氙气（XENE）：癫痫医生对2026年初III期癫痫试验成功有85%的信心

2024A2025E0.00.07.5--(4.06)(3.01)(4.17) 2026E0.0(4.37)(5.43) Andrew Tsai * | Equity Analyst(415) 229-1566 | atsai@jefferies.comMatthew Barcus, Ph.D. * | Equity Associate(415) 229-8703 | mbarcus@jefferies.comJohn Cox, Ph.D. * | Equity Associate+1 (415) 229-8708 | jcox1@jefferies.comBrian Balchin, ACA * | Equity Analyst(415) 229-1522 | bbalchin@jefferies.com Exhibit 1 - Focal Onset Epilepsy Studies: XEN-1101 vs Comps.CompanyPRAXPRAXDrugPRAX-628PRAX-628TrialRADIANTSingle-armPh2POWER1registrationalPh2/3Start DateJan-25Oct-24Enrollment Finish--Primarycompletion onclinicaltrials.govJul-25-Topline (reportedby Co)mid-252H25Enrollment Length(months)--Sites11-Patients50250Patientsenrolled/month--Source: Jefferies ResearchPlease see important disclosure information on pages 8 - 15 of this report.This report is intended for Jefferies clients only. Unauthorized distribution is prohibited. The Long View: XenonInvestment Thesis / Where We DifferOur positive view on XENE centers around (1) XEN1101 for focal epilepsy (60%of all epilepsies), PGTCS epilepsy (20-30%), and depression, which sharesthe same mechanism as GSK's ezogabine (Potiga), the only Kv7 potassiummodulator approved for epilepsy.•As a next-gen Kv7, XEN1101 is a cleaner version of ezogabine that hasbetter properties and enhanced safety, likely enabling '1101 fetch at least$750M-$1B+ in peak sales in focal epilepsy.•We see upside potential for '1101 in depression (Phase II data in 2023) andPGTCS (currently in Phase III).•XENE could introduce pediatric formulations of XEN1101, as well as newKv7s, NaVs, and other ion channels for CNS/neuro disorders.Base Case,$65, +115%•Our base case of $65 is based on a sum-of-the-parts(SOTP)analysis of XENE's keyprograms, including (1) XEN1101 for refractoryfocal onset seizures, PGTCS seizures, and MDDdepression;(2)NBI-921352 for SCN8A-DEE(NBIX partnership).•For each indication,we build revenue andcash flow streams to 2030+ before probability-adjusting our DCF.Sustainability MattersTop Material Issue(s): 1)Product Quality and Safety:Lead drug XEN1101 has a differentiatedtherapeutic profile than other epilepsy drugs, including rapid onset action, no titration, and differingAE profile. XENE should continue to demonstrate XEN1101 is safer and more convenient than itscompetitors, as this is a major point of differentiation.2)Employee Engagement, Diversity and Inclusion:Smaller biotech companies must ensure that they have sufficient talent to develop drugs (whereas largepharma/biotech may provide more stability). This is especially critical as companies look to supplementtheir commercial portfolio with newer drugs and or BD opportunities.Company Target(s):NoneQs to Mgmt: 1)What gives you confidence in the safety profile of your epilepsy drugs vs competitors,including Potiga (predecessor drug) which had pigmentation risks? 2) What steps have you taken toprepare for 5+ Phase II/III studies in epilepsy and depression (e.g. employee and/or Board hires)?ESG Sector Deep Dives: US Biotech, Pharma, and Specialty PharmaPlease see important disclosure information on pages 8 - 15 of this report.This report is intended for Jefferies clients only. Unauthorized distribution is prohibited. Upside Scenario,$85, +181%•Our upside scenario of $85 assumes a higherprobability of success (vs the base case) for thekey programs.•We consider valuations (albeit small) for earlier-stage programs, including Nav1.1 for epilepsy,Nav1.7 for pain. Downside Scenario,$15, -50%•Our downside scenario of $15 assumes a lowprobability of success for each key program andexcludes value for earlier-stage programs, but itdoes consider next-12-months cash.•Assumes potential for safety issues to arise andfailure to meet the primary endpoints for keystudies.Catalysts•June 2025: First investor webinar•Mid-2025:Enrollment completion for 1st PhaseIII dataset of XEN1101 in focal epilepsy (X-TOLE2)•Mid-2025: Initiate XEN1101 in 2nd Phase III trialfor MDD (X-NOVA3)•Mid-2025: Initiate the 1st of 2 Phase III trials forbipolar depression•Early 2026:Pot'l Phase III data of XEN1101 infocal epilepsy (X-TOLE2)•2026:Potential Phase III data in focal(X-TOLE3)and PGTCS (X-ACKT)•2026+:Phase III data for XEN1101 indepression 3 Background on XEN1101 Phase IIb X-TOLE study andOngoing Phase III X-TOLE2/3 StudiesXEN1101 X-TOLE Phase IIb data: As a reminder, Phase IIb X-TOLE data for oral XEN1101 readout inOctober 2021 in broad epilepsy exceeded investor expectations, showing superior efficacy and cleansafety vs existing drugs (even Xcopri), notably in highly refractory patients.On efficacy (N=323),(1)High-dose of 25mg achieved a stat-sig 35% pbo-adj reduction in seizures (53% vs 18% pbo;p<0.001), which exceeded Street expectations of +15% and even beat Xcopri's 31% delta (highefficacy pill).(2)Responder rates (>50% seizure reductions; important for EU) of 55% vs 15% pbo(p<0.001) look highly competitive, falling at the high-end of the typical 35-55% range.(3)Pbo-adjseizure-freedomresults(share