Rigel Pharmaceuticals Inc. (New) 12th Annual Cantor Fitzgerald Global Healthcare Conference

Dean Great. Take it away.

Great. Thank you, Kristen, and thanks again for having us to your conference this year. Thank you all for your interest in Rigel. I am excited to tell the story today. There is a lot of great news from the company. Before I get started, I will be making some forward-looking statements today, so I would encourage you to look at our investor site at rigel.com and our SEC filings. You will also see our complete corporate deck. There is more information I will be moving through today that you can see there. Rigel's transformational growth strategy. We are really proud and excited about the progress we are making. As we look at these 4 strategic imperatives, they are all interrelated. We have our growing our commercial business.

Before the launch of VEPPANU, which I will describe in more detail today, 3 commercial products growing nicely, and really a foundation to the rest of the business I describe. We had and have continued aspirations in in-licensing and business development. The VEPPANU transaction I will describe is really a key piece of progress in that initiative. Advancing the development pipeline. We have some opportunities in the development pipeline to really have transformational growth out into the future, primarily in our IRAK1/4 program and R289 in lower-risk MDS, and I will describe that today. But incremental opportunities beyond that. Wrapped around all of this is maintaining financial discipline. The last 8 quarters we have been profitable. Those profits have allowed us to generate cash, and therefore our financial footing is extremely sound to fund the development opportunities and the business I described today.

Since our Q2 conference call, the big news is that VEPPANU is now available in the U.S. We closed the transaction in mid-June. On August 13, we announced that VEPPANU was available. Later that week, patients started to receive drugs. Very proud of the pace at which we brought VEPPANU to the market, 60 days from the close of the transaction. It is really a tribute to the efforts of our team, our ability and our experience in launching new drugs, now this is our fourth drug, as well as just our infrastructure, our ability to leverage our commercial organization, our MSL organization, our market access teams, to efficiently and effectively launch products. I will be talking about this more today.

At the beginning of the year, we shared this slide, and it is really a progression of Rigel going back to 2020, where we were a single-product company with a limited pipeline. In 2025, as we exit 2025, we had three commercial products. We had our IRAK1/4, R289 program in lower-risk MDS. We had become profitable. We had had a strong cash position. Our aspiration was to grow that commercial portfolio, we now have four products, VEPPANU, and then to have transformational pipeline development opportunities, and that is our R289 program. We are progressing nicely towards this 2030. Again, I will talk through two of the key components, the VEPPANU and IRAK1/4 program. Briefly on the commercial business Q2, we grew our net revenues 14% year-over-year, $8.1 million. You are seeing nice continued growth across our commercial portfolio.

Globally, we have got a great set of collaboration partners, a great global footprint. We had $11.7 million of collaboration revenues in Q2. That is driven off of sales of TAVALISSE globally with Grifols in Europe, with Kissei in Japan, as well as Medison in Canada and Israel. Knight is our partner in Latin America, and they are making great progress there. From a REZLIDHIA perspective, we have collaborations with Kissei, as well as Dr. Reddy's to make REZLIDHIA available internationally also. In licensing business development, the second strategic imperative, this really is where VEPPANU fits in, and we will move into that grow our commercial business. VEPPANU, vepdegestrant is indicated in adults with ER-positive, HER2-negative, estrogen receptor 1 mutated advanced or metastatic disease following a line of endocrine therapy. A large market opportunity I will describe. In a market where physicians are actively embracing new therapeutics to treat these patients.

We have said really since we have closed the deal in June that this can be a transformational asset for the business. Notably, this is the first and only FDA-approved PROTAC, and I will describe the PROTAC mechanism of action, which is differentiated from oral SERDs and other therapeutics, which is a key differentiator in our access to this market. I will describe the novel mechanism. From a launch perspective, our commercial organizations as well as our MSLs, market access, and all of our teams are ready for the launch, which is extremely important, and we have described that this can be our largest product, larger than TAVALISSE. An exciting opportunity for the company. The mechanism of action, as I said, is critical to the differentiation of the product. VEPPANU is a PROTAC, a proteolysis targeting chimera.

It's a heterobifunctional protein degrader, and this, kind of moving from left to right on this slide, the bifunctional design is such that the right side of the molecule first binds to the estrogen receptor that then recruits the E3 ligase complex, tags it with ubiquitin proteins that are recognized by the proteasome and then degraded. What's unique about VEPPANU is that the molecule is then released after degradation and then can attract other estrogen receptors and continue this catalytic process, which is differentiated from other mechanisms that a single molecule will degrade an estrogen receptor and then lose its function at that point in time. This is an important distinction that we'll be certainly educating the community on. From a market potential perspective, there's about 170,000 mostly women who have metastatic breast cancer. About 70% of those women are ER-positive, HER2 negative.

The typical therapy for these patients are endocrine therapy with a CDK 4/6 inhibitor. Many of them, we estimate 40% will develop an ESR1 mutation, so that's 47,000 patients. Then about 60% of them, we estimate, will be identified and treated, of which that subset, the second and third line is about 20,000 patients. So large market opportunity for us. We describe this as a billion-dollar-plus market opportunity. We think it could be well in excess of $1 billion. So really an important opportunity for patients with the disease, but also for Rigel. As we look at the market dynamic, you see here on the left, you see the second and third line treatment, which is where we're indicated. The oral SERDs have been rapidly adopted, the blue lines here. So physicians are excited about and welcoming new therapeutics for this group of metastatic breast cancer patients.

You'll see on the left that the oral SERDs, it's the majority of treatment at this point. You'll see it's about 30% in the third line. Then you'll see continued use of chemotherapy in both the second and third line. There's certainly opportunities to introduce a new mechanism of action, a new treatment paradigm into this. The other important thing to note here is that 80% of the patients are seen in the community setting, and the community setting is a bit slower in the adoption at this point in time. That's where our sales force, we have 40 sales representatives currently in our business who are calling on those community doctors. We have about 10 field sales representatives calling on the academic centers. This group is well-trained and ready to go to advance VEPPANU into these markets.

We believe that VEPPANU and what really excited us about VEPPANU when we in-licensed it is this can be a leading treatment in this segment of metastatic breast cancer. From an efficacy perspective, the VERITAC-2 phase III trial had the following response as VEPPANU was compared to fulvestrant. Improved progression-free survival, a 2.4-fold increase or 2.9 months, a very meaningful increase. We also saw, compared to fulvestrant, increases in ORR as well as clinical benefit rate. From a tolerability perspective, so we've talked about the mechanism of action being differentiated. Another key differentiation is the tolerability. When we announced the transaction, Dr. Erika Hamilton, who's the principal investigator on the VERITAC-2 trial, made some comments about the low gastrointestinal toxicity with respect to VEPPANU, as well as the low discontinuation rates and low dose reduction rates, the 2% and 3% rates with VEPPANU.

So that was all seen in the VERITAC-2 trial, important in the treatment paradigm, and again, we think a differentiating feature for VEPPANU. From a real-world applicability perspective, 100% of our patients in the VERITAC-2 trial were treated with both endocrine therapy as well as a CDK4/6 inhibitor. That's an important feature. Based on the totality of the evidence, the NCCN decided to include VEPPANU in their guidelines. From a readiness perspective, again, we closed in June. Over the next 60 days in advance of product availability, as well as through today, our teams have been ready and fully deployed. This now is our main focus of our commercial and medical affairs efforts.

We started with our collaboration partners and made sure that all of our partners were aligned throughout the process, really starting with Arvinas and Pfizer, who've been great partners in the process, all the way through to our distribution channel. We've leveraged our knowledge, our people to create the most successful launch possible. We then started coordinating again on day one with our key customers. We started to meet with KOLs and key customers as well as the payer community and across the spectrum. When products became available, people and processes were ready for VEPPANU. Then we leveraged our capabilities broadly, our incremental capabilities. So we had the veppanu.com ready. We had our sales force trained and ready to go. We also had our patient services, our variety of patient services and support networks ready to support patients as well as physicians.