Oct 27, 2026 earnings call — Advancing RNA therapies for obesity and AATD
Ended Q3 with $431 million cash, funding operations into the third quarter of 2028.
Revenue $0.0B (est $0.0B) · EPS $-0.30 (est $-0.33)
Key quotes
"Importantly, when we think about the challenges of sustaining chronic long-term incretin therapy, WVE-007 offers new potential to prevent weight regain with just a once or twice a year dose."
"As Chris Wright will speak to in further detail momentarily, following our recent meeting with FDA, planning is now underway for a single registrational trial of WVE-006 for AATD, offering an efficient path to full as well as potentially accelerated approval without the need for a separate confirmatory trial."
"Beyond our internal pipeline, our PRISM platform and proprietary chemistry continue to demonstrate their value, as evidenced by GSK's recent development candidate selection."
Analyst Q&A 17
FDA trial size and approval basis
Q (Rick Bienkowski · Ladenburg): How large a pivotal trial might be for WVE-006, and will full approval be based on biomarkers or require functional outcome evidence?
A: Management said the plan is a single efficient study that can support both accelerated and full approval with an interim analysis at one year and full approval at two years. They said they won't disclose detailed biomarker strategy for competitive reasons but noted validated LC-MS assays are available to quantify protein.
"So the predicated design is for that single study without the need for a separate confirmatory study." — Paul Bolno (CEO)
stereochemistry value and role at Wave
Q (Joon Lee · UBS): How does the Nobel Prize validate Wave's stereochemistry platform and how will Monika approach her role at Wave?
A: Management said recognition of chirality validates the importance of stereochemistry in biology and drug design and that Wave has built a consistent, programmable platform enabling efficient translation from mouse to human. Monika said she will jump into partnering discussions immediately and work on mid- and long-term plans for clinical, preclinical, and platform partnerships.
"I have been following Wave for over a decade, and it has been on my radar for partnering as it matured to emerge as the leading siRNA and RNA editing company." — Monika Vnuk
WVE-007 weight loss and AATD enrollment
Q (Reem Al-Ahmad · William Blair): Can WVE-007 hit 5% weight loss at 12 months given higher baseline adiposity, and how will AATD enrollment compare to competitors?
A: Management said higher baseline adiposity in phase II-A is consistent with moving to phase II/III and supports a path to potential 5% weight loss at one year based on modeling and preclinical translation. For AATD, they plan to leverage patient registries and engagement with foundations and KOLs, expect good enrollment globally, and will study patients with both lung and liver disease.
"Working together with them, and we are going to leverage those registries, which have actually several thousand patients in them for our trial." — Chris Wright
one-year interim bar for accelerated approval
Q (Jean · Citi): What bar must be met at the one-year interim for accelerated approval and do current data meet it?
A: Management said they won't disclose specifics but the interim is predicated on delivering an MZ-like result at one year. They clarified that means increased M of 50% or greater or in the MZ range, decreased Z, and recapitulating the acute phase response, which their data have already shown.
"As Paul mentioned, really, we're looking to restore the MZ-like phenotype where individuals would have increased M of 50% or greater, or in the range of an MZ patient, decreased Z, and then recapitulating the acute phase response so that M increases at the time that there's infections or a lung inflammation, at the time that the tissue most needs protection." — Chris Wright
body composition endpoints beyond weight
Q (Ananda Ghosh · H.C. Wainwright): Have you discussed with FDA using DEXA, waist circumference, or other body composition measures beyond weight loss?
A: Management said they expect ongoing engagement with FDA and patient groups about focusing on healthy weight loss driven by fat loss and visceral fat reduction rather than scale weight. They noted these body composition measures are already captured in their trials and align with shifting clinical and regulatory narratives.
"We're very much set up to how do we deliver on a regulatory threshold and get to build on the labeling with what's going to be meaningful for patients in the long term, which is this improvement in body composition, all of which are captured across the clinical trials that we're running." — Paul Bolno (CEO)
single trial vs confirmatory studies
Q (Salim Syed · Mizuho): Did FDA treat RNA and DNA differently, or did Wave propose the single trial design to cover accelerated and full approval?
A: Management said they believe harmonization at FDA is improving and praised their team's strategy to design a single trial that can enable full approval with a two-year duration and accelerated approval at one year. They emphasized the single-trial approach was their strategy to be efficient for patients and capital.
"It really was our strategy and the thinking of the team that really brought us forward with the single trial design, which would enable us to get to a full approval as quickly as possible, but also have an accelerated approval on the table." — Chris Wright
timing for registrational enrollment and phase II-A look
Q (Joe Schwartz · Leerink Partners): After WVE-006 dose lock, when will registrational enrollment start? Will there be a three-month look at WVE-007 phase II-A and when?
A: Management said RestorAATion-2 is ongoing and they'll use the 600 mg multiple-dose data to decide dose and interval for the pivotal and will provide updates then. For WVE-007 phase II-A, they may report as early as this year and will decide this quarter whether to cut data at three months or six months, with three months informative for body composition and six months for weight loss.
"Once we have the 600 mg multiple dose data, then we will be able to have a better sense of what dose and what dose interval we will be taking forward into the pivotal trial, and we will provide updates at that time." — Chris Wright
endpoints for AATD full approval
Q (Ben Burnett · Wells Fargo): What endpoints might support full approval in AATD and are some easier to power?
A: Management declined to disclose specific endpoints for competitive reasons but said FEV1 is not feasible in a reasonable timeframe or patient number. They mentioned other options like exacerbations, respiratory symptom questionnaires, and CT densitometry which has been used for approvals in Europe and could allow a shorter, well-powered trial.
"FEV1 is not really a feasible endpoint for AATD in a reasonable timeframe with a reasonable amount of patients." — Chris Wright
market adoption and combo approval bar
Q (Yun Zhong · Wedbush): What magnitude of weight loss will patients want for WVE-007 monotherapy, and for combination with GLP, is incremental weight loss enough for approval or is additional benefit needed?
A: Management said the regulatory bar is a weight-loss percentage but emphasized losing fat and preserving muscle yields health and aesthetic benefits; they argued more fat loss is needed to equal muscle weight loss. For combinations, they said if monotherapy meets regulatory bar no separate approval is needed for combination, and regulators consider additive effects of adding another medicine to incretins.
"If we achieve the regulatory bar, then you do not need a separate approval for the combination." — Paul Bolno (CEO)
what 600 mg WVE-007 data will show
Q (Whitney Ijem · Canaccord Genuity): What should we expect from the 600 mg WVE-007 data and could 600 mg be used for maintenance vs combo?
A: Management said the 600 mg single ascending dose will give safety, PK/PD, and duration information to complete the exposure model and inform dose interval for once- or twice-yearly dosing. They noted lower single doses already showed substantial knockdown and expect the chosen phase II-A regimen to have substantial durable knockdown.
"600 mg is to get more information about the dose, the duration, the dose interval." — Chris Wright
incremental benefit of 600 mg for WVE-006
Q (Dani Brill · Truist): Given an MZ-like phenotype is already shown, what incremental benefit will 600 mg provide and how will you justify less-than-monthly dosing?
A: Management said 600 mg will help complete the modeling curve to assess total exposure and duration, enabling optimization of regimen and dose frequency for the pivotal. They emphasized prior doses (200 biweekly, 400 monthly) inform exposure and 600 will help refine the model for subsequent studies.
"Having 600 monthly will help us complete the modeling curve so that we could look at total exposure duration, so drug product on board, and be able to optimize that regimen." — Paul Bolno (CEO)
assay flexibility with FDA for AATD
Q (Steve Seedhouse · Cantor Fitzgerald): How flexible was FDA about the assay for AATD phase III and will industry need standardized assays?
A: Management said FDA dug deeply into their assay, were satisfied, and are comfortable with Wave using that assay in the registration study. They added that having a well-characterized assay that can be used from early studies through registration provides consistency and allows cross-comparison with natural history cohorts.
"On the basis of them really digging deeply into our assay, they were comfortable with us utilizing that as we move forward as part of our registration study." — Paul Bolno (CEO)
dose response 400 mg vs 600 mg
Q (Catherine Novack · JonesTrading): What dose response do you expect between 400 mg and 600 mg monthly and can multi-dose improve MZ ratio?
A: Management said GalNAc distribution and time allow sites to recover protein production and that even low doses produced robust responses, achieving MZ-like percent M in natural history cohorts. They suggested multi-dose regimens may impact Z faster and that existing data already deliver the expected MZ profile.
"Again, in terms of what one needs to achieve, and this gets back to some of the conversations that we were having in the profile of going into what needs to be achieved to deliver on an MZ-like phenotype. We're delivering right at the percent of M that's seen in the natural history cohorts of MZ." — Paul Bolno (CEO)
Q4 WVE-006 data, dosing frequency, EU approval
Q (Madison El-Saadi · B. Riley): What would push you to biweekly vs higher monthly dose for pivotal, and could the trial support EU submission and approval?
A: Management said modeling of the Q4 data makes monthly dosing highly likely based on 200 and 400 doses, and 600 will help assess total exposure for dosing frequency. They noted CT densitometry is accepted in the EU and could open a rapid path there as part of their registration plans.
"You might be aware that in the E.U. they have accepted CT densitometry as a primary endpoint for a pivotal study in the past." — Chris Wright
GSK partnership history and outlook
Q (Luca Issi · RBC): How has the relationship with GSK evolved since 2022 and where is it headed now?
A: Management said the collaboration has been mutually beneficial, helping both companies learn about cell types, targets, and modalities, and that asset decisions reflected portfolio alignment and leadership changes. They said it's good to see GSK move forward with certain assets and that the collaboration helped select WVE-007 earlier, implying constructive ongoing engagement.
"I think on both sides, I would like to think that each of us are getting out of it what we went into it saying this was going to be aligned with a portfolio construction and, with us, and now having full ownership of WVE-006." — Paul Bolno (CEO)
lean mass preservation in higher BMI patients
Q (Alec Stranahan · BofA): With higher adiposity patients who may have more muscle, how do you view lean mass preservation and any planned FDA meetings before pivotal AATD trial?
A: Management said preserving lean mass can accelerate fat loss and sustain metabolic rate, making body composition more relevant than BMI and aligning with patient and clinician views. They declined to comment on individual regulatory interactions but said they will be well prepared when initiating the WVE-006 trial.
"As it relates to WVE-006, we do not comment on individual regulatory interactions, but it is safe to assume that we will be well prepared when we go into that trial to deliver." — Paul Bolno (CEO)
maintenance prevention of weight regain
Q (Cha Cha Yang · Jefferies): What magnitude of weight-regain prevention would be clinically meaningful for a post-incretin maintenance trial?
A: Management said they will share study design details when the maintenance study initiates and pointed to DIO data showing prevention of fat regain with a slight lean mass increase, keeping total weight flat. They emphasized the need to report both total weight prevention and the composition of regained weight, since preventing fat regain while regaining some muscle is advantageous.
"What you would expect to see when we provide that update is a requisite update on not just prevention of weight gain as a total poundage number, but also both as a function of how weight is being regained, right?" — Paul Bolno (CEO)