Prelude Therapeutics Incorporated H.C. Wainwright 28th Annual Global Investment Conference

Yeah, absolutely. First of all, thank you for the opportunity to participate in the conference. Prelude, as you said, is a precision oncology company. We're clinical stage, and we're advancing multiple differentiated programs against clinically validated targets. Why is our patients with cancer need better therapies? We have the team that we've built over the years that have tremendous amount of experience in discovering and developing novel molecules, and we are really target-centric and modality flexible. Given our technical capabilities and expertise, we don't need to be a sort of a kinase or a degrader or any of the specific target types. We are able to go across multiple target types, and we really focus on mechanisms that are clinically validated, meaning that the biology is de-risked, and there is still a significant opportunity to improve upon what's out there.

Our current pipeline is very much reflective of that, and I'll spend a couple minutes going over that. But over the course of next 12 to 15 months, we have a number of very important data catalysts and potential value inflection opportunities, and we are laser focused on executing on what's ahead of us. Our lead program, or the one that's farthest along, is our JAK2 V617F selective inhibitor. It's a kinase inhibitor. The space is MPNs or myeloproliferative neoplasms, where there is three of them, and there's 200,000 patients in the U.S. alone that have these disorders, and the first-generation molecules, one of which we, our team, helped develop, JAKAFI. They're good. They're very effective from the symptom and other standpoints, but they really are not very disease modifying, right?

Because they don't target the very mutation that is involved in driving disease in majority of these patients. Our team, based on our not only discovery experience, but understanding of the clinical problems that these patients face, developed a very interesting molecule that is currently in the clinic, and we're enrolling patients. We are going after both PV, polycythemia vera, which is one of the largest number of patients within MPNs, as well as more serious disease called myelofibrosis. We can talk a little bit more about that. Our second program, a KAT6A selective degrader, we just recently announced we cleared IND, and we are about to start enrollment in the fourth quarter.

This is something that is very exciting in breast cancer, HR-positive breast cancer, more specifically, where we are seeing more and more oral SERDs that are actually coming in, but really not meeting the goal of earlier stage therapies where earlier lines of therapy where you need to be active in all patients and not just only ESR1 mutant or those specific populations. KAT6 emerged as a really exciting novel mechanism. The clinical data with Pfizer, PF-07248144, demonstrated very good response rate and PFS, but it comes with a significant hematological toxicity. That is a problem because if you want to be able to deliver a drug with full dose intensity and combine with earlier lines of therapy, such as CDK4/6s, you need to be able to have cleaner hematological safety profile.

We believe our KAT6A, based on the biology, genetics, has the ability to really do that and significantly expand the opportunity to create value for patients across all lines of therapy. That is about to start clinical trials. The third one, which we are really excited about but still in the discovery phase, is our mutant CALR degrader antibody conjugate. Again, it is a clinically validated target. The antibodies that inhibit the signaling of CALR receptor in ET or essential thrombocythemia, as well as MF can have significant clinical benefit for these patients. They appear to be primarily the benefits coming from type I mutations. There are almost half of ET patients have non-type I mutations who do not seem to be benefiting just by signaling inhibition alone.

We developed a degrader antibody conjugate where we can deliver a very potent payload that we designed to be safe and can really kill the disease-initiating cells. We will be giving a little bit more detail on that program relatively soon. Basically, we have these three assets that are going to be generating very meaningful data and have the opportunity to leapfrog the ones that are ahead of us, and we have the capital to advance these to key inflection points. 2026, rest of 2026 and 2027 will be pretty exciting years for Prelude.

Yeah, I'll start, and I'll let Bryant, our CFO, go through the mechanics of that. The idea behind that option agreement is that Incyte was in the clinic with their lead JAK2 V617F inhibitor program. We believe that they have the ability to develop these assets well. We entered into this option agreement where they can It's a time-based agreement where they can make a decision in terms of acquiring our entire program. Currently, we are responsible for running the phase I trial of our lead program, PRT3789. But if they opted it, they could take it over. Bryant, you want to talk a little bit about that?

Yeah. Just in terms of the mechanics, it was a $60 million upfront, broken into two parts, $25 million in cash, $35 million in equity. As Kris just mentioned, there is a time-based option of 15 months, not about 15 months, that expires in February of 2027, with a potential for a 3-month extension, so that would take you to May call it, and that would trigger a $100 million milestone payment. Then we move into the milestones section of the agreement, which is up to $775 million in milestones together with low single-digit royalties on the back end.

Yeah. Just to add to that, these milestones are primarily- Clinical and regulatory clinical and regulatory.

They're not something sales-based or a later stage.

No. There's two aspects to it, right? One is, a question that we often get asked is that, is there any read-through to, because of the technical challenges, issues that they had to our molecules. Answer to that is no. Because we're fundamentally completely different scaffold, completely different molecules. Our program is not built on Incyte's chemical scaffold. So there is no read-through at all related to that.