Arvinas Inc Conference Call Transcript

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

Question: Ted Tenthoff - Piper Jaffray - Analyst : Thank you so much for the update, really, really exciting. I'm trying to get a sense for -- and I know this may be a little bit early -- but the potential path forward in prostate cancer. Obviously with abiraterone and enzalutamide established, is the most expeditious path to go in abi and enza failures and then ultimately look at moving up in lines of therapy? How do you foresee ultimately advancing that in later stage clinical studies?

Question: Ted Tenthoff - Piper Jaffray - Analyst : That's super helpful. And maybe just as a quick follow-up question, does the -- are you at a point where you have sufficient confidence or proof of concept to really accelerate development of PROTACs against other undruggable or difficult to treat -- or difficult to drug kinase targets for oncology? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: Eliana Merle - Cantor Fitzgerald - Analyst : Congrats on the update. Just a quick question on the ability to measure degradation. How reliable a metric of degradation is it to look at sort of AR or ER levels in circulating tumor cells? And I guess of the patients that you've dosed so far, have you been able to measure this? And then also in terms of pre- and post-tumor biopsies to measure degradation, have you been able to measure this in the patients you've dosed?

Question: Eliana Merle - Cantor Fitzgerald - Analyst : Got it. And I guess just based on your preclinical modeling and now seeing the PK, I guess what is your estimate or expectation for what proportion of AR is being degraded at the 280 milligrams dose with ARV-110?

Question: Eliana Merle - Cantor Fitzgerald - Analyst : And then last question from me -- just is there any evidence so far on ARV-110's ability to degrade AR-V7 mutants?

Question: Eliana Merle - Cantor Fitzgerald - Analyst : In the patient, I'm sorry.

Question: Eliana Merle - Cantor Fitzgerald - Analyst : Got it. And then, sorry, just one last PK question. I guess just based on the preclinical modeling and now what you're seeing in terms of exposure, I guess -- I know you haven't seen the hook effect in vivo, but I guess what's sort of your expectation for at what dose level you might see if at all the hook effect in patients.

Question: Terence Flynn - Goldman Sachs - Analyst : Congrats on generating your first set of clinical data. Maybe just two from me. Recognizing you're still planning to release the first efficacy data next year for 110, maybe just remind us what you are hoping to see here to make the decision to expand into a larger trial. And then also on 110, the dose escalation, just how much headroom do you think you have to dose higher than 280 mgs based on your preclinical studies and is that something you'd consider?

Question: Terence Flynn - Goldman Sachs - Analyst : Sure, just wondering what you are hoping to see on the efficacy side for the 110 study to make a decision to expand into a larger trial. What you want to see on PSA, RECIST? What would give you confidence to move into further studies?

Question: Terence Flynn - Goldman Sachs - Analyst : Okay. And then anything on the safety front with respect to Grade 1 AEs. I know, again, it sounds like no DLTs, nothing on grade 2 through 4, but anything in the Grade 1 AEs to call out?

Question: Yigal Nochomovitz - Citigroup - Analyst : Kudos on the first clinical data for your program. At one point you had mentioned that you would potentially consider using the [PD HT] PET as a way to monitor degradation of the AR molecule. But it was unclear to us whether that was sensitive enough given that it may be able to detect a bound AR molecule, but not whether the AR was degraded. So, I'm just wondering whether you could provide any more comments as to whether you are using FDHT PET in your strategy to assess degradation.

Question: Yigal Nochomovitz - Citigroup - Analyst : Okay, got it. And then could you just comment with respect to the 280-milligram dose for 110? How does your calculation in terms of the human equivalent dose of the 30 mgs per kg in dogs where you saw the diarrhea and GI tox? How does that 30 mgs per kg translate into human equivalent dosing and is it still above the 280 mgs?

Question: Yigal Nochomovitz - Citigroup - Analyst : Okay, and sort of the same question for the rats, the highest -- I don't remember, I think you said 80 mgs was the DLT in the rats. How does that compare to your next dose for -- Your next human equivalent dose for 471?

Question: Yigal Nochomovitz - Citigroup - Analyst : for 110, sorry, for 110?

Question: Yigal Nochomovitz - Citigroup - Analyst : Okay, and then just my final question is obviously you sort of exceeded expectations in terms of showing us the initial data for 471, at least the plasma exposure data. So, I was just curious as to why you're still sticking to the two half 2020 timeframe for showing the biomarker and preliminary efficacy data. It would seem that it could arrive sooner now.

Question: Robbie Marotta - Evercore ISI - Analyst : Let me add my congrats to the data. So, Ian, if I go back to an answer you gave to a previous question -- to one of the previous questions, I guess I would start out by saying exposure may not necessarily be the right way to handicap a protein degrader efficiency because sim PK may not be indicative of [intra-tumoral] concentration given the enzymatic nature of PROTACs. Given that and given the half-life that you observed in the clinic of three to seven days, is there potential for adaptation of future clinical studies? And a question for you, John. You talked a little bit about this. but I'm going to ask it again. At what stage of data do you need to get to to say, hey, I'm very confident with our new modality and let's now expand the modular nature of our platform and basically give us an indication of what the next targets you are going after will be?

Question: Robbie Marotta - Evercore ISI - Analyst : Yes.

Question: George Farmer - BMO Capital Markets - Analyst : Given that you appear to be achieving the adequate exposure to see activity in humans potentially, do you think you need to dose to DLT?

Question: George Farmer - BMO Capital Markets - Analyst : Yes, thanks. And regarding the 471, you mentioned that you didn't see any remarkable adverse events there. Would you expect to see some adverse events related to other ER targeting strategies like hot flashes or nausea and the like? And did you get any indication in your patients so far? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.

Question: George Farmer - BMO Capital Markets - Analyst : Okay. And then you said with 110 that you're estimating a half-life of three to seven days. How about for 471? Do you have any feel for that yet?

Question: George Farmer - BMO Capital Markets - Analyst : Okay, great. And one more if you don't mind. Did any metabolites emerge in your analysis that might be concerning or might require further analysis?