Asked for perspective on AZK's 12-week seizure freedom data from X-TOLE2 compared to XCOPRI, considering cross-trial differences and XCOPRI's titration requirement.

Ian Mortimer highlighted that AZK's X-TOLE2 population was more refractory than XCOPRI's trial population. He noted XCOPRI's 400mg dose is rarely achieved in practice and that AZK's RR100 (100% responder rate) in the last 4-6 weeks of the double-blind period is higher than XCOPRI's 200mg data. Chris Kenney emphasized the importance of long-term seizure freedom (12+ months) seen in AZK's OLE data (40% at 48 months) and the ease-of-use of AZK (no titration, no DDI) for general neurologists. Darren Cline added that XCOPRI is largely an epileptologist drug, and general neurologists struggle with its use, making AZK's profile more appealing. “I would actually say that our RR100 is higher than the cenobamate data seen at their 200-milligram dose.”

Asked if investors should anticipate any data this year from the pain assets, specifically Phase I SAD/MAD data.

Ian Mortimer confirmed that Phase I healthy volunteer studies for both XEN1701 and XEN1120 will complete this year. He stated that they are comfortable they will have enough receptor occupancy and exposure for a good shot at proof-of-concept in Phase II, but whether the Phase I data will be broadly shown publicly is "to be determined" for competitive reasons. “Yes, we're very comfortable in saying that the Phase I healthy volunteer studies for both 1701 and 1120 will complete this year.”

Asked about pre-NDA meeting status, FDA feedback, and timelines for DEA scheduling and approval.

Chris Kenney confirmed a pre-NDA meeting is expected between top-line data (March) and NDA submission (Q3 2026). He stated they have had thoughtful interactions with the FDA and don't foresee problems. The timeline includes a 6-month period from top-line data to NDA submission, a standard 12-month review, and 3 months for DEA scheduling, leading to an anticipated launch end of 2027 or early 2028. “We're expecting a standard review of 12 months and then DEA scheduling is expected to be 3 months. Which is why Ian stated in his comments that we expect approval end of 2027 or early 2028.”

XENE

Xenon Pharmaceuticals (XENE) Q1 FY26 earnings call: guidance and Q&A

Earnings call· Mar 2026 (Q1 FY26)· Health Care· May 7, 2026

Source: earnings call transcript

Executive summary

Xenon Pharmaceuticals Q1 FY26 — Strong X-TOLE2 Data and Extended Cash Runway

Xenon Pharmaceuticals reported a strong first quarter, highlighted by positive Phase III X-TOLE2 data for azetukalner in focal onset seizures, reinforcing its potential as a differentiated treatment. The company also secured substantial financing, extending its operational runway and enabling continued advancement of its neuropsychiatry and early-stage pain programs. Management is focused on preparing for AZK's anticipated NDA submission and commercial launch, while also exploring broader therapeutic applications and pipeline expansion.

Highlights

Reported positive Phase III X-TOLE2 study results for azetukalner (AZK) in focal onset seizures, exceeding expectations with a 53.2% median percent change reduction for the 25mg dose.
Achieved significant long-term seizure freedom in the X-TOLE OLE data, with 40% of patients treated for at least 48 months being seizure-free for 12 months or more.
Successfully completed a $747.5 million financing, extending the cash runway into 2029.
Progressed three Phase III depression studies for AZK, with top-line results from X-NOVA2 expected in H1 2027.

Concerns

Anticipated AZK launch timing is end of 2027 or early 2028, subject to standard FDA review and 3-month DEA scheduling.
Cross-trial comparisons for seizure freedom data are challenging due to different patient populations and reporting methodologies, particularly when comparing AZK to cenobamate.
The Dravet syndrome market is crowded, requiring clear differentiation for the Nav1.1 program.

Guidance & targets

Category	Target	Timeline	Confidence
NDA submission	NDA submission to the U.S. Food and Drug Administration high materiality	Q3 · FY26	High
Anticipated launch timing	End of 2027 or early 2028 high materiality	FY27-FY28	Medium
X-NOVA2 top line results	First half of 2027 medium materiality	H1 2027 · FY27	High
Cash runway	Into 2029 high materiality	FY29	High
XEN1701 first-in-human studies completion	Later this year medium materiality	FY26	High
XEN1120 first-in-human studies completion	Later this year medium materiality	FY26	High
NBI-921355 Phase Ib data	Next year low materiality	FY27	High

Deals & partnerships

Neurocrine Biosciences Collaboration on NBI-921355, an investigational selective inhibitor of voltage-gated sodium channels Nav1.2 and Nav1.6, for certain types of epilepsy.

Neurocrine is progressing a Phase Ib study for NBI-921355, with data expected next year.

Risks & headwinds

Anticipated launch timing for AZK is subject to standard FDA review and DEA scheduling. End of 2027 or early 2028 for launch.

Standard review period (12 months), DEA scheduling (3 months).

Mitigation:Base case assumption is standard review; ongoing thoughtful interactions with FDA.

Difficulty in directly comparing AZK seizure freedom data to competitors like cenobamate due to differences in patient populations and reporting methodologies.

X-TOLE2 population was more refractory (median 13 seizures/month, 5 prior ASMs) than cenobamate's trials; cenobamate's 400mg dose rarely achieved in practice.

Mitigation:Focus on long-term OLE data and ease-of-use attributes for AZK; providing detailed breakdowns of responder rates.

The Dravet syndrome space is crowded with existing and developing therapies.

Multiple people are working on this devastating disorder.

Mitigation:Differentiating Nav1.1 program by targeting underlying pathophysiology with an oral small molecule, aiming for disease modification beyond seizure control.

Long-term development strategy for acute vs. chronic pain for XEN1701 and XEN1120 is still being worked out. Coming months and years.

Still need to figure out chronic versus acute and a whole sorts of different things.

Mitigation:Initial focus on acute pain proof-of-concept studies; mechanisms are not limited to acute pain, potential for broad development if promising.

What to watch in Q2 FY26

Completion of XEN1701 and XEN1120 Phase I studies

later this year

Current Ongoing

Target Completion of first-in-human studies

Why it matters

These completions will enable advancement to Phase II proof-of-concept studies in pain, leveraging novel non-opioid approaches.

We're looking forward to completing our first-in-human studies for our novel pain programs this year.

Find out whether XENE delivers this. Inve re-checks your case every morning.

Q&A highlights

Asked about derisking safety issues for Nav1.7 in Phase I and specifics on Phase II acute pain studies (size, scope, arms).

Ian Mortimer stated they are at high enough exposures for receptor occupancy in Phase I Nav1.7, feeling confident in safe dosing and therapeutic index. Phase I studies for both XEN1701 and XEN1120 will complete this year. Phase II acute pain studies (bunionectomy/abdominoplasty) are planned, with design details (number of arms, doses) still being finalized after Phase I data. Chris Kenney confirmed they have what's needed to proceed to Phase II.

“I think sitting today, we feel really good that we can safely dose, have the appropriate therapeutic index and give this mechanism a real shot to show proof-of-concept data in Phase II.”

asked by Paul Matteis · answered by Ian Mortimer

2 min read 4 chapters

Detailed narrative

AZK in Focal Onset Seizures

The Phase III X-TOLE2 study for azetukalner (AZK) in focal onset seizures (FOS) exceeded expectations, demonstrating a 53.2% median percent change reduction for the 25mg dose and 34.5% for the 15mg dose, compared to 10.4% for placebo. The study population was highly treatment-resistant, with patients experiencing a median of 13 seizures per month and having tried a median of 5 prior ASMs.

Data presented at AAN highlighted rapid onset of efficacy, dose-dependent responder rates, and a consistent safety profile, with no titration and once-daily dosing being key differentiating attributes.

AZK in Neuropsychiatric Indications

Xenon is broadening AZK's potential beyond epilepsy, with three ongoing Phase III studies in neuropsychiatry: X-NOVA2 and X-NOVA3 in major depressive disorder (MDD), and X-CEED in bipolar depression (BPD). Top-line results from X-NOVA2 are expected in the first half of 2027.

The rationale for Kv7 openers in depression is supported by preclinical, clinical, and genetic evidence, with physicians keenly interested in AZK's novel mechanism, rapid onset, and potential benefits on anhedonia.

Early-Stage Pipeline Advancement

The company is progressing its early-stage ion channel programs, including first-in-human studies for XEN1701 (targeting Nav1.7) and XEN1120 (targeting Kv7) for pain, with completion expected later this year. These programs aim to address large unmet medical needs for non-opioid pain therapies.

Additionally, IND-enabling studies are ongoing for the Nav1.1 program in Dravet syndrome, with preclinical data showing potential for disease modification by targeting the underlying genetics.

Commercial Readiness and Financial Strength

Xenon is actively building its commercial infrastructure and go-to-market strategy for AZK's anticipated U.S. launch in late 2027 or early 2028. This includes increasing scientific engagement with HCPs, expanding field-based capabilities, and initiating discussions with payers. A successful public offering of $747.5 million has fortified the balance sheet, providing $1.3 billion in cash, cash equivalents, and marketable securities, extending the cash runway into 2029 and supporting the transition to a commercial-stage company.

Summary of the company's earnings call; see how call summaries are prepared. Not investment advice.