Thank you for standing by. At this time, I'd like to welcome everyone to Arvinas's third quarter 2024 earnings call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you'd like to withdraw your question, again, press the star one. I will now turn the conference over to Jeff Boyle. Please go ahead. Good morning, everyone, and thank you for joining us. Earlier today, we issued a press release with our third quarter 2024 financial results and a corporate update, which can be accessed in the investor section of our website at arvinas.com. Joining the call today are John Houston, Arvinas's Chief Executive Officer, President and Chairperson. Noah Berkowitz, Chief Medical Officer, and Andrew Saik, Chief Financial Officer. Angela Cacace, our Chief Scientific Officer, will join for the Q&A portion of the call. Before we begin, I want to remind you that today's discussion will contain forward-looking statements that involve risks, uncertainties, and assumptions. These factors are outlined in today's press release and in the company's recent filings with the Securities and Exchange Commission, which I urge you to read. Our actual results may differ materially from what is discussed on today's call. I'll now turn the call over to John Houston, our CEO, President, and Chairperson. John? Thanks, Jeff. Good morning, everyone, and thank you for joining us for our inaugural earnings conference call. So, why are we starting earnings calls now, some six years after our IPO? Well, we have a truly exciting year ahead of us, and we are on the cusp of a huge transition for the company as we await our first pivotal data readout coming by the end of 2024 or the first quarter of 2025. In addition, we continue to make significant progress with our novel approach to discover, develop, and commercialize a new class of medicines for the treatment of cancers and neurodegenerative diseases. As we look now forward to providing updates each quarter as we move closer to our goal of becoming a multi-product commercial stage organization with a robust pipeline across several indications. We have a lot to discuss this morning, so I'd like to provide an overview of the topics we'll be covering. I'll begin with a brief overview of Arvinas, our PROTAC discovery platform, and an update on our pipeline. Noah will then provide an overview of our expectations for the VERITAC-2 trial and discuss our confidence in the combined ability of vepdegestrant or vepdeg with other metastatic breast cancer treatments. And finally, Andrew will provide an overview of our third quarter financial highlights. I'll add some closing remarks, including what we believe is the opportunity for vepdeg, both as a combination and monotherapy, before opening the call for Q&A when, as Jeff mentioned, we will be joined by our Chief Scientific Officer, Angela Cacace. In the 11 years since our founding, we have taken major strides towards our mission to improve the lives of patients with serious diseases. Our pipeline of PROTACs, or PROTAC protein degraders, have been designed to harness the body's natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. This groundbreaking protein degradation platform has enabled us to create an exciting pipeline, driving some of the most significant breakthroughs in targeted protein degradation in the industry. These breakthroughs include designing degraders with drug-like properties that are orally bioavailable and, when needed, able to cross the blood-brain barrier. Very soon, we'll have in hand the first-ever phase III data readout for a PROTAC. While the majority of our call this morning will be focused on our progress with vepdeg, we will also briefly cover the advancements we've made with our other clinical programs. In future calls, we will provide a deeper dive into our exciting pipeline that spans oncology and neuroscience. Our most advanced program, vepdeg, is an orally bioavailable PROTAC protein degrader, specifically designed to target and degrade the estrogen receptor for the treatment of patients with ER-positive, HER2-negative breast cancer. vepdeg works by degrading the estrogen receptor to block signaling through the pathway. By degrading the estrogen receptor, we believe vepdeg could potentially benefit patients with breast cancer who have ER-positive, HER2-negative disease. As a reminder, in 2021, we entered a global 50/50 collaboration agreement with Pfizer to develop and commercialize vepdeg as a potential next-generation ER-targeting backbone therapy of choice in breast cancer, as both monotherapy and in combination with other therapies. Together with Pfizer, we initiated the first-ever phase III trial with a PROTAC, the VERITAC-2 trial. This is a randomized, open-label, multi-center trial of vepdeg versus fulvestrant in patients with ER-positive, HER2-negative advanced breast cancer whose disease progressed after prior endocrine-based treatment for advanced disease. The readout of data from this pivotal phase III clinical trial will be a landmark event for Arvinas. We are on track to share top-line data by the end of 2024 or the first quarter of 2025, based on timing of events. If positive, these results will support our first new drug application and our potential transition to a commercial stage company. If proven effective, vepdeg can offer an oral monotherapy treatment in the second-line setting, which could be a promising option for appropriate patients progressing on a CDK4/6 inhibitor-based regimen. For context, approved ER-targeting treatments provide a few months of progression-free survival in this setting. A once-daily oral monotherapy that offers a clinically meaningful improvement in PFS, and is well tolerated, could be an important advance for patients and commercially very attractive in a highly fragmented second-line treatment landscape. Additionally, we continue evaluating vepdeg in combination with other agents, including the approved CDK4/6 inhibitors, ribociclib, and abemaciclib, in the ongoing phase I-B/II TACTIVE-U umbrella trial. We look forward to presenting initial phase I-B data from the abemaciclib sub-study of TACTIVE-U in a poster at the San Antonio Breast Cancer Symposium later this year. The TACTIVE-K trial, which is evaluating vepdeg in combination with Pfizer's CDK4 selective inhibitor, atirmociclib, continues to enroll patients. I will now turn to our earlier stage programs, where we see exciting potential opportunities for PROTACs across oncology and neuroscience targets. First, neuroscience is an area where the unique properties of PROTAC degraders are particularly well-suited, especially given the potential drawbacks of other drug modalities like antibodies and antisense oligonucleotides. Our most advanced neuroscience program, ARV-102, is a novel oral PROTAC designed to cross the blood-brain barrier and target leucine-rich repeat kinase 2, or LRRK2, which is a large multi-domain scaffolding kinase. We have shown that ARV-102 achieves deep brain region penetration and degradation of LRRK2 in non-human primates. We've also observed differentiation from inhibitors by showing improved effects on lysosomal dysfunction and movement of disease-relevant biomarkers in the central nervous system in preclinical studies. We intend to explore the potential of ARV-102 in two severe neurodegenerative disorders that are linked to LRRK2 dysregulation: progressive supranuclear palsy, a disease with a strong genetic link implicating LRRK2 with faster progressing disease, and Parkinson's disease, where LRRK2 has been shown to contribute to the pathology of the disease. Earlier this year, we initiated dosing in a first-in-human phase I clinical trial of ARV-102 in healthy volunteers. This ongoing phase I trial is primarily designed to establish the safety of ARV-102, but will also measure LRRK2 degradation in the periphery and cerebrospinal fluid, or CSF, to establish the ability of ARV-102 to cross the blood-brain barrier and degrade LRRK2 in humans. The learnings from this phase I trial will be valuable as we strive to address the incredibly high unmet need in neurodegenerative diseases. We look forward to sharing initial data for ARV-102 in 2025. We are also working with The Michael J. Fox Foundation's Parkinson's Progression Markers Initiative to identify novel LRRK2-dependent proteins that are altered in non-human primate CSF following administration of ARV-102. We recently presented at The Michael J. Fox Foundation's annual Parkinson's Disease Therapeutics Conference, where we disclosed new preclinical biomarker data for ARV-102. To our knowledge, this is the first data set to demonstrate that the degradation of LRRK2 induces changes in pathway biomarkers of lysosomal function and inflammation in the CSF of non-human primates, an exciting discovery suggesting that the PROTAC mechanism may lead to differential outcomes versus LRRK2 inhibitors. The presentation is posted in the scientific publication section of our website. Turning now to our third clinical program, we are also pleased with the preclinical profile of ARV-393, our PROTAC designed to degrade B-cell lymphoma 6 protein, or BCL6, a transcriptional repressor and a major driver of B-cell lymphomas. The BCL6 protein facilitates B-cell tolerance of rapid proliferation and somatic gene recombination through the repression of cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response, which becomes dysregulated in several types of non-Hodgkin lymphomas. PROTAC-mediated degradation has the potential to overcome the traditional undruggable nature of BCL6. We are recruiting patients with non-Hodgkin lymphoma in a phase I clinical trial of ARV-393 and look forward to updating you on our progress next year. Finally, we are preparing to file an investigational new drug application in 2025 for our KRAS G12D program. KRAS is a driver oncogene in several major tumor types and is associated with poor prognosis and resistance to standards of care. We are also developing a novel pan-KRAS degrader and look forward to sharing more about this as we progress this promising program. With that, I'll turn the call over to Noah for a more detailed overview of the vepdeg program. Noah. Thanks, John, and good morning, everyone. I'm happy to provide an update on the progress we and our partner, Pfizer, have made with our vepdeg program. Let me first note that even with the recent advances in treatment options, there is still a high unmet medical need in ER-positive, HER2-negative metastatic breast cancer. Despite the availability of multiple therapies, as patients move into the late-line setting, most will experience disease progression within a few months of initiating treatment. Also, the tolerability and/or route of administration of available therapies may adversely affect patients' quality of life. We believe vepdeg has the potential to become a best-in-class backbone ER-targeting therapy with superior efficacy and tolerability, which could support it becoming a preferred and valuable treatment option for physicians and their patients. This is why I'm excited to discuss the VERITAC-2 trial, our second-line plus phase III trial with vepdeg, which is on track for a top-line data readout by the end of 2024 or in the first quarter of 2025, with timing driven by accumulation of PFS events. The trial is evaluating the efficacy and safety of vepdeg compared with fulvestrant in patients with ER-positive, HER2-negative advanced breast cancer. The patients enrolled in VERITAC-2 have previously received and progressed on a combination of CDK4/6 inhibitors and endocrine therapy. VERITAC-2 has two co-primary endpoints: progression-free survival, or PFS, in the ITT or intention to treat population, and PFS in the ESR1 mutation subpopulation. PFS will be assessed by blinded independent central review. Secondary outcome measures include overall survival, anti-tumor activity, including the objective response, duration of response, and clinical benefit rate, and safety and quality of life assessments. Although important progress has been made in treatment of metastatic breast cancer for patients who have received prior treatment with CDK4/6 inhibitors, the most recently approved oral agent has an approval limited to patients with ESR1 mutations and has shown a median PFS of 3.8 months. The VERITAC-2 study of vepdeg is in CDK4/6 inhibitor experienced patients and was designed to demonstrate a benefit over fulvestrant in both the ITT and ESR1 mutant subpopulations. Now, let's discuss our expectations for the VERITAC-2 trial. Based on our study design, we expect to show a meaningful improvement over fulvestrant. We look forward to sharing top-line data in the coming months and submitting this for review to health authorities. If successful, this may result in the first-ever regulatory approval of a PROTAC degrader and act as the first step in establishing vepdeg as a backbone therapy of choice. In addition to the phase III VERITAC-2 trial, as John mentioned, we and Pfizer continue to evaluate data from several additional studies to inform the design of the potential phase III combination trials that we anticipate will start in 2025, pending regulatory feedback. One is the second-line plus setting, and the other is in the first-line setting. We will evaluate data from TACTIVE-U, TACTIVE-K, and the study lead-in portion of VERITAC-3 to inform our decision about which agents can be combined with vepdeg. Preliminary data from the combination of vepdeg and abemaciclib will be presented at the San Antonio Breast Cancer Symposium in December. We believe these data will show a manageable safety profile at the full doses of both agents and that the preliminary PK safety and early efficacy will reinforce the potential of vepdeg to be used in combination with standard-of-care breast cancer agents. With respect to other sub-studies within TACTIVE-U, enrollment is ongoing, and we anticipate that initial data from the ribociclib combination will be available next year. We expect these data will further show vepdeg 's potential as a backbone therapy of choice. We are also making progress in the phase I/II TACTIVE-K trial, which is evaluating vepdeg plus Pfizer's novel CDK4 inhibitor, atirmociclib. We and Pfizer look forward to evaluating data from this trial later this year, which we will use to inform the design of our phase III trial in the first-line setting. Overall, we believe vepdeg has the potential to provide superior efficacy and tolerability, both as a monotherapy and in combination for patients with breast cancer who are in need of new treatment options. With that, I'll now turn the call over to Andrew for a review of our financials. Andrew? Thanks, Noah. I'm pleased to share financial highlights for the third quarter ended September 30th, 2024. As a reminder, detailed financial results for the third quarter are included in the press release we issued this morning. As we near our first phase III trial readout, we are in a strong financial position with cash on hand sufficient to support our operations into 2027. At the end of Q3, we had $1.1 billion in cash, cash equivalents, and marketable securities on the balance sheet. This allows us to progress all of our key strategic objectives, which include progressing the vepdeg clinical program, including two expected phase III programs starting later next year, preparing for our first launch of a commercial product, and advancing our promising portfolio of PROTAC degraders. Let me now turn to financial highlights from the third quarter. During the quarter, we recorded $102.4 million in revenue. That was compared to $34.6 million in revenue for the same period in 2023. The increase of $67.8 million was primarily due to revenue from the Novartis license agreement of $76.7 million, offset by a decrease in revenue from the vepdeg collaboration agreement with Pfizer of $7.6 million, and a decrease in revenue from Bayer of $1.1 million. General and administrative expenses were $75.8 million in the third quarter, compared to $22.6 million for the same period, 2023. The increase of $53.2 million was primarily due to the termination of our laboratory and office space lease with 101 College Street of $43.4 million, as well as increases in personnel and infrastructure-related costs of $5 million. Research and development expenses were $86.9 million in the third quarter, compared to $85.9 million for the same period in 2023. The increase of $1 million was primarily due to an increase in personnel-related expenses of $2.8 million, partially offset by a decrease in program-related expenses of $2.2 million. As we embark on a pivotal year for Arvinas, we are focused on making strategic investments in programs that are meaningful to patients and truly differentiated. I'm confident that a strong balance sheet will enable us to accomplish our objectives. With that, I'll turn the call back over to John for closing remarks. John? Thanks, Andrew. This is clearly an exciting time for Arvinas. We are well on our way to becoming a commercial-stage organization with strong leadership and a rich pipeline across multiple therapeutic areas. In partnership with our colleagues in breast cancer at Pfizer, we have an exceptional team of experienced leaders who stand ready to bring vepdeg to breast cancer patients in need of new treatments. We believe that the upcoming top-line data from the phase III VERITAC-2 trial will be the first step in establishing vepdeg as a backbone therapy, first as a monotherapy, and over the next few years in combination with other treatments. Every year, nearly 40,000 patients with metastatic breast cancer are treated in the second-line plus setting, with approximately one-third receiving monotherapy treatment. In the first-line setting, another 40,000 patients are treated every year, and most of these patients will receive a therapy as part of their treatment. By establishing vepdeg as a monotherapy in the second-line plus setting, we have an opportunity to lay the foundation to potentially change the treatment paradigm for many thousands of patients with advanced ER-positive, HER2-negative breast cancer. In addition to vepdeg, we're advancing a broad pipeline of product candidates across several therapeutic areas, including hematology and neurology, with our PROTAC discovery engine. Before opening the call to your questions, I'd like to thank the patients and physicians who are participating in our clinical trials. I'd also like to thank our talented and dedicated Arvinas team and our partners in breast cancer at Pfizer for the hard work and passion they bring every day. Our progress would not be possible without their commitment. And lastly, I'd like to thank our shareholders for their continued support. With that, I'll now turn the call over to Jeff to begin the Q&A portion of our call. Jeff? Thanks, John. Before I turn the call over to the operator, I'll ask that you limit yourself to one question per cycle to make sure we're able to give appropriate time to everyone. Feel free to rejoin the queue for any follow-up questions. And with that, operator, can you please open up the queue? Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a question, please press star one on your telephone keypad to raise your hand and join the queue. If you would like to withdraw your question, simply press star one again. If you are called upon to ask your question and are listening via loudspeaker on your device, please pick up your handset and ensure that your phone is not on mute when asking your question. And your first question comes from the line of Akash Tewari with Jefferies. Your line is open. This is Manoj in for Akash. Thanks for taking our question. So just one. Should investors' base case be that Pfizer moves with their CDK4 combo with the vepdeg, not only for the first line but also for the second line? Why would IBRANCE or any other CDK4/6 combination be used at all in your pivotal studies if CDK4 inhibition shows meaningfully better hematologic toxicity? Thanks for the question. Could you just repeat the beginning of the question? Should the base case be like Pfizer moves with the CDK4 inhibitor combo with vepdeg in the first line and second line? I see. So you're asking whether or not our base case should be in the first line, CDK4 plus vepdegestrant, is that right? Yes. Yeah. No, it's a great question. And clearly, first of all, we're very excited about the fact that our data is right on our doorstep. So by the end of this year or beginning of next year, we'll have our pivotal data. We're also excited by the fact that we have a combination ongoing with atirmociclib. Clearly, that's a very exciting asset. I think if we end up choosing, as with Pfizer, that that is the combination partner, I think that would be a great step forward. But obviously, we've got data ongoing with our palbociclib combination. We'll have that data this year and allow us to make decisions next year with Pfizer and the combination. But yeah, I think we'd be very excited if the data tells us that the CDK4 vepdegestrant combination is the right one. We'd be very excited. Yeah. Thank you. Thank you. Next question comes from the line of Brad Canino with Stifel. Your line is open. Good morning, and thank you for the updates. Question for me on the upcoming abemaciclib combo data. Could you help frame that expectation relative to the palbociclib combo data you presented last year, where you had the 11-month PFS and a strong response rate, activity in both ESR1 mutant and wild type? Is that the bar as we think about additional CDK combos that you will be unveiling over the next several quarters in these pretreated phase I-B populations? Thank you. Yeah. Thanks. Great question. Clearly, we were very, very excited about our data set with the palbociclib combination. And I'm going to hand this over to Noah in a second. The thing to remember is that data set, that was not 100% patients that were CDK4/6 experienced. 86% of patients are CDK4/6, and then 14% didn't. In this trial with abemaciclib, when you see this data, it's 100% post-CDK4/6. So just with that caveat, I'll ask Noah to make some comments. Sure. So we had the benefit when we reported the results of the palbociclib vepdeg combination last year to have long follow-up of patients. And so that's why I think you referenced the median PFS we observed there. But in addition, as you suggested, we were able to look at response rate and safety in that population. So I would view this smaller data set that we're going to be presenting from abemaciclib with shorter follow-up as a data set that can inform about the efficacy of the drug, but looking at things like the response rate, which can mature further, and similar for CBR. And then on top of it, the safety profile, which will include actually even more recently treated patients and will be a larger data set. And then you can make that type of comparison. Got it. Thank you. Next question comes from the line of Etzer Darout with BMO Capital Markets. Your line is open. Great. Thanks for taking the question. Thank you for the updates today. Just a question around the fulvestrant control arm for VERITAC-2. We've gotten questions on that. Sort of if you could maybe frame your expectations, and do you think sort of there's anything we can read through to the Lilly upcoming data sets around sort of where sort of that control arm lands and how it actually could perform for VERITAC-2? So anything incremental on your expectations around that? Thank you. Yeah. Great question. And again, I'll be handing over to Noah just to give you some detail in terms of the answer there. Clearly, the design of our VERITAC-2 trial was based on standard of care, which was fulvestrant, still is. And our design is to show that we can be superior to fulvestrant. We're also very excited to see what the EMBER-3 data will show when it comes out. And clearly, we want to be able to look at the different patient populations there. Again, VERITAC-2 will be 100% CDK4/6 experienced patients. And when we look at EMBER-3 data, you want to be able to look at that data and be able to do the kind of like-for-like comparison. Noah, do you want to say any more about the fulvestrant control arm and how that might be compared to what the Lilly might do? Sure. Thanks, John. And thanks for the question. So overall, it's difficult, obviously, to predict exactly what we're going to see from the fulvestrant arm. We expect that given the prior treatment that patients have experienced, it'll be somewhere in between what was observed in the EMERALD study and what was observed in the postMONARCH study. So we would expect it to be somewhere in the three- to four-month range. And by comparison, we would hope to see a few months better for the vepdeg arm. And in terms of that second part of your question about EMBER-3, we don't know exactly what to expect from that. What we'll be looking at is what is the safety and tolerability of that combination, and also in what patient population. When you look at the inclusion criteria for EMBER-3, it looks like patients who were not CDK4/6 exposed could be enrolled in the study. So we'd have to understand the results in the context of prior CDK4/6 exposure to draw any comparison to our study. Great. Thank you. Next question comes from the line of Ellie Merle with UBS. Your line is open. Hey, guys. Thanks for taking my question. So I guess into VERITAC-2, how are you thinking about the potential for success in the non-ESR1 population? And if you could sort of review the reasons you think that this could be successful. And then what do you think is the minimum threshold for success here on PFS to be able to get this broader label across ESR1 and non-ESR1 patients? Thanks. Thanks, Ellie. That's a great question. And again, I'll be handing over to Noah for the specific answer. Clearly, in this second-line plus patient population, we are fighting against the biology of the disease. Obviously, a significant part of the disease is driven by ESR1 mutation. We think around 40% of the patients will have tumors that are still endocrine sensitive. And then there's a large group of patients with tumors that have got wild type and other driving mutations. And we think a slice of that patient population will also be able to react well to vepdegestrant. So just remember that there's that biology there, the disease that we're fighting against. But yeah, Noah, do you want to be specific about? Sure. Not a lot to add there because I think you addressed it, but I would say that our expectation is, as you know, we have co-primary endpoints in the study. We're looking at the ESR1 mutant and ITT population. So our expectation is that we're going to be successful with those primary endpoints. Our base case for what will be approved is the ESR1 mutant subpopulation more than anything else because that's the precedent that's been set at regulatory bodies. What we'd have to see, though, in the non-mutated patients would be some type of. I would assume regulatory bodies will want to do some post-hoc analysis, and we'll be looking at that with them. And we'd want to see some benefit, though I'd remind you that the study is not powered for that population. We believe that it would be successful, as John outlined, because the underlying biology of the wild type population is that many of those patients are still endocrine sensitive and don't have alternative driver mutations that might limit their responsiveness to vepdegestrant. So we remain pretty confident that we can see a positive result for ESR1 mutant and for the ITT population. Thanks, Ellie. Great. Thanks. Next question comes from the line of Derek Archila with Wells Fargo. Your line is open. Good morning. This is Yvonne for Derek. Thanks for taking our question. One from us, can you help frame a little bit the market for vepdeg, assuming you hit stat sig in both ESR1 mutant patients and wild type? And what if you only hit in the ESR1 mutant patients? Are there any good analogues there? Thanks. Yeah. Thanks for the question. And clearly, we think there's a significant opportunity here, specifically for monotherapy, then even bigger opportunity as we move into second-line combination and first-line combination. I think, as I said earlier, nearly 40,000 patients with metastatic breast cancer are treated in the second-line setting. And right now, about a third of them are getting monotherapy treatment. And then in the first-line setting, it's another 40,000 patients that are diagnosed every year. And the majority of those patients will receive any of therapy as part of their treatment. So we believe the game plan of establishing vepdegestrant and its potential as a monotherapy in that second-line plus setting will give us the opportunity to lay that foundation to potentially change the treatment paradigm for those many thousands of patients that have got ER-positive HER2-negative breast cancer. Of course, if we can show a PFS in line with combination therapies, we believe we can grow the monotherapy opportunity significantly. I just wanted to offer one comment, not addressing the underlying market question, but you had mentioned stat sig for wild type and for ESR1 mutant. So again, I wanted to remind that the study design is to look at and we'll be doing our statistics on the ESR1 mutant and for the ITT population. We're not doing stats for the wild type subset of the ITT population. I just wanted to make sure that was clear. Next question comes from the line of Li Watsek with Cantor. Your line is open. Hey, good morning, guys. And thanks for taking our questions. I guess for the phase III combo trials in first-line and second-line, wondering if you can elaborate a little bit on the key regulatory inputs that you still need before you nail down the final design and how much of that is still dependent on the data that you'll need to generate? Thank you for the question. Yes. The question is about the key regulatory thinking in terms of the path forward for our first-line and second-line combos. Noah, do you want to talk to that? So again, these are ahead of us. So after the VERITAC-2 results, which we're expecting in Q4, Q1, we head into the planning for next year that I think you're alluding to, which is combinations for first and second line. Each of those requires a health authority discussion. You've seen in our guidance that we and heard in our conversation a moment ago that we're looking to combine in the second line with palbociclib and/or another CDK4/6 inhibitor. And in first line, we can be combining with the atirmociclib or palbociclib. And we've also shared that we're very excited about that opportunity if we can combine with the atirmociclib. So there are different considerations for each. It depends on what is the comparator arm for in each of these studies. We haven't announced that. So that would be a discussion point with regulators, the exact patient population that's being chosen. And particularly in first line, there's no doubt we'd get into a deeper conversation about contribution of components if we're using two novel agents. But we believe that there are a lot of supportive data that will allow us to navigate that discussion. But at this point, that's probably the most guidance we can offer about what the regulatory discussion might look like for combinations in those settings. Next question comes from the line of Ted Tenthoff with Piper Sandler. Your line is open. Great. Thank you very much. And thanks, guys, for hosting this call today. It's nice to get to hear from you and get the update. I know there's a lot going on. I know most of the questions have been on vepdeg, but just to ask with Novartis and ARV- 766, what's the latest there? And how do you and they anticipate advancing that in prostate cancer? Thank you. Thanks, Ted. Great question. Yeah. As you know, we did the out-licensing of ARV-766 earlier this year, and we spent the last several months in the process of handing over data and materials, all the information that's needed to get Novartis up and running to progress ARV-766. Clearly, the excitement for us in terms of doing that out-licensing was Novartis's commitment to go into early prostate cancer, and that is the game plan that they still have, so they'll be looking at early and late-stage prostate cancer using ARV-766, and we think, based on the interactions we've had, they're well on track for that. Obviously, now with it being out-licensed, all of the kind of significant updates will come from Novartis themselves. But we are really pleased with how the transfer of information material went and the game plan that Novartis has actually shared with us on ARV- 766. 766. And of course, we'll be able to share in the future scenarios for ARV- 766 as it progresses. And we're looking forward to getting updates from Novartis as it does. Thanks, John. Thanks, Ted. Next question comes from the line of Tazeen Ahmad with Bank of America. Your line is open. Thanks. Good morning. Maybe to switch topics to ARV-102, can you talk about the size of the PD population that you're specifically examining that have this elevated LRRK2? And how are you going to use the biomarker to determine segmentation of the population? Thanks, Tazeen. Great question. We have in the room here with us Angela Cacace, our Chief Scientific Officer. And I'll hand directly over to her to talk about the answers to those questions. It's a great question, so the estimated size of the population that's believed to have elevation of LRRK2 is about a third of the idiopathic Parkinson's disease population, pretty sizable, and so it is still under active investigation how you would actually employ the biomarkers that we've recently described at The Michael J. Fox Foundation Therapeutics Conference, and so we're partnering with that group, so both the Parkinson's Progression Marker Initiative as well as their LRRK2 Initiative to really understand how do you stratify patients, but we're really encouraged by the data that we have that suggests that we can study both inflammatory markers as well as lysosomal markers to stratify the patients appropriately to conduct a reasonable clinical trial. Yeah. And I might build on what Angela said, just reminding you that we are currently running a study with ARV-102. We completed the single ascending dose portion of the healthy volunteer study. We're currently in the multiple ascending dose portion. But the take-home message is that in this study, we're looking at all comers, and these are healthy volunteers. They don't necessarily have elevated LRRK2. We're going to move next and look in patients who have Parkinson's disease. You heard from Angela that we expect a third of patients will have elevations. There's going to be no selection at the start of that study. But we're going to learn from doing these, from looking at our degradation of LRRK2 at various doses of the drug and looking at those downstream biomarkers, what our overall approach is. And I think at this point, there's a wide open field. We can end up being not selective of patients at all, or we could end up choosing to look at patients with elevations. It will depend on the data that we generate and how we interpret it. Next question comes from the line of Michael Schmidt with Guggenheim. Your line is open. Hey, thanks for taking my question. I just had a follow-up on ARV-102 and the phase I study. How should investors interpret the phase I data in healthy volunteers next year? Are there specific PD markers, perhaps, other than LRRK2 degradation that you're assessing? And how predictive are those for potentially improving outcomes longer term? Right, so the healthy volunteer portion of the study is really designed to understand the PK/PD relationship of the drug and track what we're doing peripherally and, more importantly, in the central nervous system, is monitoring the drug and the LRRK2 expression in the CSF. We don't expect that healthy volunteers will have elevated downstream biomarkers that are associated with the neurodegeneration that's seen with this disease. That's something that we'll be looking at more confidently, obviously, when we move to patients as opposed to healthy volunteers. But I think that what we can walk out of this confident about, if things are successful, is that the modeling that we did to predict dosing of the drug and its impact in the CNS compartment, the modeling we did in the cynos, is so promising that that can be recapitulated in human beings, that this can drive the right dose selection, and then that sets us up for success when we move to, when we're looking for this on-target activity at the right dose in patients with PD. And I think that's helped quite a lot right there. Next question comes from the line of Tyler Van Buren with TD Cowen. Your line is open. Hey, guys. Thanks for hosting the call. I just want to follow up on your response to an earlier question for the VERITAC-2 trial readout. So if the control for Verzenio arm does three to four months on median PFS, and you hope to see a few months better per your earlier comment or a three-month plus delta in the ITT population or a near doubling, how do you expect median PFS to improve for both arms for the ESR1 population analysis? Thanks, Tyler. Noah, do you want to take that? Sure. Well, I just want to go back to the earlier comments. I think what we said. I said part of that, but I'm not sure all of it. Our expectation is three or four months in the fulvestrant arm, a few months better on the treatment arms. We haven't differentiated what we're going to see for the ESR1 mutant or for the total population. We would expect that ESR1 mutant patients will do a little better because they have this dependency on the ligand-independent estrogen receptor-driven binding, estrogen receptor-driven proliferation for their tumors. So we just haven't gotten into those specifics or gone through the operating characteristics of the statistical plan. But suffice it to say, a few months better, as I outlined. Next question comes from the line of Jonathan Miller with Evercore ISI. Your line is open. Hi, guys. Thanks for taking the question. I'd like to talk more about the vepdeg combo phase IIIs that you're talking about getting started next year. Can you contrast VERITAC-3 phase III portion with these new phase IIIs that you're talking about? And it seems like the PR suggests you're focused on palbociclib and CDK4. It seems like you're not pursuing ribociclib or abemaciclib combo as in first line. At least it wasn't called out. So can you talk a little bit about how the data from what you're still waiting for from the TACTIVE trials to make the decisions about ultimate combo partner, A, a nd, B, given the CDK4 combo data you mentioned will be available internally this year for use in deciding about those combination phase III, is it fair to expect that you'd give some key details on the CDK4 vepdeg combo data when you decide on a phase three course? Because I noticed you haven't given guidance on when we could see that TACTIVE-K update. Yeah. Thanks. Yeah. Great question. And I think clearly there's a number of different trials we have ongoing that are going to generate data that's going to really influence our decision-making. We have VERITAC-2. We have the abemaciclib combo. We have the atirmociclib combo. We have the palbociclib SLI. We also have the ribociclib combo ongoing as well. There's a whole bunch of data that's coming out now and through into the early part of next year that, sitting down with our colleagues with Pfizer, we'll be able to decide what is the right combination. Obviously, there's preferences there, but we'll wait for the data to actually drive that decision. But Noah, do you want to go into any more of the specifics? Yeah. Maybe we could dive in a little more. And thanks for the question, Jonathan. So let's look at first line, and then we can look at second line. So first line, I think the original intent some years ago was to go with a vepdeg, palbociclib, and first line. And that was an obvious choice. Palbociclib was the most prescribed drug in that CDK4/6 in that setting. Pfizer is our partner, and so they could supply it. And unfortunately, we weren't able to roll straight into that because we were challenged to find a lower dose of palbociclib that would satisfy benefit-risk from the perspective of health authorities. And so we started the VERITAC-3, which is the second-line portion is reading out, as John mentioned. But in the meantime, we will have the fullness of that data set, but also have now done the work for a atirmociclib. And we're very excited about it in a atirmociclib combination for the first line because it would be a very differentiating combination, possibly a best-in-class CDK4 or CDK4/6 drug combined with what we believe would be a best-in-class PROTAC in this setting, which would be superior to the SERD alternatives. And it would fit perfectly in this partnership as well. So we're waiting for that study. But we weren't considering things like ribociclib and abemaciclib because I think they don't really solve for those problems, right? Atirmociclib gives us that differentiation, and palbociclib was ease of use. In the second-line setting, we've guided to either using a palbociclib combination because we have great results in this setting that we've already shared, and maybe offering some choice to prescribers or to investigators in this case by allowing another CDK4/6, which could be presumably something like abemaciclib. We're not guiding specifically to this. The idea is that we may end up doing it. You should just look forward to the San Antonio breast cancer data to make your evaluation of this abemaciclib vepdeg combination and the viability of that in the second-line plus setting. What we really like, of course, about all of these opportunities is that vepdeg is a very combinable drug. While we did see that there was more neutropenia with full-dose palbociclib and vepdeg in the original data set we performed, we will now be sharing more data about the broad combinability of this drug. You'll see the abemaciclib data set. You'll see some work about better understanding of metabolism with the midazolam study. And then, as we've said, next year, we'll provide some updates as the data mature for the ribociclib portion of the TACTIVE-U as well as the atirmociclib combination seen in TACTIVE-K. Next question comes from the line of Paul Choi with Goldman Sachs. Your line is open. Hi, everyone. This is Khalil calling in for Paul. Thank you so much for taking our question, and congratulations on the first earnings call. I guess a quick modeling question from us is one, I guess real quick, is as you have a lot of these earlier stage assets entering the clinic or IND filings, how should we think about the cost ramp for next year, maybe the year after? And then just on the Novartis agreement, given the revenue recognition that you had this quarter, I suspect I'm thinking there's about $930 million in additional payments, or is that how should we think about the cadence of that going forward? Thank you so much. Yeah. Thanks for the question. I'll hand over to our CFO, Andrew, to answer these questions. Yeah. Thanks for the question. Yeah. Look, we haven't given specific guidance on our expense structure, and we're not planning on doing that in the near term. Obviously, the mix of projects that we have, programs going out, is changing, right? So previously, the company had the two phase IIIs. We've outlicensed the one to Novartis. That was done consciously by the company to manage expenses and manage our burn. As we have these other programs coming through the clinic, clearly, they're going to start costing a little bit of money. We're well aware of what we're going to be spending on them, and we're very confident in the guidance that we've given in terms of cash into 2027 with our current balance sheet. I think you had another question on Novartis. Can you just repeat that? I'm not sure if I heard that. Yeah, of course. So just given that we assume that the $150 million upfront payment has already occurred, and then you reported today like $67 million or so in revenue from that agreement, our understanding is that there's a total of about a billion-ish in payments that are contingent on certain milestones. Obviously, those I don't think have been disclosed, but we were just wondering if you could share any color on how we should think about the cadence of revenue from that agreement in 2025? Yeah. So the revenue that you're seeing on our P&L right now is all deferred revenue from the upfront. So that doesn't have anything to do with future milestones, etc. We amortized the upfront from the Novartis agreement over this year because that's the period during which we were handing over responsibilities for the trials. And so we still had responsibilities. With Pfizer, it's much longer. So we obviously had the large upfront from them, and that's a co-op. That's a deal that's a 50/50. So we're actively engaged in that. So we're amortizing those revenues over a longer period of time. So you'll actually see the Novartis drop off this year. The Pfizer will continue on for some years. Got it. That's really helpful. Thank you so much. Next question comes from the line of Yigal Nochomovitz with Citigroup. Your line is open. Hi. Thank you for taking the questions. And I just wanted to follow up on some of the questions regarding the frontline strategy and the comments Noah was making on contribution of components. So if it turns out that you pick and you and Pfizer pick an atirmociclib plus vepdeg, are you going to be able to do a trial where it's an atirmociclib vepdeg versus palbociclib fulvestrant? Or given the consideration of contribution of components, is it going to potentially be more complicated with including a palbociclib vepdeg arm as well as an atirmociclib fulvestrant arm? I'm not sure how that would work if you could comment. And then I'm just also curious if you've generated data to date to support the fact that you won't have a DDI with an atirmociclib and vepdeg. Thanks. Thanks, Yigal. Great questions. Noah? Okay. I'll try and tackle this. Let's jump in with a follow-up if I missed part of that. So first of all, so in first line, we're not guiding to the exact design of the study, but I think we're going to be I think you can be confident that we would be focusing more on an AI combination in that setting rather than fulvestrant. So that's the initial. Whether it's palbociclib alone or CDK4/6 choice on the part of physicians, these things are not defined, haven't been resolved with regulatory authorities yet. In terms of but I think that kind of addresses what you asked. Is there something else that. First, related to the design part. Yigal has a secondary question related to do we have any idea we have a DDI with atirmociclib? I mean, what Yigal would say about that is we believe that the data, which you'll start to see from the San Antonio Breast Cancer Symposium and onward, will show that vepdegestrant is the compound that is going to be very broadly combinable with any of the kind of medications in the breast cancer space. That would include atirmociclib. Clearly, in all of our studies, we're tracking this now, and as I say, the data will come out and show that this is a non-issue from a clinical perspective. Okay. Appreciate it. Thank you very much. Thanks, Yigal. Next question comes from the line of Billal Jahangiri with Truist Securities. Your line is open. Hi. Thanks for the call. This is Bill on for Kripa. We were wondering what's going to be the final deciding factor or maybe factors on choosing which combo to take forward? Is it strictly on efficacy, or is there some sort of strategic IP factor involved too that you're thinking of as well? Thanks. Obviously, it's going to be based on all the data that we're going to be generating and are generating. As I mentioned earlier, we have ongoing combination trials with abemaciclib, with the atirmociclib, with ribociclib, that type of, and the SLI data on palbociclib. All of that data will be in our hands till end of this year, first half of next year, and that will really drive the data-driven aspect of our decision-making. It won't all just be looking at the efficacy. We'll be looking at safety, tolerability, so we'll get a true Gestalt view of our overall data set, so I think we'll actually be in an incredibly good position to make a really smart decision about the combinations. As I said, we clearly have some biases, but the biases will be influenced completely by the data set. Yeah. And I would just add a small point on that. When it comes to efficacy, look, we're sharing data about what we see in the second line setting. And I think the efficacy there is characterized by things like ORR and CBR. In first line, the efficacy that would be at our disposal is probably those type of data points. We're not going to wait for median PFS. Obviously, in first line, where you have median PFSs that can exceed two years, one wouldn't wait for that. We would use other signals when looking at efficacy and obviously then safety to make a decision. Great. Thanks. And is there any sort of? Next question comes from the line of Matt Biegler with Oppenheimer. Your line is open. Hey, guys. Thanks for squeezing me in. I realize we're at the top of the hour. It's like covering a large cap with the number of analysts here. I just wanted to ask about the statistical plan for VERITAC-2, to the extent you can tell us. Is it hierarchical testing, or are the co-primary endpoints effectively the alpha split between the ESR1 and the ITT population? And secondly, do you think a 0.7 hazard ratio would be good enough for an all-comers label? Thanks. Okay. So thanks for the question, Matt. In terms of the hierarchy, we have two co-primary endpoints, and we can win on either one of them. But for all purposes, we think that the ESR1 mutant is obviously going to be even more likely than the ITT. That's just the nature of the disease we're treating in. There is some hierarchical testing that goes on from there, the specifics of which we haven't defined yet. In terms of what was the second part of your question? Remind me. It was about the hazard ratio. Yeah. So we haven't gone to the specifics of the hazard ratio. I will say that we would expect a better hazard ratio or are expecting to achieve a better hazard ratio in the ESR1 mutant than in the ITT population. But more specific than that, I won't go into. Appreciate it. Thank you. Next question comes from the line of Michael Schmidt with Guggenheim. Your line is open. Oh, hey, guys. Thanks for taking the follow-up. I just had a clarification question regarding your earlier comments on VERITAC-2. I think you said you expect about three-to-four months PFS for fulvestrant in the control arm. And yeah, I was just wondering, what are or are there any major differences in enrollment criteria relative to the postMONARCH trial where fulvestrant obviously did much better than that? Yeah. Well, the fulvestrant didn't do much better than it, a little better. There was four months in the interim analysis, and I think 5.3 months in the final analysis. People are hard-pressed to understand why the median PFS improved, and was there a change in the patient population between those two analyses, which were both presented at the same time at ASCO. But the differences are that we have the ability to have patients that were treated like with an endocrine therapy twice. They may have had an exemestane, let's say, after an initial treatment with a CDK4/6 and an AI. So we will have some patients that are third line, technically. Not all our patients will be second line, but I think the large majority will be. And they were a pure second-line study. Is that helpful? Great. Thank you. Great. Thank you. Yeah. It makes a lot of sense. Yeah. I really appreciate the clarification. Thank you. Next question. question. Comes from the line of Jonathan Miller with Evercore ISI. Your line is open. Hi, guys. Thanks so much for squeezing in my follow-up here. I figured since nobody's asked about it, I'd love to ask one question about the upcoming KRAS PROTAC programs that you're working on, the G12D and the pan-KRAS that you discussed during your prepared remarks. Can you compare these programs to other G12D or Pan-KRAS approaches, and how do you think a degrader is going to be better suited than some of the other approaches, notably the inhibitors? How will a degrader compare to a RevMed-like molecular glue pan-RAS approach? Yeah. Great question. And thanks. And yeah, we're very excited about our KRAS programs, G12D, and the pan-KRAS. And Angela and Noah can discuss the answers to the questions you're posing in terms of the profile and what it looks like in terms of the competition. Sure. We've been actively comparing both our G12D PROTAC lead degrader to the inhibitors that have been described and have shown superiority, and we've disclosed some of those data. But we've been also actively comparing both our G12D and our pan-PROTAC degraders in a range of non-clinical models to examine the known inhibitors that are out there, and so generally, we're looking really very favorable with respect to our non-clinical profile, and we're very encouraged to pursue these molecules in clinical studies. So I'm going to hand it over to Noah for further commentary. Thanks, Angela. So I guess I can address just the comparative part. But look, we haven't entered the clinic yet. That's forward-looking and something we're excited about for next year. But I think what we've seen from the competition suggests that there still is opportunity. So when we look at the first data, for example, I won't address the Revolution, but you look at Astellas's KRAS G12D degrader, and we see that there's modest ORR, and there are some liver toxicities at higher doses. These are opportunities for us to catch up, differentiate, and demonstrate first-in-class, which would be needed in this space. And I think we could go through those types of specifics for other agents, but probably a little premature for us right now. This concludes our question-and-answer session. I will turn the call back over to John Houston. Thank you. And thanks, everybody, for calling into our first-ever earnings call. And hopefully, we'll be able to give you updates over the coming months of the very rich data sets that we'll be getting from the various clinical trials. But thank you for your time this morning. Appreciate it. This concludes today's conference call. You may now disconnect.