Good day, and thank you for standing by. Welcome to the Arvinas First Quarter 2026 Earnings Call. Operator instructions: Please be advised that today's conference is being recorded. I would now 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 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. And 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 remain confident that vepdegestrant has the potential to become a meaningful treatment option for patients with metastatic breast cancer. Our optimism was validated by the recent FDA approval of vepdegestrant, 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+/HER2- 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 3 trial set, the approval of VEPPANU brings renewed hope to patients who need additional options. The approval of VEPPANU was the first ever approval of a heterobifunctional PROTAC degrader. In our industry, few biotechs are successful in bringing a molecule from discovery through approval. Fewer companies still make it on to 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 10 years ago. It also strengthens our confidence in the breadth and versatility of our exciting Phase 1 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. And 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 1 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. Good morning, everyone, and thank you for joining us today. We have an exciting year ahead at Arvinas, beginning with the recently presented Phase 1 data for our lead program, ARV-102 at 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 in cerebrospinal fluid, and modulates downstream disease-associated proteins. At AD/PD, Phase 1 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 twofold 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 advancements 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 roughly 25,000 patients in the U.S. I also want to provide an update on the timeline for initiating our Phase 1b 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 toxicology studies in nonhuman primates prior to authorizing the initiation of the Phase 1b 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 EU. So there's no change in our guidance on the start of the Phase 2 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 cancers. 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- to 40-fold greater potency than clinical stage KRAS G12D inhibitors and degraders. These data also showed 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 enrollments of the dose escalation for once-weekly administration in our ongoing Phase 1 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. Finally, turning to ARV-393, our PROTAC BCL6 degrader. We continue progressing through the Phase 1 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 1 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.

Thanks, Noah, and 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, and 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 1 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 out-licensed to Novartis in 2024, is progressing through multiple Phase 2 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 break 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. So inhibition alone doesn't fully shut it down, degradation does. And 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. And 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. So stepping back, we believe this program has the potential to really change the treatment paradigm in the 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.

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, 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 and 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 personnel 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 continue 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.

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 1 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, and 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 1b 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 the 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. And as a reminder for everyone, we're available to take questions offline if you aren't able to join the queue. But for now, I'm going to ask the operator to open up the line for Q&A. Operator?

Our first question comes from the line of Srikripa Devarakonda of Truist Securities.

This is Ana on for Kripa. 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? And remind us what the ongoing development activities are that Rigel is expected to contribute that $40 million towards?

Thank you very much for the question. And yes, I just want to start by saying how happy we are to get that done, right? So 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. 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 it over to Andrew to talk about that.

Yes. Thanks, Randy, and thanks for the question. Yes, the way to think about our out-license and our deal with Pfizer, Pfizer and us both have a 50-50 interest. So when you read things like milestones and royalties, think about Pfizer and us splitting those right down the middle for the duration of the out-license, 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.

Our next question comes from the line of Etzer Darout of Barclays.

This is Luke on for Etzer. For ARV-806 and KRAS G12D, can you talk about the scope of the data that we did later this year around like the number of patients, follow-up time, et cetera? And what you're viewing as the bar of success for advancement in the future development? And then for ARV-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? Or is this really just going to 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 ARV-806, those data will be coming out this year. As you know, we're in a Phase 1 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 the 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 going to be some of the most important information for comparison. So that's the story for ARV-806. Maybe for ARV-027, Angela, the question on translatability of models.

Sure. So 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. 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. So what we're hoping to achieve clinically is just that in muscle. 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. So our goal is to translate that ultimately into the disease. But first, we need to show pharmacodynamically that we impact the target in muscle, and that's our goal with the Phase 1 trial in healthy volunteers.

Our next question comes from the line of Yigal Nochomovitz of Citigroup.

This is Caroline on for Yigal. 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?

Yes, that is exactly our thinking. But in terms of patients with Parkinson's and other neurodegenerative diseases where LRRK2 is playing a role, it's generally double. So that is the thinking there.

Sure. So 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 Phase 0 studies doing assessments of CSF have different measurements. But we recognize that healthy volunteers—think of it roughly as healthy volunteers having a little below 10 picograms per milliliter as their median LRRK2 level and patients with Parkinson's disease having about twice that. And as Randy said, our goal would be to reduce the Parkinson's disease patient levels towards what's seen in healthy comparators.

And the good news there is that that's exactly what we have seen in our studies to date. So in the studies that we showed at AD/PD in our Phase 1, if you compare the healthy volunteers to the patients with PD, we do, in fact, see that the patients have somewhere on the order of double the LRRK2. And 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. So we feel like we certainly have a path to get there.

And 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 will normalize neuroinflammation as well and the biomarkers that Noah and his team have shown. We hope that will alter the course of the disease.

Great. And just to clarify, do you expect the same for PSP patients as the Parkinson's patients?

Right. So we also expect that there's—well, there are data that have been published by others, demonstrating an association of LRRK2 with PSP. We understand 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 PSP patients, which would lead to an improvement in the tau deposition or reduction in it.

And to add to what Noah said, there's elevated LRRK2 in peripheral monocytes. So biomarkers are elevated. LRRK2 is elevated in PSP, and this is correlated with more rapid progression clinically within a year in that already progressive disease. That indicates to us that reducing LRRK2 could move the needle in that disease.

Our next question comes from the line of Sudan Loganathan of Stephens.

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 any ongoing trial developments, how is that going to be structured in the way that you or Rigel or Pfizer will be managing it? And then secondly, I wanted to ask if there's any combinations with ARV-806 for the KRAS G12D degrader, if there's any combination options when you are looking at the different solid tumor indications you're going after?

Yes. 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, it will make sense to wait a little bit for us to get through the appropriate reviews and get that transaction fully closed before talking about that. And 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 VEPPANU and getting that to patients. In terms of ARV-806 combinations, Noah, would you like to join in?

Sure. So we have shared some data previously and are continuing to share about combinations of ARV-806—you can look at 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.

And just to add that 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 daraxonrasib. We've also shown functionally that we don't inhibit T-cell receptor function, which is different than daraxon. So we feel that we have opportunities there as well.

Our next question comes from the line of Michael Schmidt of Guggenheim.

Maybe one on the BCL6 program. Could you comment on potential for differentiation from the Bristol Myers Squibb program? And just help us understand what you're doing in the Phase 1 study, the monotherapy study. Is that in all comers? Are patients selected in any way? And how should we think about the efficacy bar in B and T-cell lymphomas?

Thanks for the question, Michael. Right. So ARV-393, our BCL6 degrader, it's a program in our Phase 1 dose escalation as of now. And that's a program that when we began it really was considered an undruggable. So we've been gratified to see some of that early data from BMS around response rates in B-cell tumors. And as we reminded folks this morning, while that Phase 1 is ongoing for us, we mentioned last fall that we have seen some early responses in both the B and T-cell lymphomas. In terms of the potential for differentiation, Noah, would you like to speak?

Sure. I just want to clarify though—the question was differentiating us from BMS's BCL6 program, correct?

Yes, the BCL6 program.

The BCL6 degrader that they've published on demonstrates activity in follicular and large B-cell lymphomas. So we're obviously looking at that. The way we've differentiated our dose escalation study is that we've queued 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 shock where patients will progress pretty rapidly on average in about a year or less, there really isn't a good standard of care. And 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. You—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 stated is an area of more interest to us, there is also unmet medical need, but still a significant 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. And we envision a future where we'll be combining with bispecifics and impacting large B-cell lymphoma. So 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.

Our next question comes from the line of Ananda Ghosh of H.C. Wainwright Co.

I have two questions, one on KRAS and one on the LRRK2 degraders. Maybe start with KRAS. AACR 2026 had a pretty good disclosure of data on how the competitive landscape for KRAS inhibitors and degraders look. So my question is, what were the learnings from the AACR data reads with respect to tolerability, efficacy, the efficacy bar and resistance aspects 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 are pleased to see the recent data come out, which helps clarify even some of the different levels of data and efficacy that we see in different populations. So it's certainly a space that we're watching very carefully, both as we move the programs forward and plan our own data disclosures. And 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 degrader and the pan.

Yes, there definitely have been great learnings over both at scientific conferences and with competitive announcements. This is an area of active and intense development because of the potential impact for patients. We recognize the transformative nature of the first pan-RAS inhibitor. At least by what's been presented for the impact as monotherapy in second-line PDAC, it is transformative. What we also recognize is that with that tremendous efficacy doubling overall survival, there's also toxicity burdens. It's an amazing drug, but patients also are experiencing a lot of toxicity, and maybe this is because of the broad targeting beyond KRAS of NRAS and HRAS as well. So 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 about 10% to 15% in CRC and several percent in non-small cell lung cancer, or if you're looking at a pan-KRAS. And that's why we've chosen to develop drugs in this direction. Beyond the potential for differentiation by more targeting, if you can reduce the toxicity that's seen—particularly the skin toxicity that's seen with pan-RAS—then that also creates the opportunity for broader combinability. So 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 receptor therapies in CRC or to combine with chemotherapy in PDAC, and to use higher effective doses. We recognize the intense competition in the G12D space. That's why we're keeping our heads down, charging forward and look forward to sharing data later this year on our G12D program.

Great. Maybe if I have time, can I ask one question on the LRRK2 program?

Please.

Given the data which you disclosed at AD/PD, it would be interesting to know the factors which drove the decision to look at the PSP trial—whether it is a mechanistic point of view, a biomarker point of view, or from an indication point of view, which might lead to a faster registrational trial. So just wanted to understand what the strategic thoughts were that went into the decision?

Yes, absolutely. I'll pass to Noah on the design and thinking about PSP as an indication. On those AD/PD data, and we talked about it in the prepared remarks, what we're doing there is unique. We've been able to show both reduction of LRRK2 and downstream disease-relevant biomarkers, which we think stands apart from what others have shown. We're moving downstream biomarkers important for neuroinflammation and driving disease in a way that we think requires a degrader to address all functions of LRRK2, which could be relevant in PSP as well as other diseases.

Thanks. I think all the reasons you highlighted—indication, mechanism, biomarkers—support the focus on PSP. Let me be clear: there's no pivot here. We did a study in Parkinson's disease because those patients are readily available and it was an informative next step after the healthy volunteer study to prove some biomarker points 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 you can run a study with fewer patients and see the effect of your drug. From an indication point of view, there's less competition, more homogeneity and meaningful unmet need. Mechanistically, you have endolysosomal dysfunction and degeneration of synapses and circuits in the brain driven by 4R tau pathology, which ties directly to the biology we're targeting. From a biomarker point of view, we've already demonstrated in PD that the drug can degrade LRRK2 in the brain predictably and decrease biomarkers associated with lysosomal dysfunction that drive 4R tau accumulation. That allowed us to choose a dose range for our Phase 1b and registrational Phase 2 program.

Our next question comes from the line of Jon Miller of Evercore.

Congrats on all the progress. I'd like to focus on the RAS programs as well. You're moving into the expansion cohorts—Phase 2 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 KRAS relevant spaces, and I know you know that the landscape is evolving rapidly there. So what drove you into PDAC specifically? Have you considered doing expansion cohorts in other RAS-relevant indications? And when could we hear more about some of those combo approaches that you mentioned in previous answers? And then on the pan-KRAS side, I was really interested to hear and to see the recent publication of the improved synergy with anti-PD-1. 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 the question. I'll start and then pass to Noah on PDAC and Angela on the pan-KRAS observations. As this space evolves, we're looking at what's changing. What hasn't changed is our preclinical data. Our preclinical data gave us reason to believe based on data in our hands that we could be more potent in terms of tumor growth inhibition versus clinical-stage inhibitors and degraders. That potency could result in durability, preventing resistance, and opportunities around combinability and tolerability. When a program like RevMed's changes the space, there will be new opportunities. It's not only about head-to-head comparisons. We'll be looking at all those things. Noah, on PDAC and combos?

Thank you, Jon. Building on Randy's point about potency, which we saw preclinically, we recognize that potency could be a big deal. We know that some competitors had to limit dosing due to DLTs in their Phase 1 study. When daraxonrasib combined with gemcitabine and nab-paclitaxel for first-line PDAC, they had to reduce dose. All of those signals suggest that a more potent drug might achieve target engagement while avoiding some toxicities. Practically, we've done our dose escalation and need to choose a recommended Phase 2 dose, which requires expansion. PDAC makes the most sense because it's a monotherapy space, patients are accessible, the need is high and we've seen pace of enrollment that supports it. We need to understand the best monotherapy dose first and then consider combinations and other indications thereafter.

Thanks, Jon. We presented an oral pan-KRAS poster at AACR showing differential impact versus daraxonrasib in the tumor microenvironment, where daraxon inhibited T-cell function by several measures. In our studies we see not only recruitment of T-cells but recruitment of other immune cells to the tumor. We see greater complete responses because of that alteration in the microenvironment. We showed induction of MHC and increased antigenicity of the tumor. We will share more mechanistic information on what's going on in the tumor microenvironment—it's an exciting time for degraders.

But Angela, just to clarify, it sounded like you were suggesting this is a pan-KRAS effect where sparing some of the broader activity of daraxon might be the key here rather than a degrader effect. I'm curious if it's possible to tease those two things out at this point.

So to clarify, we believe that through degradation—whether with G12D targeting like ARV-806 or through a pan-KRAS degrader—the degrader has a differential effect relative to the KRAS (ON) inhibitor in the tumor microenvironment. We observed increased T-cell recruitment and increased tumor antigenicity. Functionally, we also showed that our degrader does not inhibit T-cell function in three different T-cell functional assays, whereas daraxon did. So we think both the mechanism of degradation and the selectivity profile contribute to the improved synergy with anti-PD-1.

Our next question comes from the line of Paul Choi of Goldman Sachs.

Congrats on all the progress. I want to turn back for a moment to ARV-027 and the spinal and bulbar Kennedy's disease program. Just curious if you could 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 what level of effect may be necessary to get to a clinically meaningful benefit here in your opinion? That's my first question. And my second question is on VEPPANU and just what the latest status or plans are for European and other global filings, and how we should model that going forward now that it's partnered with Rigel.

Great. For ARV-027 for SBMA, that program began earlier this year. While both ARV-027 and the earlier AR degrader 766 (luxdegalutamide) degrade AR, ARV-027 was specifically selected for its ability to degrade AR in muscle. That property is important because SBMA is a neuromuscular disease where the target activity in muscle matters. Luxdegalutamide was selected as a prostate cancer therapeutic and thus has a different distribution and clinical profile. Regarding VEPPANU filings ex-U.S., further regulatory work will be managed by Rigel as our new partner. We have an antitrust and administrative closing process to finish; after that, it will be best to connect with Rigel for updates on international filings and commercial plans. We're excited for them to take it forward.

Our next question comes from the line of Derek Archila of Wells Fargo.

This is Jacob on for Derek. 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, yes. For ARV-102, after filing the IND, we entered the 30-day review period where the FDA can either allow the trial to proceed or request additional information. The FDA requested final chronic toxicology data from nonhuman primate studies prior to authorizing the Phase 1b in the U.S. As a result, no patients have been dosed in the U.S. and that trial is currently on clinical hold until we provide those data. The trials outside the U.S. are not affected and can proceed.

Yes. A couple of years ago, before we started this program, we met with the FDA and outlined what would be necessary to start in the U.S. At the time, we had already made a strategic decision to run the healthy volunteer and Parkinson's disease studies in Europe to get the program started. They had outlined requirements for chronic treatment toxicology. We provided a package, and now they requested final chronic tox data prior to starting in the U.S. We'll provide those data and continue the conversation with the FDA.

Our next question comes from the line of Jeet Mukherjee of BTIG.

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? And any view so far on what a potential pivotal study could look like in terms of length and primary endpoints?

Thanks, Jeet. Patients with PSP are typically initially misdiagnosed as Parkinson's disease because they present with tremor, stiffness and instability. A differentiating clinical feature is vertical gaze palsy that leads to falls. Clinically, patients with Parkinson's often respond to L-dopa, whereas PSP patients do not, which helps differentiate them. It's a rapidly progressive disease with time from diagnosis to death of about five to seven years. Patients are seen at centers of excellence, but most neurologists will see PSP patients at some point. There is a history of running clinical trials globally in PSP. In terms of a pivotal study, we've said in broad strokes before: it's a few hundred patients, likely two dose levels versus placebo, and it will require a year of treatment with clinical endpoints like the PSP Rating Scale.

Our next question comes from the line of Tyler Van Buren of TD Cowen.

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? Or could the Denali LRRK2 inhibitor Phase 2 data later this year support advancement into Parkinson's disease?

I think the short answer is no in the sense that we believe the data we've generated so far in healthy volunteers and Parkinson's are translatable to both Parkinson's and PSP. We expect the PSP data will give us more confidence in the drug's ability to degrade LRRK2 in the brain and modulate downstream biomarkers. Regarding other LRRK2 programs, we're focused on the differentiation of ARV-102 as a degrader addressing multiple LRRK2 functions, and we will proceed based on our data and regulatory discussions.

Yes. To add, we are encouraged by our biomarker data in PD and believe that provides a predictable basis for dosing and translation to other indications. We'll continue to evaluate other programs' clinical data in the field, but our approach and the data we've generated support advancing in PSP and keeping Parkinson's disease as a meaningful target.

Our next question comes from the line of Akash Tewari of Jefferies.

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 2 trial of ARV-806 rather than just one dose selected from the escalation portion. Just trying to understand the rationale of those two dose levels going randomized into Phase 2. And also what endpoints will finally decide the final dose selection like ORR or KRAS degradation—just trying to understand the rationale there.

Yes, you're right. As we head into dose expansion, we are planning to explore two doses, which is fairly typical in oncology to ensure we identify the optimal balance of safety, tolerability and efficacy. Noah, anything to add?

All of those factors will go into the final dose selection. When you do a dose expansion and try to optimize the dose for Phase 2, you look at overall response rate, durability, safety, PK/PD, and as much degradation data as you can collect. It's a holistic decision that satisfies both internal assessment and regulatory expectations.

Our next question comes from the line of Li Watsek of Cantor.

This is Daniel on for Li. 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 space? Do you think you'll be going after pan-RAS or pan-KRAS or even targeted KRAS G12D drugs in the future?

I think you highlighted the answer, which is there are many options. The most important thing now is to show that our drug works. We need to demonstrate competitive activity in the Phase 1 escalation and expansion. Beyond that, options include different indications, monotherapy versus combination approaches, and how to address patients who have been treated with other KRAS-targeted agents as those agents enter the market. We want to focus Arvinas on where we can play to win and be differentiated. We'll share more on development plans once we disclose the upcoming data.

Thank you. This concludes the question-and-answer session. I'll 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 10 to 11 days, we've had both the approval of VEPPANU, which is the first ever heterobifunctional degrader PROTAC to get to the market. As I said earlier, it's a very short list of companies that get to take a program—all the way from inception to its first approval. I couldn't be prouder of that. Working with Pfizer to get VEPPANU licensed to Rigel for them to launch is also a huge accomplishment. And 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. So 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.