Arvinas, Inc. Q3 FY2025 earnings call

• Arvinas had a dynamic period with progress across corporate initiatives and clinical development programs, including announcements in pipeline and efficiency enhancements.
• Deep pipeline offers opportunities in oncology and neurology, with data-rich period ahead from early-stage clinical programs.
• Announced significant developments like ARV-102 clinical data, ARV-806 preclinical data, and ARV-027 preclinical data.
• Noah Berkowitz discussed ARV-102's progress in Parkinson's disease trials, showing LRRK2 degradation and biomarker responses.
• Angela Cacace highlighted ARV-806's preclinical potency in KRAS G12D, ARV-027's potential in SBMA, and ARV-6723's immuno-oncology focus.
• Andrew Saik discussed financial highlights, cost reductions, stock repurchase authorization, and expense expectations for fiscal 2026.

At the end of the third quarter of 2025, Arvinas had approximately $787.6 million in cash, cash equivalents and marketable securities. Revenue for the three months ended September 30, 2025, totaled $41.9 million, down from $102.4 million in the same period of 2024. General and administrative expenses were $21 million in Q3 2025, compared to $75.8 million in Q3 2024. Research and development expenses were $64.7 million in Q3 2025, down from $86.9 million in Q3 2024. Total non-GAAP expenses were $71.5 million in the quarter, with expectations for expenses to continue declining as cost reduction programs take effect.

• Expect expenses to continue declining with quarterly run rate spend below $75M, aiming for non-GAAP expenses below $300M in FY2026.
• Board authorized up to $100M stock repurchase, with ~2.56 million shares bought back at an average price of $7.91 per share as of end-September.
• Continuing to invest in pipeline with catalysts in 2026, including study initiations and data readouts across neuroscience and oncology franchises.

• Risks associated with clinical trial outcomes, including uncertainties in translating preclinical results to clinical benefit.
• Potential drug-drug interactions and differences in metabolism between PROTACs and other small molecules, though each PROTAC is unique in this regard.
• Competition in the biopharmaceutical space for developing effective therapies in oncology and neurology.

Q: Just a quick question on the BCL6 degrader program. Just we're going to see some updated data from [indiscernible] at ASH. I just wanted to -- if you could comment on points of differentiation there that they're doing [indiscernible] and if you could just talk a little bit about the dosing profile that you envision for the molecule and any areas you could potentially differentiate longer term of that molecule?

A: Great. Thank you so much for the question. And yes, we're very excited about our BCL6 program, and we do believe that we have a profile that will differentiate itself as the compound continues to be developed. Noah, do you want to add some comments? Sure. Thanks, John, and thanks for the question. Yes. So indeed, we -- and by the way, you broke up a little bit, but if it had to do with dosing -- yes and differentiation. So the drug is being dosed once daily in oral drug. Differentiation has to do there on a couple of different levels. Number one is that we've already demonstrated and will continue to demonstrate upcoming at ASH some kind of, I guess, a differentiated profile for combinations of a drug and even for monotherapy preclinically. So we noticed that we can achieve complete responses in various models versus tumor growth inhibitions that are seen with some competitor -- or yes, some competitor drugs. In terms of our program, we're focused in -- we've said pretty explicitly that we're focused in monotherapy for AITL, and we're interested in developing the combination with the bispecific for DLBCL. So there's, at this point, several competitors that have entered the market. One little -- one of them that has already reported data, the others seem to have just filed their IND. We believe that -- and we've shared data here that we have monotherapy activity in T-cell and B-cells. That has not been reported by the competitor that's already reported out some B-cell malignancy responses. And so that's a point of potential differentiation in the future.

Q: On your LRRK2 program, can you tell us about the first types of signals you'd be looking for in the Parkinson's disease MAD Phase I? And how long do you hypothesize you'll need to dose for the PK effects that you've already observed in healthy volunteers in Parkinson's patients to translate to clinical benefit?

A: Yes. No, thank you, Caroline. Great question, and I'll hand back to Noah. Thanks, John and Caroline. Thank you for the question. So yes, we're pretty excited about what we've seen so far with our LRRK2 degrader and the reception that we received at a recent conference at MDS. So as you state, we are currently moving pretty aggressively through a Parkinson's disease Phase I study that has 28 days of dosing. We expect that this will generate data that's principally biomarker related. And -- but we may also start to collect a little clinical efficacy data that's not expected with 28 days dosing. Now what we've shared is that we've already been able to demonstrate pathway engagement in ways that competitor LRRK2 inhibitors have been -- at least have not reported to date. So we know in healthy volunteers, we can impact endolysosomal trafficking and also neuroinflammation, at least through microglial pathways -- mediated pathways. And so now when we look at our Parkinson's disease patients, the idea would be we have patients at baseline who have more than 2, maybe even 3x the baseline level of LRRK2 in their CSF. There's much more activation of these pathways. And it will be important to see how much the degradation that we've already reported out in healthy volunteers, we can recapitulate now in this Parkinson's disease population and look at that pathway engagement. So we've guided to an update on those pathway markers next year, relatively early next year. And -- but I think that the next step for clinical data will be when we can have more than 28 days of treatment. So for that, we're working our way through the chronic tox study. And so you'll see as we file our IND next year that allows us to move into PSP that we're prepared to continue with chronic treatment of patients, and that will be an opportunity for us to demonstrate the clinical benefits in diseases like PSP and potentially Parkinson's.

Q: I just wanted to ask on your KRAS G12D. So you've mentioned before and we've seen evidence for KRAS amplification as a mechanism of resistance to inhibitors. So -- and the fact that potentially with the iterative activity of a PROTAC might be able to overcome that. So I just wanted to ask if you have any plans to potentially test ARV-806 or maybe even eventually a pan-KRAS in the clinic in a KRAS amplified population?

A: Yes. Great questions, Sarah. I'm going to ask both Angela Cacace, our CSO, and Noah to give you 2 parts to that answer. Great. Thank you for the question. We have been studying certainly our G12D degrader ARV-806 in resistant setting. And we look after -- we see amplification of KRAS G12D, and we see that we durably repress KRAS in all conditions. And then for our pan-KRAS degrader, we've also been studying the amplified setting, the wild-type amplified setting. And in the wild-type amplified setting, we're gratified to see some early data that shows that we see very nice tumor growth inhibition. And in cases of PDX models, we've also seen regression. So we're advancing very quickly with our pan-KRAS degrader program, and I'll turn over to Noah for the clinical perspective. Thanks, Angela. And so Sarah, to your question about amplification and what we've seen. So we specifically, right, in the ongoing Phase I study, we exclude patients that have been treated previously with KRAS inhibitors. So that's not something we're going to see in the dose escalation portion of our study, and you would understand why we would want the cleanest signal. We've made that choice as really anyone would. But we have learned over the past year, and this is really data that's generated outside of our company, right, that as data -- we see many reports of amplification being a principal mechanism of resistance after patients have been exposed to KRAS inhibitors. So we've obviously -- as Angela has pointed to, we've done work in our models to show that this creates a great opportunity for us moving forward. [Audio Gap] expect some updates over the course of the next year in terms of if we want to expand our targeting or thinking in this regard. It certainly is compelling science.

Q: For the BCL6 asset, what combination partners do you believe are most exciting? And where do you think it's most likely to exist in the lymphoma treatment paradigm if successfully developed?

A: Thanks for the question. Yes, there's a lot of potentially exciting combinations that we can carry out with BCL6. I'll ask Noah to maybe give an overview of where we're thinking. Sure. So we've shared data about the ability to combine this drug, which uses an orthogonal approach to many of the agents that are currently approved in the B-cell malignancy setting. And we see just beautiful synergies and combinability with -- preclinically with EZH2 inhibitors, BTK inhibitors, BCL2 inhibitors, and also anti-CD20 agents. So those -- that's a whole set of opportunities for combination. We recognize that the way the field is evolving, there's going to be a significant outsized role for bispecifics targeting CD20 in the -- eventually the first-line setting, but in the second- and third-line setting as well for large B-cell lymphoma. We think that's our -- we want to be laser-focused as a company, and we recognize that's a significant opportunity where we can combine these therapies that have non-overlapping toxicities. Ours -- we first have to identify a toxicity. But obviously, there is CRS with the bispecifics, and we should be able to combine favorably with those. And that would be our plan. That's why we've announced that next year, we expect to be moving ahead in our Phase I study with combinations with bispecifics.