WAVE Life Sciences Ltd Positive RestorAATion-2 Clinical Data Update Call Transcript

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

Question: Joseph Schwartz - Leerink Partners LLC - Analyst : Congratulations on these groundbreaking results. I was just wondering, does it seem like there's an asymptotic set point above which it's hard to drive M-AAT, AAT protein levels when it's not needed? And why do you think that is? And how do your models predict repeat dose 400 milligrams will work? Will it push the envelope further or push on a string?

Question: Joon Lee - Truist Securities Inc. - Analyst : Congrats on the data. Given competitive dynamics, including those from base editing, prime editing and gene writing and some questions around the levels of M-AAT, do you have any plans to assess clinical outcomes to potentially differentiate from a commercial standpoint? And also, as a quick clarification, in your Cohort 2, how many actually had both liver and lung manifestations or one or the other? Just wanted to understand the baseline characteristics in terms of the liver versus lung patients.

Question: Joon Lee - Truist Securities Inc. - Analyst : And just a quick follow-up. Are there plans for Cohort 3? And what does Cohort 3 look like in terms of the dose and dosing frequency?

Question: Salim Syed - Mizuho Securities USA, LLC - Analyst : Congrats on the data. Just one for me on Cohort 3. Paul, Chris, do you guys feel -- Erik, do you guys feel like you have what you need here in terms of total AAT and AAT, just especially now given what we understand with the acute patient data? Or are you more focused on durability or still pushing the actual levels here of AAT, M-AAT? And then just related to that, just kind of with what we understand now with this acute patient data, it seems like we're still trying to understand the biology. Is there any room in the protocol here to add an additional cohort if you feel like you need to for the -- all time? 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: Benjamin Paluch - Citi Investment Research (US) - Analyst : This is Benjamin Paluch on for Sam Semenkow. Recognizing that it's only a nano 1 with the patient that had the acute phase response, do you think the levels achieved with that patient could be sufficient to support approval?

Question: Roger Song - Jefferies LLC - Analyst : Congrats for the data as well. Just a little bit more on the dose response from 200 to 400. So very helpful to have the spider plot for the 200 SAD and the MAD patients. As far as I can tell, so since the 200 SAD is the mean peak is driven by two patients. So just curious how consistent for the 400 SAD, because you didn't give us the plot. Just want to understand a little bit about the dose response from 200 to 400 on the SAD population and the MAD.

Question: Yun Zhong - Wedbush Securities, Inc. - Analyst : So I just want to confirm that when comparing data from single-dose cohort versus repeat dosing cohort and the most -- well, the biggest impact is really the increase in M-ATT protein level instead of total ATT protein level. So it doesn't seems to be quite same as what you probably saw from preclinical data and because the mouse continue to show increase in total ATT level as well. And is that a correct observation, please? 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: Yun Zhong - Wedbush Securities, Inc. - Analyst : Great. Would you expect a higher editing efficiency, say, with the 600 milligram?

Question: Catherine Novack - JonesTrading Institutional Services LLC - Analyst : Okay. Great. Just trying to think about what is the scope of this study before turning the program over to GSK? Obviously, you mentioned most of the patients were F0. But if there's a handful of patients who have some liver fibrosis, would you have the opportunity to look at improvement so that we can kind of get beyond this focus on biomarkers between RNA and base editing and really look at some clinical outcomes? 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, Inc. - Analyst : I just wanted to ask, why go from 200 mg biweekly to monthly in the 400 mg arm? Just wondering what drove that decision? And should we expect monthly dosing in the higher dose cohort? Or has that decision been made yet? And then secondly, I guess maybe what's really driving the temporal change? How much of this is GalNAc pharmacodynamic related versus editing efficiency related?

Question: Steven Seedhouse - Cantor Fitzgerald & Co. - Analyst : Congrats on the milestone of really successfully translating safety, efficacy and consistency, it looks like of RNA editing into the clinic. I had actually two quick questions. First, can you comment on the LC-MS assay for quantifying AAT, the rationale for implementing that, sort of when it was implemented? It looks like that's potentially new based on the LLOQ. And then also, can you clarify or confirm if the acute phase response patient was one of the first two that were treated in the 200 mg SAD cohort?

Question: Angela Qian - Canaccord Genuity LLC - Analyst : This is Angela on for Whitney. Just wanted to ask, is there a long-term extension cohort here? I don't think we've seen any, but curious if there's been any efforts to open one, so patients could roll over and additional repeat dose data could be gathered to maybe capture more of these acute phase responses over time? 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: Angela Qian - Canaccord Genuity LLC - Analyst : That's helpful. Then maybe if I could just add a quick one. Has there been any discussion either internally or externally around a serum AAT during the acute phase reaction as a potential path forward, like capturing that kinetics as a potential path?