My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler. And before I begin, I'm required to point out certain disclosures regarding the relationship between Piper Sandler and Arvinas that are posted at the back of the room and also at the registration desk. Arvinas is a leading protein degrader play developing vepdegestrant, formerly ARV-471, to treat breast cancer with Pfizer. And they're also conducting phase one studies of ARV-393 targeting BCL6 for B-cell malignancies and ARV-102 targeting LRRK2 for Parkinson's disease. And earlier this year, the company partnered androgen receptor degrader ARV-766 with Novartis for prostate cancer. Here with us today from Arvinas are Chief Medical Officer Noah Berkowitz and also Andrew Saik, the CFO. Great to have you both here, and nice to get to meet you in person. It's a pleasure. Great to be here with you. So I'll start off with Vepdegestrant. You guys are conducting a broad clinical development plan here in metastatic breast cancer. Maybe you can start by reminding us of the phase 2 VERITAC monotherapy data that you reported and really why you selected the 200 mg Vepdegestrant dose? Yeah, thank you for the question. So we reported out some of the results from that expansion last year. This was on the heels of work we did in phase one to look at different doses. In the end, we were also looking at a 500 mg dose. But when we looked on balance at the exposure response relationship we were able to model and also the safety profile of the drug, we decided that we could get just about all the benefit we were at a slightly lower dose than that 500. So we decided to move ahead with 200, not dissimilar from how most, I think, all companies would make a decision. And we were pleased with our decision because as we reported out last year, the 200 mg monotherapy dose was able to prove itself in patients with hormone receptor positive metastatic breast cancer in the second plus line setting. So when we were looking at patients that had been heavily pretreated, so they were really mostly third, fourth, fifth line treatment, we observed that with the 200 mg dose, they were able to achieve median PFS of about 3.5 months in wild-type patients and 5.7 months in patients with ESR1 mutations. When we looked at how heavily pretreated these patients were, that benefit was seen despite the fact that patients had prior CDK4/6 therapy and 74% of patients had prior fulvestrant therapy as well as chemotherapy. So it was a very compelling data set for demonstrating that monotherapy can have impact in this setting. Yeah. On the basis of that, we chose to move ahead with that dose and schedule in the second line setting. I'm sorry, in a phase three study called VERITAC-2. That sounds about that. Yeah. Tell us about the trial design and we should be getting data out. I think you're either done dosing patients or we should be getting it kind of early next year if I'm not mistaken, right? Right. So we've guided to top line results in the first quarter of next year. This is a study that started two years ago in which we randomized patients to fulvestrant or to vepdegestrant at 200 mg a day. These patients are being treated until progression, which is common in this setting. We've accepted patients that have had, they need to have had prior CDK4/6 therapy. They may not have had fulvestrant or chemotherapy in the past, and they should have had, and they must have had, I should say, at least six months on their prior endocrine therapy. So this was designed to ensure that we'd have a study that's more like in the second, third line setting and also would enrich for patients that have endocrine sensitivity, which would help us. We expect to do extremely well in the ESR1 mutant population I described earlier, 5.7 months median PFS, but on top of that, we are hoping that we can enhance endocrine sensitivity in the wild-type patients, so we randomized the patients, 624 in the end. We completed enrollment in the second half of this year as we had projected, and as the data have matured, we've had to move out the primary completion date a little bit as we wait for events, but our guidance now is for the first quarter of next year, which isn't too far away. Remind me, is the trial stratified for ESR1 versus wild-type? Tell us sort of how the readout could come? Sure. We have co-primary. We do stratify patients for ESR1 mutation or wild-type or non-mutation. There are two co-primary endpoints in the study for which we split our powering. We're looking at the ESR1 mutation patients alone, and we'll look to compare, you know, create a hazard ratio comparison for vepdeg versus fulvestrant. Then we also look at the entire patient population. That will include the ESR1 mutants and the wild-type patients. We call that the ITT or intent to treat population, all-comers. That also we are comparing the vepdeg to fulvestrant. We haven't guided towards what our operating characteristics are for the statistical plan in the study, but suffice it to say we plan to see, you know, three to four months of median PFS in the fulvestrant arm and a few more months of median PFS in the investigational arm. And that's on PFS, yeah. Now, you guys are also planning to combine Vepdeg with really other agents, including Pfizer, CDK4/6, palbo, their selective CDK4, atirmociclib, or even other CDK4/6 as that landscape's changing just a little bit in first-line patients. Remind us of the phase 1b palbo-vepdeg combo data that you've reported. And what's going to go into this decision of what you take forward? Sure. So just taking a step back, and I'll get to that in a second, one could say that we have a three-step process for bringing this drug to the broadest market. We're starting off with the monotherapy in the second line setting. And hopefully within a year, we can have approval of that drug in that setting. But then on the heels of that, we expect next year to start a first line combination study, as you said, with either Palbo or atirmociclib, atirmociclib being their up-and-coming and very promising CDK4 inhibitor. And in the second line, to start a second line study with Palbo and/or another CDK4/6 inhibitor. Now, those will read out in a few years. So imagine two years after our initial approval for monotherapy in the second line setting, we can expand that with a combination therapy in the second line setting. A year or two after that, read out a first line study and gain approval in the first line setting. So it would grow the opportunity for this drug, but obviously make it available to more patients in need. So that's the overall intent. In terms of first line, we reported out some exciting results last year, just a year ago now at the San Antonio Breast Cancer Symposium, which is this year's conference is next week already. We demonstrated that when we combined Vepdeg with Palbo at the standard 125 mg dose for Palbo, that we were able to achieve an 11-month PFS on average. And also about 60% of patients achieved a clinical benefit rate. And almost 40% of patients had an objective response. So that was very promising because those types of results hadn't been seen for any combination of a CDK4/6 with other agents in the second line plus setting. We observed that there was a lot of neutropenia, though. And when we spoke to health authorities, it was recommended that we find a lower dose before bringing that into the first line. And so two things have happened over the course of this year. We've moved ahead with finding a safe and efficacious dose for Palbo at lower doses to be combined with Vepdeg in the first line. And we've also now combined Vepdeg with atirmociclib, that's that up-and-coming CDK4 inhibitor, Pfizer. And we've been dosing patients. We're in the expansion portion of that phase one two study. And if we could find you know a safe and effective dose with atirmociclib, I think we and Pfizer would be very excited just to move forward with that because that represents the future, not the past. Palbociclib was a great drug a few years ago. Atirmociclib is going to be the leading drug, we believe, in a few years. And so we're well on our path to establish that. And we hope to provide updates next year about this plan and narrow it. And if all goes well, maybe with atirmociclib. Great. Awesome. We'll look forward to that. Now, I know there's some other studies too that are running TACTIVE-U, for example. That's what some of the other CDK4/6 is. So that could read forward into your future second line study, whether it's with palbociclib or one of those. Also with everolimus and TACTIVE-E, neoadjuvant. And then I think you guys are in a cohort in I-SPY, which is that kind of big investigator-sponsored, but it's really a cohort group trial. What should we expect for any of those? Do they add to this sort of three-tier strategy to get vepdegestrant approved? Or are they sort of maybe things that have kind of fallen off in importance as the landscape's changed? Right. I don't think that these fall off in importance in any way, but they aren't necessarily going to lead to an obvious registration path. I think it's important in drug development to not only map out some broad indications to make sure that you have a label that can support patients with metastatic breast cancer, but you want to make sure that physicians have data available to them to use it in other combinations if they choose to. We won't promote on that basis, but they ask for the data, and we want to provide it. And that's why we've done work to combine with everolimus. We're sharing data next week at the San Antonio Breast Cancer Symposium about the TACTIVE-U study abema arm. So we'll show a cohort of 16 patients who receive Vepdeg and Abema and how they tolerate it well. The safety profile appears to be similar to what Abema single agent or combined with fulvestrant does. Then we'll share the efficacy already. That wasn't in the abstract, so I'm not going to mention it here. People will have to look at our poster next week. The idea is to look at what is the CBR, what's the objective response rate, how does this compare with what we showed last year for Palbo. That can inform a second line study, but also just practice for physicians when the drug is eventually approved. It's true for the other combinations you mentioned as well. I-SPY is certainly not a registrational intent study or not preparing for one, but again, finds matches physician interest with the novelty of this new drug. That's important in drug development to maintain that level of innovation and interest. Yeah, I agree. I'll just pause quick to see if there's any questions from the audience on vepdegestrant. So in April, you guys partnered ARV-766 for castrate-resistant prostate cancer with Novartis. Can you remind us the deal terms and what really are Novartis' development plans from here? What can you share with us? Yeah. So the deal terms, what's public is, you know, $125 million upfront and then milestones and royalties on the back end, right? So we handed that over to them, phase 3 ready. And, you know, the deal rationale, Ted, was really around, you know, you're looking at financial considerations in partnering, right? So from a financial standpoint, we're an early stage biotech company. We can't do everything. So by giving that to Novartis, freed up cash to progress the rest of our pipeline, including LRRK2, BCL6, et cetera, right? The other consideration is that Novartis was interested in doing earlier stage, which would have been really challenging for us. And I'll let Noah speak to the development program, although it's in Novartis' hands now. But that was a program that we wouldn't have been able to do. So the impact to patients, it's actually better off in Novartis' hands because they're going to get more reach in terms of the studies that they're doing. Yeah. And just to add on that point, Andrew, so we had done the work for castration-resistant prostate cancer patients and ready to march forward there. But the larger opportunity and maybe greater need for innovation is in the castration-sensitive patient population. Novartis is evolving as a leader in the prostate cancer space. They had a great interest in the castration-sensitive population, are developing a rapidly expanding portfolio around Pluvicto, their radioligand therapy for prostate cancer. They were the obvious choice for this licensing. And we're really pleased that they'll be able to bring this drug to as many patients as possible. Yep. Awesome. So huge fan of the pipeline progress and appreciate, you know, taking those dollars and focusing it on some of the earlier stage degraders. ARV-393 targets BCL6 for B-cell cancer. I know you guys are in phase one. What can you tell us about this target in this study? BCL6 has been a long sought-after target for lymphomas. We know that it's an important transcriptional repressor that allows B-cells to mature in the germinal center. So they use this protein to shut down the pathways that would normally lead to cell death because of DNA damage as they go through some DNA rearrangements in the cell to make mature B-cells. So when it goes awry, you leave this activity in place and the cell is somewhat resistant to these normal pathways of preventing tumorigenesis or in this case, lymphomagenesis. So people haven't been able to develop inhibitors and bring them to the clinic. It's been tried for decades, but hasn't succeeded. We have a degrader. So we're able to find a good binding site, build a degrader, degrade BCL6. We have great preclinical data and more to share next year. So far, we've shared mostly the monotherapy data from the preclinical models. We'll be able to move to combination therapies. And we think that this drug has a lot to offer in the lymphoma space. It doesn't appear to cause marrow toxicity. So it can combine well with many drugs that are making a real difference, such as bispecifics, rituximab, tafasitamab, and other drugs that are becoming more standards of care in large B-cell lymphoma and follicular lymphoma. ARV-102 targets LRRK2, which is an emerging and maybe not quite as well known, but a very well validated target for Parkinson's disease. Describe the target to us and some of the biology around it and why it makes sense to degrade with a PROTAC. Thanks for the question. We're very excited about our LRRK2 program. So as you say, there's been a lot of validation for LRRK2. We know that it can explain that mutations in LRRK2 can explain a lot of sporadic or idiopathic Parkinson's disease. But there are unique mutations, heritable ones that are associated with heritable Parkinson's disease. So in particular, you look in the Ashkenazi Jewish population, we see in that population, there's a higher risk for Parkinson's disease. It's often been associated with a mutation called G2019F. And so this particular mutation, if it's there, your risk is much higher. There are other types of founder mutations in the population. All of this suggests this is a gene of interest. But we've learned more about the LRRK2 involvement in an important pathway in the brain. The brain has to dispose of a lot of proteins that are produced and maybe become, also have to be degraded, right, and accumulate when their destruction and disposal is in disarray, so normally lysosomes are involved in the destruction of these proteins, but LRRK2 is important in normal lysosomal trafficking, so when LRRK2 has mutations, it may affect the normal trafficking and disposal of proteins, and it can lead to things like an accumulation of tau, for example, so Parkinson's disease and progressive supranuclear palsy, which are tauopathies, at least in part, and are diseases, as I've told you, are genetically linked to LRRK2. It looks like biologically we can link LRRK2 to those diseases as well, so with that validation, we've decided let's go after LRRK2 degradation rather than inhibition, which let's say Denali has gone after in their partnership with Biogen. What we like about degradation is that it's not just the kinase activity of the protein, of the kinase that we're eliminating, but we eliminate its GTPase activity, its scaffolding activity. There are many things that LRRK2 does. Maybe it's not enough to inhibit the kinase. And so by degrading that LRRK2, which we can do very well in animal models, we're able to potentially limit that tauopathy that accumulates. Now, we've shown in non-human primates that we can degrade the LRRK2 in the brain to very high levels. And we can correlate that degradation with an improvement in some biomarkers that are associated with LRRK2 dysfunction. We can reduce those biomarkers that accumulate. And now we're dosing human beings. And our goal is to show that we can also reduce LRRK2 in human brains by measuring the CSF, the LRRK2. And then when we go to Parkinson's disease next, which, you know, is around the corner for us, we'll also look at whether or not we can reduce those biomarkers. That's great. Really excited for our data from that. Now, are these two more examples that might be good partnerships for BCL6 because of the complexity and the combination therapy in lymphoma for 102, maybe because it's in the neuro? Or are these things you want to take further yourselves? Yeah. So we look at each compound differently, right? So to answer your specific question, for 102, we are not seeking a partner for that. We're very happy to take that through the phase 1s and hopefully at least through phase 2. It's a good space for us. We don't view ourselves as an oncology company. We are a protein degradation company. And we're building our internal knowledge in neurology and have zero problems running trials in neurology. With regard to BCL6, we'll see. So that one may lend itself to combinations and to the extent that we find a partner who has the other side of the combination, that could make sense to partner, right? But I think, you know, we have some work to do on that. We want to get through the monotherapy. We want to, you know, do the combination studies hopefully next year. And then we'll see how that goes. But that one's probably a better candidate to partner. Makes sense. Andrew, you guys ended the third quarter with cash, very healthy balance sheet, $1.2 billion. How long does this fund the company? And what's it enable you guys to accomplish? Yeah. I mean, we have cash, we believe, into 2027 as it stands. So we don't have a huge need to go out and do a big raise. Having said that, we have an exciting 12 months ahead of us, right? So we have VERITAC-2 data coming out hopefully in the first quarter. We've guided to it. We've got early stage LRRK2 data out probably in the spring, right? So we're targeting April for that. So depending upon how those studies go and how they read, that could give us opportunities to bring in new investors, in which case, you know, we would happily do that and take more money. And then it'll just give us more longevity. But we don't feel a huge need to do raises in the near term because we're well funded. Great. Excellent. Well, thank you guys very much for being with us. Thank you. Okay. Thanks. Appreciate it. Thanksgiving Day on the NFL broadcast. Yeah. Good afternoon, everybody. My name is Ted Tenthoff. I'm a senior biotech analyst at Piper Sandler. And before I begin, I am required to point out some disclosures regarding the relationship between Piper and our next presenting company, Dyne Therapeutics, which are posted at the back of the room and also at the registration desk. Dyne is developing targeted oligonucleotide therapies to treat muscular dystrophies, having reported positive phase 1/2 data on DYNE-101 for type 1 myotonic dystrophy, and also delivered data on DYNE-251 in DMD. Here with us from Dyne is President and CEO John Cox, Chief Medical Officer Doug Kerr, and also Oxana Beskrovnaya. Thank you. I am glad.