WAVE Life Sciences Ltd Q2 2025 Earnings Call Transcript

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

Question: Joon Lee - Truist Securities - Analyst : Do you guys hear me?

Question: Joon Lee - Truist Securities - Analyst : For the INHBE program, can you elaborate on your reasons for expanding Cohort 2 over advancing to Cohort 3 sooner? If the Cohort 2 dose was well tolerated, why not just advance to Cohort 3 versus expanding Cohort 2? And also, when you say Cohort 2 dose is therapeutically relevant, is that in reference to semaglutide like weight loss? And finally, is the goal of Activin E knockdown around 50% based on your human heterozygous -- heterozygotes having the protective phenotype? Or is the goal something other than 50% knockdown?

Question: Joon Lee - Truist Securities - Analyst : Just to clarify, should we be expecting a linear dose response? Or does the fat -- preservation of lean mass offset or counteract sort of the weight loss aspect coming that it is from the fat loss as you go to Cohort 3 and et cetera.

Question: Yun Zhong - Wedbush Securities Inc - Analyst : So the first question is a kind of follow-up question to a previous one asked on the call. And on the INHBE knockdown, what would you see as a desirable knockdown level that you want to see and related to the dose Cohort 2 extension versus dose Cohort 3? And do you have a plan to continue dose escalation after dose Cohort 3?

Question: Yun Zhong - Wedbush Securities Inc - Analyst : Okay. Then -- a follow-up question on the DMD program actually. I believe there were some updates on the -- at the FDA level this morning and I'm curious, would that affect your approach or strategy that you're going to take with regard to your DMD program, please?

Question: Catherine Novack - Jonestrading Institutional Services LLC - Analyst : So at the last update in May, you reported that dosing was ongoing for the 200-milligram multi-dose. Can you be specific about when dosing was completed? Did all patients receive all seven doses? And what's the minimum follow-up for reporting top line data?

Question: Catherine Novack - Jonestrading Institutional Services LLC - Analyst : Okay. Great. And if I can just ask one more. When you mentioned in the last earnings that dosing was complete with the first two Cohorts of INLIGHT. Was this before or after the expansion of Cohort 2 was triggered?

Question: Samantha Semenkow - Citibank Cameroon SA - Analyst : I have a couple of related questions on WVE-007. I'm wondering if you're able to characterize the amount of Activin E reduction you saw in Cohort 1 in relation to your preclinical modeling. Was it in line with your expectations? Or was it greater? And if it is greater, I'm wondering if you've seen any early Activin E data from Cohort 2 and if that is tracking higher than your expectations? And then just kind of pulling it all together, is there a dose response or a correlation that you see between the amount of Activin E reduction and the amount of weight loss you expect? I'm wondering if it's a linear relationship based on your understanding or some other curve on the correlation there?

Question: Samantha Semenkow - Citibank Cameroon SA - Analyst : Got it. One follow-up for me on the AATD program. I'm wondering what you believe the target conversion rate from Z to M should be. Are you looking for near complete conversion, so vast majority being M? Or is there an acceptable amount of residual Z protein in your view for the target dose that you select over time?

Question: Joseph Schwartz - Leerink Partners LLC - Analyst : Congrats on all of the progress and the update today. I have a couple of questions on 006 as well. First, following on the last question, I was just wondering conceptually how you're thinking about the amount of editing into M protein, that's possible to see from the 200-milligram MAD and 400-milligram SAD regimens based on what's known about the kinetics of the enzyme and where you're expecting to be on the editing curve based on what you've seen across your preclinical healthy volunteer and early patient experience?

Question: Joseph Schwartz - Leerink Partners LLC - Analyst : Thank you for that helpful context. And then as a follow-up, other companies developing RNA editing therapeutics for AATD claim to have designed them to have best-in-class characteristics. We've heard you say best-in-class when referring to your platform overall. But I was wondering if you could discuss the extent to which you've focused on optimizing 006 so that it's competitive with others who are following in your footsteps.

Question: Salim Syed - Mizuho Securities USA LLC - Analyst : Great. Paul, maybe just one from us on 007 and then a quick one on 006. On 007, so on this call, you guys mentioned that you saw a robust Activin E reduction at Cohort 1. You also initially structured this trial with five Cohorts in the single dose, but you're already expanding at Cohort 2. So I'm just trying to understand a little bit more about your decision to expand at Cohort 2, is there any protocol requirement here that forced you to expand at Cohort 2 before moving to multi-dose? Was there any variability you saw in the first eight patients that led to the sort of expansion in the single dose? Or is there something strategic about it that you can move this quicker to pivotal if you think Cohort 2 is really your go-forward dose? And then I'll ask my follow-up on 006. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JULY 30, 2025 / 12:30PM, WVE.OQ - Q2 2025 WAVE Life Sciences Ltd Earnings Call

Question: Salim Syed - Mizuho Securities USA LLC - Analyst : Okay. And just quickly on 006, are there any GSK milestones we need to be aware of on this upcoming data set, whether it's a 200 multi or 400 single?

Question: Salim Syed - Mizuho Securities USA LLC - Analyst : From the data or from moving it to something --

Question: Martin Auster - Raymond James - Analyst : Paul, I wanted to follow up on some of the conversation you're having on the last question earlier with Samantha. As you're moving into Cohort 3 dosing, it sounds like assessing Activin E reduction in Cohort 2 might influence what the ultimate size and whether there's going to be an expansion of that Cohort 3 might be. Can you talk about sort of when you'll be able to make that decision, how you'll communicate that and whether that would potentially shift the time line of planned disclosure for Q1 next year for that Cohort 3 and 007?

Question: Cheng Li - Oppenheimer & Co Inc - Analyst : Congrats on the quarter. Just like two quick questions from us on the INHBE program. I'm wondering if you can talk about the baseline characteristic for the Cohort 2 enrolled. And considering the weight loss is driven mostly by fat mass, I'm wondering any key metrics you would point to that maybe -- that we should keep an eye on? And the quick follow-up on the -- I will just have a quick follow-up as well.

Question: Cheng Li - Oppenheimer & Co Inc - Analyst : Okay. Got it. The follow-up question is on the data expected in 4Q. I think you mentioned individual will have at least three months follow-up. So I'm wondering by the time you release the data, whether you can have a clear idea of the dosing frequency, whether it will be every 3 months or every 6 months or every 12 months where you need more data or more follow-up.

Question: Madison El-Saadi - B. Riley Securities Holdings Inc - Analyst : A couple of questions from us. So have you initiated dosing in the subsequent RNA editing Cohorts, presumably the 400 mg dosings ongoing. I guess would you wait to complete that before moving on? Is there a trigger that could initiate that subsequent dosing or even expand the arm similar to what we've seen in Cohort 2 in INLIGHT? And yes, just what could these triggers be?

Question: Madison El-Saadi - B. Riley Securities Holdings Inc - Analyst : Correct. I was just using 007 as an example.

Question: Madison El-Saadi - B. Riley Securities Holdings Inc - Analyst : Got it. Understood, Paul. And then quickly going back to DMD. Just given the community is, I guess, newly sensitized to the AAD liability. Just wondering how enrollment is going in the open-label monthly extension Cohort? And how long do you think these boys need to be on drug before you submit your NDA package? REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. JULY 30, 2025 / 12:30PM, WVE.OQ - Q2 2025 WAVE Life Sciences Ltd Earnings Call