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

Okay. Great. Good morning, everybody. Sorry, I had some technical difficulties and hopefully, we won't lose audio during the presentation. So thanks for joining us. I'm Tazeen Ahmad. I'm one of the senior biotech analysts here at BofA. It is my pleasure to be spending the next few minutes with Arvinas and joining us from Arvinas this morning is Randy Teel. So Randy, good morning. How are you?

Good morning, Tazeen. Thank you for having us.

Of course. So maybe just do a quick overview of the company, if you could. I think most of us are familiar, but just give us a sense of what the platform is and some of the advances that the company has made over the last year, there's been a few. And then we can go into more detail about some of the things to look forward to.

Absolutely. And I, of course, have Ron Peck, our CMO, on as well, who will handle a lot of the heavy lifting when it comes to the clinical trial starts and ongoing data with respect there. But yes, thank you again for having us, Tazeen. So Arvinas was founded back in 2013 coming out of IP from Craig Crews at Yale University and it's fun to think about that 9 years later. I think we could probably come up with 40 or 50 names of protein degrader companies off the top of our heads that are better [ suppose the first ] in the space and we're proud to be where we are. So we're largely focused in oncology neuroscience. The 3 programs that we have in the clinic right now, one for estrogen receptor in breast cancer and two, for prostate cancer that target the engine preceptor, but we've also got some neuroscience programs coming on as well, at least one of which will have a name we expect before the end of 2023. And in terms of the platform, I think we're differentiated in a couple of ways. I think first is really around productivity, what we've created, which is those programs we have in the clinic, at least two of them, we consider to have proof of concept of showing some initial Phase I efficacy and tolerability and excited to be where we are and both of the programs that are out front, 471 breast cancer and bavdegalutamide or ARV-110 in prostate cancer, who will be in Phase III pivotal trials by the end of next year. So the 471 [will continue] starting by the end of this year. One is monotherapy and one in combination with Ibrance or palbociclib and ARV-110 in the Phase III study by the end of next year. So I think getting to that point, some people are quite proud of it. And then when it comes to the platform itself, we feel very confident that the strides we've made in ligand screening, progress with identifying and leveraging new E3 ligases, ability to predict and model trimer formation, building a drug like properties, we're investing to make sure we stay out front. Maybe before we pass over to Ron for some more detailed questions, I can go through what's coming up for the company. I just mentioned for ARV-471, that we'll plan to start two pivotal studies by the end of the year. In addition to that, we also plan to be or have already put in [indiscernible] the [neoadjuvant] space in combination with everolimus and an umbrella trial with our partners at Pfizer assessing some other combination agents with 471 and then we'll have data by the end of the year as well. So that's data from our Phase II, which we call VERITAC that will be coming up by the end of the year. And then on the prostate cancer side, it will actually be the second antigen receptor program, ARV-766, that we expect to share data by the end of the year for the Phase I escalation and we think we'll start its Phase II by the end of the year. So a whole lot coming up in a [couple months].

Right. Okay. So a question that we get all the time from investors still is your partnership with Pfizer. And 471 in particular, how did that come about? There are a lot of now protein degrader companies, both private and public. And I think that people want to read the tea leaves as to what Pfizer may or may not have seen. At this point, are we correct in assuming that whatever they saw is already in the public realm? And why did you think that Pfizer would be the best partner here going forward?

Yes. So we initiated those conversations back in the wake of our data around San Antonio in 2020. So in December is when we showed the first Phase I data for ARV-471. And at that point, it really gave us the confidence that based on what we had seen at that point that we could really aim to try to make ARV-471, the endocrine therapy, ultimately across the backbone of care [indiscernible]. And so that really opened our eyes to the potential, right? And we're starting with that Phase I and the Phase II in very late line refractory patients. But ultimately, we would like to move earlier to first line, likely in combination and even into the adjuvant space, which is a pretty large unmet need. And if you could get an endocrine therapy like an ER degrader into that space, I think it would have a lot of potential. And so really, we -- what we were looking for in partnership with Pfizer was we felt pretty good coming out of it in 2020. We had just done a capital raise as well. But what we really were interested in was the ability of a partner to accelerate and broaden that development. So give us the confidence and capability to move earlier into first line, ultimately into adjuvant and [indiscernible] process there and Pfizer ultimately turned out to be a great partner and has been for the past almost 1.5 years. Obviously, [aligned] in breast cancer, but that's really what the driver was -- run and accelerate the program.

Okay. Now -- so we think it makes sense to start on the refractory patient population, but how long do you think it will be before you're able to kind of move up in the lines of therapy? And how should we think about these -- the percentage of patients who have ER-independent disease in second line and higher? And how does that influence how you think about the opportunity in the earlier lines of therapy?

Well, why don't I -- I'll talk for 10 seconds and pass to the CMO. Yes, so by the end of the year, we'll start the trial in earlier metastatic breast cancer, too. But beyond that, Ron would be best equipped to...

Yes. So -- thank you for including us. So as Randy said, we are going to be starting two Phase III studies imminently. So the first in a later line, where we've seen our initial data, and we've been very excited about what we've been seeing in that setting. And then second would be in combination with Ibrance in the frontline setting. So the intent is that we would be starting these 2 studies in parallel, and that gets to the question of how soon will we move into the earlier line. We'd like to get into the earlier line as soon as we can. There's even a bigger opportunity that we have talked about since the partnership with Pfizer and that is adjuvant therapy. So we haven't provided any specific guidance on when we would be interested in going in that direction. But certainly, one step in that direction is that we will be starting before the end of this year in neoadjuvant proof-of-concept study in that earlier setting, really more just to get some data in this population. And if nothing else, it provides more momentum amongst investigators to be able to get the interest in doing a large adjuvant study. We also are very interested in looking at opportunities further down the line to build out a robust lifecycle program and that comes into the way of starting to test newer combinations. So we are initiating a trial with everolimus, which is a targeted therapy that has been used in conjunction with endocrine therapy, has been approved about 10 years ago. So we are initiating a Phase Ib study this quarter. So that's already on clinicaltrials.gov. And then we have another trial that was just posted as well with Pfizer, which is referred to as the umbrella study, which is essentially a -- we'll call it an incubator for multiple combinations that could position us for a very robust lifecycle program with the intent that 471 would be the drug of choice or the backbone of choice for all patients with ER+ breast cancer. And that trial was just posted starting with the first combination of abemaciclib.

Okay. And as far as designing these studies goes, how have you been interacting with Pfizer? Are they in charge of it? Or are they seeking your input?

So before we -- before we had the agreement signed, sealed and delivered, one of the metaphors that we had used in discussions with our partners was the concept of a co-piloted arrangement, which means that this is, aside from the 50-50 economics of the deal, this is truly both teams working together and in conjunction. We have a very experienced clinical team. A lot of us have spent years in big pharma and have even worked on breast cancer drugs. And a lot of us actually even have relationships with some of the folks in the past, who are on the other end of the deal with Pfizer. So this is -- and it's worked out quite well. So this is truly a codirected program.

So maybe a question about safety for 471. I think you will have Phase Ib safety data coming out in the beginning part of '23. Was that delayed from what your original time lines were?

So we had initially guided towards the end of the year. One thing that we have been doing in general, as we've matured as a company or a clinical stage company, is move away from interim updates. I think for our early data or bavdegalutamide especially, we were -- we had multiple interims of a Phase I study and we just thought that we did not need to do that anymore. The added thing for 471 is that we've got a partner who obviously will have the same kind of mindset. So we decided that we would wait for this Phase Ib to be more mature and put the expectation out in the first half of next year. That does not, though, in any way, mean that there is a change in our strategy. We have still guided towards the end of this year for the initiation of these 2 Phase III studies. So that does not -- that should not be interpreted as anything other than just getting away from interims.

And what should we expect to see on the safety profile based on what you know?

Well, the safety profile, it's essentially looking, of course, at the combination of palbociclib and 471 and if you just take those individual components apart, palbociclib, its main toxicity is neutropenia. There are a couple other things that don't overlap with whatever a ER-directed therapy could do. We are gratified in the safety profile that we have from Phase 1 with 471, where we had in 60 patients, no dose-limiting toxicities all the way up to 700 milligrams, very -- only, I think, one discontinuation and one dose reduction -- and overall, it's really just a profile that we've heard really good things about from the investigators. So in essence, our expectation is that we would not expect surprises. But of course, you have to do the trials to do that. So that Phase I is to see how the profile looks, make sure there's nothing unusual, untoward. And then number two is around pharmacokinetics. And so going into the trial from a PK perspective, we were not expecting essentially going into this thinking that there's a low likelihood of drug-drug interaction. And one thing I'll just bring up is that while we have not shared data, we have been just giving enough of a sort of a foreshadowing to say that thus far, we have not seen any impact on exposures for 471. We have done this because of the recent news with Sanofi discontinuing their program and their SERDs had an association with a drug-drug interaction with palbociclib resulting in lower exposure. So we felt like we needed to be preemptive to say that our drug does not have the same profile as theirs in terms of their drug being a 3A4 inducer, ours is not and we also felt the need to just kind of preempt to say that we had not been seeing the same impact on exposure. So I just wanted to kind of head that off.

Okay. Yes. We have been getting a lot of questions on that as well. Let's move to the Phase II VERITAC trial for a second. What should we be expecting for the readout for the second line plus patients? What are some of the key differences maybe in your trial design or the patient population that you're enrolling here versus what we saw for Phase I?

Yes. So to just take one small step back for the audience. So this is our Phase II expansion. It was part of -- it was a seamless Phase I/II trial, and it was looking at 2 different doses, 500 milligrams and 200 milligrams, both of which are well within exposure ranges that we were shooting for based on preclinical data. And the trial is designed to really inform the optimal selection of a Phase III dose. It was actually designed before the FDA started to put more scrutiny on optimal dose. So we were fortunate to have done the right thing in the beginning. In terms of population, it's actually quite similar to the Phase I. The one thing that we take efforts to just orient about for the trial and especially the Phase I initially was that this is a population where 100% of patients had received a prior CDK4/6 that is unlike the trials with the SERDs that have been in development in terms of Phase I data for, I think, maybe with the exception of maybe one trial. So ours is 100% [co-CDK]. That's going to also be the case for the Phase II expansion. We also do permit chemotherapy. There is a slight difference in that we have permitted up to 3 lines of chemotherapy for the frontline, which is pretty significant. And for Phase II, we limited it to one prior chemotherapy, which is essentially the same as all the other trials. So it still will be chemotherapy pretreated. So with all that taken together, what our -- what we guide in terms of what good looks like based on what we see in Phase I is, in Phase I, we saw a clinical benefit rate of 40%. That was data back at San Antonio last year. Put that into context, there's molecular profiling data that's been published to say that 2/3 of patients have ER-independent resistance once they progress through CDK. So it's important for us to orient towards that because there's a ceiling for how much -- even the miracle ER therapy could work in. So that's why we are so excited with our Phase I data. And if we can see CBR rates that are in that high 30%, 40% range, then that is a sign that we're essentially looking to max out on the benefit for those who still have ER dependency. So that piece one is CBR. And we will also have safety in all patients as well. I mentioned the safety profile from Phase I. And it's really, I think, essentially more of the same relative to safety.

And when should we expect to see on that?

That will be San Antonio this year.

Okay. Should we expect to see anything on PFS?

Well, what we said in the past is that our intent was not to include PFS. The data snapshot that was driving this abstract was really to focus on the primary endpoint, which is clinical benefit rate, which means that there has to be a follow-up of at least 6 months from the last patient. PFS doesn't normally mature with that sort of follow-up. So we just wanted to guide towards the primary endpoint of efficacy CBR. So -- but we will certainly intend to share the PFS once it's mature, sufficiently mature to share with the investor committee.