Day and thank you for standing by. Welcome to the Arvinas' First Quarter 2026 earnings call. At this time, all participants are in listen- only mode. After the speakers' presentation, there'll be a question- and- answer session. To ask a question during the session, you will need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would like to hand the conference over to your first speaker today, Jeff Boyle, Head of Investor Relations. Please go ahead. Good morning, everyone, and thank you for joining us. Earlier today, we issued a press release with our first quarter of 2026 financial results, which is available in the investor and media section of our website at arvinas.com. Joining us on the call today, we have Randy Teel, our President and CEO, Noah Berkowitz, our Chief Medical Officer, Angela Cacace, our Chief Scientific Officer, and Andrew Saik, our Chief Financial Officer. Before we begin, 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 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. A replay of the call, as well as today's press release and an updated corporate deck will be available on the investor and media section of our website. Now I'll turn the call over to Randy Teel. Randy? Thanks, Jeff, and thank you all for joining us today. Since stepping into the role as CEO earlier this year, my appreciation for the strength of the Arvinas platform, the talent and execution capability of our team, and our deep and differentiated pipeline has only grown. As the first PROTAC degrader company, we believe we've built unmatched translational expertise in the protein degrader space. I believe we're in a great position for a highly productive and value-generating 2026. Several months ago, after filing the new drug application for vepdegestrant, we announced our intention to identify a third party with the capability to maximize its commercial opportunity. During this time, we remained confident that vepdegestrant had the potential to become a meaningful treatment option for patients with metastatic breast cancer. Our optimism was validated by the recent FDA approval of Vepdeg, now known as VEPPANU, and yesterday afternoon, we were pleased to announce that we and Pfizer have entered into a global licensing agreement with Rigel Pharmaceuticals for the commercialization, development, and manufacturing of VEPPANU. I'll begin with the FDA's approval of VEPPANU for the treatment of ESR1 mutant, ER positive, HER2 negative advanced breast cancer. This is an important milestone for patients and physicians and demonstrates the potential of targeted protein degradation to treat disease. There have been minimal second line treatment options for these patients, and as the lead investigator in our phase III trial said, "The approval of VEPPANU brings renewed hope to patients who need additional options." The approval of VEPPANU was the first ever approval of the heterobifunctional PROTAC degrader. In our industry, few biotechs are successful in bringing a molecule from discovery through approval. Fewer companies still make it onto the very short list of companies, big or small, that have ever been the first to bring a new therapeutic modality from inception to approval. We believe this achievement fully validates our innovative targeted degrader platform, which Arvinas pioneered more than ten years ago. It also strengthens our confidence in the breadth and versatility of our exciting phase I pipeline across oncology, neurodegenerative disorders, and neuromuscular diseases. I am deeply grateful to the team that has worked tirelessly on VEPPANU with the unfaltering belief that it can bring renewed hope to patients who need new treatment options. We are committed to making sure VEPPANU is available for patients as soon as possible. Rigel has a fully established oncology sales team and the infrastructure needed to ensure VEPPANU is available soon. They are committed to unlocking the full value of VEPPANU, and we are confident that they are the right partner to bring this important treatment to the patients that need it. At the same time, this agreement allows Arvinas to invest in the next wave of innovation across our pipeline while maintaining a strong and disciplined approach to capital allocation. Indeed, this was the rationale for seeking a new partner for VEPPANU, so that patients could receive VEPPANU while Arvinas could dedicate itself to our next generation of degraders. I am fortunate to lead an organization advancing an industry-leading portfolio of degraders. Guided by patient genetics and by identifying the central drivers of disease, we deliberately select targets where protein degradation can deliver transformative impact. To date, we have dosed more than 2,000 patients and healthy volunteers using our PROTAC technology, and our team has had remarkable success in advancing promising compounds from preclinical studies to clinical programs. As we look ahead, our ambition is clear. We are not simply advancing molecules to the clinic. We are relentlessly focused on creating differentiated therapies that raise the bar for patients on safety, tolerability, and efficacy. We're not looking for incremental improvements, but rather working towards fundamentally changing what's possible for patients and clinicians. We are doing it from a position of strength. With a healthy balance sheet and a deeply committed team, we are well-positioned to deliver long-term value for patients, their families, and our shareholders. We are in the promising position of having four phase I clinical programs ongoing with the capital needed to reach important inflection points for each of the programs that will inform our investment priorities and ongoing development strategies. Now I'll turn the call over to Noah and the team. Noah? Thanks, Randy Teel. Good morning, everyone, and thank you for joining us today. We have an exciting year ahead at Arvinas, beginning with the recently presented phase I data for our lead program, ARV-102 with AD/PD. These results represent a key milestone and provide strong validation of our approach in neurodegenerative diseases. ARV-102 is an orally administered PROTAC designed to cross the blood-brain barrier and potently and selectively degrade LRRK2, a multi-domain protein that regulates neuroinflammation, lysosomal, and synaptic function. Elevated LRRK2 levels are implicated in disorders including progressive supranuclear palsy, or PSP, and Parkinson's disease. By degrading the full LRRK2 protein complex, including its scaffolding, GTPase, and kinase functions, ARV-102 addresses multiple disease-relevant pathways, in contrast to kinase inhibitors, which target only a single function. We have shown that ARV-102 penetrates the CNS, produces dose-dependent reductions of LRRK2 and cerebrospinal fluid, and modulates downstream disease-associated proteins. At AD/PD, phase I data in patients with Parkinson's disease demonstrated approximately 50% or greater reductions in CSF LRRK2 by day 14 across dose levels, sustained through day 28, consistent with our goal of normalizing the approximately 2-fold LRRK2 elevation observed in Parkinson's disease. Importantly, LRRK2 degradation led to dose-dependent reductions in biomarkers of neuroinflammation and lysosomal stress, including CD68 and GPNMB. To our knowledge, this degree of biomarker modulation has not been observed with LRRK2 inhibitors. ARV-102 was also generally well-tolerated, with no serious adverse events through 28 days of dosing. These findings support advancement into PSP, our immediate clinical focus. PSP is a rapidly progressive tauopathy driven by 4R tau accumulation with a typical survival of five to seven years and no disease-modifying therapies. In patients with PSP, elevated LRRK2 expression is associated with accelerated and clinically meaningful progression within one year. Preclinically, we have shown that ARV-102 impacts neuroinflammation, enhances endolysosomal function, and most importantly, reduces tau pathology in multiple relevant disease models, aligning with our clinical observations of improved endolysosomal function and reduced neuroinflammation. Together, these data reinforce our view that LRRK2 degradation offers a differentiated disease-modifying approach to the treatment of PSP, a devastating fatal disease without available therapy, which affects 25,000 patients in the U.S. I also want to provide an update on the timeline for initiating our phase I-B clinical trial with ARV-102 in patients with progressive supranuclear palsy. We submitted an IND earlier this year with the intention of initiating the trial in the U.S. during the first half of the year. Following the 30-day review period, the FDA requested final data from our chronic tox studies in non-human primates prior to authorizing the initiation of the phase I-B in the U.S. in patients with PSP. Given this requirement, while no patients in the U.S. have been treated, the planned trial is on clinical hold and will not begin until we provide these data, which we expect will be available in mid-2026. We anticipate the U.S. trial will begin by the end of 2026. We do not anticipate this will impact our plans for trials in the E.U. There's no change in our guidance on the start of the phase II study, which we are planning as a global study. Turning now to oncology, I'll begin with ARV-806, our KRAS G12D degrader. KRAS G12D is a well-characterized oncogenic driver associated with poor outcomes and resistance to standard therapies across multiple tumor types, including pancreatic, colorectal, and non-small cell lung cancer. ARV-806 is designed to potently and selectively eliminate both on and off forms of KRAS G12D, a key differentiator for a challenging target in solid tumors. Our confidence in ARV-806 is supported by compelling preclinical results, which demonstrated approximately 25-40-fold greater potency than clinical stage KRAS G12D inhibitors and degraders. These data also show durable degradation greater than 90% for seven days after a single dose, with efficacy responses across pancreatic, colorectal, and lung cancer models. As we shared on our prior call, we completed enrollment of the dose escalation for once-weekly administration in our ongoing phase I trial well ahead of schedule. We view this rapid enrollment as a strong indicator of investigator enthusiasm and unmet medical need in KRAS-driven cancers. We believe the initial data we show later this year will be the first step in showcasing ARV-806's potential as a differentiated and clinically meaningful treatment option for patients with KRAS-driven cancers. Turning to ARV-393, our PROTAC BCL6 degrader, we continue progressing through the phase I monotherapy dose escalation trial for patients with both B-cell and T-cell lymphomas who have received multiple prior therapies. We are particularly encouraged by early responses observed across both populations, including responses at exposure levels below what we predicted to be efficacious. We have also observed robust BCL6 degradation, a notable finding given that BCL6 is rapidly resynthesized. We look forward to sharing additional clinical data from our ongoing phase I monotherapy trial in patients with relapsed or refractory non-Hodgkin's lymphoma later this year. In parallel to enrolling the monotherapy cohort, we've initiated a combination trial with glofitamab in patients with diffuse large B-cell lymphoma, an important next step as we look to expand the potential opportunity with ARV-393. With that, I'll now turn the call over to Angela. Angela? Thanks, Noah. Good morning, everyone. I'll begin by talking about the patients with Spinal and Bulbar Muscular Atrophy, also known as SBMA or Kennedy's disease. These patients are living with a progressive neuromuscular disorder that steadily robs them of muscle strength and endurance. It's an X-linked disease caused by a CAG repeat expansion in the androgen receptor gene, which leads to the buildup of a toxic form of the protein, polyglutamine-expanded AR or polyQ AR in skeletal muscle. That accumulation disrupts normal muscle function, drives atrophy, and over time significantly impacts the quality of life. In other words, polyQ AR is the root cause of the disease. There are currently no approved disease-modifying therapies for these patients. With ARV-027, we've designed a PROTAC degrader specifically to eliminate the toxic polyQ AR protein from muscle cells. By removing the driver of pathology rather than just managing symptoms, we aim to preserve muscle function and alter the course of the disease. We've now enrolled the first three cohorts in our phase I single ascending dose study in healthy volunteers, which is an important step forward for the program. Given our extensive experience with AR degraders, we feel confident in our ability to translate this approach into clinical benefit. Earlier this year at the Kennedy's Disease Association Conference, we shared preclinical data in an aggressive SBMA mouse model showing that our oral ARV-027 degraded polyQ AR in muscle led to meaningful functional improvements and extended survival. As a reminder, we have a terrific track record in developing AR degraders. Our first clinical candidate was an AR degrader, and luxdegalutamide, which we outlicensed to Novartis in 2024, is progressing through multiple phase II trials in hormone-sensitive and castration-resistant prostate cancer. We are excited about the potential of ARV-027 to become the first disease-modifying therapy for patients with SBMA. Now let me turn to the discovery pipeline as we move closer to the clinic. First, ARV-6723, our oral immuno-oncology protac degrader for solid tumors. The target is HPK1, which acts as a brake on the immune system. It dampens T-cell signaling and suppresses both innate and adaptive antitumor responses. What makes the HPK1 target especially challenging is that it works in two ways, not just through its kinase activity, but also as a signaling scaffold. Inhibition alone doesn't fully shut it down. Degradation does. That's exactly what we see with ARV-6723, deep sustained removal of the protein and both of its functions. In preclinical models, the data are very compelling. We see strong single-agent antitumor activity across multiple tumor types, including both high and low immunogenic settings. In fact, ARV-6723 showed greater tumor growth inhibition, outperforming both an HPK1 inhibitor and anti-PD-1. Even more importantly, in seven checkpoint-resistant models, ARV-6723 showed activity as a single agent, while the inhibitor and anti-PD-1 were inactive. Mechanistically, this isn't just about T cells. We're seeing reversal of the immunosuppressive tumor microenvironment, as we just showed at the American Association for Cancer Research conference. ARV-6723 induces a meaningful impact on the myeloid compartment, which you typically don't see with standard checkpoint therapies. Stepping back, we believe this program has the potential to really change the treatment paradigm in immuno-oncology landscape, and we're on track to enter the clinic later this year. Finally, let me touch on our oral pan-KRAS PROTAC program. Three key points to frame it. First, we're seeing broad degradation of KRAS across multiple alterations, including wild-type amplified KRAS with selectivity over other RAS isoforms. Importantly, this works on both the on and the off signaling states. Second, what matters biologically by degrading the protein and removing the oncoprotein rather than just inhibiting it, we are seeing stronger anti-proliferative and pro-apoptotic effects, along with greater tumor growth inhibition. Third, in preclinical models, this approach shows enhanced activity, especially in combination with anti-PD-1, compared to the investigational pan-RAS on inhibitor. That gives us confidence in a differentiated pan-KRAS degradation strategy that also complements our KRAS G12D program. We'll be sharing more updates later this year. With that, I'll turn the call over to Andrew to review our quarterly financial results. Andrew? Thanks, Angela, and good morning, everyone. I'm pleased to provide financial highlights for the first quarter and full year ended March 31, 2026. As a reminder, detailed financial results for the first quarter are included in the press release we just issued this morning. Reiterating the team's sentiment, we have much to look forward to later this year and are pleased with our strong financial position that will allow us to continue to advance our pipeline into the second half of 2028. At the end of the first quarter, we had $614.9 million in cash equivalents, and marketable securities on the balance sheet, compared with $685.4 million at the end of 2025. With our healthy balance sheet and focus on our early pipeline, we are well-positioned to continue to develop our promising oncology and neurology programs. Turning to our first quarter 2026 financial highlights, revenue for the three months ended March 31, 2026 totaled $15.6 million, compared to $188.8 million in revenue for the same period in 2025. The decrease of $173.2 million was due to decreased revenue recognized from the vepdegestrant collaborative agreement with Pfizer, driven by changes to the estimated remaining program costs. General administrative expenses were $19.1 million for the first quarter, compared to $26.6 million for the same period of 2025. The decrease of $7.5 million was primarily due to a decrease in professional fees of $5.3 million. Research and development expenses were $60.3 million in the first quarter, compared to $90.8 million for the same period of 2025. The decrease of $30.5 million was primarily driven by a decrease in compensation and related personal expenses of $15.6 million and a decrease in program-specific expenses of $9.5 million. Our cost reduction programs initiated last year and finishing up midyear 2026 continued to materially reduce our expenses. Non-GAAP R&D was down $25 million compared to the same period last year, representing a reduction of 32%. Non-GAAP G&A came down by $10.1 million or 44% compared to prior year. Total non-GAAP expenses of $67.3 million is down $35.1 million from the same period last year and is representative of our new cost structure for 2026. We continue to maintain our cash runway guidance into the second half of 2028, and in doing so, we will be able to fund operations through key data milestones over the coming months and continue to support our differentiated programs that have the potential to meaningfully improve patients' lives. Additionally, our cash position will benefit from an approval milestone related to the approval of VEPPANU, which we expect to receive later in the year, and the upfront and near-term milestones from our out-licensing agreement with Rigel. With that, I'll turn the call over to Randy for closing remarks. Randy? Over the past 10 years, Arvinas has proven itself a leader in making potent, selective, orally bioavailable, and brain-penetrant PROTACs with differentiated profiles. We've now successfully developed the first PROTAC to receive FDA approval, an accomplishment we believe further validates our technology and promising pipeline. Out-licensing VEPPANU to Rigel Pharmaceuticals allows us to focus on our phase I clinical programs, each of which were advanced based on very differentiated preclinical data. We believe these programs have the potential to transform treatment paradigms across oncology and neurology. We are positioned to deliver multiple clinical updates across our portfolio, including both ARV-806 and ARV-393 later this year. We expect to bring our HPK1 degrader, ARV-6723, into the clinic in the coming months. For ARV-102, we are working diligently to provide additional data needed to enable the initiation of the phase Ib trial in patients with PSP. We anticipate beginning this trial and potentially a registrational trial in the second half of the year. This is a defining year for Arvinas. It is a year of focused execution, clinical progress, and multiple shots on goal, all powered by a healthy balance sheet and a team deeply committed to advancing differentiated first-in-class therapies. We believe the work we're doing has the potential to fundamentally change treatment paradigms and deliver meaningful impact for patients with serious unmet needs. With that, I'll turn the call back to Jeff to begin the Q&A. Jeff? Thanks, Randy. As a reminder for everyone, we're available to take questions offline if you aren't able to join the queue. For now, I'm gonna ask the operator to open up the line for Q&A. Operator? Thank you. At this time, we'll conduct a question- and- answer session. As a reminder to ask a question, you'll need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Kripa Devarakonda from Truist Securities. Your line is now open. Hi, this is Anna on for Kripa. Thanks so much for taking our question. Just two quick questions on the Rigel partnership. Congrats on that. Could you talk a little bit about the economics associated with Rigel sublicensing the drug outside of the U.S., and kind of how Arvinas and Pfizer may split the percentage of the sublicensing revenue? Remind us what the ongoing development activities are that Rigel is expected to contribute that $40 million towards. Thanks so much. Thank you very much for the question. I just wanna start by saying how happy we are to get that, get that done, right? It's been really important to us to make sure that VEPPANU gets to patients as quickly as possible now that it's approved as the first ever PROTAC degrader to get approved. You know, we really chose Rigel as a partner because we were confident in their ability to really maximize the value of the drug and get it to patients, quickly and efficiently. It's been a great process with them, and we're grateful to them for that. In terms of the economics around it, maybe I'll turn over to Andrew to talk about that. Yeah. Thanks, Randy, and thanks for the question. The way to think about our outlicense and our deal with Pfizer and us both have a 50/50 interest. When you read things like milestones and royalties, think about Pfizer and us splitting those right down the middle, for the duration of the outlicense. Okay? The economics that we put in the press release this morning largely pertain to the U.S. That's where we have our current approval. Rigel has global rights. As you may know, Rigel is mainly focused in the U.S., so they would need to find partners to launch it internationally. There would also be a royalty coming back to Pfizer and us, but we did not disclose that number in the press release as we only have a U.S. approval at this time. Thank you. One moment for our next question. Our next question comes on line of Etzer Darout of Barclays. Your line is now open. Hi. This is Luke on for Etzer. Thanks for taking my question. For the G12D, can you talk about the scope of the data that we'll get later this year around, like, the number of patients, follow-up time, et cetera, and, you know, what you're viewing as the bar of success for advancement into future development? For 027, how translatable is the mouse model into humans, and what are the relevant biomarkers that we can look for from the healthy volunteer study? would is this really just gonna be a safety assessment? Great. Thanks for the questions, and we can take them maybe in turn, and I'll look for Noah and Angela to jump in here too. On 806, those data will be coming out this year. As you know, we're in a phase I dose escalation, which has been going on since last year. Obviously, that's a space that's been evolving pretty rapidly over the past few months, and a space that we're pretty excited about having a PROTAC degrader for G12D. We've said the data will be coming in 2026. We haven't been exactly specific on where and when. We will be sharing safety, PK, PD, and some initial response rate data. Clearly, the later in the year that we get those data out, the more durability data we'll look to have, which is obviously what we think is gonna be some of the most important information for comparison. That's the story for 806. Maybe for 027, Angela, the question on translatability of models. Sure. For ARV-027, we know that we're targeting the polyglutamine repeat androgen receptor. This is the only form of androgen receptor that's expressed in SBMA. It's the root cause of the disease, and that's exactly what we're going after, right? We have a lot of experience with androgen receptor degraders. We've put many of them into the clinic, and we know that we degrade the androgen receptor clinically. What we're hoping to achieve clinically is just that in muscle, right? We've designed this androgen receptor degrader to degrade the polyglutamine repeat androgen receptor in muscle. We've proven that in this aggressive mouse model where we've shown not only very nice dose-dependent degradation of the polyglutamine repeat androgen receptor in muscle, we've also shown that we've rescued two endophenotypes that are very important for the disease, endurance and strength, right? you know, our goal was to translate that ultimately into the disease. first, we need to show pharmacodynamically that we impact the target in muscle, and that's our goal with the phase I trial in healthy volunteers. then in us. Yeah. One moment for our next question. Our next question comes to line of Yigal Nochomovitz of Citigroup. Your line is now open. Hi. This is Caroline on for Yigal. Thanks for taking our question. Can you tell us what are the average levels of LRRK2 in PSP patients, and would the 50% knockdown seen in Parkinson's be enough to bring PSP patients back into normal physiologic range? Thanks. Yeah. That is exactly our thinking. In terms of patients with Parkinson's and other neurodegenerative diseases where LRRK2 is playing a role, it's generally double. That is the thinking there. Anything else you'd like to add, Noah? Sure. We can speak towards the levels that we see with the assay that we have. I think it's important to recognize that LRRK2 is an evolving area, and different folks in clinical trials and in just general kind of phase 0 studies just doing assessments of CSF have different measurements. We recognize that healthy volunteers think of it roughly as healthy volunteers having a little below 10 picograms per mL as their median LRRK2 level and patients with Parkinson's disease having about twice that. As you said, I think you hit it spot on. Our goal would be to reduce the Parkinson's disease patient levels towards that, what's seen in healthy comparators. The good news there is that this is that that's exactly what we have seen in our studies to date, right? In the studies that we showed at ADPD, in our phase I, if you compare the healthy volunteers to the patients with PD, we do in fact see that the patients have, you know, somewhere on the order of double the LRRK2. In addition to that, we're able to show that after treatment with ARV-102, that we then knock down and reduce that level of LRRK2 by at least 50%, depending on the dose that we get. We feel like we certainly have a path to get there. just to add to that, in postmortem brain, we know, from published results that there's twofold elevation in microglia, in the brain as well, and that by normalizing, that we feel that we'll normalize, neuroinflammation as well in the biomarkers that Noah and his team have shown. We move, we hope will, alter the course of the disease. Great. Just to clarify, you expect the same for PSP patients as the Parkinson's patients? Could you say that again? Ask the question. You just seemed to respond in terms of Parkinson's patients, and I was just clarifying that, you know, you expect the same 50% knockdown in PSP patients. Right. We also expect that there's. Well, we have shared, well, there are data that have been published by others, demonstrating an association of LRRK2 with PSP. We understand that it's that in general, in these neurodegenerative diseases when the LRRK2 protein is mutated, but also when it's expressed at higher levels, it's leading to endolysosomal dysfunction, which can drive the accumulation of pathological proteins. PSP fits into that perfectly. It has the genetic association with LRRK2. There is accumulation of pathological tau, and our expectation is that we will see reductions of LRRK2 in the PSP patients, which would lead to an improvement in the tau deposition or reduction in it. To add to what Noah said, there's elevated LRRK2 in peripheral monocytes. Biomarkers are elevated, so LRRK2 is elevated in PSP, and this is correlated with more rapid progression, clinically within a year in that already progressive disease. You know, that indicates to us that reducing LRRK2 could move the needle in that disease. That's PSP. Thank you. Thank you. One moment for our next question. Our next question comes to the line of Sudan Loganathan of Stephens. Your line is now open. Thanks for having me on, and congrats on the VEPPANU approval and the Rigel deal. The first question I wanted to have was on the vepdegestrant program. For any future clinical trial developments or, you know, any ongoing trial developments, is how is that gonna be structured in the way that you or Rigel or Pfizer will be managing it? Then secondly, wanted to ask if there's any, you know, combinations with the ARV-806 for the KRAS G12D degrader, if there's any combination options, you know, as you're looking at the different solid tumor indications you're going after. Thanks. Yeah. Thank you. Thanks for the questions. On VEPPANU, the ongoing trials, as you know, are being run by us and Pfizer. As we talked about this morning in the releases, Rigel will provide some cost offsets for some of those ongoing development plans. For future development work, the economics then would fall to Rigel. However, you know, it will make sense to wait a little bit for us to get through the appropriate, you know, reviews and get that transaction, you know, fully closed, before talking about that. Really, the questions on development will go to Rigel. We're pretty excited with where we are right now in terms of what we've created for a development plan for Vep and getting that to patients. In terms of 806 combos, Noah, would you like to join in? Oh, sure. We have shared some data previously and are continuing to share about combinations of 806. You can look at, you know, upcoming congresses to see what happens, for example, when you combine with chemotherapy. We're obviously doing work to look at other combinations internally. Right now, our guidance is simply towards sharing the results of our dose escalation. Yeah, just to add that, you know, we know that, we are combinable from a degrader perspective with anti-PD-1. This is something that we've shared, and it looks different than divarasib. We've also shown functionally that we don't inhibit T-cell receptor function, which is different than divarasib. We feel that we have opportunities there as well. Thank you. One moment for our next question. Our next question comes from the line of Michael Schmidt of Guggenheim. Your line is now open. Hey, guys. Good morning. Thanks for taking my questions. Maybe one on the BCL6 program. Could you comment on potential for differentiation from the Bristol CELMoD program? Just help us understand what you're doing in the phase I study, the monotherapy study. Is that in all comers? Are patients selected in any way? How should we think about the efficacy bar in B and T-cell lymphomas? Yeah. Thanks for the question, Michael. Right. ARV- 393, our BCL6 degrader, it's a program in our phase I dose escalation as of now. You know, and that's a program that when we began it really was considered an undruggable. We've been gratified to see some of that early data from BMS around response rates in B-cell tumors. As we reminded folks this morning, while that phase I is ongoing for us, we mentioned last fall that we have seen some early responses in both B and T-cell or lymphomas. In terms of the potential for differentiation, Noah, would you like to speak? Sure. I just wanna clarify, though. The question was differentiating us from You said the CELMoD. The Bristol, yeah No, were you talking about golcadomide or their BCL-6? I just wanted to be clear in my response. The BCL-6. I'm sorry. The BCL6. Okay. The BCL6 degrader that they've published on demonstrates activity in follicular and large B-cell lymphomas. You know, we're obviously looking at that. A way that we've differentiated our dose escalation study is that we've keyed in on AITL as well. This population, angioimmunoblastic T-cell lymphoma, represents about 3% of all NHLs. There is tremendous unmet medical need because after first-line SOC where patients will progress pretty rapidly on average in about a year or less, there really isn't a good standard of care. We've described that we've enrolled such patients in our study. We've seen responses. It becomes an important area of differentiation in terms of the development plan for us. In terms of efficacy bars, there becomes a difference between efficacy bars in T-cell malignancies and B-cell malignancies. I described AITL to you. If we shift to B-cell malignancies and look at the two major ones, follicular, there's diminishing unmet medical need because patients have very long progression-free survivals with current first, second and third line therapies. In large B-cell lymphoma, which we've hinted at or not even I guess we've stated that that's an area of more interest to us, there is also diminishing unmet medical need, but still a significant enough one in second and third line, where even though you have drugs like CAR- T that can be curative and you have tremendous responses with bispecifics, fundamentally, patients are still progressing. We envision a future where we'll be combining with bispecifics and impacting large B-cell lymphomas. We already shared today that we started dosing patients in a large B-cell lymphoma dose escalation where we combine with glofitamab, so that becomes an important part of our program. Thank you. One moment for our next question. Our next question comes from the line of Ananda Ghosh of H.C. Wainwright & Co. Your line is now open. Hey. Hi, team. Good morning, and thanks for giving me an opportunity. I have two questions, one on KRAS and one on the LRRK2 degrader. Maybe start with the KRAS. You know, the AACR 2026 had a pretty good, disclosure rich data on how the competitive landscape for KRAS inhibitors slash degraders look like. My question is, what were the learnings from the AACR data reads with respect to tolerability, efficacy, you know, the efficacy bar and resistance aspect of the KRAS problem? Thanks for the question. Yes, look, on KRAS in general, and I'll pass to Noah here in a moment, I think you're absolutely right to point out the space is evolving quickly. We were pleased to see the RevMed data come out, both earlier, you know, a month or so ago, and then the recent publication, which helps clarify even some of the sort of different levels of data and efficacy that we see in different populations. It's certainly a space that we're watching very carefully, both as we move the programs forward and plan our own data disclosures. I would say that's true for both our G12D program, which is in the clinic now, as well as our pan- KRAS program, which is still preclinical. Like other companies, we think that it's going to be quite helpful to have multiple assets in this space, both the more specific mutant integrator and then as well as the pan. For more, Noah, please chime in on this space. Thanks, Randy. Yeah, there definitely have been great learnings over both at scientific conferences and obviously with RevMed's announcements. This is an area of active development, intense development because of the potential impact for patients. I think we recognize the transformative, all of us recognize the transformative nature of the first pan RAS inhibitor. At least by what's been presented for the importance as monotherapy in second-line PDAC. What we also recognize is that with that tremendous efficacy, you know, doubling overall survival, there's also toxicity burdens, right? It's an amazing drug, but patients also are experiencing a lot of toxicity, and maybe this is because of the broad targeting of beyond KRAS of NRAS and HRAS as well. This opens the door for folks that are looking at more targeted therapy, whether that means looking at G12D, which represents about 40% of that patient population in PDAC and also about 10%-15% in CRC and several percent in non-small cell lung cancer, or if you're looking at a pan KRAS. That's why we've chosen to discover and develop drugs in this direction. Beyond there's an opportunity for differentiation by more targeting, but also if you can reduce the toxicity that's seen, particularly the skin tox that's seen with the pan RAS, then that also creates the opportunity for broader combinability. We recognize that there may be opportunities to combine a pan KRAS or a G12D targeting agent that doesn't have much skin toxicity with EGFR receptors, which can move you in the CRC direction. There are opportunities potentially to combine with chemotherapy and use higher doses than a pan KRAS can use. We recognize that. We recognize the intense competition in the G12D space and, you know, that's why we're just keeping our heads down, charging forward, and look forward to sharing data later this year on our G12D program. Great. Thanks. Maybe if I have time, can I ask one question on the LRRK2 program? Please. Okay, thanks. You know, given the data, which you disclosed at the AD/PD, it would be interesting, you know, it would be important to know, kind of the factors which drove the decision to look at the PSP trial, from whether it is a mechanistic point of view, whether it is from the biomarker point of view, you know, whether it is from the indication point of view, which might lead to a faster registrational trial. Just wanted to understand what were the thoughts, you know, the strategic thoughts that went inside the decision. Yeah, absolutely. I'll pass to Noah on the design and thinking about PSP as an indication. On those AD/PD data, you know, just to reiterate that, we talked about it in the prepared remarks. I really think that what we're doing there is pretty unique, right? What we've been able to show there in terms of both the reduction of LRRK2 and also the downstream disease-relevant biomarkers, we think really stands apart from what others have shown, both pre-clinically and in the clinic, right? We're moving downstream biomarkers that we know are important for neuroinflammation, driving the disease in a way that we think is you need a degrader to get to hit all the functions of LRRK2, which could ultimately be relevant in PSP as well as other diseases. On PSP specific, please, Noah. Thanks for the question. Thanks, Randy. I think for all the reasons you highlighted, or all the general areas, indication, mechanism, biomarkers, all of that supports the focus on PSP. Let me be very clear, there's no pivot here. We did a study in Parkinson's disease because those patients are readily available, because it is a disease of interest to us, and we could see a long-term opportunity to develop the drug in that space as well. We chose that initially because it was the most informative next step after a healthy volunteer study to prove some of the biomarker points that are applicable to PSP. The PSP program has been long in planning. It's a disease of incredible unmet medical need that's rapidly progressive and allows you to identify a more homogeneous population of patients that have rapid progression, significant changes in the PSP rating scale on an annual basis, which means that you can run a study with fewer patients and see the effect of your drug. From an indication point of view, less unmet medical need, less competition, more homogeneous, and quite a significant indication in its own right. Because as we said, it's a rare disease, and, but at the same time, there are 30,000 patients in the U.S. You can make similar estimates for Europe, obviously, and Asia. That's the indication side. Mechanistically, same fundamental issue. You have endolysosomal dysfunction, you have degeneration of synapses and circuits in the brain that underlie the disease. In this particular disease, it's a tau pathology that, you know, rather than something like alpha-synuclein, where I think there's more heterogeneity there, less certainty in the community about how that works to drive disease. There's understanding that the 4R- tau in PSP is a driver of this disease, so it's something that we're going to be able to measure as well. Then from a biomarker point of view, we've done the lifting so far now in PD, and that's transferable. We know that the drug can degrade LRRK2 in the brain in a predictable way. We know that we can drive decrease in biomarkers that are associated with that endolysosomal dysfunction that I described earlier that's driving the 4R- tau accumulation. That allowed us to choose a dose range that we can bring forward for our phase I-B and our registrational phase II program. Great. Thanks, guys. Sure. Thank you. One moment for our next question. Our next question comes from the line of Jon Miller of Evercore. Your line is now open. Hi, guys. Thanks so much for taking my question, and congrats on all the progress. I'd like to focus on the RAS programs as well. You're moving into the expansion cohorts, phase II expansion cohorts. I noticed for the G12D, it seems to be specifically in pancreatic, and I was curious what led to that decision. Obviously, PDAC is arguably the most competitive of the RAS relevant spaces, and I know you know that the landscape is evolving rapidly there. What drove you into PDAC specifically? Have you considered doing expansion cohorts in other RAS relevant indications? When could we hear more about some of those combo approaches that you mentioned in previous answers? On the pan-KRAS side, I was really interested to hear, and to see, the recent publication of the apparent improved synergy with the anti-PD-1s, and I was curious what your thoughts on the mechanism there was why the pan-KRAS would have a better, or a degrader would have a better synergy with PD-1 than pan-RAS agents. Jon, thanks for that question. We'll do that in three parts. I'll start and then pass to Noah for PDAC, and then Angela can probably speak best to the pan-KRAS and the anti-PD-1. Look, I think it bears repeating, right? As this space evolves, we're clearly looking at what's changing. What hasn't changed is our preclinical data, right? Our preclinical data gave us reason to believe, you know, based on the data in our hands, that we could be more potent in terms of tumor growth inhibition versus the clinical stage inhibitors and degraders. That's what we're relying on to think that we could be better. Now, that better could result in durability, preventing resistance. There's also opportunities, as Noah spoke about before, around combined ability and tolerability. I think we'll be looking at all of those things. The other thing that I would say before, Noah, I pass to you on pancreatic, is that when you have a program come along like RevMed has, and is going to change the space, it isn't only going to be about can you win head-to-head. There are going to be new opportunities that are created in that space, as the whole, you know, treatment paradigm changes in the years to come. Maybe Noah on PDAC and combos and Angela on pan. Yeah. Thank you, Jon, for the question. Building on Randy's point about the potency which we saw preclinically, now that we look at the data from other competitors in the space, we recognize that potency could be a big deal. We know that Stellis' degrader wasn't able to achieve its originally intended maximal dosing because of DLTs in their phase I study. We know that when a drug, divarasib combined with Abraxane for their first-line PDAC study, they had to do a dose reduction, right? All of those types of signals suggest that if you have a drug that can be more potent, you might be able to achieve the target engagement and avoid some of the toxicities that one accumulates when you have to use really high doses. With that said, we're doing the practical thing. We did our dose escalation. One needs for Project Optimus to choose a recommended phase II or phase III dose, however you want to describe it. That requires some expansion. When you do that, PDAC makes the most sense because it's a monotherapy space. The patients are accessible, the need is there, and I think that's been borne out by the pace of our study so far. We don't wanna. You know, those are the steps that we've guided to, so I don't wanna go beyond that and start talking about other combinations and other indications. The focus now is to understand what's the best dose as monotherapy, and then from there, we could get into a discussion. Once we've disclosed that, we can get into a discussion about other directions we can go. I'll turn it to Angela for the KRAS piece. Sure. Thanks, Jon. Thanks for highlighting, you know, our oral pan-KRAS poster at AACR. We did show that we had differential impact versus Duraxon in terms of the tumor microenvironment, where we saw Duraxon was inhibiting the T-cell function by three different measures, right? Functionally. In the T-cell microenvironment, we know that not only are we recruiting T-cells, but we're recruiting other cells to the tumor. We are seeing greater complete responses because of that alteration that we're seeing in the microenvironment. We did show that we were inducing MHC, so we are inducing antigenicity of the tumor. Stay tuned for more mechanistic information on what's going on in the tumor microenvironment. It's an exciting time for the degrader. Thanks so much. Angela, just to clarify, it sounded like what you were suggesting is that this is a pan-KRAS effect, where sparing some of the broader activity of Duraxon might be the key here rather than a degrader effect. I'm just curious if it's possible to tease those two things out at this point. Just so I understand the question and clarifying. Right. We believe that through degradation, right, through both, you know, G12D with 806 or through a pan-KRAS mechanism, that the degrader has a differential effect relative to the KRAS inhibitor in the tumor microenvironment. That's exactly what we showed in our mechanistic study looking at the tumors themselves in terms of seeing that we're actually recruiting more of a T-cell signal. We're also seeing that we are inducing the antigenicity of the tumor, recruiting more immune cells to the environment, to the tumor microenvironment, and we are seeing greater complete responses. In addition, we also showed the difference between the impact of our molecule, a degrader, our degrader in a dose response relative to the KRAS(ON) clinical inhibitor in three different T-cell function functional assays. We're not inhibiting the T-cell function whereas Duraxon is. Great. Thanks so much. Thank you. One moment for our next question. Our next question comes from the line of Paul Choi of Goldman Sachs. Your line is now open. Hi. good morning, and thanks for taking our questions, and congrats on all the progress. I want to turn back for a moment to 027 and the spinobulbar Kennedy's disease program. just curious if you'd maybe provide some context on how it compares to the 766 program for prostate cancer since both degrade androgen receptors and just sort of its potency and sort of what level of effect may be necessary to get to a clinically meaningful benefit here in your opinion. that's my first question. my second question is on VEPPANU and just what the latest status or plans are for European and other global filings and just thinking about, you know, how we should model that on the forward here, given it's now partnered to Rigel. Thank you. Good. Thanks. For ARV-027, for SBMA, that program began earlier in the year, and you're right to remind of the luxdegalutamide deal we did with Novartis a few years ago for prostate cancer. The key difference between the molecules is that while both degrade AR, ARV-027 was specifically selected for its ability to degrade AR in muscle. It really gets into muscle well, which is really important as that's the site where we'd like it to be active for the neuromuscular disease of SBMA, not the case for ARV-766 or luxdegalutamide, the one that's for prostate cancer with Novartis. In terms of Vep and going forward, obviously we have the U.S. approval. The further regulatory work will be done by Rigel, the new partner. Certainly we've got an HSR period to get through. After that point, it probably makes sense to connect with Rigel on all questions regarding the future development. We're certainly excited for them to take it over for both commercialization and the potential further development of Vep. Thank you. One moment. Great. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Derek Archila of Wells Fargo. Your line is now open. Morning, this is Jacob on for Derek. Thanks for taking our question. I just wanted to clarify, did you say the ARV 102 is on hold in the U.S., but still going ahead ex-U.S.? Effectively, that's correct. for 102, right, as Noah said, after filing that IND, you know, we get to the 30-day period, and the FDA essentially has two options, either to move forward or to put it on hold. while that trial has not yet begun in the U.S., we have not dosed any patients in the U.S. Technically, yes, it's on hold. the trials that have been going on outside the U.S. are not affected, and the thinking is that as we move forward, you know, speaking with both the FDA and ex-U.S. regulatory authorities, we'll consider down both paths in parallel. I see. Thanks. What are the gating factors there for starting in the U.S., versus ex-U.S.? Why don't, Noah? Yeah, Teal. Essentially a couple of years ago, before we started this program, we met with the FDA, and we described or we asked them what would be necessary to start in the U.S. At the time, we'd already made a strategic decision to run the healthy volunteer and eventually do the Parkinson's disease study in Europe to get the program started. Very common in neuro drug development. They had outlined for us that for chronic treatment you need to provide the following information. We provided that information, and now they were asking for more than had originally been requested. We have to get it in order. We'll share it with them. The conversation will continue. Okay. Thanks for the color. Thank you. One moment for our next question. Our next question comes from the line of Jeet Mukherjee of BTIG. Your line is now open. Hey, thanks for taking the question. Just coming back to PSP as an indication, can you remind us how these patients are diagnosed and where they're frequently treated? Are they concentrated at certain centers of excellence? Any views so far on what a potential pivotal study could look like in terms of length and primary endpoints? Thanks. Thanks for the question, Jeet. Noah, please. Sure. Yeah. Thanks, Jeet. The patients are typically diagnosed after having been mistakenly diagnosed with Parkinson's disease, right? Because you have someone that's coming in with a tremor, stiffness, instability. These are common presentations for Parkinson's disease and are also present in PSP. There's kind of a clinical differentiating feature, which is that they have a vertical gaze problem that leads to falls. There's a clinical management indicator that also drives you in the direction of PSP, which is that patients with Parkinson's disease will be treated with L-DOPA of some kind, and they will show some improvement typically. When you have a PSP patient, they do not respond to that. Think of it as an initial commonly misdiagnosed unless they present with falls when it would be more obvious. They have this diagnosis, and unfortunately, it's a rapidly progressive disease and differentiates from Parkinson's disease in that way. As we said, the time from diagnosis to death is five to seven years or so. That is the. Now you asked where are the patients treated. There definitely are at some centers of excellence, but it's something that is seen broadly. You know, most all neurologists will see PSP patients at some point. There are centers that see quite a lot of them. There is a history of running clinical trials at various centers in the U.S. Right now, the only other phase III program that is going to be concurrent with this, it looks like, is Novartis' study because they've announced an ASO targeting tau that's moving into phase III, and that involves quarterly injections, intrathecal injections of an ASO. We believe that we'll be able to recruit our patients successfully 'cause there's a long track record of global recruitment for PSP trials. We think there may even be a preference for this type of study that we're running. In terms of endpoints and knowing how the size of that study, we've said in broad strokes before, it's a few hundred patients. It'll be two dose levels, presumably, versus placebo and require a year of treatment. Thank you. Jeet, does that settle it? Thank you. One moment for our next question. Our next question comes to the line of Tyler Van Buren of TD Cowen. Line's now open. Hey, guys. Thanks very much for taking our question. This is Nick on for Tyler. Moving back to the LRRK2 program. While you are prioritizing PSP for the reasons that you mentioned before, is there anything that you could see in your PSP data at some point that would affect your decision to move forward in Parkinson's disease? Could the Denali LRRK2 inhibitor phase II data later this year support advancement into Parkinson's disease? Thanks. I mean, I think the short answer is no in the way that I wouldn't expect. We think that the data we've generated so far in both healthy volunteers and patients with Parkinson's can be translated to both patients with Parkinson's and PSP. I guess from that perspective, there's certainly work we could do in PSP and data that we could see that would give us more confidence that in our ability to do what we've already started to show, which is have 102 be an orally available brain penetrant drug that reduces LRRK2 right where we want it to degrade it in deep brain regions. When it comes to the Biogen readout, certainly something we're looking at. As a reminder, you know, we're talking about 102 as a degrader here, focused on all three aspects of LRRK2's function, which we think is important for the reasons that we've already outlined on this call. For that reason, you know, we are certainly hopeful that the trial is positive for patients. We think that if it is, we think we can show a benefit beyond that with the technology that we have. If it's not, we think that the differentiation that we've already shown, both in the clinic with biomarkers as well as pre-clinically with things like endolysosomal function, the ability to reduce tau, you know, we think there's a lot of data we've already shared that shows how different we are from that program, so we'll be moving ahead. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Akash Tewari of Jefferies. Your line is now open. This is Manoj on for Akash. Just one from our end on ARV-806. It seems like you are going with two dose levels randomized in the phase II trial of ARV-806, rather than, like, just one dose selected from the escalation portion. Just trying to understand the rationale of those two dose levels going randomized into the phase II, and also what endpoints will kind of finally decide the final dose selection, like ORR or KRAS degradation, tolerability or like, just trying to understand the rationale there. Thanks. Yeah, you're right. As we head into the dose expansion, we are planning to explore two doses, which I think is fairly typical in oncology. Noah, anything to add on the Uh- design there? Yeah. All of those factors will go into it. Meaning the, when you do, when you do a dose expansion and you're trying to optimize the dose, satisfying for yourself that you have the right dose, but also you're satisfying, the FDA. Let's be frank. It's very important for them. You look at all these factors. We'll look at the overall response. We'll look at as much degradation data as we can collect. You're looking at the safety, and the other indicators of efficacy. It all goes in there. I think we're looking at a pretty typical expansion here. Thanks. Sure. Thank you. One moment for our next question. Our next question comes from the line of Li Watsek of Cantor. Your line is now open. Hi, team. This is Daniel Bronner on for Li. Thank you so much for taking our question. How do you view the patient population in the future for your KRAS program? I noticed on the KRAS G12D degrader you have so far, based on clinicaltrials.gov, excluded any pretreatment with KRAS-targeted agents. Do you think you will be developing it in the same phase? Do you think you'll be going after pan-RAS or pan-KRAS or even targeted KRAS G12D drugs in the future? Yeah, I think you're highlighting the answer, right? There's a lot of options here. The most important thing to do first is show that our drug works, right? We need to show that in the phase I we're able to be competitive, and that's what we're looking to do with both the escalation and the expansion. Beyond that, as your question and others have alluded to, there's options in different indication. There's options for monotherapy versus combination. You mentioned KRAS pretreatment. Other programs come onto the market and get used, certainly that's going to create a new opportunity to follow that and other therapies, and we'll have to figure out a way to play in that space. You know, one thing that I've been pretty consistent in saying since taking over the CEO role a few months ago is that we're not interested in producing incremental and me-too sorts of programs. It's important for us, especially as a company that has four programs in phase I right now, with a fifth entering in the second half of the year, it's really important that we focus Arvinas on where we can play to win and where we can be differentiated, and we need to show that we can be. As we create that development plan, we'll move forward if we are. Again, sort of goes back to saying that look forward to sharing those data this year, and that'll be the point to sort of to share a bit more on the development plans beyond the initial stages of monotherapy expansion, and escalation. Thank you. Thank you. This concludes the question- and- answer session. I would now turn it back to Randy Teel for closing remarks. Well, thank you very much, everybody, for joining. I probably can't say this enough, but I really couldn't be prouder of the team and where we are. Just in the past ten days, eleven days, we've had both the approval of VEP, which is the first ever heterobifunctional degrader, PROTAC to get to the market. As I said earlier, you know, it's a very short list of companies that gets to take a program, take a technology all the way from inception to its first approval. Couldn't be prouder of that. Working with Pfizer to get the program, VEPPENU, licensed to Rigel for them to launch, also a huge accomplishment. You know, as I reiterated a moment ago, we've got four programs in the clinic. We've shared some data for one already this year, have a couple more coming with some trial starts. a lot to look forward to, and we look forward to keeping you updated along the way. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.