Oct 29, 2026 earnings call — Phase III progress and FDA meeting for zorevunersen
Approximately 110 of the 162 enrolled patients have completed week 28; data readout expected Q3 2027.
Revenue $0.0B (est $0.0B) · EPS $-1.08 (est $-0.93)
Key quotes
"The study is progressing very well. All 162 patients enrolled in the U.S., U.K., and Japan are through week 8 of the study, which means that they have received either the 2 loading doses of 70 milligrams of zorevunersen or sham."
"An important outcome of our meeting was the FDA's willingness to accept a multicomponent assessment of Vineland-3 data for purposes of evaluating the key secondary endpoint related to changes in cognition and behavior."
"Dosing is now underway in the third cohort of our Phase I OSPREY study, and we expect to initiate the fourth dose cohort in early 2027."
Analyst Q&A 11
Vineland data collection and regional plans
Q (Kevin Strang · Goldman Sachs): They asked how the trial is designed to ensure Vineland-3 data quality across sites and time points, and whether the multicomponent analysis differs between the U.S. and Europe.
A: Management said they use a trained central rater, encourage the same family member to report each time, and have an internal reviewer checking data nearly daily. They added that the MC4 multicomponent approach is for the U.S., while Europe still uses net treatment benefit on individual Vineland subdomains and Biogen controls the European filing.
"So the collection of the data for the Vineland study is vitally important." — Barry Ticho
AdCom, rolling submission, background medicines
Q (Laura Chico · Wedbush): They asked whether an advisory committee (AdCom) is likely, what remains to resolve before rolling submission, and how the OLE protocol handles changes to background antiseizure medicines.
A: Management said they do not anticipate an AdCom and that they plan to submit data throughout the first half of 2027 and complete submission in the second half of 2027 to give FDA the option to review early. They explained background antiseizure medicines are kept stable during an 8-week screening and for at least the first 6 months through the week 28 endpoint, so effects of zorevunersen are assessed on top of stable baseline medications, and they will analyze week 28 with and without any medicine changes.
"As far as submitting data for the NDA, we anticipate submitting data throughout the first half of 2027 with a completion of the submission in the second half of 2027." — Ian Smith (CEO)
What Vineland score changes mean
Q (Pete Stavropoulos · Cantor Fitzgerald): They wanted examples of what small Vineland treatment effects mean for families and why the 1-year time point is sufficient versus 18 months under the MC4 approach.
A: Management explained Vineland items score 0, 1, or 2 and gave examples: a shift from never to sometimes for actions like saying one’s name or following a simple instruction is meaningful for families. They said the multicomponent (MC4) basket increases power by averaging four domains, and noted the 12-month MC4 result had a low p-value despite suboptimal dosing in that dataset.
"And the -- so that means that a score of 0 would mean for a particular activity, that child would never do that." — Barry Ticho
Biogen comments and FDA meeting topics
Q (John Cox · Jefferies): They asked how management views Biogen’s comments about ex-U.S. differentiation and pricing, and what other topics came up in the FDA meeting besides Vineland-3.
A: Management said they wouldn't speak for Biogen and that European single-payer markets are more challenging than the U.S., where the totality of data matters; Biogen can clarify Europe. They said other FDA topics included the MC4 Vineland approach, submission timing, and whether OLE data can be included in the label, with FDA calling that a review issue.
"I think Vineland-3 getting to the multicomponent 4 assessment was the priority focus." — Ian Smith (CEO)
Whether one subdomain can drive MC4
Q (Sumant Kulkarni · Canaccord): They asked if a subdomain’s large contribution matters and whether an average that meets clinical relevance could still be valid if 1–2 subdomains drive most of the difference.
A: Management said each of the four subdomains is assessed equally and the MC4 score is a simple average, which gives more evaluable data and more power. They added there is no one subdomain that is more important and the multicomponent approach smooths variability so extremes are averaged out.
"The way it does work, and I'll keep it simple, which is you do assess equally each subdomain." — Ian Smith (CEO)
Using MMRM and no hierarchy
Q (Yaron Werber · TD Cowen): They asked whether MMRM handles dropouts and missing data, and whether the multicomponent endpoint still requires hierarchical testing or multiplicity control.
A: Management confirmed they are using MMRM for the Vineland, which uses all visits up to the time point and can accommodate missing data. They also said the multicomponent endpoint will be assessed as all four subdomains together with no hierarchy, per agreement with FDA.
"As far as the MMRM, yes, we're using the MMRM for the Vineland." — Barry Ticho
Alpha split between endpoints
Q (Joseph Stringer · Needham): They asked how changing to MC4 affects alpha allocation across the primary (week 28) and the seizure and Vineland secondary endpoints.
A: Management said they have updated powering assumptions given more retained patients (162 enrolled, 110 through the primary endpoint) and an assumption of 150 evaluable patients, and they reported the treatment effect sizes needed to reach p-values for seizure and Vineland endpoints. They clarified there is no alpha split: the week 28 seizure reduction is the primary, week 52 seizure is first secondary, and Vineland is second secondary.
"In terms of split, there is no alpha split." — Barry Ticho
Clinically meaningful seizure reduction and p-value
Q (Jessica Fye · JPMorgan): They asked what experts consider a clinically meaningful seizure drop, whether 40%–50% is an expectation or threshold, and whether success in EMPEROR requires p<0.05 or p<0.01.
A: Management said clinicians and market research aim toward seizure freedom but expect a disease-modifying treatment to deliver roughly 40% to 50% additional reduction over control; fewer seizures are always clinically meaningful. They also confirmed statistical significance is set at 0.05 for the primary and key secondaries.
"I think if you ask them what's clinically meaningful, fewer seizures is always clinically meaningful relative to more seizures." — Jason Hoitt
OLE 5-year data and MC4 forest plot
Q (Marc Goodman · Leerink): They asked whether the FDA comment that 5-year OLE data is a 'review issue' meant it could be used if the study just misses, and whether MC4 can be positive if benefit is concentrated in 1–2 subdomains.
A: Management said whether a miss matters depends on how close the results are and the totality of primary, secondary, and tertiary data; they view the OLE data as strengthening their position and the FDA called inclusion of OLE on the label a review issue. They also said FDA advised they want a forest plot to understand what drives the MC4 score and that hitting the MC4 p-value is acceptable even if driven by some subdomains.
"They've actually gone as far with us in the discussion to advise us that they would like to see it as a forest plot because they want to understand what drives the MC4 score." — Ian Smith (CEO)
ADOA safety readout and biomarkers
Q (Guofang Li · Wolfe): They asked what bar for visual benefit will support dosing selection, whether OPA1 protein levels are measured, and if further dose-ranging is needed before pivotal.
A: Management said preclinical and field data support raising OPA1 could improve vision, but the Phase I is primarily a safety study and will also look at visual acuity and a mitochondrial function biomarker to inform decisions. They said OPA1 protein level is not being measured, they will review the data to decide on next steps, and they are considering ways to accelerate the program given unmet need.
"So the Phase I study is designed primarily as a safety study, which will be an important readout." — Barry Ticho
ADOA cohort learnings and spend guidance
Q (Yatin Suneja · Guggenheim): They asked what was learned from the first two ADOA cohorts and how to model spend in 4Q and in 2027.
A: Management said the primary endpoint is safety and a safety monitoring committee reviewed the first two cohorts and recommended moving to the third cohort. They added that doses of 0.3 milligrams and 0.5 milligrams move into the therapeutic range and they expect safety and efficacy results in the first half of 2027, and for near-term spend guidance they suggested modeling Q4 similar to the quarter-to-quarter increase seen from Q3 to Q4 in 2026.
"We do have a safety monitoring committee that reviews the results, and they did review the results of the first 2 cohorts." — Barry Ticho