WAVE Life Sciences Ltd 48-Week Results from FORWARD-53 Trial of WVE-N531 in Duchenne Muscular Dystrophy Call Transcript

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

Question: Joon Lee - Truist Securities - Analyst : Great. Congrats on the impressive data the myogenic stem cell uptake of 531 is impressive. How much do you think that contributed to your clinical improvement, which looks numerically superior to other exon 53 skippers? And how confident are you that your follow-on antisense oligos for other exons can also enter the muscle stem cells and demonstrate similar magnitude efficacy. And I'd be remiss if I didn't ask, but can you elaborate on the dystrophin level at week 48, that is numerically lower than what you've shown at week 24, despite stable exiting.

Question: Joon Lee - Truist Securities - Analyst : I have a quick follow-up. Any plans for even deeper settle architectural studies because as you mentioned, location of these things matter a lot. I thought it was interesting to see that the maturation of the muscles as evidenced by the location of nuclei and things like that are important. But like just further cytoarchitectural, EM, whatever studies that may show that your dystrophin that is made is being localized to the right place at the right time to do what is you be doing?

Question: Jenny Gonzalez-Armenta - Leerink Partners - Analyst : It is Jenny on for Joe Schwartz. Congrats on the consistent and comprehensive data set that you presented today. Just one question on the inflammation data. That's not something we typically see from exon skipping and gene therapies and DMD. Can you help us understand that a little more but in the context of what's happening with these patients on this front? And what are the implications of reducing these two biomarkers?

Question: Mike Linden - Mizuho Securities USA - Analyst : This is Mike Linden on for Salim. Congrats on the data. Now that you're planning to file an NDA in 2026 for N531, what commercial prep should we expect to see across '25 and into 2026? And then similarly, specifically for Europe, what are possible plans here? Would you go it alone or potentially partner in Europe? And then quickly, just a clarification. Were any of the 11 boys and FORWARD-53 switched from a prior therapy like a PMO.

Question: Ron Feiner - JPMorgan - Analyst : I wanted to ask -- first of all, congrats on the data. And we wanted to ask maybe what parameters are going to satisfy filing for the months of dosing. Are you going to need to add anything additional beyond the PK? Is there an opportunity to do any additional assessment of dystrophin beyond the biopsies? And what clinical parameters affect that decision? And then I have a follow-up.

Question: Ron Feiner - JPMorgan - Analyst : Okay. That's very helpful. And then maybe, I guess, as you somewhat added to that, but like -- if you can give some additional color on the time line of 0.26 and not by early 2026, I guess, you just said you need to -- you will be adding the monthly dosing data to this? Is that why it will take a bit longer than maybe early 2026?

Question: Roger Song - Jefferies - Analyst : Congrats for the data quick ones from us. The first one is, it seems you're really building up the very differentiated skipper therapy for the DMD. So in terms of those muscle and functional endpoints, you just elaborated quite a lot, so what will be the key for the confirmatory study? You mentioned TTR may be sufficient for approval. Any other endpoint will be important for regulatory? And also based on the investigator feedback, will be the key endpoint will drive the clinical or commercial adoption for the therapy?

Question: Roger Song - Jefferies - Analyst : Yes, sure. So another -- yes just how --

Question: Roger Song - Jefferies - Analyst : Great, just one last question related to other exon program. So should you have any feedback from the regulator in terms of how you're going to pursue other exon maybe in a large basket trial?

Question: Ananda Ghosh - H.C. Wainwright & Co., LLC - Analyst : I have three questions. I mean the first one on the function and the TTR, which is absolutely interesting, given the new data we saw at the NDA. One question is -- is there any long-term data which can correlate the TTR NSA and SA 95c given the data -- given the consistency in terms of dystrophin expression or in terms of where the dystrophin is expressed in the sarcolemma. Do you have -- is there correlation which one can make between TTR and NSAA or SV95C.

Question: Ananda Ghosh - H.C. Wainwright & Co., LLC - Analyst : Right. Just a follow-up on that question. Like in the EMBOG data, there was a particular way in which they calculated the external control. how does it translate to the way you have calculated the external control when you are comparing the TTR?

Question: Ananda Ghosh - H.C. Wainwright & Co., LLC - Analyst : Got it. And the third is since you have been focusing on differentiation, right, from the which is reflected with the immuno inflammatory data, et cetera. Do you plan to -- there was a lot of discussion at the NDA in terms of the use of muscle in the DMD as well as in the FSHD patient population. So do you plan to introduce muscle MRI as you get through the long-term extension studies? And does it add value if you're thinking about from the perspective of level in the future? 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: Tiago Fauth - Wells Fargo Securities, LLC - Analyst : Just a couple of follow-ups for me. You mentioned that you're going to include additional boys on the monthly dosing regimen for FORWARD-53. How many additional patients do you expect to enroll in? Are they also potentially going to be a part of the regulatory package that you intend to submit? And then a bigger picture question, just thinking about capital needs and prioritization, right? You're going to have a confirmatory trial, potentially expanding the exon skipping platform with other DMD mutations. There's AATD and [Hibini] Huntington's. Like how are you thinking about that right now in terms of creating the best value path forward?

Question: Catherine Novack - Jones Trading - Analyst : Okay. Great. I have a question about cardiac outcomes. You mentioned cardiac expression in preclinical models. Is that something you'd ever explore clinically, understanding that these measurements could be high burden to patients, but if you believe this to be a differentiating factor, is there a way to look at that in future studies?

Question: Catherine Novack - Jones Trading - Analyst : Got it. And then just one more about the confirmatory study. As you think about designing this, are you open to considering a European regulatory path? Or how much does that factor into the way you're designing the functional outcomes of this study? 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: Madison El-Saadi - B. Riley Securities - Analyst : Congrats on the extensive update here. It really seems the regenerative data here seems to be one of the take-home messages I admit so back adjusting it. But -- are you seeing regenerative data as well in the non-ambulatory patients, I believe we have one non-ambulatory patients enrolled? And then do you know what percent of stem cells are being transfected. And how do you interpret the decline in the number of stem cells and myofibers with internalized nuclei. And then a follow-up.

Question: Madison El-Saadi - B. Riley Securities - Analyst : Got it. Got it. And then secondly, just quickly, how many additional patients will be enrolled in this new expanded cohort? Just wondering what the total patient exposure requirement is?

Question: Ryan Deschner - Raymond James - Analyst : Based on the results in your comments today, would you expect to continue to see meaningful decreases in muscle fibrosis and necrosis at later time points. And will we see additional fibrosis data in the extension or later in confirmed from studies? And I have a follow-up.

Question: Ryan Deschner - Raymond James - Analyst : Okay. That's helpful. And then also just briefly, were there any additional decreases in AST or stabilization seen at week 48. 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: Joon Lee - Truist Securities - Analyst : Also really intrigued by the reduced model destruction and turnover as evidenced by the lower multiple stem cells. I guess it's like seeing a complete blood count, lower radiculocyte count, which is a good thing. Do you think that could have impacted your dystrophin Western blot at week 48 could reduced muscle turnover have led to reduced cooking synthesis overall, including dystrophin, which may actually have been a good day. Thank you.

Question: Joon Lee - Truist Securities - Analyst : Yes. And just following up on Ryan's question, I know that you're not doing any more biopsies, but would you be following up with serum biomarkers of multiple health, including CK and LDH and things like that, that could help us gauge the health of the multiples that are being regenerated? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.