Arvinas Inc at UBS Global Healthcare Virtual Conference Transcript

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

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And maybe high level, can you talk about the benefits of a PROTAC versus a small molecule inhibitor and the vision that you see for your platform over the next 1 to 2 years as well as long-term and the applications of PROTAC?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Absolutely. That's a helpful overview. And just in terms of the differences between different types of degraders, such as particularly molecular glues versus heterobifunctional, can you talk about how these are different and what the potential advantages and possible disadvantages are of PROTACs versus molecular glues?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Absolutely. And then just thinking from a kind of platform perspective and all of sort of the years of know-how that you guys have built up and your internal work around assays, the unique PK/PD. Can you describe some of the sort of the processes that you've developed? And I guess, why it's so hard to make a PROTAC? I mean, in principle, it sounds like a simple concept, but I think in application, it's proving to be much harder than maybe the concept suggest. Maybe what are the things and internal know-how that you've developed? And if you could talk a little bit more about that.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Great. That's helpful. And then a question for John, just on kind of strategy and prioritization. There's obviously a lot of areas of potential growth for the field across novel E3 ligase identification, novel ligand identification for the "undruggables" or even just creating PROTACs for the druggable molecules where you see that you can improve on a traditional small molecule inhibitor. How do you prioritize investment across these various sort of spectrums and then thinking about kind of the strategy for the company and further growth? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 25, 2021 / 2:00PM, ARVN.OQ - Arvinas Inc at UBS Global Healthcare Virtual Conference

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And on the E3 ligase, I'm sure you're probably not going to answer this, but I have to try. How should we think about when we could potentially see an asset with a novel E3 ligase sort of enter IND-enabling work or potential IND filing? I know you guys have spoken a lot about your E3 ligase identification work. Any more color that you can give us beyond that.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Got it. And I see a question from the audience here just in terms of the partnerships with Roche, Pfizer. Can you talk a little bit about sort of the progress that you've made with those collaborations, say, in the past couple of years since those were formed?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Got it. That's helpful color. And then just like big picture, maybe for Ian or -- I guess, I'll turn it to both of you guys for this one. Just in thinking about long term, the mechanisms of resistance against degraders, I know there's some emerging literature around that. How are you thinking about what the key drivers of resistance could be and how you're sort of developing your strategy around that?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : And I think just in terms of the ability to measure degradation and sort of the proof point, I know we've seen some initial biopsy data, both from ARV-110 as well as 471. But I guess from a mechanistic and kind of platform approach perspective, how do you measure the difference between degradation versus inhibition in patients and particularly across various tissue types and in terms of being distributed across the body?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Yes. And just a follow-up on that. I mean, there was some variability across patients. I understand the assays and sort of the availability of the data, limited also dose escalation study. But I guess how are you thinking about the feasibility of getting up to that like 90% degradation level in all patients? Is that something that's feasible at higher doses? How are you thinking about the ability, both, I guess, with 471, but also broadly, when you think about the PROTAC platform?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Got it. Those are very helpful. Yes, I think that's a good point around looking at not the percentage, but sort of the ending level and what proportion are sort of near that below level of quantification. I guess maybe just pivoting to the neurology side of things. Maybe, John, can you comment from a strategic perspective, maybe why you find neurology a compelling area for PROTACs and sort of your vision there in terms of target selection and how you view sort of the validation of some of these targets like mutant huntingtin, tau, alpha-synuclein?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Got it. That's exciting. Makes sense. And then just in terms of like the challenges of crossing the blood-brain barrier with the PROTAC being sort of a larger small molecule. I guess, what were some of the key ways that you were able to achieve this without sort of giving away your secrets off, but -- and maybe some of the risks that we should think about as you move from preclinical into the clinic? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 25, 2021 / 2:00PM, ARVN.OQ - Arvinas Inc at UBS Global Healthcare Virtual Conference

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Got it. Makes sense. And then turning, I guess, just to the clinical programs. Maybe just big picture for ER and 471, obviously, a competitive space. A lot of players in development in both the oral search space but also breast cancer requires kind of much larger studies to reach sort of the earlier lines of therapy. How are you thinking about this from a development perspective in terms of segmenting different patient populations as well as longer term potentially a strategic option in terms of collaborations or things like that in terms of funding these probably potentially large trials?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Got it. And then maybe just from a scientific perspective, what drives your conviction that ER degradation would be superior to, say, other forms of ER modulation such as inhibition? And how do you think about this and the key advantages of a PROTAC? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MAY 25, 2021 / 2:00PM, ARVN.OQ - Arvinas Inc at UBS Global Healthcare Virtual Conference

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : That's helpful. And then maybe just to think about the second half of the year update for 471 to the extent that you can comment, how should we think about what we can expect in terms of patient numbers, data update and maybe what you're looking for? And I understand if you decline to answer, but I figured I'd try.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Yes, pretty exciting time. Just a question from the inbox on sort of the safety profile of PROTAC. I guess, given that we're sort of "hijacking" a natural part of the body protein disposal system. How are you thinking about the safety of this long term, particularly given some of the resistance mechanisms that might develop?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Got it. That's very helpful. I think we have 3 minutes left, so I'm going to open it up to the audience if anyone wants to put some Q&A in the question box here on the webcast. But meanwhile, just taking a step back. I mean, how do you, I guess, full strategic, but also kind of maybe execution on target-based. In a couple of years from now, where do you see the company in terms of developing and potentially commercial resources as well as sort of investment in R&D? And what are your priorities in terms of as a company where you want your focus to be, particularly as some of these assays head towards later stage and maybe some of the genetic subtype populations?

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Okay. Great. Well, with that, I think we'll close it off. But John, Ian, thank you so much. Great speaking with you. As always, I could ask you questions all day, but unfortunately, we have only 45 minutes to ask them. But thank you so much. Really appreciate it, and thanks for attending the conference.

Question: Eliana Rachel Merle - UBS Investment Bank, Research Division - Analyst : Thanks, Bye.