Arvinas, Inc Wells Fargo 21st Annual Healthcare Conference

Thank you very much for having us.

Absolutely. Thank you again for having us. It is definitely a time of good change for us. I would say maybe four things to start off. First of all, it is great that we have a product that is in the market now. Vepdegestrant, which we have sold and another company is now commercializing, is getting to patients. Being a company that has invented a technology and then brought the first one all the way through regulatory approval is really rewarding, and we are excited to see that. I think two is, we are at a point where we have turned a corner from having the attention be on the pipeline writ large to the programs in that pipeline now getting very close to having data.

The conversations that we are having today and this week are very different than we were having 3 months ago, now that we have multiple programs which we will go through that all have data really coming in the next 15 months or so. Across the pipeline, we have got four essentially in the clinic now. ARV-393 is a BCL6 degrader in hematology. That program will have its first phase I clinical data by the end of the year. The second one I will highlight is an SBMA program. Kennedy's disease is a rare disease, and we have a program that degrades polyglutamine repeat AR, or androgen receptor. That program will have its first phase I clinical data in the first half of next year in both healthy volunteers and in patients with SBMA. ARV-102 is our LRRK2 degrader for neurodegeneration, relevant for both progressive supranuclear palsy and Parkinson's disease.

That is a program that has completed a phase I in Europe, and we have now got a number of regulatory body conversations going on at once across the U.S., Europe, and Japan. In the middle of that, we will share some additional biomarker data from the phase I study next month at MDS, so data coming there. The fourth program is an HPK1 degrader called ARV-6723. That program is just beginning in the clinic in this current quarter. It is our first IO program, so wouldn't guide to data there yet, but maybe expect by the end of next year or so. That means that now, as we have turned a bit of a corner from vepdegestrant to the pipeline, the pipeline is really coming into relief, which allows us to talk about expectations, lets investors really ask questions in detail about what is coming.

I would say on the backdrop of that, I would say that since I took over as CEO about 6 months ago, I have been really clear to say that we will invest and be very careful to invest only where we think Arvinas is the right company to do that, and also look for opportunities to partner where it makes sense. I think we have already taken some decisions, most specifically around our G12D degrader, that illustrate that program. That will actually have data coming, but we have already said we will only progress if a partner is found to take that forward. The last thing I would say is from a capital perspective, our current guidance says cash into the second half of 2028, which allows us to get comfortably past all the milestones that we will talk about today.

It's a great place to be. As I've taken over leadership this year, we've continued to focus on making sure that we are running as efficiently as we can be to make sure that we can get to the most important milestones, which are, of course, the clinical data that's now coming up. It's a great time to be looking at Arvinas and talking about it as we've transitioned to the pipeline and now very specifically to the programs that are about to share data.

Yeah. From a high level, the BCL6 program was one of our first programs that was squarely aimed at an undruggable target. Our first historical targets were AR and ER. BCL6 was one that no one had degraded before. It's been gratifying to see that as multiple companies have come to the clinic with that as a target, it certainly looks like a good target to be degrading. The program that we're running right now is a phase I dose escalation study. We have a broad range of patients across both B-cell lymphomas and T-cell lymphomas. The data that we will share by the end of this year or so will be biased towards the patients with T-cell lymphomas. We're also already thinking about a 2027 disclosure where we will share data and focus on B-cell lymphoma patients, both as monotherapy and in combination.

That's a program that most folks are asking about, that data coming up in the very near term. In terms of the benchmarking that we're doing, as we think about T-cell patients, most studies in their phase I dose escalations have not been run in patients with T-cell lymphomas. They're generally large basket trials across B-cell and T-cell. As we look at what good could look like, we look at what's on the market now, and if you're a patient who's being treated for second-line AITL, what are you expecting to receive? At that point, you're expecting something like a 35%-40% response rate. Again, for therapies that are on the market.

In a dose escalation trial where we already know that a large number of the patients will be dosed below the efficacious range, hitting that as a target would be great to do. But we will look even harder at efficacy as we get into expansion phases and start to expand at doses. What is really clear in the NHL space is that while there is a lot of competition for bispecifics and CAR-T and so on, there are not a lot of oral therapies that could look to displace non-oral therapies and either displace chemo in some settings combined with others and really provide new options to deepen and extend responses for patients across NHL.