WAVE Life Sciences Ltd Q2 2024 Earnings Call Transcript

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

Question: Joon Lee - Truist Securities - Analyst : Congrats on the progress and looking forward to a lot of data readouts in the next five months. Glad to hear that you have submitted the opt-in package to Takeda with decision by year-end. Regarding the conversations with regulators, is Takeda involved in those conversations? Or is it just REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 08, 2024 / 12:30PM, WVE.OQ - Q2 2024 WAVE Life Sciences Ltd Earnings Call between you and the FDA? And what has been the feedback so far on the possibility of using imaging as a surrogate biomarker? Thank you. And I have a quick follow-up.

Question: Joon Lee - Truist Securities - Analyst : Great. And on DMD, just looking at the approved antisense oligos in DMD, about 42% exon skipping for the 53 from Viltepso lead to around 4.8% dystrophin. So would you say the bar for N531 is around 5%. Is there some internal bar for efficacy you'd like to see in the forthcoming data? Thank you.

Question: Joon Lee - Truist Securities - Analyst : Great. Thank you and I'm looking forward to the R&D event in the fall. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. AUGUST 08, 2024 / 12:30PM, WVE.OQ - Q2 2024 WAVE Life Sciences Ltd Earnings Call

Question: Salim Syed - Mizuho Securities Co Ltd - Analyst : Good morning, guys, and congrats on the progress. Paul, I wanted to follow up a little bit on the Takeda stuff that we're going to get this year. So could you just clarify for us, is this -- are you anticipating that the feedback we're going to get to the Street, is it going to be one event or two events? In other words, are we supposed to expect the regulatory feedback as one event and the Takeda decision as another event? Are these two things linked? And then also just what is the disclosure format, if you can just clarify for us, are we just going to get that some time as it happens? Or are you going to wait for the quarterly -- the next quarterly call? And then just lastly, just related to that, as you're considering financing the company, just given DMD is a third quarter event and the feedback from the regulatory body in Takeda could be potentially a 4Q event, would you wait for that to occur? Or would you be willing to finance on DMD given your runway is now at 4Q '25? Thank you.

Question: Salim Syed - Mizuho Securities Co Ltd - Analyst : Got it. Thanks so much, Paul.

Question: Lisa Walter - RBC Capital Markets - Analyst : Great. Thanks so much for taking our questions. This is Lisa on for Luca. First on the Takeda opt-in, just wondering, should Takeda ultimately choose not to opt in, just wondering what are your options for the program if that happens? And secondly, on INHBE, given the target can potentially reduce fat and maintain muscle, wondering if you are thinking about any ways to assess muscle preservation in the clinic? Any color there would be helpful. Thank you so much.

Question: Nick Econom - Raymond James Financial Inc - Analyst : Hi. Thank you for your question. This is Nick on for Steve. Just wanted to clarify for the RestorAATion-2 update in Q4, do you plan to show changes in AAT protein concentration? Or do you plan to only show the proportion of corrected M-AAT versus Z-AAT? And as a quick follow-up, will the

Question: Nick Econom - Raymond James Financial Inc - Analyst : Thank you.

Question: Lili Nsongo - Leerink Partners LLC - Analyst : Hi. This is Lili, thanks for the opportunity, on for Joe. I was just wondering if you could give us a little more insight into the data that's been generated so far to support caudate atrophy and what will be needed to establish that biomarker as reasonably likely to predict benefit? And can you tell us kind of what you're expecting? How soon you might see meaningful changes in this biomarker? And if the proposed study design might include some interim analogies? Thank you.

Question: Tiago Fauth - Wells Fargo & Company - Analyst : Great. Thank you so much for taking the question. I had one just on the AATD. Just wondering if you can discuss more of your expectations about the translatability of the dose finding studies in animal models into humans, there's some questions mostly from the mutations of those animal models and the novelty of the approach. So what gives you confidence that those dose levels you're taking forward are actually likely to be at a therapeutic relevant range in humans? More details on that would be appreciated.

Question: Tiago Fauth - Wells Fargo & Company - Analyst : Got it. Perhaps just one quick follow-up there. Because again, there's mix expectations from investors on what's the actual bar given the perceived to be competitive AATD landscape. So at your optimal dose, is crossing the 11 micromolar range enough? Do you need to get to an MM phenotype? Oe how are you guys thinking about the product profile? Thank you.

Question: Tiago Fauth - Wells Fargo & Company - Analyst : Understood. Thank you very much for taking the questions.

Question: Joon Lee - Truist Securities - Analyst : Hey, guys. Thanks for taking our follow-up question. We recently conducted a Carewell call discussing the data that's been generated in the Huntington space? Can you PTC, UniQure and Roche? And regarding the safety signal of hydrocephalus seen with Tominersen and AMT-130, there are sort of two petting or maybe complementary theories. One is hydrocephalus due to defective cilia due to nonspecific knockdown of wild-type huntingtin leading to defective CSF flow. And the other is what you described as pseudoatrophy due to reduced inflammation within the caudate and the basal ganglia driving that sort of pseudoatrophy and having concerns of hydrocephalus. Would love to hear your thoughts on these theories and what your evidence -- what sort of evidence you have in your preclinical models and whatnot to support one versus the other? Thank you.

Question: Joon Lee - Truist Securities - Analyst : (multiple speakers)