Thank you for standing by. At this time, I would like to welcome everyone to our Arvinas Second Quarter 2025 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. Thank you. I would now like to turn the conference over to Jeff Boyle, Arvinas Vice President of Investor Relations. Please go ahead. Good morning, everyone, and thank you for joining us. Earlier today, we released a press release with our second quarter 2025 financial results, which is available on the Investor and Media section of our website at arvinas.com. Joining the call today are John Houston, Arvinas' Chief Executive Officer, President and Chair; Noah Berkowitz, our Chief Medical Officer; Angela Cacace, our Chief Scientific Officer; and Andrew Saik, our Chief Financial Officer. Before we begin the call, I'll remind you that today's discussion contains forward-looking statements that involve risks, uncertainties, and assumptions. These risks and uncertainties are outlined in today's press release and in the company's recent filing 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. Now I'll turn the call over to John. John? Thanks, Jeff. Good morning, everyone, and thank you for joining us today. As outlined in our second quarter earnings release this morning, our business is in a solid position with strong momentum. It was an eventful and exciting quarter at Arvinas, with significant clinical and regulatory progress across our pipeline of protein degraders. We continued making significant strides across our early-stage programs, where we are enrolling patients in three phase I trials across our neuro and oncology portfolio, including the recently initiated trial with our KRAS G12D degrader ARV-806. During the quarter, we also presented compelling first-in-human data from ARV-102, our LRRK2 degrader, and preclinical data for our BCL6 degrader ARV-393. I'm also pleased to share an update on our androgen receptor degrader luxdegalutamide, which we licensed to Novartis in 2024. We are pleased to see that Novartis is rapidly progressing the asset and announced the recent initiation of two combination phase II trials that will further advance luxdegalutamide towards patients. One trial is in metastatic castration-resistant prostate cancer, and the other is metastatic hormone-sensitive prostate cancer, and both will identify recommended phase III doses and we believe further validate our ability to develop potentially best-in-class protein degraders. As a reminder, our license agreement with Novartis includes up to $1 billion in development, regulatory, and commercial milestones, as well as tiered royalties. The accomplishments from across our portfolio are the latest in a long stream of successes at Arvinas. At the same time, we have recognized the ongoing need to enhance our financial position and set Arvinas up for future success. To that end, last quarter, we announced a company-wide restructuring that extended our cash runway and included two key elements. First, we reprioritized our research pipeline, cutting a number of programs and continuing investment in our assets with the greatest potential value. Second, we streamlined operations across the organization by reducing our workforce by approximately one-third. While difficult, these decisive actions bolstered our financial profile and drove efficiencies across the company. They also enabled us to turn our full attention to our near-term imperatives, which are first, working with Pfizer or identifying another partner to advance vepdeg towards commercial launch, second, achieving critical data milestones from our pipeline in the next 12 months, and third, carefully allocating capital to support those milestones efficiently. I'll return to those three imperatives in a few moments, but I'd first like to say a few words about the recent announcement of my planned retirement and the CEO transition for Arvinas. Having recently strengthened our financial profile and with a clear line of sight into those near-term imperatives, the board and I agreed it is the right time to initiate a search for a new CEO. As with any public company, succession planning is a priority for our Board of Directors, and I have been talking to the board about the potential timing of this transition for well over a year. While there never seems to be a good time, we agreed that waiting until after our first pivotal data readout was essential. We are now conducting a rigorous and thoughtful CEO search process, spearheaded by independent directors on our Nominating and Corporate Governance Committee, with the assistance of a leading executive search firm. The board is fully engaged and intent on finding the right CEO to lead Arvinas into our next chapter and help shape our long-term strategy to create value for shareholders and deliver on our mission to serve patients. I'm also honored to continue as Chair of the Arvinas board once I step down from the CEO role. For now, our long-term strategy is driven by the imperatives I mentioned above: advancing vepdeg to launch by Pfizer or another partner, achieving critical data milestones, and efficiently allocating capital. I'll spend a few minutes discussing our vepdeg strategy before turning the call over to Noah and Angela, who will provide updates and discuss upcoming milestones for our clinical programs. Andrew will then provide a financial overview and some thoughts on capital planning. First, regarding vepdeg, our collaboration with Pfizer was signed in 2021 with the intention for vepdeg to be developed as a monotherapy and in combinations across the adjuvant first and second-line settings. With that plan, the idea of having 50-50 co-development and commercialization was very attractive. We are now on the threshold of vepdeg potentially becoming a best-in-class treatment in its first indication, second-line monotherapy treatment in ESR1-positive, HER2-negative metastatic breast cancer. However, the recent decision to remove the combination pivotal trials from our development plans with Pfizer has created a situation where a 50-50 co-commercialization agreement no longer makes sense, and we're actively reworking our collaboration. Should the negotiations le ad to vepdeg being returned to Arvinas, we are prepared to seek a party to commercialize and further develop vepdeg. Reaching a positive conclusion for vepdeg is a critical step in maximizing its value while also allowing us to focus on a promising clinical pipeline. Preclinical data has shown that ARV-102, ARV-393, and ARV-806 are all differentiated from inhibitors and other degraders. With compelling clinical data milestones over the next year, we believe our maturing pipeline will be a significant value driver for the company and our shareholders. Taken together, we are advancing a very exciting pipeline and applying our PROTAC technology to new areas in both neuroscience and oncology, where we can truly differentiate from other mechanisms of action. Operating from a strong financial position, underpinned by an extended cash runway, efficient capital allocation, and a development strategy that unlocks the potential of our platform to bring patients important treatments, we are confident in our path forward and in our ability to maximize value for shareholders and benefits for patients. With that, I'll turn the call over to Noah. Thanks, John, and good morning, everyone. Our pipeline continues to progress at a remarkable pace, demonstrating the vast potential of our PROTAC platform. I'll begin with our most advanced neuroscience program, ARV-102. We have designed investigational oral PROTAC degraders to cross the blood-brain barrier and selectively degrade leucine-rich repeat kinase II, or LRRK2. LRRK2 is a large multi-domain scaffolding kinase that plays a critical role in effective endolysosomal trafficking. Unlike traditional small molecule inhibitors that only block LRRK2's kinase activity, LRRK2 degraders eliminate pathologic scaffolding function, GTPase activity, and the kinase activity of LRRK2 implicated in this disease. We believe our lead LRRK2 degrader, ARV-102, is particularly well positioned to be evaluated in two diseases where there are no disease-modifying therapies available. The first is Parkinson's disease, or PD, a disease where increased LRRK2 expression and activity contributes to neurodegeneration and its pathogenesis, making it a rational therapeutic target. The second is progressive supranuclear palsy, or PSP, a disease where genetic variations in LRRK2 are associated with PSP progression. Additionally, we have published data associating the tau pathology of PSP with LRRK2-mediated endolysosomal dysfunction, which again makes this a very rational therapeutic target. ARV-102 is the only PROTAC we know of in the clinic to demonstrate deep brain penetration in non-human primates and now blood-brain barrier penetration in humans. As presented at the AD/PD Congress, ARV-102 is well tolerated at single doses up to 200 mg and at multiple doses up to 80 mg. No serious adverse events after single and multiple oral doses in healthy volunteers were observed. Single and multiple doses of ARV-102 demonstrated dose-dependent exposure in the central nervous system by cerebrospinal fluid, or CSF, sampling. This was associated with substantial degradation of LRRK2 protein in the peripheral blood and the CSF and on-target activity with levels of engagement not reported with inhibitors currently in the clinic. We believe the high levels of target engagement, enhanced potency, and pathway engagement demonstrated with ARV-102 will differentiate it from clinical stage inhibitors, which in preclinical studies have not shown the same ability as ARV-102 to move important biomarkers in the CSF. These PK and PD properties and acceptable safety and tolerability profile support further study of LRRK2 degraders in PD and PSP. Dosing of the phase I single ascending dose cohort in patients with Parkinson's disease is complete, and we expect to present initial data confirming pathway engagement later this year. We will also initiate multiple dose cohorts in patients with PD in the coming weeks, as well as a trial in PSP in the first half of 2026. In parallel to the advancement of ARV-102, we are making nice progress with ARV-393, our BCL6 degrader, and ARV-806, our KRAS G12D degrader, which entered the clinic in the second quarter. It is too early for me to share clinical results for these exciting new clinical stage assets, but Angela will share some of the compelling preclinical data supporting the advance of both in the clinic. I would like to provide some regulatory updates regarding vepdeg. We have submitted the New Drug Application for vepdeg. This represents another significant first for Arvinas, the first PROTAC degrader to enter clinical trial and have a positive readout in a phase III trial. It's also the first ever New Drug Application submitted for a PROTAC. The NDA was supported by VERITAC-2 data that were presented at the ASCO oral late-breaking session and simultaneously published in the New England Journal of Medicine. The enthusiasm among physicians generated by VERITAC-2 data was very rewarding. Later this year, we plan to present the patient-reported outcomes data from the VERITAC-2 trial. We believe these data disclosures reinforce vepdeg's profile as a potential best-in-class monotherapy. I'll now turn the call over to Angela. Angela? Thanks, Noah, and good morning, everyone. ARV-393, our investigational oral PROTAC designed to degrade B-cell lymphoma 6 protein, or BCL6, is an exciting asset that demonstrates the power and breadth of our platform. BCL6 is a previously undrugged transcription factor, a master regulator of multiple cellular processes during B-cell development, including proliferation, survival, and apoptosis. Altered BCL6 activity has been implicated as an oncogenic driver in several subtypes of non-Hodgkin lymphoma, making it a rational therapeutic target with initial clinical validation emerging. PROTAC-mediated degradation has the potential to overcome the historically undruggable nature of BCL6. With its iterative activity, ARV-393 potently and rapidly degrades the BCL6 protein, which is critical to overcoming its rapid resynthesis rate and sustaining anti-tumor activity. In the second quarter of 2025, we presented two sets of preclinical data for ARV-393. First, at the American Association for Cancer Research annual meeting in April, we presented new preclinical data highlighting the therapeutic potential of ARV-393 in combination with standard of care biologics, chemotherapy, and small molecule inhibitors targeting cooperative oncogenic drivers. ARV-393 combinations demonstrated increased tumor growth inhibition, including tumor regression in preclinical models of aggressive B-cell lymphoma. These data underscore the potential of ARV-393 to become a backbone therapy for the development of rational, mechanism-informed, chemo-free, or all-oral therapeutic options with the potential to improve patient outcomes and convenience. In June, at the European Hematology Association Conference, we presented new data demonstrating the potent single-agent efficacy of ARV-393 in patient-derived systemic models of angioimmunoblastic T-cell lymphoma and transformed follicular lymphoma. To our knowledge, these are the first preclinical evidence of an efficacious BCL6-targeted degrader in human models of these diseases. These data highlight the broad utility of ARV-393 across non-Hodgkin lymphoma subtypes with unmet need beyond DLBCL. Later this year, we also expect to share preclinical data showing the combinability of ARV-393 with glofitamab, a CD3/CD20 bispecific antibody and an emerging standard of care for DLBCL that supports our plan to evaluate this combination in an upcoming trial. We are excited about the potential here given ARV-393's ability to increase CD20 expression, which provides rationale for the exploration of ARV-393 with CD20-targeted agents and in the context of low or loss of CD20 expression. We also plan to share the initial clinical data with ARV-393 later this year. As you heard from Noah, I'm pleased to report that we have initiated a phase I clinical trial of ARV-806, our novel protein degrader targeting KRAS G12D. The trial has progressed rapidly through the first patient cohort, reflecting strong interest from clinical investigators and underscoring the high unmet need for effective KRAS-targeted therapies. KRAS G12D is a well-characterized oncogenic driver associated with poor prognosis and resistance to standard treatments across major tumor types, including pancreatic, colorectal, and non-small cell lung cancers. ARV-806 has demonstrated compelling preclinical activity with high potency and clear differentiation from both KRAS inhibitors and other degraders currently in the clinic. Notably, because of the catalytic activity of our protein, ARV-806 has shown it can overcome KRAS resynthesis and increased expression, a major clinically relevant emerging mechanism of resistance that existing inhibitors have failed to address. Our protein binds to and degrades both the active and inactive forms of KRAS G12D, achieving potent and durable elimination of the target rather than inhibition in all models tested. In preclinical studies, ARV-806 achieved in vitro potency approximately 25x greater than KRAS inhibitors and 40x greater than the leading clinical stage degrader, demonstrating strong potential for differentiation from both KRAS inhibitors and degraders currently in the clinic. Furthermore, ARV-806 exhibits dose-dependent, selective, robust anti-tumor activity, culminating in regressions across preclinical models of KRAS G12D mutant cancers. These results highlight the strong therapeutic potential of ARV-806 and support its continued and rapid advancement in the clinic. We look forward to updating you on our clinical progress and anticipate sharing preclinical data from ARV-806 and the first ever data from our oral pan-KRAS degrader program later this year. With that, I'll turn the call over to Andrew to review our quarterly financial information. Thanks, Angela, and good morning, everyone. I'm pleased to provide financial highlights for the second quarter ended June 30th, 2025, and expand on our approach to capital allocation and development strategy. As a reminder, detailed financial results for the second quarter are included in the press release we issued this morning. During the quarter, we took significant action to reduce costs and increase efficiency across the organization. These actions included a reprioritization and reduction to our research portfolio, as well as a reduction of approximately one-third of our total workforce. When combined with the announced changes to our vepdeg development plan, our cash runway was extended into the second half of 2028. These changes will make us leaner and more efficient as we work towards a promising stretch of catalysts over the next 12 months. As I mentioned previously, the restructuring was focused on reducing internal costs without having an impact on the clinical stage programs that will drive value over the next several years. We will maintain our disciplined and focused approach to capital allocation, and our development strategy will be focused on bringing pipeline programs to major clinical inflection points. With respect to vepdeg, we anticipate relatively minimal costs to prepare the market in the coming months. Our current agreement with Pfizer includes establishing a go-to-market strategy that will benefit both sides of the partnership. While we continue to believe that vepdeg is a potentially best-in-class asset, given the changes to the development plan, we have determined that it is no longer viable for us to build out our commercial infrastructure as we had previously planned. As John said earlier, we are in active discussions with Pfizer to rework our collaboration to determine the most efficient way to make this important drug available to patients if approved. Across our pipeline, we have a rich set of catalysts coming up in the next year for both our oncology and neuroscience portfolios. With our strong balance sheet, we have sufficient resources to move these exciting programs forward to key value inflection points. We've seen great clinical success here in the past, both in the development of vepdeg in partnership with Pfizer and in the platform validating out-licensing of luxdegalutamide to Novartis. We are excited to continue development of the next generation of Arvinas PROTACs. I'll now briefly touch on some key financial highlights for the second quarter of 2025. At the end of the second quarter, we had approximately $861.2 million in cash, cash equivalents, and marketable securities on the balance sheet, compared with $1.04 billion as of December 31st, 2024. Revenue for the three months ended June 30th, 2025, totaled $22.4 million compared to $76.5 million for the three months ended June 30th, 2024. The decrease of $54.1 million was primarily driven by $45.6 million of decreased revenue from the Novartis license agreement and the Novartis asset agreement, both of which were entered into during the three months ended June 30TH, 2024, and were completed by December 31ST, 2024, as the technology transfer of our ongoing planned clinical trials of luxdegalutamide were transitioned to Novartis. Revenue from the vepdeg collaboration agreement with Pfizer decreased $6.8 million related to the removal of two phase III trials from the development plan during the first quarter of 2025. General and administrative expenses were $25.3 million in the second quarter compared to $31.3 million for the same period of 2024. The decrease of $6 million was primarily driven by a decrease in personnel and infrastructure-related costs of $4.8 million and professional fees of $2.2 million, partially offset by an increase in costs related to developing our commercial operations of $1.1 million. Research and development expenses were $68.6 million in the second quarter compared to $93.7 million for the same period of 2024. The decrease of $25.1 million was primarily driven by a decrease in the vepdeg program of $10 million, a decrease in the luxdegalutamide program of $9.5 million, and decreases in personnel expenses and non-program-specific expenses of $10.3 million, offset by an increase in the LRRK2 program of $2.1 million and the KRAS program of $1.5 million. Restructuring costs in the quarter amounted to $7.4 million of cash expenses, consisting primarily of employee-related expenses, which were offset by a reversal of non-cash employee stock compensation and bonus expenses of $6.4 million. The announced restructuring is now complete, and the full benefit in terms of cost reduction will be seen starting in the third quarter. We are maintaining our prior cash runway guidance into the second half of 2028. We are focused on staying disciplined by investing in areas that will maximize shareholder value as we move towards important catalysts in the coming months. In addition, we will continue to look at ways to reduce costs and increase efficiency while continuing to focus on our goals of progressing our very promising early pipeline. With that, I'll turn the call over to John for closing remarks. John? Thanks, Andrew. As you've heard, we've seen multiple near-term milestones across our clinical development and regulatory efforts. Our programs offer a rich set of catalysts over the next 12 months, including clinical data from ARV-102 and ARV-393, and potentially initial clinical data from ARV-806, and of course, the potential for the first ever approval of a PROTAC. During this time, we will also advance ARV-102 in its ongoing trial in patients with Parkinson's and initiate a trial with ARV-102 in progressive supranuclear palsy. Before opening the call for Q&A, I'd like to reiterate our confidence in our near-term plan to create value for patients and shareholders. This includes advancing vepdeg to launch by Pfizer or another party, achieving the important data milestones I just described, and allocating capital to ensure we reach those milestones efficiently. While we made sweeping changes in the first half of 2025, we are always evaluating the best ways to create shareholder value. With that, I'll turn the call over to Jeff to begin the Q&A portion of the call. Jeff? Thanks, John. Operator, can you please open the queue? Thank you. A reminder to ask a question, you will need to press Star then the number one on your telephone keypad. To withdraw your question, press Star, one again. Our first question comes from the line of Ted Tenthoff with Piper Sandler. Your line is open. Thank you very much. Andrew, just one quick housekeeping. The restructuring contract you mentioned, was that primarily in the G&A line? I have a pipeline question for you guys. Yeah, hey, Ted. No, it was actually split up between research and development and G&A, and indeed most of the stock-based comp would have been recorded in the R&D section. Great. That makes sense. Awesome. Can you give us a little bit more color on what to expect from ARV-102 data this year? I know that we've still got more to hear about the healthy volunteers for the multiple ascending cohorts. What should we expect from the single ascending doses from Parkinson's patients? Thanks. Thanks, Ted. The trials were going well. I'll hand over to Noah to give you some of the details. Hi, Ted. Thanks for the question. Hey, Noah. Good morning. As you said, I think you summed it up. We're going, we expect a conference, an upcoming conference, to summarize the full healthy volunteer data set that we assembled. In addition to that, if things work out, we'll be able to present some SADS data, you know, which will, I'm not going to go into the details of what we'll present exactly, but you know, should be able to signal that we're on track with, you know, when you compare it to the healthy volunteer ones. Great. All right, looking forward to that and excited about the emerging pipeline. Thanks, Ted. Next question comes from the line of Jonathan Miller with Evercore ISI. Your line is open. Hi guys, thanks so much for taking the question and congrats on, I should say, congrats maybe is the wrong word, but good job on getting your restructuring going. I'd love to follow up on the 102 question. Maybe it's a little too early to say exactly what you'll give us in patients this year, but maybe could you talk a little bit about what you hope to see in a more full patient data set? What are your bars for success in patients that can give you confidence going into later on in efficacy readouts? Thanks, Jonathan. Noah? Sure. Jonathan, so yeah, thanks for the interest here. I think we've outlined that we expect to start a Parkinson's disease multiple dose study over the course of the next month or so. While I can't really comment about when those data will be presented, the idea is that we're enrolling patients with the insights gained from healthy volunteers regarding a dose range, and that will allow us to establish that in patients who have higher baseline LRRK2 levels and also patients that are more elderly because healthy volunteers tend to be very young, like a little more than college age, and Parkinson's disease is going to be more than twice that on average, I suspect. We'll be able to demonstrate that we have the same exciting results that we previously reported in healthy volunteers of orally bioavailable brain-penetrant protein degrader and the ability to move biomarkers, which also now we have much more insight into than we did many months ago. We continue to do work to understand what are the best biomarkers that we can track and are going to be most predictive of an impact in the endolysosomal trafficking and neuroinflammation that is characteristic of Parkinson's disease and PSP. We expect we can start tracking this in real patients rather than the healthy volunteers. Awesome, thank you. On the BCL6, you mentioned in the press release in this call the glutamate combination result that you present this year, but you've presented on a number of different combos preclinically. Can you give us a sense of where you might want to start in the patients, which combo therapies you might want to start with? I think we've been signaling in conversations, you know, we can certainly speak clearly, you know, very directly about it here, that our interest for BCL6 is to learn what, you know, find the dose in monotherapy. It's something we're obligated to do, but the real interest is moving forward in combinations, in particular in DLBCL. It should be clear to everyone that bispecifics in second line plus DLBCL and maybe eventually in not that far in the future in first line are important drugs in that space. If we can combine with bispecifics in human beings and get results that look anything like what we've seen preclinically, we think we're well positioned for a new modality of therapy with a real orthogonal approach that enhances the activity of the bispecific. Remember, one of the great combination properties here is that we recognize that our ARV-393 can increase the expression of CD20, which could potentially make the bispecifics even more active. On top of that, you know, we've been reporting out the great potency with our drug that if that translates into the clinic, then that gives us a great competitive advantage against the only other degrader that's in the clinic currently. Thank you so much. Next question comes from the line of Derek Archila with Wells Fargo. Your line is open. Good morning. This is Karl calling in for Derek. Thank you for the question. For ARV-102, could you talk a little bit more on the elevated LRRK2 level in CD patients in terms of how much do we expect and how to maybe feel confident that similar, more than 50% degradation can be achieved in CSF? On the vepdeg, the label potentially, could you talk about maybe the base case? What could be some potential differentiations you could expect versus your competitors? Thank you so much. I think I captured the second question with vepdeg, but there's a lot of cracking in the transmissions in the first question. Did anyone here catch that? Could you maybe just repeat the first question? Yeah, of course. Just the first, Sure. For the ARV-102, I think the question is the elevated LRRK2 level in PD patients. Could you talk about the expectation of the elevation and how to feel confident that more than 50% degradation in CSF can be achieved? Yeah, I think it's a great question. Fundamentally, I think it's been established by external sources that there's increased LRRK2 protein expression in the brain and in the CSF of patients with Parkinson's disease. In our own hands, we've already seen in the SAD that there are higher baseline levels of LRRK2 than we observed in the healthy volunteers. That's already kind of consistent, but not a surprise to us at all. That was the expectation. In terms of one of the great properties of the degrader that I think differentiates it beautifully from an inhibitor is that we've already established in the healthy volunteers that we can get really good target engagement in the brain. We know that the inhibitors just don't do that well. They're only achieving 30% or so inhibition in the brain. We know preclinically they're not reaching deep brain regions as effectively as our degrader can. We're getting higher engagement. Because we have a degrader here, which has that iterative property that at even lower exposures, you get continued degradation of the target, we think we should be well poised to reduce LRRK2 levels. That's the underlying premise that's been borne out in preclinical models. We've shown it in healthy volunteers, and now we think we can confirm it in the multiple doses in Parkinson's disease patients. Regarding the second question, I think the question was, what differentiates us essentially with our vepdeg from competitors in the space? More or less, it comes down to efficacy, the better PFS that's been seen when compared to fulvestrant control, monotherapy control, which in our hands, we're talking about three months improvement, which other drugs really haven't achieved. On top of that, we're leaning into some PRO data that you'll see soon that show that the patients experience the drug very well. Certainly, the adverse event profile is more attractive, which is to say that there's a lot of GI toxicity seen with other agents in this space. We have reported half or even 33% of that when you compare to different drugs. I think that combination of benefit-risk really stands out for vepdeg when compared to other agents. Thank you. Next question comes from the line of Tazeen Ahmad with Bank of America. Your line is open. Hi, good morning. Thanks for taking my questions. I maybe wanted to focus on some commercial questions. As you think about vepdegestrant and the upcoming launch, you're obviously bullish about its place, potentially in monotherapy, but you also talked about needing to be careful about how you're prepping for the launch. How does this work in terms of setting up a sales force? When do you start prepping for that? How has that plan changed relative to what you would have planned for before? Secondly, if Pfizer returns rights for the program to the company, would there be a gap in between when Pfizer returned the rights and when you'd be able to secure a new partner, or are you, you know, kind of in process now for seeking a potential replacement should Pfizer return those rights? Thanks. Thank you for the question. In the second part, I'll talk about first, really, we're in negotiations with Pfizer right now. The original deal that we signed in 2021 was a 50-50 co-development, co-commercialization, very attractive deal at the time. We had plans for doing second-line monotherapy, first-line and even adjuvant. That would have been a very significant market and a very significant opportunity to share 50-50. With the decision not to go forward with first-line or the second-line combo, it puts us into a position where vep at the moment is only focused on second-line monotherapy. A smaller market really doesn't move the dial for Pfizer in terms of 50-50 and not particularly attractive for Arvinas either. The dialogue we've been having actively with Pfizer is about how we redo the collaboration so that either they get more of the economics or we get more of the economics. In the scenario where potentially we get the asset back, our plan is clear that we would immediately look to find a next partner that would help to develop vep and launch vep. Which gets back to the first question, which is, as we stated, we are really not building out a sales force at all. Right now, we're focused on, first of all, getting vep approved and also getting launch ready, which is a relatively minimal amount of money that we're spending between now and the end of the year. The idea would be that with that launch readiness, if we got the asset back, we'd run an active process and be in a position for another company to take on the development and launch of vep fairly rapidly. We're hoping there wouldn't be a particular gap. Okay, as of today, could there be a gap between when it got approved and when it launched if you are not able to secure the right terms? No. Okay. Sorry, say the last bit again. Say the last bit of the question, sorry. I just wanted to clarify whether there would be a gap in the launch if you wouldn't find a suitable partner in time once it's approved. They said the suitable partner. At the moment, the plan is there'd be no gap between getting approval, ideally having a partner in place, or having Pfizer launch. There'd be no gap at all. I think your question there is if you don't get a, if you get the asset back and you don't get a partner, then yeah, we'd be taking stock of that. Our plan is that we'd find a partner. Okay. Thanks again. Next question comes from the line of Andrew Berens with Leerink Partners. Your line is open. Hi everyone, this is Amanda on Andy. We wanted to get your thoughts on the recent readout from the phase III trial evaluating vepdeg in second-line HR positive breast cancer in patients that don't have a PIK3CA mutation, which then would include some ESR1 mutant patients. We're wondering how does this change, or if this changes your outlook for second-line ESR1 mutation patients, and if you would ever consider a combination with vepdegestrant to address a broader population. Thank you. Thanks for the question. Noah? Sure. Yeah, we really are not surprised by the result. We recognize the opportunity for PIK3 mutation-directed drugs in breast cancer. There is overlap, as you had suggested, between ESR1 mutations and PIK3CA. The question comes down to whether it's in our modeling. Overall, my impression is that it will have little impact on the modeling. I could turn it over to my colleague Alex from commercial to offer further comments. Part of your question was whether we would develop it with an agent like that. The answer to that is someone may, but we won't because we've already established that we're not doing further development on the drug, initiating new studies and combinations. It would be something that should be very much of interest to another company. We've already scattered that out, but it's not something that will be important. Next question comes from the line of Li Watsek with Cantor Fitzgerald. Your line is open. Hey, good morning guys. Thank you for taking questions and nice progress on the pipeline. I guess for vepdeg NDA submission, it sounds like you know the PDUFA date very soon. Should we anticipate a priority review here? Any guidance on your part for the global filing strategy? Do you need maybe to wait for more mature OS data? Yeah, with the second part of that question, I'll hand over to Noah. For the first part, we're still awaiting details from the FDA, and as soon as we get that information, we'll pass that on. We don't have the PDUFA date yet. Noah, do you want to tackle that second part of the question? Yeah, what we've shared, what we've offered guidance to is our filing of the NDA in the U.S., and obviously we're waiting on feedback regarding PDUFA date. Regarding global strategy, we haven't offered guidance on that yet, so I think it would be premature. Okay. In terms of finding maybe a potential new partner for vepdeg in the case that you got the molecule back, can you elaborate on the considerations that you prioritize? What's important for you guys in terms of maximizing the value? Yeah, it's a great question. I mean, clearly, we believe vepdeg is an important drug. We believe it has a lot of value. Because of the partnership we're in with Pfizer, decisions have been made. Maximizing that value is going to be somewhat difficult. That's why we're in discussion with Pfizer about changing the nature of the collaboration. Ideally, as I said, either Pfizer or Arvinas should go forward with the asset with more kind of sole economics. In the scenario where maybe we get the compound back, yes, we'd be looking to partner. Ideally, a partner that does have the kind of the deal and interest to develop the asset further, both from the U.S. and a global setting. Our involvement in that, I think, would be relatively minimal in terms of development. Our view is that we want vepdeg in the hand of a partner, be it Pfizer or another company, that really takes the compound forward, launches it, and progresses it with further development. Next question comes from the line of Akash Tewari with Jefferies. Your line is open. Hey, this is Manoj on for Akash. Thanks for taking our question. What are your expectations around the Dynately LRRK2 data in the first half of next year? If that trial fails or doesn't meet expectations, what signals from that study would you be looking for to give confidence for your own degrader program? Thanks. Yes, thanks for the question. If the question was, you know, expectations for the Dynately program last year, I think it's a fantastic question. We think that LRRK2 is an outstanding target. I think the entire key opinion leader community would agree with us on that. The question is, what is the best drug to address that target? We see some virtue in an inhibitor, but it has challenges. I outlined that earlier, that the inhibitor doesn't seem to penetrate the brain as deeply as, let's say, our degrader. On top of it, it doesn't necessarily engage its target as effectively. We have a broader engagement. Not only are we binding it and degrading it, and we're eliminating because of that degradation, the LRRK2 kinase sensitivity, the GTPase activity, and scaffolding function. All of those features make a degrader more attractive than an inhibitor. We think that they may succeed. We know they have the right target. We're looking forward to learning from their results, learning if there's something about patient selection that could be incorporated, and overall, you know, whatever signals can come out of their trial. Thanks. Next question comes from the line of Evan Seigerman with BMO Capital Markets. Your line is open. Hi there, this is Connor McKay on Evan, and thanks for taking our question. We just had a quick one on the submission of vepdeg. Given the current environment at FDA, we were just wondering if you'd be willing to characterize your recent interactions with the agency and, you know, maybe comment on the level of alignment there. One quick follow-up on ARV-806. Would you be able to share a little bit more on how you're thinking about positioning this asset versus the pan-KRAS agent you mentioned today? Thank you. Yeah, thanks for the question. The second one, I'll hand over to Noah and Angela. The first one, I'd have to say our whole process with the FDA has gone very smoothly. The interactions have been excellent. Their timing and sense of getting back to us has been really good. Even though we know that there's lots of other pressures on the FDA and it could impact timelines, we haven't seen that yet with our interactions on vepdeg, which is a really good positive thing for us. Noah, do you want to tackle regarding ARV-806? I'll make some comments about clinical, and I'll turn it when I'm done to Angela. We may have some comments about some of the interesting differentiation we've achieved preclinically. This drug entered the clinic a little faster than we expected because of great efficiencies. That's the team, though. What we noticed is that there's tremendous appetite for drugs like ours in this space because our cohorts are in demand. We're advancing through early dose escalation now. Overall, we expect that there are going to be five or fewer dose levels in this escalation. That's going to at least give you a sense of where we're headed. The key is to look at where we are in monotherapy, compare ourselves to data that's out for inhibitors and the very, very modest and unimpressive data that have been presented by a degrader in the clinic, which is limited at dose-limiting toxicity relating to a pancreatic function. We'll compare ourselves to that. We have good go-no-go criteria. The intention is to move our IV degrader, which has once a week, possibly once every two-week dosing. That's something we'll learn from this dose escalation in combination with EGFR inhibitors and with chemotherapy. That's built into our plan, and that allows us to start moving into, eventually, first-line colorectal cancer and pancreatic cancer and also opportunities in non-small cell lung cancer. I'll turn it to Angela. Sure. Thanks, Noah. Just to comment on some of the other differentiation features of our ARV-806 molecule, it's very potent with respect to its activity. We're 25x greater in terms of potency for antiproliferative activity with respect to the inhibitors, and then 40x more effective than the clinical stage degrader. The other piece that I'll mention is that catalytic activity that we have overcomes this KRAS resynthesis rate that has been observed as a major mechanism of resistance in the clinic with RMC, certainly with RMC- 6236. It's something we're excited about. We think this is a very strong differentiator. Of course, we'll see what happens clinically. I hope that helps. Yes, thank you. Next question comes from the line of Srikripa Devarakonda with Truist Securities. Your line is open. Hi, this is Anna on for K ripa. Thanks for taking our question. In regards to ARV-102, I know you mentioned the elevated LRRK2 levels in Parkinson's. Could you remind us as to what percent of Parkinson's patients could be eligible for an LRRK2 targeting drug? A second question, just in regards to the neoadjuvant vepdeg and that potential data readout, how would this potentially inform any room for vepdeg to be used earlier in the treatment paradigm, and besides commercializing in second line as monotherapy and that CAP6 combo, any additional plans for development? Thank you. Thank you for the question. Noah, do you want to go to the LRRK2? Yeah. LRRK2 levels are higher in the Parkinson's disease patients. Now, we haven't made a choice that we're only treating patients with elevated LRRK2. By the way, I should say that that's something that might be on the table. It's something that we're going to explore. We're going to look at our own data sets as they evolve. We'll look at what's coming out of the Denali program if it's shared. That's a possibility. If your question implies, you know, genetically, since LRRK2 is so implicated genetically in diseases like Parkinson's disease, when we move forward in Parkinson's disease, what percentage of patients have LRRK2 implicated disease? In familial Parkinson's, about 15% of patients have LRRK2 mutations. There's a higher percentage that have LRRK2 pathway mutations that contribute to other types of familial Parkinson's disease. When you look at idiopathic, it's down in the few percent range. Beyond those LRRK2 mutations themselves, there are all kinds of pathway perturbations that suggest that LRRK2 could be at the center of this endolysosomal dysfunction that is characteristic of Parkinson's disease in PD. You start to have 30% of patients that can have SNPs and other biomarkers that are associated with this LRRK2 dysregulation and may lead to LRRK2 elevation. We have a particular interest in that subset of patients, and that's why we're engaging in a lot of biomarker analysis. We've been a long-time collaborator with the Michael J. Fox Parkinson's Disease biomarker Initiative, and this is bearing fruit for us. I think that we have no kind of guidance yet about whether we're doing patient selection or patient enrichment or going for all comers, but these are the types of questions we are investing in right now to ensure that we have the best development plan. The second question was about neoadjuvant vepdeg. Positioning the potential for vepdeg in an illusion. We have to keep in mind there have been no evidence to date to suggest that vepdeg shouldn't be working in the adjuvant setting and in first line. We have every reason to believe that we can be very effective in that space. We know the drug is very tolerable. Cross-study comparisons suggest maybe we're more tolerable than aromatase inhibitors. That could be very important in both of those settings. Ultimately, a decision is being made in this partnership that because of where we are with timing and the interest probably more than with our partner, in this case, Pfizer, in first line, that we're just not going to be going forward in those early lines. That's why we've been giving so much guidance for our intent to out-license this, you know, or proceed with renegotiation with Pfizer. I don't think that we should draw any conclusions that there are any problems in the adjuvant setting or in first line. Great. Thank you so much. Next question comes from the line of Jeet Mukherjee with BTIG. Your line is open. Great. Thanks for taking my question. Perhaps just coming back to the discussions with Pfizer over vepdeg you've talked about scenarios where perhaps Pfizer gets more economics or you get more economics or perhaps you find a new partner altogether. Based upon where your discussions are right now, would you say that you and Pfizer have very different views on how to maximize value for vepdeg? Are you in active dialogue with other partners? If yes, how are those discussions going? Thanks. Yeah, great question. I would say that Pfizer and our ongoing discussions we are having are aligned in terms of what the best way to get value for vepdeg is. Even though we may have different views about the development future of vepdeg, I think Pfizer and our business truly believe there's value to be had there. That's why we're in these discussions. Clearly, if the asset does come back, and again, that's just one of the scenarios. The other scenario is that Pfizer takes the compound forward. In the scenario where it comes to us, yes, we'd run an active process. Obviously, we cannot run an active process right now because we're in a collaboration with Pfizer and we don't have the ability to do that. Our belief is if we get the asset back and we run a process, there would be companies extremely interested in taking a new approved drug with the potential to develop it not only in the first-line setting, but even earlier. We're very pleased with the progress in terms of discussion with Pfizer. Like I say, if they want to take it forward aggressively and the launch themselves might be extremely positive. If they don't and the outcome is we get a compound, then yes, we run an active process. Next question comes from the line of Ellie Merle with UBS. Your line is open. Hi, this is Tejas on for Ellie. Thanks for taking our question. I think you talked a little bit about some of the preclinical data for the KRAS inhibitors. Can you talk a little bit more about what we should expect with more data later this year, and you know, how might that inform what we think about in the phase I? Great, thanks for the question. I'll hand o ver to Angela. For the KRAS inhibitors, for ARV-806, certainly, you can expect to see some preclinical data just showing the differentiation profile that we see relative to inhibitors that are in the clinic. We'll also show some additional data just showing the combinability of the molecule. Noah had mentioned with EGFR mechanisms that's difficult with the pan inhibitors, certainly in the clinic, showing some side effects that would basically preclude that combination. We'll also show data that we think is really compelling from our oral and KRAS program, showing that we're making really great strides there as well. Other additional comparative data that we'll have will include some other models where we're looking at combinabilities with immuno-oncology approaches and some of the unique features of PROTACs, we think, in this space, also with respect to the resistance mechanisms and overcoming that upregulation that is seen clinically with the inhibitors as well. We think we have a very differential profile, and it's an exciting opportunity, certainly. We're seeing that with the over-enrollment and the interest from the investigators that treat patients. I think it's an exciting time, and I'm sure Noah and his team will be sharing clinical data as soon as we have it. That helps. Next question comes from the line of Peter Lawson with Barclays. Your line is open. Great. Thank you so much. Maybe just leading on from the prior question. For the KRAS G12D and the updates, when should we expect the initial first-in-human data update? If you could talk through how enrollment is going and the number of sites that are open and any other details around that trial. I have a follow-up. Thanks, Peter. Noah you can go ahead. Sure. Peter, we just announced that we opened this study for enrollment a little ahead of schedule, and the immediate reaction seems to be very favorable. We haven't offered guidance yet on when we will be sharing data. You know you're going to get it soon. You'll get the guidance soon, meaning it'll be sometime next year, obviously. In terms of, I would suggest just track things on clinicaltrials.gov because we wouldn't typically be giving you site numbers and things like that for a phase I study. Thank you. I apologize. I arrived late on the call. For the BCL6 set, so that's what, 393, the data in the second half, and then what should we focus on with regards to the data? Kind of other metrics that we may be delivering in that data set? Noah? Sure. We've shared that we'll provide some update of our data sets in the second half of this year. I really don't want to get ahead of ourselves and share what that disclosure will be. The idea is that we're advancing through our dose escalation program. Obviously, in dose escalation programs, the data that you're going to see are going to be more like a buy, before y ou're done with it, safety, EK, and early signs of efficacy. I think you can look for those. Obviously, as we approach the completion of that, or as we achieve the completion of that dose escalation or are ready for expansion, we would be armed with more efficacy data, but still a focus on target engagement through PK and PD. Gotcha. Would that be kind of like the range of 10- 20 patients, or, and I presume kind of heavily pretreated? Any details there? Yeah, I would say that's a reasonable guess. Perfect. Thank you so much. Next question comes from the line of Sudan Loganathan with Stephens. Your line is open. Hey, this is Kesav on behalf of Sudan. Thank you for taking your question. Regarding the recent clinical data published by Celcuity under advanced breast cancer asset, could you kind of just comment on your insights and what your perspective on that data is and where do you like see vepdeg's competitive positioning within the treatment landscape? Thank you. No, thank you for the question. Noah, I know you're tied to the toilet. Yeah, I'm not sure if I have more to add than what was said earlier. We have always recognized that a drug like Celcuity could demonstrate attractive benefit-risk in the second-line setting and in the first-line setting. There is overlap between ESR1 mutant and PI3 kinase targeting agents. You know, in the end, what physicians are looking for are oral PROTAC, hypo-oral degraders. In our case, the PROTAC that has an attractive benefit-risk profile. We think we're delivering that. Physicians kind of want to avoid toxicity as much as possible and get all the benefit they can after first-line therapy before adding drugs that have some toxicity. The impact on market opportunity in that second-line setting is probably modest, but we haven't been offering specific guidance on market opportunities, so it's difficult to measure that modest degree. Thank you. Next question comes from the line of Michael Schmidt with Guggenheim Partners. Your line is open. Hi, this is Sara on to Michael. Thanks so much for taking my question. I wanted to quickly circle back to the oral pain care system that you mentioned. I would love to hear more details on that, and specifically how you would expect to differentiate from later-stage pain care. Sorry, we couldn't understand the question. Could you repeat it one more time? There's a lot of echo. One second. Oral PROTACs, and I would differentiate other PROTACs. Yes, exactly. The question was about the pain care rats and any thoughts on differentiating from later-stage pain care rats and pain rats programs. Sure. As you know, we differentiate at least with ARV-806 from what we said publicly. Our KRAS program, we aim to have the same level of potency differentiation as well. We do bind to and degrade, so we degrade. We don't inhibit. We avoid that upregulation that's observed clinically. As you're aware, the clinical inhibitors of the KRAS inhibitor have shown a major mechanism of upregulation of KRAS as a resistance mechanism in the clinic. They're claiming around 20%- 30% of patients they're seeing this. It's pretty profound. We think we have an opportunity there. Our oral KRAS also will have great combinability. We'll speak a bit about some of the differential profiles of our molecule relative to the KRAS molecules that are in the clinic. We expect that we'll have greater combinability with the immune stimulatory mechanisms like Keytruda and other IO agents because we will not inhibit T cell receptor activity. We think that combinability will also provide a major advantage to other mechanisms clinically. There are a number of other differential activities that we're observing that we'll be discussing as we move forward and advance the program. It's an exciting time for us. Stay tuned for more data this year at the triple meeting. Great. Thank you. Next question comes from the line of Terence Flynn with Morgan Stanley. Your line is open. Hi, good morning. This is Chris on for Terence. Just one question from us. For ARV-393, beyond safety, what do you need to see in order to advance the asset into a combo trial with glofi? Thank you. Thanks, Chris. Noah, do you want to? Sure. We don't, probably not a lot. Like we weren't expecting any hematopoietic toxicity, which would be the principal toxicity of glofi beyond the CRS seen in the first cycle, but well managed with glofi's dosing over the first month or first three weeks. It's just a matter of reinforcing that we're not seeing any unexpected toxicities. I don't have much more to add to that. Pretty clean drug treatment. Yeah. Thank you. Next question comes from the line of Yigal Nochomovitz with Citi. Your line is open. Hi, this is Jong Kim on for Yigal. Thanks for taking our question. Maybe just one quick one from us. Can you comment on whether AI was utilized to facilitate the compilation and submission of modules from vepdeg to the FDA? More broadly, any potential utilization in the early drug development pipeline? Thanks. That's a great question. I suppose it's a definition of AI. We've certainly used a lot of kind of artificial intelligence in all of our research programs, and Angela could talk to the different features of that. I wonder whether or not it was used in the actual NDA application. Noah, I'm not sure if I should... Part of the NDA or the submission process, we do work with some vendors. There is AI that's going on there through our vendors. In terms of our business overall or the development part of our business, think of AI as being able to help us with a lot of medical writing, right? We're going to be able to take documents that we have previously generated across different assets and learn from them. These are things we're doing currently and learn from them to impact our medical writing cost and efficiency in the future. Think of it also as something that helps in clinical operations to more efficiently review our vendor management, our contracts, so that there's more clear accountability and roles and responsibilities across different contracts for a company that does rely on a lot of externalized work and cleanups. Obviously, we're using it all the time with our staff's programming. That's something that's been ongoing. There are many other areas in the company that are beginning to use it, but at least that gives you a sense of how it could have been used for an NDA and in our development programs. I can comment on how we're using it in research. We have computational chemistry and computational biology teams that use AI all the time in machine learning algorithms. We've been applying AI to our PROTAC design features. As we've been in this for 13 years, we've actually accumulated a lot of real-world data on PROTAC activity and optimization. We are applying that and learning from it. We iterate our PROTAC design much faster now, and we're seeing a big benefit in how we move with speed in research. This includes pharmacokinetic properties of these molecules and absorption features as well, which, as you probably know, is really key for PROTAC design. On the computational biology side, we're using it all the time for how we go about analyzing our ligand identification data. This enables us to go after previously undrugged targets and optimize those warheads to utilize in PROTAC for targeted protein degradation. In addition, I would say we use AI to mine real-world data from biomarker features that exist in publicly available data sets. This sets us up well for deep understanding of pathway biology. This is how we've been approaching our Parkinson's disease and also our PSP, as well as other neurodegenerative diseases, and really mining CSF protein changes in those diseases and how to set the clinical group up really well to understand how we might use those biologic features to stratify patients. Thank you for the question. Got it. Thanks so much. Next question comes from the line of Tyler Van Buren with TD Cowen. Your line is open. Hi, this is Deanna on for Tyler. Thank you for taking our question. Just to go back to the vepdeg and Pfizer collaboration, has Pfizer indicated its willingness to revise the collaboration or give back rights to vepdeg? Why would they be motivated to give vepdeg back given the amount they've invested to date? Wouldn't that require a significant cash outlay by Arvinas? Are you willing to use the existing cash on hand with milestones or royalties to do that? Yeah, just to reiterate, we're in a current 50-50. The attractions of that 50-50 was the planning on second-line, first-line, and neoadjuvant, sorry, adjuvant trials. Now we're currently left in a situation where it's only second-line monotherapy, so less attractive in terms of our market size for Pfizer. They have shown no interest to develop that further. That's the first important thing, that that would not be developed further by Pfizer. We're in negotiation right now about what's the best way forward in terms of moving away from the 50-50 collaboration we had where either Pfizer takes the asset and launches it and gets more economics, or they hand the compound back to us. I've said really clearly, I'll say it again, if the compound comes back to us, we are not spending any money on the further development of that. None at all. We'd be running a process to find a partner who would then ideally launch the drug and ideally further develop the drug. Again, in the benefit, the forward benefit of seeing the drug on the market. We have no plans to further develop that if we got the compound back. Thank you. That concludes our Q&A session. I'd like to turn the call back over to John Houston for closing remarks. Thank you, operator, and thanks to everyone for joining us this morning and all the fabulous questions. We look forward to providing additional updates in the coming months. Thank you so much for your time today. Ladies and gentlemen, that concludes today's call. Thank you all for joining, and you may now disconnect.