WAVE Life Sciences Ltd Q3 2024 Earnings Call Transcript

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

Question: Steven Seedhouse - Raymond James - Analyst : Good morning. Thank you. Congrats on all the recent progress. First on the AAT program, can you just review any key efficacy assessments that you're evaluating both lung and liver in the multi dose cohorts and any that you would plan specifically on sharing with the next update? And then Second on that program, do you anticipate being able to assess circulating levels of the protein around times of infection or illness or vaccination just to assess the acute phase response of the protein?

Question: Steven Seedhouse - Raymond James - Analyst : Okay. So, I mean the patients were assessed for things like FibroScan, I think at baseline right to enroll them just to meet eligibility, but I guess you're not assessing something like FibroScan (multiple speakers) Anne-Marie Li-Kwai-Cheung - WAVE Life Sciences Ltd - Chief Development Officer Of course, there are exploratory endpoints in the study such as that, but this is a study that's really focused on safety, tolerability, PK and PD.

Question: Steven Seedhouse - Raymond James - Analyst : Understood. In Huntington then, just last question for me. You mentioned the interest you're receiving from strategic partners. I think there's a lot of interest in just sort of how that could play out. So, could you comment on, I guess, just the anticipated total cost of the Phase 2, Phase 3 program that you are conceptualizing right now? And just what partnership structures in terms of cost and economics are you open to or looking for with that program? Thank you. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 12, 2024 / 1:30PM, WVE.OQ - Q3 2024 WAVE Life Sciences Ltd Earnings Call

Question: Steven Seedhouse - Raymond James - Analyst : Thanks so much.

Question: Joon Lee - Truist Securities - Analyst : Hey, congrats on the progress and thanks for taking our questions. Looking down the road for INHBE, how do you envision registration trial to differentiate INHBE from GLP-1s from a labeling perspective? Specifically, at obesity, we clearly shared post op analysis of SURMOUNT-1, which showed about 11% mean body mass loss. How concerning is that from an ADL standpoint? And is that something the FDA may be noticing as a potential safety concern? Thank you.

Question: Joon Lee - Truist Securities - Analyst : Great. Looking forward. Thank you.

Question: Salim Syed - Mizuho Securities USA - Analyst : Hey, guys. Thanks for the color today. I guess one for me on just the Huntington's piece here. So, I guess as you're thinking about trying to design the Phase 2, Phase 3 study, it sounds like you don't have full agreement from the FDA that CAUTIATE attribute could be used as an endpoint for potential approval. Do you get the sense that the FDA doesn't even want to approach this topic of like getting to a full agreement on using it prior to the design? Or is there a scenario here where they come to that agreement prior to you actually finalizing the details here. And then just sort of as related to the design as well, how are you sort of factoring in the pre-symptomatic HD population? Is that something that you would add on at a later point? Or do you think that's going to be part of the initial design? Thank you.

Question: Salim Syed - Mizuho Securities USA - Analyst : Okay. And maybe just a follow-up. So, if we don't have like full certainty that caudate atrophy could be used for Exito approval, I presume here the base case thinking here is that you will need to have an extended trial here or at least potential two points of where you could file 1 on the accelerated. One where you'd actually have to run it all the way to get total to assess functional capacity. Is that the right way to think about it?

Question: Salim Syed - Mizuho Securities USA - Analyst : Okay, got it. Thank you so much.

Question: Luca Issi - RBC Capital Markets - Analyst : Great. Thanks so much for taking my question. Congrats on all the progress. Maybe two quick ones. One circling back on Huntington, just to be 100% clear here. Are you considering running a pivotal trial solo or is finding a partner gating to start a pivotal? So any color there much appreciated. And then on alpha-1, you mentioned that the IV is suboptimal versus subcu, which we all agree with in terms of convenience for the patients. But how are you thinking about editing efficiency. It looks like at least preclinical, maybe IV can drive higher editing efficiency for subcu. So, wondering how you're thinking about that trade off? Thanks so much.

Question: Luca Issi - RBC Capital Markets - Analyst : Got it. Thanks so much.

Question: Catherine Novack - Jones Trading - Analyst : Hi, good morning, guys. I just wanted to touch on the DMD program for a minute. You mentioned that you're going to discuss accelerated approval with the FDA. I guess, are there any unknowns regarding the accelerated approval pathway with regard to exon therapies and exon skipping therapies and dystrophin? And then how can we think about how much weight we can give functional outcomes at 48 weeks with some of the DMD drugs failing confirmatory studies? Do you get a sense that FDA is starting to look more at clinical outcomes? Or is accelerated approval still primarily just looking at skeletal muscle dystrophin? Thanks.

Question: Catherine Novack - Jones Trading - Analyst : Okay, great. That's helpful. And then just one last one on the HD partnership. You kind of mentioned that you think regulatory alignment is needed, but is there a chance that future partners would want to be involved in regulatory discussions given the importance of getting a novel surrogate endpoint approved?

Question: Catherine Novack - Jones Trading - Analyst : Got it. That's helpful. All right. Thanks, guys.

Question: Madison El-Saadi - B. Riley Securities - Analyst : Hi, guys. Congrats on the progress and thank you for taking my question. Are you able to talk to the schedule of GSK milestone payments as part of the RNA edit collaboration, including what's related to the initial human proof of concept data? And then wondering if this informs the cadence of how you may look to reveal MAD data through 2025. And then secondly, regarding FDA Huntington discussion you spoke of collecting biomarker data. So, could you clarify, would that be from the current select patients at a longer follow-up past the point when one would expect to see functional separation? Thanks. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. NOVEMBER 12, 2024 / 1:30PM, WVE.OQ - Q3 2024 WAVE Life Sciences Ltd Earnings Call

Question: Madison El-Saadi - B. Riley Securities - Analyst : Got it. That's helpful. And then if I could squeeze in one more. So, it sounds like the regulatory clarity alignment is certainly key to kind of bringing a strategic on board. Just wondering if, to the extent you can mention, what is kind of the next topic that regularly comes up that you guys are focused on it. And if procuring a partner is necessary to initiating dosing in second half. Thanks.

Question: Madison El-Saadi - B. Riley Securities - Analyst : Got it. Helpful. Thanks guys.