Incyte Genomics Inc 2026 European Society for Medical Oncology (ESMO) Annual Congress

Good evening, everybody. Those of you here in Madrid, it's been a wonderful ESMO for us at Incyte, and we're really excited about telling you a lot of the progress we're making in solid tumors. Thank you very much for joining us here today. We will be making forward-looking statements that you can see here. We have a great set of speakers today. You can see them here. Our own Steven Stein, Chief Medical Officer and Head of Late Development at Incyte, Dr. Elena Garralda, who's Co-Director of the Vall d'Hebron Clinical Research Program and Group Leader for the Vall d'Hebron Early Clinical Drug Development group, among many other titles, and Dr. Manuel Hidalgo, Professor of Medicine, Director of Gastrointestinal Cancer Center at the Perlmutter Cancer Center at NYU. We're really pleased, and we're very grateful that they agreed to join us here today.

We have a great agenda. I'm going to make a couple of very quick comments to get us started, and then we're going to shift to reviewing the data for two key programs, 890 and 734. Our speakers will review the data for you, and will give you an overview of how we're developing these programs going forward. I'm going to make some closing remarks, and then we'll have plenty of time for Q&A. Please prepare your questions. All our speakers will be available for the Q&A. The focus today is the solid tumor development strategy at Incyte. I think over the last couple of years, we've been busy at work to build what I would consider a world-class solid tumor franchise. The focus today will be more on GI oncology, but we're building a broader solid tumor franchise within the organization.

We are focused on three basic principles to build that strategy, to build that franchise. One, we're trying to go out to novel targeted therapies, whether we are to novel biology, that in the case of TGF-β by PD-1, or we approach a particular target at G12D with a different mechanism from what was there before. Instead of an on inhibitor, in this case, we go with an on-off inhibitor, for example. We are focused on cancers of high incidence. We're trying to address large medical needs in patients that have limited treatment options. One thing that we've done pretty consistently in both programs, as well as in our CDK2 program, is go as quickly as possible to frontline. We believe that that is where the largest patient benefit resides, and obviously the largest commercial opportunity as well.

That's something that has been a consistent pattern in these programs, and you'll see it as we review the data. This is our portfolio today. We have one approved medicine, Zynyz, we shouldn't forget about that. It's approved for patients with anal cancer. The first PD-1 approved in combination with chemotherapy for frontline anal cancer, as well as Merkel cell carcinoma. 890 and 734 will be the bulk of the presentation today. Of course, on the right side of the slide, 667, a CDK2 inhibitor, which is in pivotal trials for patients with ovarian cancer, and will continue to progress in the clinic. The three programs address approximately 250,000 new patients per year. You can see the numbers here, taking into account only the indications that we've listed in the slides, which are the initial approvals for these programs.

For 734, pancreatic cancer with G12D mutations, for 890, MSS colorectal cancer, and for 667, CCNE1 overexpressing ovarian cancer. Almost a quarter of a million patients with very poor outcomes today. Not only is this a very large opportunity for us as a business, but is a very important medical need that needs to be addressed with better medicines for these patients. The programs have grown and will continue to expand, and this slide gives you an idea of what we're doing. Steven, after Dr. Garralda and Dr. Hidalgo show the data, Steven will give you an idea how we're deploying our resources in this program. For 890, our first indication in pivotal trials is colorectal cancer. We'll talk more about that.

Let's not forget that we've shown evidence of efficacy in head and neck cancer, ovarian cancer, and non-small cell lung cancer, all in patients that most of which had poor likelihood of response to PD-1 inhibitors. We moved initially in first-line colorectal. We are already implementing an adjuvant proof of concept study in colorectal cancer, very important, and we've generated data that was seen in this meeting as well in late lines. Very important for both programs is to expand into novel combinations. With 890, not only we've done chemotherapy FOLFOX, that is the bulk of the data you're going to see today, but recently we announced a collaboration with the next generation anti-CTLA-4 antibody.

We think that's an important approach to be tested with what we believe is a better PD-1, and we are in conversations to collaborate with an EGFR antibody, as well as a novel ADC, and you'll hear more about those in the next few weeks. For 734, our lead indication is pancreatic cancer. However, as you saw today, over the weekend, we presented data in colorectal cancer as well in late line in combination with cetuximab. That is going to be implemented as a pivotal trial. In first-line pancreatic, we're well underway. The enrollment is going on globally and accelerating as we speak, and we're moving into the adjuvant setting in pancreatic cancer as well. In addition to the combinations with chemotherapy and cetuximab, we announced today and on Friday, three very important collaborations to continue to expand the scope of this program.

Those are with navlimetostat, PRMT5 inhibitor, with SNV1521, a PARP1 inhibitor. On Friday we announced a collaboration with petosemtamab with a focus on colorectal cancer. These novel combinations will allow us to continue to expand and improve, hopefully, the results that we're seeing with combinations with chemotherapy and existing EGFR inhibitors. Highlighting one more time the importance of the breadth of these programs that we're trying to address, a number of patients across two core indications to begin with, colorectal cancer and pancreatic cancer. A very strong focus for us initially on gastrointestinal oncology. As I mentioned, we have interest in continuing to expand and grow within GI oncology as well as other therapeutic areas. With that, I'm going to hand it over to Steven Stein. He's going to walk you through elements of the development strategy for these two programs.

Dr. Garralda and Dr. Hidalgo will then walk us through the data, and we will come back with more details.

Thank you. Thanks, Pablo. As Pablo said, we are going to focus on the solid tumor side of our development at Incyte.

Just to start you off on our brilliant logic on our numbering systems, INCA, and the A is the antibody, 33890 is our TGFβR2 antibody. It gives you some sense of the number of compounds that are screened before these things get into the clinic. I will refer to it as 890 going forward. Then INCB, in this case, a small molecule, 161734. I will refer to as 734 going forward, our G12D mutant-specific small molecule. I will take you through some of the development highlights related to this. We had four rapid oral presentations at ESMO, and I hope most of you saw them, but in case you did not, we will go through the data in them tonight.

Firstly, 890 in first-line MSS colorectal cancer in combination with standard of care chemotherapies. Very importantly, the ability to show you data with FOLFOX + bev in this setting, both in terms of response rates and some evidence of durability. In terms of 734 presentations in pancreatic ductal adenocarcinoma, and again, very importantly, with standard of care chemotherapies in both gem/Abraxane and modified FOLFIRINOX, which is somewhat of a differentiator for this compound. Then 734 in second-line colorectal cancer in combination with an EGFR inhibitor, cetuximab, was also an oral presentation. Lastly, not the focus of tonight, but as Pablo mentioned, 667, our CDK2 inhibitor in CCNE1, overexpressing in this setting platinum-resistant ovarian cancer with bevacizumab, but is a very good setup for going forward our maintenance study in platinum-sensitive ovarian cancer, but not the focus of tonight's presentation. Let us talk about TGFβR2 by PD-1.

We think, and as Pablo alluded to, this has the potential to be a next-generation immunotherapy backbone. Go beyond PD-1 alone and addressing probably the two most important tumor mechanisms in terms of evading the immune system in PD-1 and TGFβR2. Broadly speaking, the takeaways we would like you to get from what we are going to show you tonight is the ongoing development of this bispecific antibody in MSS colorectal cancer being the lead indication, and as Pablo said, well underway and enrolling very well, but with expansion opportunities in additional solid tumors. The first-line activity that we will take you through tonight we think is enabling in a large way for the ongoing first-line study.

We'll show you the FOLFOX-bev response rates and way above historical benchmarks for standard of care chemotherapies, and then the durability thereof as a read-through to potential down the line, both progression-free survival and an overall survival signal. In keeping with the rationale of the bispecific, the really encouraging and notable activity in liver metastasis, which themselves are TGFβR2 high expressing and supportive of the rationale in its entirety for developing this clever construct in terms of the bispecific antibody. Expanding, again with a phase II study, but an elegantly designed proof of concept in patients with MSS colorectal cancer who have had curative resection, attempted adjuvant chemotherapy, but are then ctDNA positive and then are treated with 890 for up to 12 months, and I'll show you that schema. High TGF-β tumors are PD-1 inhibitor resistant.