The following is excerpted from the question-and-answer section of the transcript.
(Questions from industry analysts are provided in full, but answers are omitted - download the transcript to see the full question-and-answer session)
Question: Eric Joseph - JPMorgan - Analyst
: Okay, great. Thanks, Paul. So just by way of starting out Q&A, I want to start with the alpha-1 antitrypsin deficiency program, and you're sort of
setting what you think might be the threshold of M protein that you need to achieve in order to see disease correction or disease modification.
Your preclinical data show that you're kind of getting well surpassing that threshold of 30 micromolar. Can you just talk about how durable that
rise in serum M protein is, maybe perhaps speaking to the half-life of M protein, I guess is there an initial steady state level of M protein needed to
ensure that you're having adequate distribution to lung tissue where at least for a good subset of patients it needs to be active?
Question: Eric Joseph - JPMorgan - Analyst
: Okay. So in just thinking about dosing, dose level selection in Restoration I and Restoration II in this program, maybe just skipping all the way to
the MAD portion of the study, can you talk a little bit about sort of the dosing intervals that you are evaluating or are you looking to study? Is it
multiple treatment intervals in addition to dose strengths that you're looking at?
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JANUARY 10, 2024 / 11:00PM, WVE.OQ - WAVE Life Sciences Ltd at JPMorgan Healthcare Conference
Question: Eric Joseph - JPMorgan - Analyst
: So I guess maybe just kind of putting some contours around the initial data readout sometime this year, I guess what do you hope to read out in
terms of sort of anything beyond sort of initial data from the low-dose cohort in Restoration II? And then I also wonder whether there's sort of a
Question: Eric Joseph - JPMorgan - Analyst
: Okay. All right. And just given the sensitive liver health for a good subset of ZZ patients, one, I guess, can you just talk about the work that you've
done to get comfortable with the liver tolerability profile with WVE-006 and whether the patients coming into Restoration II would allow you to
at least be of a liver phenotype that would allow you to appropriately assess that parameter?
Question: Eric Joseph - JPMorgan - Analyst
: For your Inhibit E program, I guess it's still fair to say that we really don't have a great full understanding of the mechanism behind weight loss with
the GLPs. How well-defined is the role of activin E, which is what's being downregulated here, to fat metabolism? And then, I guess, how do you
see the Inhibit E axis differentiating clinically from the incretin-modulating agents?
Question: Eric Joseph - JPMorgan - Analyst
: Are you inviting competition? Can you speak to how your sRNA chemistry is different from some of the other well-known platforms in the industry?
Question: Eric Joseph - JPMorgan - Analyst
: Okay. Maybe just a final question on WVE-003, I believe, in Huntington's, of which we'll learn more about later this year, but can you just talk about
its intrathecal administration, if I have that correct, so can you just talk a little bit about sort of volume of substance being administered there and
really the question is around tolerability. And I guess programs have kind of run into perhaps inflammation responses. I guess what do you
understand so far for the propensity for that to kind of happen? How do you see it de-risked from a tolerability standpoint?
Question: Eric Joseph - JPMorgan - Analyst
: Okay, that's clear. All right. Well, certainly an exciting year ahead. Thanks for your time, Paul. This was great.
Question: Eric Joseph - JPMorgan - Analyst
: Thanks very much for coming.
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consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies.
JANUARY 10, 2024 / 11:00PM, WVE.OQ - WAVE Life Sciences Ltd at JPMorgan Healthcare Conference
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