ARVN 3Q26 Earnings Call - ARVINAS INC

Good day, and thank you for standing by. Welcome to the RVNES Q3 2026 earnings call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker, Jeff Boyle, the investor relations. Please go ahead. Good morning, everyone, and thank you for joining us. Earlier today, we issued a press release with our third quarter 2026 financial results, which is available in the investors and media section of our website at arvenis.com. Joining us on the call today, We have Randy Thiel, our president and CEO, Angela Kikasi, 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 filing with the Securities and Exchange Commission, which I urge you to read. Our actual results may differ materially from what is discussed on today's call. A replay of this 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 Thiel. Randy? Thanks, Jeff, and good morning, everyone. I'll start by reiterating our commitment to prioritizing investments in programs where emerging evidence supports the greatest potential for value creation, letting the data drive our capital allocation decisions. If we execute on that commitment, we believe our business can create important medicines for patients and significant long-term value for shareholders. We are entering an important period of clinical milestones that we believe will further define both our individual programs and the broader potential of our platform. During the call, I'll provide an overview of our portfolio and plans. Angela will share additional information on our clinical programs, and Andrew will give an overview of the program. I'll begin with ARV 393, our oral BCL-6 degrader, and a great example of a program with strong scientific rationale for differentiation. BCL6 is a key driver of lymphoma biology, and we believe our ability to degrade this classically undruggable transcription factor could offer a differentiated approach to treating B and T cell lymphomas. We see the potential for our BCL-6 degrader to become a backbone of future treatment strategies as both a monotherapy and in combination with standards of care. This could include reducing, delaying, or sparing chemotherapy for patients. During the quarter, as we continued enrolling the monotherapy and combination cohorts of our phase one trial, we submitted our initial monotherapy dose escalation data for presentation at the ASH conference in December. This will be the first of two data readouts for the program, with a second readout expected in mid-2027. The first disclosure will focus on patients with T cell lymphomas where there are limited treatment options available. These data support our belief that ARB393 is an active degrader of BCL6, with the potential to be very competitive as we continue development. The data we share in 2027 will include a greater proportion of patients dosed at levels expected to reach efficacious exposures in B-cell lymphomas, more robust data on durability, and initial data from the combination with glofitamab, the first of our planned combination cohorts. I'll move next to ARV 027, our first-in-class oral androgen receptor degrader targeting the root cause of spinal bulbar muscular atrophy, or SBMA, also known as Kennedy's disease. This degrader targets the polyglutamine repeat androgen receptor, or PolyQAR, which is found in patients with this genetically defined disease. SBMA is an X-linked disease where the PolyQAr aggregates and gains a toxic function, driving progressive muscle weakness and functional decline. By eliminating the toxic accumulation of PolyQAR in muscle, we have the potential to create the first-ever disease-modifying therapy for patients with this rare neuromuscular disease. The SBMA program is advancing through multiple dose cohorts in its Phase I trial, and we intend to share initial data from the Healthy Volunteer cohorts in the first half of 2027. We also intend to begin dosing patients with SBMA in the 1st half of 2020. If successful, we believe the Phase 1 data for this program will significantly de-risk the program, and we will begin discussions with health authorities about initiating a registration-enabling trial. I'll turn next to our first immuno-oncology degrader, ARV6723. By impacting the immune system beyond the ability of current IO therapies, we believe this first-in-class oral HBK1 degrader could become an important treatment for patients in three distinct ways. First, following a checkpoint inhibitor. Second, in combination with a checkpoint inhibitory. And third, in indications where checkpoint inhibitors have not shown benefit. Based on promising monotherapy and combination preclinical data, we initiated a phase 1 trial in the third quarter. Monotherapy dose escalation is ongoing, and we plan to initiate dosing in combination with pembrolizumab in the first half of 2027. HPK1 is a protein that dampens multiple parts of the cancer immunity cascade, and мы believe that by removing it, our degrader has the potential to harness the body's natural tumor immunity to fight cancer. We look forward to providing initial data from this program in the second half of 2027. Rounding out our clinical progress, I'll next provide a brief update on current plans for our LRRK2 degrader, ARV102. Following scientific advice from CHMP, we're now prioritizing the initiation of a Phase 1b trial in the EU and the UK. Next month, we plan to submit clinical trial applications for a Phase Ib trial in patients with progressive supranuclear palsy, or PSP. Trial initiation is targeted for 2027. In parallel, we are in consultation with Japanese health authorities to inform potential development in Japan as part of a long-term global clinical strategy. In the U.S., we continue discussions with the FDA about the ongoing clinical hold of our IMD. Our current objective is now to include U. S. sites in future trials after completing the Phase 1b trial in the EU and the U K. Last month, we reported additional and novel biomarker findings from our Phase 1 trial, including improvements in an objective and quantifiable measure of impaired eye movement associated with Parkinson's disease. The totality of evidence from our Phase I trial strengthens our belief in the potential of LRRK2 degradation to create novel clinical breakthroughs for patients with devastating neurodegenerative diseases. What's common across all of our programs is the scientific premise that by degrading the proteins that cause disease, we can create transformational treatments to address unmet patient need. We are pursuing targets where removing the protein has the potential to change the treatment landscape and improve outcomes for patients. The progress we're making today is laying the foundation for the next wave of innovation at Arvinas and advancing our mission of delivering transformative medicines to patients. With that, I'll turn the call over to Angela. Angela? Thank you, Randy. As we approach Keynes Pipeline Milestones, I will highlight how our preclinical data support our differentiated science, inform clinical development, and position our portfolio to deliver value. Starting with ARV393, our strategy is to establish its potential both as a single agent and in combinations that could expand treatment options for patients with lymphoma. We've shown strong single agent activity in preclinical DL-BCL models with enhanced activity, including complete tumor regressions when combined with chemotherapy, biologics, and investigational oral agents. The results with RCHOP and bispecific antibodies support the combination strategy we are advancing in the clinic. The first phase one disclosure will provide an early look at safety and tolerability, drug exposure, target engagement, and anti-tumor activity. These initial cohorts were treated at doses below those predicted to be efficacious in preclinical DLBCL models. Even at these early dose levels, we have observed responses across NHL subtypes, including B and T cell lymphomas. The disclosure will focus on safety, PK, and PD from all patients, and preliminary efficacy from early cohorts in patients with T-cell lymphoma where treatment options remain limited. These data will help guide dose selection and expansion plans. Our next update, expected in mid-2027, will include more patients with B-cell Lymphoma treated at doses in the predicted efficacious range with longer follow-ups along with initial combination data with glifidamab. Turning to our PolyQ AR Degrader, ARV-027, our Phase I study is designed to establish safety and tolerability and determine whether the drug degrades the androgen receptor in skeletal muscle. Importantly, we are seeing profound preclinical activity in muscle strength and endurance, two of the most fundamental manifestations of SBMA disease progression. In an aggressive mouse model of SBNA, ARV-027 induced poly-QAR degradation in muscle, and we are excited by the data showing rescue of muscle strength, endurance, and survival. Our therapeutic goal builds on the internal data and literature evidence showing that approximately 50% reduction in poly-QAR in muscle improved mouse model strength and restored treadmill endurance. We believe that the forthcoming multiple ascending dose data in healthy volunteers and patients with SBMA will help determine whether ARV-027 produces the biologic effects needed to support the advancement of ARV-027 into a registrational trial. These results, together with chronic toxicology data and regulatory interactions, will guide dose selection and our SBMA clinical trial design. We look forward to sharing initial data from our phase one trial in the first half of 2027. Now, let's turn to our first-in-class immuno-oncology asset, ARV6723, our oral HPK1 degrader, now in its first in-human phase one trial. By removing HPK-1, we aim to eliminate both its kinase and scaffolding functions to release the brakes on innate and adaptive immunity more fully than kinase inhibition alone. Specifically, our preclinical data demonstrate three compelling findings. First, robust single-agent antitumor activity across seven checkpoint-resistant models where a clinical HPK1 inhibitor and checkpoint therapies showed no activity. Second, complete tumor regressions with anti-PD-1 combination treatment. And third, intratumoral immune effects extending beyond T-cell activation, including enhanced interferon signaling and remodeling the myeloid compartment. This broader remodeling of the tumor microenvironment may help explain oral ARV6723's differentiated activity and its potential to address tumors that respond poorly to current immunotherapies. Later this week, at the Society for Immunotherapy of Cancer Annual Meeting, we will present additional preclinical data, reinforcing this differentiation, and supporting our monotherapy and combination development strategy. Our phase one monotherapy trial will assess safety, drug exposure, HPK1 degradation, and biologic effects in tumors. Measures of immune activation, including NK and T cell activation, will enable us to translate the promising preclinical biology to patients and further guide clinical development. Moving to ARV-102, one of the central goals of the program has been to establish a comprehensive understanding of how LRRK2 degradation affects biologically relevant pathways associated with neurodegenerative disease. The phase one data presented at MDS conference last month expanded our biomarker evaluation and further informed our understanding of the molecule's pharmacology. The data showed ARV102 achieved brain penetration and retained its potent and deep reduction of LARP2 in the cerebrospinal fluid, or CSS, of patients with Parkinson's disease. ARV102 also reduces endolysosomal and neuroinflammatory markers in the CSF that have been shown to be elevated in neurodegenerative diseases. Importantly, we presented novel data showing improvements in an objective measure of impaired eye movement associated with Parkinson's disease. The data showed that reductions in LRK2 and CSF after treatment with ARV102 is correlated with changes in ocular motor function and in synaptic biomarkers associated with enhanced plasticity and cognitive resilience. These findings strengthen our confidence in ARV 102's potential to advance treatment for neurologic diseases such as Parkinson's disease, and progressive supernuclear palsy. As we continue development, we are building on these results with biomarkers and functional measures to connect target degradation with downstream biologic effects and potential patient benefits. In closing, we're excited about the potential of each of these programs, with key data insights providing evidence to guide their advancement. We look forward to sharing our progress over the next several quarters. With that, I'll turn the call over to Andrew to review our financial results. Thanks, Angela, and good morning, everyone. I'm pleased to provide financial highlights for the third quarter of 2026. As a reminder, detailed financial results for the third quarter are included in the press release we issued this morning. We are entering a period of meaningful clinical data with an innovative portfolio clear milestones and the financial resources to deliver impactful clinical data that will help us make decisions on our key programs at the end of the third quarter we had 558.9 million dollars in cash cash equivalents restricted cash and marketable securities on the balance sheet compared with 685.4 million at the end of 2025 with our healthy balance sheet and projected cash into the second half of 2028 we are well positioned to continue developing our promising oncology and neurology programs i am happy to announce that we booked our first royalty under the license agreement with rigel in the third quarter the royalty of 0.5 million dollars can be found in the revenue section of our pnl and the associated yale royalty can be sound on the cost of license revenue line General and administrative expenses were $12.6 million for the third quarter, compared to 21 million for same period of 2025. The decrease of $8.4 million was primarily due to decreases in personnel and infrastructure related costs of 4.2 million, costs related to developing our commercial operations of 1.8 million, and professional fees of 1,5 million. Research and development expenses were $46.9 million in the third quarter, compared to $64.7 million for the same period of 2025. The decrease of $17.8 million was primarily driven by decreases in our program expenses of $7 million, non-program specific expenses of $3.5 million, and a decrease in compensation and related personnel expenses of 6.5 millions, which are not allocated by program. Non-GAAP R&D expenses were down $12.6 million compared to the same period last year, representing a reduction of 22%. Non-GAP G&A decreased by 5.4 million, or 37% compared to prior year period. Non-gap expenses for the quarter were $53.5 million compared to $71.5 in the prior year. The 25% year-over-year reduction in expenses reflects reduced spend across the organization, including spend on development and reductions in GMA. Spend this quarter is a good representation of what our spend is expected to be for the next few quarters as we continue to progress our early-stage pipeline. We've maintained a disciplined approach to portfolio decisions and capital allocation throughout the year, and our cash runway into the second half of 2028 allows us to fund operations through multiple key data milestones. Our commitment to investors is simple. We will allocate capital carefully, communicate transparently, and let the data determine where we invest. By executing on that commitment, we will be well-positioned to create important medicines for patients and significant long-term value for shareholders. We believe this creates a compelling opportunity to build long-term value as the next wave of clinical evidence emerges and demonstrates where protein degradation can offer meaningful benefits for patients. With that, I'll turn the call over to Randy for closing remarks. Randy? Thanks, Andrew. As we look ahead, we have a number of meaningful clinical milestones approaching in the coming months, beginning with the first of two data disclosures for our BCL-6 Degrader planned for December, followed by a second disclosure in mid-2027. We're also on track to share Phase I data for our PolyQAR degrater in the first half of 2027, and initial data from our HPK1 degrator in the second half of 2026. And we are also working tirelessly to gain approval for the initiation of a Phase Ib clinical trial with our LRRK2 degrader in patients with PSP in 2027. I'll leave you with what I believe is most important. Arvanis has already accomplished a big win, moving from scientific promise to the first ever FDA-approved Protact-Agrator. What's ahead is to show that this was just the beginning of what we expect to be multiple successes in bringing important new options to patients in need. Thanks, Randy. Operator, will you please open the queue? As a reminder, to ask a question, you'll need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile our Q&A roster. Our first question will be coming from the line of Edward Tenthoff of Piper Sandler. Your line is open. Edward Tentshoff, Piper Sanler, Great. Thanks. Good to hear you guys. Nice update across the pipeline. Two quick questions, if I may, first on the clinical hold on 102. Just remind us sort of where we are on resolving that with FDA. What steps need to be done? And then maybe a quick one for Andrew, can you remind us what the parameters are for the Yale Royalty, both in terms of percentage, and does that apply to all of the programs? Thanks. Andrew Gould Thanks, Ted, and good to hear you as well. Yeah, so for 102, as we said today, the plan will be to move forward with the Phase 1b CTA process in Europe. respect to the U.S., we still have ongoing conversations with the FDA to work on getting off that kind of hold. At this point, investors should assume that the Phase 1B will begin without U.F. patients, but that's not to say that later in the development plan we couldn't bring U.U.S. back in. It's hard to say a lot with the conversations ongoing with the FDA, but I think that's where we are now. We feel confident that we can execute that Phase 1b in Europe as we get through the CTA process, if that's successful, but that's how we'll proceed for now. Andrew, on the Yale license agreement. Yeah. Hey, good morning, Ted. Thanks for the question. So, yeah, on the Yale agreement, we have a royalty. It's a slightly low royalty of about 1% on royalty revenue. So that's going to be ongoing into the future. That does not apply to all of our programs. I don't believe that we've disclosed which of our problems are subject to the Yale royalty and which are not. I think we'll do that as we get closer to commercialization on the other programs because it's a complicated, you know, agreement that we have with Yale. So, and then when we get milestones and up front, it's slightly higher number. You could probably go back and look at what we paid to Rigel. I'm not going to disclose that number, but it's lightly higher, still low single digit. Is that helpful, Ted? Thanks, guys. And our next question will be coming from the line of Yigit Mukherjee of U.S. Bancorp, BTIG. Your line is open. Great. Good morning. Thanks for taking the question, and congrats on the progress. Two questions. First, are you looking for an approximate 50 percent reduction in AR among healthy volunteers for your PolyQ AR Degrader Program, and what endpoints will be evaluated in the SBMA cohort you'll be dosing the first half of next year. Yeah, thanks for the question, Gene. I'll start and then pass to Angela. And just as a review here, we're dosing healthy volunteers now. We'll get to SPMA patients ideally in the first Half of next Year. The short answer to your question of degradation of 50% is yes, but I'll let Angela dive into the detail on that. Sure. So we're targeting 50% reduction in poly-QAR, and the goal here is really to retain some androgen tone while proving that we can reduce 50% androgen receptor, which in our preclinical models and also in the published literature led to rescue of very important endpoints like muscle function and endurance in those models. So that, I hope that explains why. Thank you for the question. Thanks. And just one follow-up, if you don't mind. Just on ARV102, how well do improvements on oculomotor function correlate to overall disease progression or motor symptom improvement in Parkinson's? Thanks. That's a great question. So, this is a novel endpoint that we measured, which is the amplitude of saccadic hypometria. It does have concordance with the UPDRS based on published literature, but it remains to be proven how well that concords and translates into clinically meaningful improvement. That said, we are encouraged by our data showing two different synaptic endpoint changes, one being CSF improvement in meaningful biomarkers like neuronal pentraxin 2 that is associated with cognitive resilience, and also, again, the psychotic eye movement, which is a measure of basal ganglia synaptic activity. The other thing I'd add, Jeanne, is, and I think this is, you asked about 027 and 102, and I thing the point is similar for both, is that doing work to explore potential biomarkers to use in the trials or with patients over time is really important. These are both rare diseases, both in their first trials for approval will likely be rating scale-based trials, but that doesn't mean at the same time we can't be exploring biomarkers that may correlate over time. That's true for both 102 and 027. And on the 027 front, you know, the most important biomarker is the degradation of PolyQAR itself, which in this case is actually driving the disease. So the biomarking here will be important over time, and we think there's opportunities to pursue them across both programs. And our next question will be coming from Yagal Noshimovitz of Citigroup. Your line is open. Yeah. Hi. Thank you. I just wondered if you could provide a quick update with respect to the partnering prospects for ARV806, your KRS-G12 and 80-grader. Yeah. Thanks for the question, Yagul. So we had announced that that program will only move forward with a partner. So we'll look to provide an update on that if and when a partner is found. That program, which we had pronounced that earlier this year, will have some data coming next month, or this month at a conference, so you can look for that as well. But, again, that program is only going to move forward with a partnership. So we're going to stick to providing guidance for the programs that we continue to push forward in Phase 1 as wholly-owned programs. Okay. Thanks. And then, with regard to ASH, so you're in what you've described as sort of below. Give us a little more commentary there with respect to, you know, what we might expect in terms of efficacy. Are you seeing efficacy at a lower dose than you may have initially predicted? And what kind of clues might you have with that early signal that would support, you know, moving higher? Yeah, thanks for that as well. Yeah, so the first disclosure for the 392 program, the BCL-6 reviewer, will be at the end of the year, as you suggested. We'll have another in the middle of next year. So we really think of it as a two-parter. The most important thing to show in a first data disclosure is the translation of the preclinical work into the clinic. So it'll always start off with things like safety and PK and PD, tolerability will be really important, especially for a program like this that over time, the development plan will include both monotherapy and combinations. So we have said before that we need to make sure we see good PK. We have also disclosed that we began dosing at quite low doses, well below exposures that we would expect to be efficacious. We want to see good degradation of BCL-6. This is a transcription factor that's rapidly resynthesized, so we need to see solid degradation of BCl-6, and on the efficacy front, we're going to focus the first disclosure on T-cell patients. If you are a second-line plus patient with MTFHL right now, you're getting something like a 35% to 45% response rate with drugs that are on the market now, despite there being no specifically approved therapies for second- line T cell patients like this, which is actually a good reminder of the unmet need in this space. So with therapies on the market getting something like 35% to 45%, in a first-dose escalation study with low doses like we're in now, we and the investigators would be pretty excited with anything over really a 30% response rate. Certainly would look for that to go higher as we dose higher, but in an early setting like this with most patients dosed at doses below where we were expecting efficacy, that would be a reasonable bar to set. Hope that helps, Nicole. Yeah, no, thank you. That's very helpful. Thanks. And our next question will be coming from the line of Jonathan Miller of Evercore ISI. Your line is open. Hi, guys. Thanks so much for taking the question, and congrats on the progress. I'll follow up on Yigal's question on ASH. Given that you're primarily going to disclose efficacy in T-cell patients where your competitor in the degradation space is very focused on B-cell patient, I was wondering how we should think about read-through from one indication to another and how we could think about the relative potency of your molecule relative to the competitor and how should we think about moving beyond B-cells into B-cel indications for the next year? Yeah, great question, John. Thanks for it. So as we said, we'll focus the disclosure in the middle of next year on the B- cell patients or bring them in from the efficacy perspective. And the reason for that is pretty simple, right? The modeling that we talk about, you know, when we talk about dosing below exposures that are expected to be efficacious, that is really done in B-cell, LBCL models. And so that's where we believe that if we take the patients that we have now and you cut down the end by the number of patients that are dosed at a level that you'd expect efficacy with various indications, with response-available capabilities or factors, that number gets to be pretty small. And we want to make sure that the data that we are presenting is informative for investigators and investors. So that's why we focus the first disclosure on T-cell and we'll wait on the B-cell disclosure for fuller disclosure on B-cel when we have more patients at higher doses and the ability to show durability and also the ability of showsome combinability with GLOFI as that trial is ongoing, and we'll have more patients that we can share by the middle of next year. With respect to translatability, we have seen responses in both B-cell and T-cell patients at lower doses. We said that even a year ago, so I think that there could be some transferability, but it'll be more informative to wait until we show the data in B-Cell patients where you can really get a good sense with more patients, higher doses, more durability. Great. Thank you so much for that. And if I can sneak in one more on LARC2, I was wondering if we could talk more medium to long term about how this Phase 1B in EU and UK is going to translate to potential registration paradigms. What's your updated thought on timeline to getting into registration? Yeah, good question, thanks. So the thinking now, and John, you'll remember that we had, you know, maybe a year ago talked about the potential for two trials, a Phase 1B in the U.S. and a more global registrational trial. What that's folding into now is the Phase 1b trial first that, as we said, will be in Europe and then look to move to registration after that. So it's a little early to give too much in terms of specifics for that trial, but we'll want to be dosing patients with PSP now for a longer time period. A reminder that we had dosed in the healthy volunteer and PD patients only for 28 days. So this would be longer and enough time to get a good sense of safety, PK, PD as always, and also perhaps some efficacy-oriented endpoints as well, where the goal of that phase 1B trial is to get the confidence to move into a registrational trial that's larger and later on. So that's how it plays out now. Going back to the remarks we made on the call, there could be an opportunity at that point to make it a more global development program, potentially including Japan and the U.S. and other geographies. But we'll need to get through the Phase 1b trial first. And as we said on the called, we'll look to start that trial in in 2027 after getting through the CTA process in the EU and the UK. And our next question will be coming from the line of Nick LaRusso of TD Cohen. Your line is open, Nick. Hey, guys. Thanks very much for taking our question. Moving back to 393 again, so you provided the bars for the early data at ASH, which is very helpful. but looking to the data mid-next year, what are you looking for there with the potentially higher doses as well as the Glowfit combo? And could you quickly move to a registrational path following these data? Thanks. Thanks for the question, Nick. So I'll answer the second one first. Yes, I think that's possible with respect to T-cell patients, whereas we've talked about there's a pretty significant unmet need. With respect to how we think about what does good look like, which I know is really your question. This is a program that was really our first undruggable, right? So moving into BCL-6 after the early success with AR and ER was an opportunity to show what a degrader can do in a space where no degraders had previously moved into, sorry, where no programs for BCL6 had moved into the clinic. The inhibitors hadn't made it there. So the question of what does good look like for BCl6 is starting to get answered by our competitors in the space already, which is great news because it shows that the target we picked a while ago had some efficacy. So with respect to what does good actually look like, that bar is going to get set, right? It's a little early to talk about it now, but right now patients on a monotherapy BCL6 to greater, which you've seen some other players, have had response rates of over 50%. While we don't think this is a winner-take-all setting, we certainly do see it as an important setting to show that we can be competitive in. I'll make a specific comment on the Glophe combo. The GlopHe combo that we're running, you know, GlopHE is quite an active agent. So the objective of the GlophE combo will really be around showing combinability. Certainly the efficacy can't be worse than GlopE already has, but we would expect good responses from GlopHee already. And in a small dose escalation trial, that is not the place to be looking for, you know, a better performance than GlophHee. So, really, the outcome there that we're looking for is combinability and, of course, continued translation of safety PKPD. And then just to add to what Randy said, the strong B-cell combination rationale also is due to the enhanced CD20 expression that we see, where we would expect to see enhanced combinability with rituximab, so R-CHOP, and then also the bispecifics like glofidamab. So, really excited about establishing D-cell response depth and durability. Thank you very much. It's very helpful. And our next question will be coming from the line of Edser DeRote of Barclays. Your line is open, Edser. Great. Thanks for taking the question. I guess a couple of follow-up ones. Will the decision to enter SDMA patients with ARV027 be contingent on hitting the muscle degradation threshold, you noted earlier in Healthy Volunteers. And then for the PSP phase 1b study with ARV102, just trying to understand, is the start in EU-UK primarily differences in the requirements for chronic toxicology data for the asset? Is that the real driver here in terms of being able to start the study there versus the U.S.? Any thoughts there would be helpful. Thank you. Thanks, Spencer. The first one around SVMA patients, no. I think the way I understand your question is, will it be gating in the healthy volunteer studies to begin the SVMA patient? Do we need to see a certain level of degradation? Really, the answer is no. The multiple-dose portion of the healthy volunteer study is really intended to find a dose, a single dose, that we can then continue the phase one in patients with SPMA. It's a rare disease, so it is not super easy to find, you know, a lot of patients to be using in a phase one study, especially when, as we've said, that phase one steady will be pretty de-risking and should provide the evidence from a biomarker perspective to move into a registrational study. We would love to be saving patients to move into a registrational study before too long. Anything else on that, Angela, before we go on to the 102? I think that's great, Randy. I think going to a single site to run a Phase I study in Healthy Volunteers and move to SBMA is really sensible given the experience of the single site that we're using for the study for biomarker collection. Great. And then on the question around ARB-102 and the differences in the different regulatory discussions, really hard to comment on those ongoing discussions. But what you should assume, Etzer, is that each of those conversations is multifactorial. And based on the fact that we're saying we'll move to the CTA process with Europe, you can assume that we've gotten scientific feedback that we think provides a path forward to those CTA conversations and starting a trial in the next year. whereas in the U.S. it looks like it will take a bit longer. We want to make sure that we are moving the program to get to proof of concept as rapidly as we can. We think that's really important to show the value of the program. We have confidence that we can do that with studies in Europe, so that's what we'll focus on. Great. Thank you. A question will come from Tazin Ahmad of Bank of America. Your line is open. Hi, guys. This is Jeremiah on Tazim. Thanks for taking our question. Maybe a question on ARV-027. Maybe just what are you guys looking for on safety and tolerability in the healthy volunteer cohort, just as you work towards that around 50% degradation level? And then longer term, if you're able to achieve that level in SBMA patients. Just curious on how you're thinking about how long it would take to see translation into functional benefits. If there's any read-through that you guys have from your mouse work that informs that timing. Thanks. Thanks for the question, Angela. Please dive in. Yeah, so ARV-027 is not unlike any other molecule being tested for safety. We'll be looking at all aspects of safety and tolerability in that phase one dose escalation. You know, hitting that 50% mark comes from our preclinical data, where we did hit 50% reduction in poly-QAR, so removal of that disease driver, rescue, strength, endurance, and survival in that model, and also has been shown in other models to do the same. So, you know, it's very difficult to translate time in terms of clinical benefit, but what is exciting is that as we move to the clinic, we'll be looking at muscle integrity. We're taking a close look at natural history data and are grateful to patients as well as NITO for providing us with their data to take a closer look at clinical endpoints that we'll be looking to translate in our registrational SVMA trial. So I'll just think that covers it. I'll add one thing, because I don't think we said this on the call or reminded folks of this. ARV-027 degrades both wild type and poly-QAR roughly equally well. But in patients with SVMA, they only have the mutant form of poly-KAR. So it's an X-linked disease where patients only have one kind. But that's why we think that the studies that we're doing in Healthy Volunteers First should be quite predictive of what we can see in patients with SPMA with respect to, can we get O27 to be orally bioavailable, get into muscle, and degrade the target protein where we need to degrade it? And then degradation of the wild type should predict degradation of poly-Q, which, as we've said, is a pretty clear marker since that's actually the protein-causing disease. Thanks. And our next question will come from the line of Lee Watzik of Cantor Fitzgerald. Your line is open. Good morning. Appreciate the update. Maybe a follow-up on the 393-ish update. How many T-cell lymphoma patients should we expect? Are there enough patients to perhaps assess dose response? And what about, you know, durability, given, you know, many agents here have shown quite modest, you know, PFS? Yeah, thanks, Lee. So, with respect to T-cell patients, as we look at efficacy, think mid-teens or so, with the same caveat that clearly the patients that have been dosed at the highest levels, which is where you'd be more likely to see efficacy, will have the shortest follow-up just by definition in a dose isolation trial. So, the durability information in this update will be fairly limited, and you should expect to see more next summer as we bring in both T-cell and B-cell patients. We will show some, but to my point, the patients dosed at the highest levels will be the ones by definition with the shortest follow up, but I think mid-teens or for T cell patients. And I also have a question on your HPK1 degrader program. Just curious how much, you know, proof of concept data do you plan to generate before you refine the next steps? And then just how does the next-gen IO agents, like, you knows, PD-1 VEGF impact your thinking around where you might fit in. Yeah, thanks for that question. I think the short answer is not much. I mean, we've begun that phase one trial of HBK1 to greater and think that that's a program that could have applicability well beyond what PD-1 therapies have done. So the PD-2s have been great at getting over T cell exhaustion, but there's multiple points in the immune cascade that we think HPK1 acts as a depressor, and so degrading should have a benefit. So that's a trial ongoing, expected to get to its first date in the second half of next year, and is going to be entirely in patients that are post-checkpoint inhibitors. Haven't seen a lot of success there with other agents, but we think that we can see that with HPK-1. But the proof that we have there to move to that step has really been in the preclinical work where we've overcome something like seven immune checkpoint inhibitor-resistant models and shown better data versus both PD-1 therapies as well as a prior HPK1 inhibitor. And you'll see more of that data this week at CITSE if you see our poster there. And our next question. Oh, Lee, I didn't answer your question about next generations, BDS and so on. Look, we think an oral new access of an IO therapy could have a lot of applicability, regardless of what the other next generations are doing. It's not really, I don't really see it as a competition there. This is a different target with a different set of functions in the body that we can be acting on. And we intend to start combinations with PEMBRO. like we said, in the first half of next year, but you should not assume that's the only combination we could do. And preclinically, we'll be disclosing data in the not-too-distant future around other combinations that you mentioned and other activities that we see within the tumor microenvironment that we think are very exciting for ARV6723 as an oral agent. And our next question will be coming from the line of Kripta Devarkonda of Truist Securities. Your line is open. Hi. This is Alex Long for Krippa. Thanks for taking our question. The question on capital allocation, what clinical milestones are fully funded with the current runway in the second half of 2028, and what trials and expansion cohorts does that include? Yeah, thanks for the question. Look, we're fully funded, first off, on BCL-6 through next year, right? So the ascending monotherapy, the combination is all funded. We've also funded some of the expansions where we're going to start looking at combinations. I'm not going to get into it because I don't think we've given our full development plan on that, but we plan on expanding and testing combinations starting next year and a number of therapies. Those are all funded. We have funded SBMA through, you know, through our guidance period. Obviously, the trial goes a little bit further than we have a cash guidance, so we'll have to tidy that up at some point in the future. But, you know, I think if those are the major programs, that's probably where I'll stop with the guidance. We're very careful to make sure that we have cash through to the next key readouts, right? And with cash into the second half of 2028 and all those funded, we think that we're there. So hopefully that helps. Yeah, that'S great. Thank you. As a reminder, to ask a question, please press star 1-1 on your phone and wait for your name to be announced. Our next question will be coming from the line of Derek Arcilla of Wells Fargo. Your line is open. Good morning. This is Jay Gamon from Derek. Thanks for taking our question. Just one from us on LRRK2. Should we be expecting oculomotor and biomarker data, similar to what you've done in PD, to also be generated from the PSP1B study? And if so, how should we be thinking about it with respect to either comps or natural history data? That's a really good question, Jacob. I'll let Angela chime in on the details on the oculomotor work, which is really interesting. Yes. So, you know, particularly for PSP, it's an entirely different earlier onset of this palsy gaze that occurs. And so we're actually turning our digital biomarkers to what we think are more important movement and falling endpoints in that disease. So we'll be using those endpoints. Certainly, eye tracking is something that will be studied. But also looking, again, at endolysis somal function markers as well as inflammatory markers and importantly, translating the pathologic tau reductions that we observed that are the principal hallmark driving PSP. So, you know, we're excited about looking at those endpoints as well as the synaptic markers that are key for progression of PSP, including neuronal health markers like neurofilament light chain. So just to give you an idea of some of the additional markers that we're looking at in that PSP trial relative to what we looked at in PD. Very helpful. Thank you. And I would now like to turn the call back to Randy Teal for closing remarks. Thank you very much, Operator, and thanks, everyone, for joining this morning. Thanks especially also to the patients and physicians and all of our team members here at Arvinas that make all this work possible. And we look forward to providing updates to the community in the coming months. Thanks all very much. Graham, thank you for participating. You may now disconnect.