Biogen (BIIB) investor relations material

Alzheimer's disease pipeline and tau-targeting strategies

• Tau is considered a key pathological driver in Alzheimer's, with its progression closely linked to cognitive decline, and the current focus is on testing whether reducing tau levels can modify disease outcomes.

• The BIIB080 antisense oligonucleotide (ASO) approach aims to knock down all tau isoforms, with early studies showing CSF and PET evidence of target engagement and ongoing CELIA trial assessing 18-month clinical impact.

• Safety is managed by targeting partial tau reduction (up to 60%), supported by genomic data suggesting this level is tolerable, with ongoing dose and safety monitoring in trials.

• The CELIA study is a proof-of-concept, not registrational, designed to inform future development by evaluating safety, dosing, and clinical endpoints, with further studies anticipated.

• Peripheral and central biomarkers (CSF, PET, plasma) are being used to understand tau dynamics, with reliance on imaging and CSF for pharmacodynamic assessment.

Pre-symptomatic Alzheimer's intervention and trial design

• The AHEAD 3-45 study, in collaboration with Eisai, targets pre-symptomatic patients with varying amyloid burdens to assess if early intervention with lecanemab can prevent cognitive decline.

• The study uses the PACC5 endpoint over four years and includes both higher and lower amyloid groups, aiming to detect treatment effects in early disease stages.

• Early data suggest greater treatment effects in low/no tau subgroups, with up to 70% showing no cognitive decline and 50% improving at four years in open-label extensions.

• Diagnostic advances, especially blood-based biomarkers, are expected to facilitate broader screening and enable primary care involvement in early Alzheimer's treatment.

• The AHEAD 3-45 readout is expected in 2028, with the study designed to provide robust, multi-year data for regulatory and clinical decision-making.

Neuromuscular pipeline: Salanersen and Spinraza

• Salanersen, a novel ASO for SMA, is designed for once-yearly dosing and has shown promising safety, biomarker, and clinical milestone data in a Phase 1b study of post-gene therapy patients.

• Both 40 mg and 80 mg doses were well-tolerated, with rapid and sustained neurofilament reduction and some patients achieving new developmental milestones.

• Three Phase 3 studies are underway: STELLAR-1 (treatment-naive infants), STELLAR-2 (post-gene therapy), and SOLAR (teens/adults, including risdiplam switchers), aiming to define salanersen's role across SMA populations.

• High-dose Spinraza remains a key part of the portfolio, with ongoing efforts to optimize dosing and address unmet needs, especially as patients may transition to salanersen if approved.