Arvinas, Inc. (ARVN) Earnings Call Transcript & Summary

All right. Good afternoon, everybody. Thanks so much for joining us at the Bank of America Healthcare Conference. I am Tazeen Ahmad, I'm one of the Smid biotech analyst here. It's my pleasure to have our next presenting company, management with us from Arvinas. I have 2 members from the team sitting right next to me on my right is Sean Cassidy, who is, of course, Chief Financial Officer. And to my left is Randy Teel, who handles Corporate and Business Development. Gentlemen, good afternoon. Thanks for coming out here to Vegas to join us at the conference.

Thanks for having us.

Yes, thanks for having us and Randy is going to wear another hat today, Chief Medical Officer for a good portion of these questions.

Oh excellence, can't wait.

The only thing he's missing is his stethoscope.

But we're not being on camera, so we could pretend that you're wearing a stethoscope anyway.

Perfect.

So maybe for those who may not be as familiar with the company. Randy, can you give us an overview of Arvinas, some of what you're known for and then we can go into more details on upcoming catalysts and programs?

Sure, absolutely. So -- and again, thanks for having us out here. It's nice to be in Vegas for a few days. So, Arvinas was founded 10 years ago. It's our 10th birthday this year, first company in protein degradation, our founder was Craig Crews. So we made a lot of progress in that time. And to fast forward all the way from those 10 years to now, I think we're at a point where we've got programs that are in late-stage development. We've got one program in Phase III right now, ARV-471, estrogen receptor degrader. It will start a second Phase III trial this year and another Phase III trial starting this year with ARV-110, which is our androgen receptor degrader. So multiple programs in late stage development. We announced earlier this year a couple of programs that we'll start and get to their IND stage this year, LRRK2 in neuroscience and BCL6 in hem-onc. So that will round out and then also planning to -- by the end of the year have a couple more programs get to their IND-enabling stage. So over the past 10 years to get to that point, obviously, a lot of milestones hit. We'd like to hope we're the first company to make oral degraders, get them across the blood-brain barrier, get them into the clinic, get some proof of concept and get into pivotal studies. And now that we're in the pivotal studies, we're looking forward to next year where we plan to have our first top line readouts.

Okay. Perfect. So there's a few protein degrader companies that investors take a look at. You're known specifically for your PROTAC discovery engine. Can you spend maybe a minute talking about how that works and how it is differentiated from other companies that call themselves protein degrader companies?

Good, Sean, do you want to take that one? Or do you want to...

Yes, I might well just take that, right? So if Ian Taylor was here, our Chief Scientific Officer, he'd tell a great story about the world-class organization that we have in our platform group, right? We're out there discovering new E3 ligases. We are using our internal [ del ] capabilities to find binders to those E3 ligases, find binders to undruggable targets and other things that are in our portfolio. And it is quite honestly a world-class organization as you look at that, potentially compare that to other protein degradation platforms. We are by far at the top of the stack. I think the best way, though, to evaluate the quality of a particular platform is the products that it actually produces. I think in terms of the number of products that the Arvinas platform has produced over the years, as well as the quality is just quite frankly second to none. As Randy mentioned in some of the opening comments, we have our Vepdegestrant program that's currently in Phase III trial, right? That's a partnership with Pfizer. We have bavdegalutamide, which is progressing towards Phase III in the second half of this year. We have a Phase II asset 766, which is a second androgen degrader. And Randy mentioned a couple of the other programs that have recently come out of research. And you can almost look at those particular programs as Arvinas 2.0, going after neuroscience targets like LRRK2 or going after BCL6, which is an undruggable target, really taking a look at the platform and not just deploying of those -- not just deploying the platform into known targets with known biology, where degradation gives you a different outcome, but looking at even harder to target.

Okay. So you mentioned several of your programs, maybe let's start off with the focus on breast cancer, which is, I think, where we all tend to get most of the questions regarding your partnership with Pfizer. So recently, you had some efficacy results from Part C of the Phase Ib study in combo with vepd and palbo. Can you just highlight what those top line takeaways were and what that might mean for the future of the program?

Yes, absolutely and you're right. I think for a little while now we've gotten a lot more questions on 471, but it has been true. I think today, we've seen an uptick in AR, so we'll make sure we talk about today as well. Yes, so the parts that you mentioned is a Phase Ib trial of ARV-471 or Vepdegestrant with palbociclib. And that is really a safety dose finding trial to identify the right dose of 471 to use palbociclib in the planned Phase III trial that is planned to start at the end of this year. And the data you're referring to actually to wind a little bit from that back last fall, we announced actually in January, just ahead of the conference in January, that is part of that trial, we've seen an elevation in the exposure of palbociclib and decided to go to the agency and talk about how to address that issue and came up pretty rapidly and we can go into this in a bit of how to address that with the safety lead-in for the Phase III trial. At the same time -- and when we did that, we decided that it didn't make sense to continue with the plan that had been the case to talk about that Phase Ib data in the first half of this year. We felt that it would be better to get through the FDA interaction before planning for a scientific disclosure. But we didn't want to let the year go by without any attention on that Phase Ib trial or the 471s potential in combo with palbo in that Phase III trial. So we did in our earnings release last week, announced that we had about a 60% CBR in that Phase Ib trial, which was a bit of an upside surprise for us since based on the results from the pace study last year, we hadn't really been expecting a benefit of palbo after palbo and -- but that 60% was versus about a 40% CBR that we had shown in our Phase I and 2 studies with 471 as a monotherapy. So it was nice to see that, good to see that in that Phase Ib trial, even though there were some patients getting dosed down due to concern, we still had a fairly robust CBR and we'll look forward to talking a lot more detail about that study and what else we've seen there in the second half of the year at a medical conference.

Okay. I think people also would appreciate getting some context around how that data looked in comparison to SERDs for example. Where do you think you have room for improvement just based on a limited amount of data that you have so far?

Well, the -- I mean, in terms of room for improvement, I think that for 20 years, a lot of companies, including us, have been looking for the next best fulvestrant oral degrader. And we think that 471, which is the only PROTAC degrader in the space, the others are all acting through a different mechanism. We do think that what we've seen preclinically will translate to the clinic as well. And we've been really happy with what we've seen both in the trial we just mentioned, but also in the VERITAC Phase II trial, where we've continued to show a very robust CBR higher than you'd really expect based on having patients that are all post CDK4/6. So we've been really happy with seeing that and keeping in mind how late the patients in our Phase I/2 have been, how many have been post-fulvestrant which is about 80% post metastatic chemo. We think that the efficacy results we've shown so far bode really well for the Phase III you talked about and the one we haven't talked about yet, which is the VERITAC-2 study, which is ongoing as monotherapy already.

Right. So let's maybe talk about VERITAC-2. Why is that going to be important?

Yes, so VERITAC-2 has the chance to be the first pivotal readout of a PROTAC degrader. And we're really happy with how we've designed that trial. And obviously, in doing that, look back at some of the trials in the space that have been successful like for elacestrant is now in the market, which is great for patients to have another option in late line care, as well as some of the trials that were less successful. And we think that, that trial where patients unlike in our Phase I and 2, those patients in VERITAC-2 won't have had prior fulvestrant, won't have had prior metastatic chemo. And when we look at those patients, even as a subset from our Phase I and 2 trials, we like what we see and we think it's a pretty high odds trial to be running. And like I said, that's planned to read out in the second half of next year and be our first option to actually get to patients.

And how big of a patient population do you think that would be?

Well, so that's a late -- it's a second line plus population. So we don't talk a lot about numbers of patients, but basically, everybody who comes into metastatic breast cancer is going to progress at some point and go beyond that CDK4/6 combination setting, pretty much everyone does that. And I think it's good to have another combination -- sorry, another treatment alternative besides chemo. So we think that opportunity is pretty sizable. We've been asked a lot of questions since the elacestrant approval about ESR1 mutant versus wild type. And we think we have -- we've designed that trial to be able to hit on either or both of ESR1 mutant population or overall. And as a reminder on that 40% CBR from our Phase I and 2 trials that I mentioned, that has roughly broken down to about 50% for ESR1 mutant patients and about 30% CVR for wild type. So we think there's very good reason to think we'll be able to hit both groups, which what I think would give us a big advantage in the late line setting.

Okay. Excellent. Let's maybe backtrack a little bit to the Phase Ib study that we talked about a couple of minutes ago on the combo. You were going to have more data present later this year. Can you just frame for us what exactly that was -- that will be and what we should consider to be good data from that?

Yes, absolutely. So, we've been pretty consistent despite the release last week that this is a safety and dose finding study. And obviously, with the release that we had in January, we've already gotten a little hint at both. So in January, we talked about the elevation by about 50% of palbo exposures versus historical. And for context for that, the palbo exposure is generally a sort of plus/minus 30% range. So we were a bit above that. And we had grade 3/4 neutropenia that was 76%, I believe, which was elevated from, I think, the mid-60s, which is what palbo had in its historical settings. So good would look like no other untoward effects besides what we've identified there. And I think in January, we said we haven't seen other effects beyond what you'd expect from each therapy as monotherapy. So that's the key thing. Obviously, now with the safety lead-in for the Phase III study, some of that dosing question is ending up -- has a little bit more information behind it. It looks like the 471 dose will be 200 and then the question in the safety lead-in for the Phase III is will palbo be 100 or 75 milligrams. So that's what we'll be looking to have more information on by the end of the year. And the Phase Ib will really be a traditional look at -- here's all the patients, here's tolerability. What we had last week didn't have a lot of the details that people will want. What percentage of those patients were ESR1 mutant or not or post CDK or not or plus fulvestrant or not. So there's a lot of questions that we'll answer in the second half of the year.

So in terms of venue, a medical conference to present that, should we think fall like ESMO or late in the year like San Antonio?

Second half of the year, there aren't a lot of options...

Yes.

You've named some good ones.

Okay. What's the rate limiting step here? Like when would, for example, you need to submit data to ESMO and that hasn't already passed?

Oh, for ESMO, no, it has not passed.

Okay. Got it. Is it realistic that it could be as early as September?

It's realistic, the thing in the second half is realistic.

Okay. Perfect.

But you've named the good options.

Okay. We're also trying to make sure that we book our flights early, so any help you can give with that would be great. So let's talk about VERITAC-3. Just give us an update on where you are with that right now?

Yes, so VERITAC-3 is that Phase III first one study. So we've said with Pfizer, we'll start that safety lead in the second half of the year. And the safety lead in and the randomized portion of the Phase III are 2 portions of the same trial. So that will get underway. We are very happy with that outcome. We definitely race through the holidays to get that FDA meeting request in and really got a really good outcome, which was that we could start planning for that safety lead in while we're also doing other work to better identify what that potential DDI could be and how exactly that would work. So we are set to start that safety lead-in portion in the second half of the year, get as quickly as we can to a view of the 75 versus 100. Yes, we'll have to go back to the agency there to finally align that and then hopefully get into the randomized portion of the study as quickly as we can.

Yes, I think we also were curious as to how that meeting with FDA went when you talked about wanting to add this lead-in portion in, was it as price to them? Do they give you the idea of what you would need to do in order to check off all the boxes? Or was this all kind of this proposal coming straight from Arvinas?

Well, we and Pfizer as well, I want to give them full credit because the back story here is we had been -- we had done our end-of-phase meeting in August with the FDA and then we're asked to come back with full dose data, right? So at that point, we had a lot more data for one of the doses than the other. And so there was no issue at that point, there wasn't the sign of the palbo question, but they said come back. So we did the data cut in November to go back in December, but as we were working through that data cut in December, that's when we saw the elevated 50% increase in exposure in the neutropenia question. So we decided at that point, it didn't make sense to push forward with the plan because clearly patients were getting down dose from the 125, so that's when we went with Pfizer to the FDA with that plan. And really it is, I think, what we wanted. That's what we went in with. Clearly, 125 wasn't the dose, 175 could both work. And so that's what we're now set to resolve.

So how much does this delay you versus where you might have been if this observation didn't happen?

Well, it's clearly a delay, right? I mean we didn't plan to start the study in the first quarter of the year and it's hard to predict exactly how long we'll have to go, do the lead in, get those data, take it back to the FDA, get the clearance to go ahead. But I think the upside of that is that normally when you start a randomized trial, you've got that period before the hockey stick starts. And since it's a seamless trial with patients that beginning on that same protocol, we think it will be very rapid to get going once we are in that randomized portion. So clearly, it's a setback, haven't talked timing specifically and I think we're all motivated to get it going as rapidly as we can.

Okay. Now I guess keeping in theme with the SERD universe, what's your view about -- I guess, there was a recent approval for or SERD u. What do you think does that change anything about your own internal views about what the bar needs to be -- to be a successful drug?

I don't think so, from a regulatory perspective, it's not the borrow rate, it's not what we're being compared to. I think certainly, when we're out in the market and patients have options, I think we need to show that we're better sure, I think that's fair.

And by better, like maybe just give people a context just a little bit better...