WAVE Life Sciences Ltd Virtual Research Day Transcript

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

Question: Joon Lee - Truist Securities - Analyst : Great. Thanks for hosting this event and taking your questions for the inhibit E program. How would you be benchmarking the efficacy when you get the data? Would you be benchmarking to semi blue tide or take a more holistic approach? And the second part of that question is, what is the duration of follow up for both sad and mad portions of the study? And what would trigger data disclosures there? 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. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day

Question: Joon Lee - Truist Securities - Analyst : Great Thank you. Just a quick follow up. If I may 1 of your peer RNA I company who you alluded to during the presentation also disclosed plans to knock down the LLC seven for the active knee if I understood correctly, any thoughts on that strategy. And have you also considered that? 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. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day

Question: Joon Lee - Truist Securities - Analyst : Thank you so much.

Question: Salim Syed - Mizuho Securities - Analyst : Hey guys, thanks for all the color today. One for me or maybe like a couple parts to this question, but on the Huntington's piece here, to appreciate all the color around Kate atrophy. And, and the total functional, the total functional piece here in the correlation. But Paul, as we sort of get to that regulatory feedback from, from the FDA here, could you maybe book and for us, what the scenarios are that you think could potentially come out of there? Like what would you view as a best case scenario in terms of regulatory feedback and, and what sort of would be maybe a less a less favorable scenario? And just sort of what, what would be the disclosure strategy there once you get that regulatory feedback? Thank you.

Question: Salim Syed - Mizuho Securities - Analyst : How would you disclose, would you disclose it once we got the feedback? Is that something that you do right away or we got to wait for the. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day

Question: Salim Syed - Mizuho Securities - Analyst : And just, just one related to that just on the clinical meaningfulness numbers that were part of the discussion. I don't know if this move for doctor long, if he's available or yourself? Just what's the sort of tightness around that band like when you're sort of doing your market research? Is it really this 40% slowing cottage atrophy one year delay? Is that, is that really sort of like pretty well agreed upon or is there a range on that sort of number?

Question: Salim Syed - Mizuho Securities - Analyst : Okay. Got it. Thanks so much guys.

Question: Steven Seedhouse - Raymond James - Analyst : Hey, Ron, thanks for the question. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day Can I just confirm up from the, the animal data for 07? Was that all from dil mouse models?

Question: Steven Seedhouse - Raymond James - Analyst : So just following up on that, what I think, you know, there's some, there's some other companies and just some other experiments in that mouse model with semaglutide doses going up to 30 per K and it looks like you use 10 animal per cake. So I just wanted to ask about that. Are, are you sort of intentionally modeling a lower dose of semi when you get into the clinic? Would one of the ideas be here if you combine with semi, you could sort of alleviate a lot of the G I tolerability issues by combining with a low dose or what was the, what was the rationale, I guess in general, just for that particular combination study and the dio mice.

Question: Steven Seedhouse - Raymond James - Analyst : I have two questions on RN A editing the first, I just one more on an HBI if I could the once or twice a year dosing, like if I'm looking at slide 54 these mice are gaining weight again by it looks like about week six. Is that just because this is an aggressive model or what do you have like knock down data out to month six or what's your conviction in that dosing regimen?

Question: Steven Seedhouse - Raymond James - Analyst : All right. All right, thanks Paul the on R editing. So that what was the limited detection in the A at assay? And do you suspect you're actually getting increased release in zaat into circulation as well as obviously the MA A T production?

Question: Steven Seedhouse - Raymond James - Analyst : Last question. Thanks again, Paul. Last question, just on the P MP L A three program is the. So the genetics seem to point to almost like a preventive medicine paradigm. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day I'm just curious if you think you can also sort of have activity and advanced disease. Like I think you said you're going into mass. Do you think you can get into a late stage fibrosis population or reverse fibrosis? Just comment on strategy there.

Question: Steven Seedhouse - Raymond James - Analyst : Right. Yeah. Well, thanks. Thanks for the update. Really appreciate it. And congrats on all the, all the.

Question: Eric Joseph - J.P. Morgan - Analyst : Can you hear me? All right now? Okay, good. Sorry, thanks. Sorry about that. Yeah, so just a couple of questions. Thanks for taking them. Just circling back on it. It would be, I'm hoping you guys looking for you guys to maybe elaborate or delineate a little bit more between the sr and a pharmacology and maybe the biology of activity signaling that might contribute to the duration of the fact that you're anticipating, thinking that you might have semiannual or maybe even annual dosing frequency. I'll leave the first question there and come back for a follow up.

Question: Eric Joseph - J.P. Morgan - Analyst : Okay. Okay. Got it. And just when it comes to just this the phenomena of sort of preserving muscle mass, and maybe having a different or more more durable effect because of preserving muscle mass, I guess there's been some discussion about you know, really muscle for obesity related sarcopenia, right? Or metabolic myositis, which kind of goes under address by the GOP ones. Is it possible or have you been able to sort of model that or look at that phenomenon in the dio mouse model? And to what extent do you plan to look at inflammation markers in the phase one study?

Question: Eric Joseph - J.P. Morgan - Analyst : Okay. On the P&P, can you just talk a bit more about to what extent, sort of that loss of that gene function is a prognostic indicator for patients that do have fatty liver disease relative to those who are, you know, competent there. And just to what extent they might be responsive to sort of the, REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day the metabolic interventions that are approved or in development right now, thinking about the GOP ones for the, for, for that indication T Hr beta and also the FGF 21. Do you see a difference in terms of how they they respond to that or do we know to those agents relative to those with without mutations?

Question: Eric Joseph - J.P. Morgan - Analyst : Maybe one last one. If I could just on the L DLL DLR just given that you're stabilizing intro introducing a stabilizing change basically to the both the MRN A&I guess also the protein or is it primarily the stabilization of the Mrna? I guess what I'm wondering is, is whether there might be sort of like ethical regulatory concerns about sort of having a super physiological stabilization of the receptor and whether, you know, there may be sort of launch from a characterization to to get comfortable with it being a broadly, broadly safe.

Question: Eric Joseph - J.P. Morgan - Analyst : That all makes sense. I just wonder whether, you know, you're actually changing, I guess the residue identity to what extent it might be immunogenic or something like that because of the, the edit that you're doing to stabilize.

Question: Luca Issi - RBC Capital Markets - Analyst : Can you guys hear me? Okay.

Question: Luca Issi - RBC Capital Markets - Analyst : Great, great apologies. Hopefully my video will come on as well. Two very quick questions here. So maybe the first one, Eric, I appreciate this is very early days still. But how are you thinking about path for registration for alpha one? I think in Hris was actually asked by the FDA to run head to head trial power to show statistical superiority versus augmentation therapy. So wondering if that is the right comp for us to think about it. But again, that's much appreciated and then maybe all quickly on IP. Can you expand a little bit more on IP? You know, obviously pro QR is out there making REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day an argument that they have some of the foundational IP around you know, R&A editing and you know, maybe other players may not have freedom to operate. So what will be your, your push back to that? Thanks so much.

Question: Luca Issi - RBC Capital Markets - Analyst : Got it, got it super helpful and then maybe super quickly two more. If I may on alpha one, anything notable on the immunogenicity side? I mean, these patients are all Zy. So they kind of never expressed the wild type protein before. So is there anything that is notable on the immunogenicity side? So any thoughts there much appreciated and then maybe the last one on HD again, appreciate you're very excited about this data, but obviously Canada decided to pass on it. So maybe just can you just expand on what was behind that decision to pass on that asset? Thanks so much. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day

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

Question: Madison El-Saadi - B. Riley Securities - Analyst : Hi, everyone. Thank you for taking my question. First, if I can start with CALDIC Volume endpoint, I thought that was a really powerful slide showing the volume change next to the uhdrs. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. OCTOBER 30, 2024 / 2:00PM, WVE.OQ - WAVE Life Sciences Ltd Virtual Research Day So is, is CALDIC volume as a surrogate endpoint more like say Heparin sulfate and MP S where you have very clear, straightforward data, straightforward implementation or is it more analogous to something like CTD and A and oncology where you have strong data, strong rationale, but the adoption there has been slower because there are questions about implementation challenges and kind of your sense on where the FDA is on that and what they need to see. And then secondly, if I may, so your, your, your thoughts on 007. In combination, we talked about combination like GLIP ones. But what, what are your thoughts on combination with a Myostatin drug that, you know, we don't currently have, but presumably will have in the future. I think I'll leave it there and maybe ask a follow up. Thanks.

Question: Madison El-Saadi - B. Riley Securities - Analyst : Got it. Thank you. And then if I may squeeze in one more on 006, Just wondering how infrequent you think you may be able to go while still potentially approaching that 25 to even 30 micromolar serum a at level. And I'm asking because I'm thinking, you know, if you could go to even as you've mentioned quarterly, but maybe even six months, you know, that would suggest that we may not see mad data until mid year. I, is that an accurate assumption on my part? Thank you.

Question: Madison El-Saadi - B. Riley Securities - Analyst : Got it. Thank you, very helpful. And congrats again on all the impressive data.

Question: Joseph Schwartz - Leerink Partners - Analyst : Hi. Thanks for taking my question. Actually, I have two on the HBI program. So I was just curious, did you look at objective biomarkers like insulin resistance like oral glucose tolerance test, which are often evaluated in preclinical studies alongside weight loss in your work with OO seven. And if so, how does that data compare to the GLIP ones or other in lowering agents?

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay. And did, were, were most of the preclinical studies that you did using an unrestricted diet and, and did you track food intake? I'm just wondering because of the very different mechanism from the GLIPS, you know, it could even be a positive attribute. Selling point if there could be, I don't know if diet liberalization is a good concept to think about. But you know, enjoying food, you know, more might not be a bad thing and, you know, the entire you know, experience for the patient could be very different from the glimpse which just work totally opposite to this.

Question: Joseph Schwartz - Leerink Partners - Analyst : Okay, great. Thanks for taking my questions.