Prelude Therapeutics Incorporated Chardan's 10th Annual Healthcare Conference

Sure. Great. Gautam, thanks for having us. It's great to be here. It was almost a year ago to the day that we announced a pivot of the company in which we were going to focus on three programs. The first being our JAK2, JH2 program. The second is our KAT6 degrader, and then third is the mCALR program. Each of these have one sort of thing in common, if you will, and each of them are clinically validated targets, and that really formed the basis of our pivot.

Since then, and as led by Kris, our founder and CEO, we have been just focused on execution, making sure that we are able to advance JAK into the clinic, which we did in the second quarter of 2026, advancing KAT6 as fast as we can for breast cancer, and having that program in the clinic, which we just had the IND clear for, and we anticipate enrolling fairly soon. Then advancing the mCALR program, which is an important target for the MPN community. In terms of the next 12 to 18 months, it is really going to be marked in two halves. The first half is we are going to have clarity, if you will, on whether or not Incyte will exercise the option.

Right. That should give us, if the option were to be exercised, $100 million in non-dilutive financing.

Number two, by the second half or in the second half of 2027, we anticipate revealing initial proof of concept data for our KAT6 degrader program, which, as I suggested a minute ago, is just entering into the clinic shortly. So hope that gives you a little bit of a sense of where we are in 2027 as well.

Yeah, I can start with that. With the KAT6 biology, it's pretty clear that KAT6A is amplified in ER-positive breast cancer. Being amplified and overexpressed, it really drives the whole estrogen signaling biology as well as Myc regulation and cell cycle genes. So it really has a strong role in driving breast cancer growth and survival. I think the Pfizer data has really validated that. They see in ER-positive breast cancer monotherapy responses of about 10%, and especially in combination with fulvestrant, they have responses in the mid-30s.

Yeah. Then progression-free survival of 10, 11 months.

So it's pretty striking data. Ours is a differentiated approach to build on that. Pfizer as well as Olema and maybe 10 more KAT6-targeted therapies target both KAT6A and KAT6B, and they're inhibitors. Ours is very different. Ours is a KAT6A selective molecule, and we're a degrader. We think that's important for a couple of reasons. One is, we think by targeting KAT6A selectively because it drives the tumor biology, and sparing KAT6B, which has a role in bone marrow development- that we can have a greater therapeutic index.

The main dose-limiting toxicity observed with the Pfizer compound is neutropenia.