Arvinas Inc at UBS Virtual CNS Day Transcript

The following is excerpted from the question-and-answer section of the transcript.

Question: Ellie Merle - UBS Financial Services - Analyst : With that being said, maybe just a high-level question for you, Ian. Can you give a high-level overview of Arvinas's strategy for development in CNS indications? And what's the company's philosophy, in general, when considering indication selection and target selection in this area?

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely. And maybe just a high-level platform question. I guess you alluded to this a bit, but I think it's important to dive deeper into this. I guess, what are the potential advantages of using the PROTAC modality in the CNS versus other more conventional modalities?

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely. And maybe for both of you, I guess, what do you think makes a good target in the CNS, and what are you looking for when selecting targets?

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely. And being able, I guess, to get both the intracellular and extracellular, I think, will be really important here.

Question: Ellie Merle - UBS Financial Services - Analyst : I guess, historically, the way PROTAC has been talked about as that maybe they're larger than a standard small molecule, I guess, how should we think about PROTAC's ability to cross the blood-brain barrier and penetrate the CNS?

Question: Ellie Merle - UBS Financial Services - Analyst : And how should we think about the pre-clinical data around the delivery and distribution. I guess, what drives your confidence that clinically, we will see PROTACs cross the blood-brain barrier?

Question: Ellie Merle - UBS Financial Services - Analyst : Love the confidence. And I definitely want to add, once we get to the clinical studies, sort of how you will measure this distribution. But maybe first, Angela, can you tell us a bit more about LRRK2 and the connection between LRRK2 and Parkinson's disease biology and maybe kind of your confidence in this as a target? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 18, 2024 / NTS, ARVN.OQ - Arvinas Inc at UBS Virtual CNS Day

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely, and maybe we can dive into this a little bit more. Can you sort of -- just given that there are these LRRK2 inhibitors in development? Can you maybe compare and contrast inhibiting versus degrading LRRK2?

Question: Ellie Merle - UBS Financial Services - Analyst : Yes, maybe if you could tell us a little bit more about questions around potential lung toxicity, what the theoretical concerns are there and how degraders can get around this? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 18, 2024 / NTS, ARVN.OQ - Arvinas Inc at UBS Virtual CNS Day

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely. From a theoretical perspective, what's the ideal level of degradation? Do you want to fully degrade LRRK2? Is there a sweet spot where you degrade most, but not all. How are you thinking about that?

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely. And when we talked about the differences versus from degraders versus inhibitors, I mean, a couple of the components you highlighted were the scaffolding function and lysosomal protein clearance. Maybe just help us understand specifically in the context of Parkinsons the importance of this, particularly with LRRK2.

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely. And maybe I guess, just starting with the Phase 1 in healthy volunteers, I guess, can you give an overview of this trial design and the initial biomarkers of focus there in healthies?

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely. And maybe just -- how do you measure the distribution of the effect? I mean -- I guess, first, just high level being able to show that you cross the blood-brain barrier in humans, I think, will be important. But then, I guess, what does that look like from measuring the CFS? And then second, I guess, how do you measure the distribution of the degradation across the different brain regions?

Question: Ellie Merle - UBS Financial Services - Analyst : Interesting, that will definitely be an important measure. Maybe on that note -- I know there's probably only limited that you can say. But I guess, how should we think about when we could potentially see initial data from this trial, and I guess what we should expect from the initial update?

Question: Ellie Merle - UBS Financial Services - Analyst : Exciting. And then beyond looking at the measures in the CSF, are there other biomarkers that you're focused on, both in healthies as well as when you move into patients?

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely. And I guess if you were sitting in our seat, how would you compare -- and we want to compare inhibitors versus degraders. What are the key measures that maybe -- that you're looking at to compare when you either get initial data in healthies or in patients?

Question: Ellie Merle - UBS Financial Services - Analyst : When do you think the right time course is to intervene with LRRK2 in terms of ballpark in terms both Parkinson's as well as PSP? Is there a time point in the disease course that would be too late, and how should we think about that in terms of longer-term clinical endpoints?

Question: Ellie Merle - UBS Financial Services - Analyst : Absolutely, and last question for you, guys. Moving to your pre-clinical programs for other targets, you've disclosed programs for tau, alpha-synuclein, and mutant huntingtin. Can you tell us a bit more about your progress for each of these programs? And I guess, what about these targets do you think make them attractive for the PROTAC modality?

Question: Ellie Merle - UBS Financial Services - Analyst : Great. Well, lots of exciting things to come. Angela, Ian, thank you both so much for joining us today. And we look forward to seeing some of this data.