Arvinas, Inc Morgan Stanley 24th Annual Global Healthcare Conference

Yeah, thank you very much, Terence, and thanks for having us at the conference. Maybe also definitely talk about that as we go through the day or through the half hour. I want to talk a little bit about the company and where we are right now.

Sure. Mainly because we've been around a little while, right?

The company is now 13 years old and has certainly gone through some phases. We really have led the way in PROTAC discovery and development, and it's been really gratifying that just in the past few months, the first program that we invented is now in the market and serving patients. So it's off treating second line plus breast cancer patients, which is obviously pretty thrilling for all of us at the company to have discovered the technology and have the first drug out in the market. We have now shifted, as we'll talk a lot about, to our earlier stage pipeline. So we decided to not invest in the commercialization of that, but to focus our capital on the phase I programs that we have, that we now have 4 of.

I think one important feature for investors looking at Arvinas these days is that we've been talking for a while about milestones and catalysts from that pipeline coming out in the future, and now the future is very rapidly approaching. So as we sit here in September and look out over the next year and a half, all 4 programs, including one that's just starting in the clinic this quarter, I would expect to have important data coming out. So just to set the scene a little bit, we've got 4 programs in the clinic. The first is a BCL-6 degrader for hematology indications and subsets of NHL. That program will have its first data by the end of the year. We've got a neurodegeneration program that degrades LRRK2 that will have some important biomarker data coming up at a conference next month.

We just began a rare neuromuscular program for Kennedy's disease, also known as SBMA. Started that in the beginning of the year. It's been enrolling well, and we expect to have data in the first half of next year. To round it out, we have an HPK1 degrader for use in immuno-oncology indications just starting in the clinic in this current quarter. No commitments on data yet, but starting the trial now, maybe we'd expect to have data in a year or so. We've been pushing those programs forward, I think, very effectively. We have made some important decisions. To get to your point on priorities and prioritization, over the first 6 months of my tenure here, we've tried to be very focused. I've tried to lay down a very clear priority that where we invest, we're going to invest to win.

If we don't feel like we're positioned to do that will be a place for someone else to jump in, and we'll talk a bit about that. The last point I would make is, from a capital perspective, our guidance is into the second half of 2028, so we certainly have the capital we need to get through these important inflection points. When it comes to my initial priorities, it has really been to look at the pipeline. I've been at the company for 8 years, so it is not as if I've learned a great deal about the company in my first few months as CEO. I certainly continue to be impressed and amazed and proud of the team that we have and how well we've done at moving important programs into the clinic.

Right now it's really about moving those phase I programs to their inflection points and seeing where the data are, where they end up, what makes sense as next steps for each program, whether that's to pile in and invest more, whether that's like happened for the KRAS program earlier this year, we decided that would only move forward with a partner, whether that's the call. That's what we're thinking about. Also making sure that we turn ourselves a bit from being a company that was on the precipice of being a commercial company to now being back to a company that's in phase I. Those companies look different. They operate differently, they feel differently, and it's been very important to me and the team that we ensure that we are acting like a young phase I company and not a company that is about to be a commercial breast cancer company.

Yeah. ARV-393 is a degrader for BCL-6. BCL-6 really, given our history, I'd say our formative years in AR and ER as our first targets, BCL-6 was one of our first targets that's certainly an undruggable. There had been BCL-6 inhibitors moving through preclinical studies, none really that I know of made it to the clinic. One reason for that is, and that makes BCL-6 an ideal target for a PROTAC degrader, is that deep degradation of BCL-6 is important. It's rapidly resynthesized. BCL-6, just for a little more stage setting, is an important factor in B-cell development, functions in germinal centers to allow B-cells to rapidly allow to develop into mature B-cells and allow some DNA mutation without apoptosis that's important for B-cell maturation. It should turn off after that. If it doesn't turn off, that's where you start to have problems with BCL-6.

Yeah. The study that we're running is in subsets of NHL.

We are enrolling pretty broadly across both B-cell lymphomas like LBCL and T-cell lymphomas like AITL. The landscape in that setting, which is an important context, is pretty crowded when it comes to other therapeutic modalities. If you're looking at antibodies, bispecifics, chemo, there's CAR T therapies, there's transplant as an important modality. It's pretty crowded. If you're looking for oral therapies it's not very crowded. If you're looking for BCL-6 target agents, it's not very crowded. The way that the space has typically evolved is to add on additional therapies to deepen and extend responses, and that's what we'd like to do with a BCL-6 grader. You made a point in your question about the conduct of that trial.

We have been clear to say that, for a couple of factors, we began that trial dosing at levels that we did not expect to be efficacious. We've made it through a few rounds of enrollment in different cohorts at levels that, especially in B-cell lymphomas, we would expect to be below an efficacious range. As we get to that first data, what we've decided to do is focus the first data release, by the end of this year, more on the T-cell lymphoma patients, and then save a disclosure for B-cell lymphoma patients more for the middle of next year or so. That allows us to focus on a population with very high unmet need, which later line, second-line plus T-cell patients certainly are.

Also, just through the way the trial was run, we mentioned about a year ago that we had seen responses in both T-cell and B-cell lymphomas. I think that unmet need absolutely led to an enrollment of a disproportionate number of T-cell patients versus what we would have expected. So we are going to focus on them first. The other thing that does is that as we get to the B-cell patient disclosure, more focused on those patients next summer, we also can discuss our ongoing combination therapy. We have an escalation ongoing with ARV-393 as monotherapy, but we are also dosing with glofitamab in patients as well. That will allow us to disclose both of those next year. So when it comes to this first data disclosure, there really is no specifically indicated therapy for second-line plus T-cell lymphoma patients.