WAVE Life Sciences Ltd Interim Data from FORWARD-53 Clinical Trial Transcript

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

Question: Joon Lee - Truist Securities - Analyst : Hey, congrats on the impressive data, and thanks for taking our questions. I have three quick questions. First, is the sixth month pretty much when you see plateauing of dystrophin expression, or are you still in the dynamic range, especially given the stem cell exposure? And question number two, appreciate that you have shown dystrophin induction in the diaphragm and the cardiac muscle in preclinical models, but any indirect evidence of that in the DMD boys? And three. Viltepso 4.81% reported was normalized to myosin heavy chain in Western blot. Would that be comparable to your 9% or your 5.5%? Thank you.

Question: Joon Lee - Truist Securities - Analyst : Excellent. Thank you so much, and congrats again on the exceptional data. 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: Salim Syed - Mizuho Securities USA - Analyst : Great. Good morning, guys, and congrats on the data. I guess three for me as well, if I can. Anne-Marie or Paul, I know you mentioned the functional measures were taken at 24 weeks, there really wasn't much detail in the slides, and I appreciate that you might need the 48-week data for that, but just curious if you can maybe speak to perhaps some of the visual changes, anecdotally or early data that you've seen there on the functional side. Number two, just on the regulatory, do you anticipate needing anything from the 48-week data set, either dystrophin are functional to file for accelerated approval. And then just lastly, number three, just on the platform trial design, just early thoughts how that could potentially be constructed, just considering some of the exons, I believe, like exon 44 typically present with higher baseline dystrophin. Thank you. Anne-Marie Li-Kwai-Cheung - WAVE Life Sciences Ltd - Chief Development Officer Yeah, thank you very much, Salim. So, as you said, in six months, the progression that you would expect in this population is somewhat slow, so you wouldn't be able to detect that you're slowing anything on that basis. And that's true, actually, of all the functional measures, including 95% stride velocity, the digital measure, which is likely to be the most sensitive of all of them. I think what is really encouraging, actually, is the serum biomarkers. So this reduction, this clinically meaningful reduction that we're seeing in CK and AST, actually, I think is one of the most encouraging things we're seeing with these data. The CK reduction is greater than what you see when you introduce steroids. And of course, all these boys are already on steroids, so this is over and above whatever benefit they're getting from their steroids. So I think we can conclude from this, it's really encouraging, coupled with the dystrophin and what we're seeing in the tissue, and certainly the KOLs have looked at our tissue, have all said this looks really healthy muscle. So, encouraged. You asked about the 48-week date and the regulatory pathway. So we'll be engaging regulators on the pathway to the accelerated approval. We'll be finishing the study. All of this is going to become available in Q1 2025, and we'll be able to speak more to that then. But we're in the right zone with these encouraging data to be having meaningful conversations. And then finally, about the platform study, I think this is a really important point. So FDA has recently issued draft guidance signaling their understanding of when you have a therapy that can be applied as a platform, which is absolutely the case for DMD where there are multiple exons. They are proposing ways in which that development could be made much more efficient. So the sort of thing that this would encompass would be clinical trials with shared placebo arm. That's obviously really important in this rare population where the burden of placebo for patients is considerable, and so that would make studies much quicker and less expensive to execute and will also benefit the patient from not having as many on placebo. You're absolutely right that exon 44 is different from the other exons and so for exon 54 you would need to have exon 50 -- 44 placebo. But they could still be in the same platform. You could adjust for that. So this would be an extremely encouraging approach that would allow us to hasten all of the other exons that we have in scope with 53.

Question: Salim Syed - Mizuho Securities USA - Analyst : All right. Great. Thank you so much. Congrats again.

Question: Eric Joseph - JPMorgan - Analyst : Hi. Morning. Thanks for taking the questions, and congrats on the data. I guess just following up on the point of dosing and being in the dynamic range of expression. Is there any benefit, further benefit that you see to dystrophin expression from perhaps dosing higher? It seems from the data, the safety data, you've -- perhaps have the margins to explore that. Any plan to do so as you kind of move to monthly dosing? And then secondly, just with respect to the one patient, where you didn't get to that 5% threshold. Anything notable there, perhaps a reaction to treatment that sort of might undermine the level of expression? Your expectation that that might kind of get above the 5% threshold with continued treatment. Thank you.

Question: Eric Joseph - JPMorgan - Analyst : Thanks. Maybe as a follow-up, if I could, just as you look to interact with regulators, how much, if any, additional clinical work would be needed to support an initial registration using once-monthly dosing. Or is that a plan? Would you look to register with a once-monthly regimen or perhaps with the data that you have in hand first and backfill for a longer dosing interval? Thank you. Anne-Marie Li-Kwai-Cheung - WAVE Life Sciences Ltd - Chief Development Officer So we're switching our patients in the FORWARD-53 study to monthly dosing. So at the end of the study, it will include data on monthly dosing.

Question: Timur Ivannikov - Raymond James - Analyst : Yes. Hi. This is Timur Ivannikov on for Steve Seedhouse. So just a couple of questions about your analysis, Western blot analysis. Was it something that you did in-house, or did you have to send it to a third party to analyze? And how do you think this assay compares to NS Pharma's analysis for Viltepso? 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.

Question: Timur Ivannikov - Raymond James - Analyst : Okay, got it. And then can you talk about any correlation that you may have seen for week 24 dystrophin expression with respect to the type of exon deletion or baseline dystrophin expression, especially for ambulatory patients who had a lower expression at week 24? Did they have a different type of exon deletion or perhaps lower baseline dystrophin? Anne-Marie Li-Kwai-Cheung - WAVE Life Sciences Ltd - Chief Development Officer There weren't any patterns that would lead us to believe any particular expression responds better or worse. I think the response was pretty consistent with the majority of patients meeting the 5% or greater threshold.

Question: Timur Ivannikov - Raymond James - Analyst : Okay. And then the final question we have is, so what type of functional measurements are you expecting to report at week 48? And then could you remind us about the primary endpoint, approvable endpoint for full approval, that you will report. Thank you. Anne-Marie Li-Kwai-Cheung - WAVE Life Sciences Ltd - Chief Development Officer It's the usual functional measurements, things like NSAA, all-step climb, time to rise, pull, et cetera. This information is in our clinicaltrials.gov disclosure if you want to look in more detail. For full approval, so what you're talking about is a confirmatory study. Other sponsors have used things like six-minute walk, NSAA, et cetera. And of course, these are things we'll be discussing with FDA when we engage them to talk about the pathway to accelerated approval.

Question: Timur Ivannikov - Raymond James - Analyst : Okay, thank you very 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.

Question: Lisa Walter - RBC Capital Markets - Analyst : Oh, great. Thanks so much for taking our questions. This is Lisa on for Luca. Maybe just another one on the regulatory path. Given the FDA has increased scrutiny over the accelerated approval pathway in recent years, is it fair to assume that accelerated approval would not be granted until a Phase 3 study is well underway and perhaps close to full enrollment? And just another on the confirmatory Phase 3, just wondering how you might be thinking about the trial design here. Would this include a placebo control or would you have to do a head-to-head study versus VYONDYS 53? So any color here would be helpful. Thanks so much.

Question: Lisa Walter - RBC Capital Markets - Analyst : Great. Thanks so much for taking our questions.

Question: Madison El-Saadi - B. Riley Securities - Analyst : Hi, good morning, guys, and congrats on the really great data for taking our questions. So a couple from us, looking at the serum CK chart, so it looks like you have this more than 50% reduction when almost it's kind of binary distribution, where the slope is not yet plateauing. I'm wondering if you're thinking that is going to go lower with subsequent readings, and how does this inform what one could expect on your functionality endpoints, especially also giving the high exposure and localization within the myocyte nuclei? And then secondly, I'm just wondering what additional color we may could expect I believe that you're late breaker at World Muscle Society in October. Thanks.

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

Question: Joon Lee - Truist Securities - Analyst : Hey, guys. Thanks for taking our follow-up question. Taking a step back, how are you able to get into stem cells, diaphragm, and cardiac tissues? My guess is that it's got something to do with the steroid control and PN chemistry, but is this something that you can start to rationally design into your other oligos going forward or maybe apply AI to improve upon? And what is Chandra's thinking on this as you plan to tackle other exons? Thank you.

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