. Then there are about 20,000 of those patients who are in the second and third line where VEPPANU is indicated. So the very large market opportunity, we estimate it is a billion-dollar plus, but we think it could be well in excess of a billion dollars. So important medical need for these patients with metastatic breast cancer and VEPPANU fits nicely into that treatment paradigm. This is a dynamic market, so we are entering into this large market opportunity that I described.

In the blue here, you see that physicians have rapidly moved to new therapeutic options. They've adopted the oral SERDs. You see on the left side with the second line that the majority of patients are now receiving oral SERDs, and about 30% of the patients in the third line are receiving oral SERD. Which means that there's still significant chemotherapy use, about 25% in the second line and over 60% in the third line. So tremendous opportunity for continued therapeutic advancement such as VEPPANU into this segment of breast cancer. Important to note that about 80% of patients are seen in the community setting. So it fits very well with our commercial organization, where we have 40 dedicated field sales representatives who call on the community docs. They do that already, and they have access to those physicians.

Then we have about 10 representatives who are calling on the academic center. So this fits very nicely, metastatic breast cancer, into our current commercial organization as well as our medical affairs and the rest of our organization, and we'll be able to leverage that organization very nicely. VEPPANU really has the potential to become a market leading in this segment of breast cancer. From an efficacy perspective, we saw in the Phase III VERITAC-2 trial, we saw improvement in median PFS, and this is versus fulvestrant. 2.1 months with fulvestrant, up to five months with VEPPANU. So a 2.4 fold increase, 2.9 months. Very meaningful for patients. We also saw improvement in ORR as well as CBR.

From a tolerability perspective, Dr. Erika Hamilton, the principal investigator on the VERITAC-2 trial, in a conference call with us recently, really highlighted the tolerability and the advantage of VEPPANU and the strength of the tolerability profile. It's noted that there's low rates and severity of GI-related events, and then the discontinuation and the dose reductions at 3% and 2% mean that this is a very well-tolerated drug. From a study perspective, the VERITAC-2 trial, it should be noted, this was really a real-world population where 100% of patients had received both endocrine therapy as well as a CDK4/6 inhibitor. The totality of that evidence has resulted in an NCCN listing for VEPPANU.

From a commercialization perspective, as I said, from the point we had the transaction closed in mid-June, our teams were working with our collaboration partners, Pfizer and Arvinas, tremendous partners in this process, all the way through our existing distribution channels. We started to work with and engage with our key customers, the payer community, and we leveraged our assets. veppanu.com was up and running. Our sales force was readied and trained to speak with our customers, and our patient services resources like RIGEL ONECARE were up and running, all to create a successful launch. On top of that, we had all of our various assets ready. Upon the close of the transaction, we had now approved assets. Upon the commercial availability, we had now available. We're in the process of working through our branded campaign, and you'll see those assets in the upcoming months.

Moving on to the advance in the development pipeline. VEPPANU, extremely important. The development pipeline is similarly important, and these really are transformational growth opportunities as we look out into the future. Three potential areas of hematology and oncology expansion for us. Key focus today, R289 in the IRAK1/4 inhibitor program, where we're evaluating a phase I-B in relapse refractory lower risk MDS. I'll describe that in more detail here today. From a vepdegestrant or VEPPANU perspective, Pfizer, Arvinas had initiated a variety of combination studies with abemaciclib, ribociclib, and others. The enrollment has been completed, and we're following up in those efforts, and we look forward to reviewing that data, seeing the safety and efficacy. At that point, Rigel will decide what the next steps are with respect to our potential vepdegestrant development programs, whether it be Rigel-led studies or ISTs or a combination of those.