Our Take On Detailed Phase II Data For Diranersen

Research evidence excerpt

Our Take On Detailed Phase II Data For Diranersen

C O M PA N Y N O T E

J u l y 1 4 , 2 0 2 6

• A word on secondary endpoints. Diranersen showed statistical separation on ADAS-

COG 13 (Alzheimer's Disease Assessment Scale–Cognitive Subscale) and MMSE (Mini-

Mental State Examination), both of which are measures of cognition, for all doses. More

specifically, treatment with the low dose yielded a slowing of cognitive decline per ADAS-

COG 13 of 42% versus placebo (p=0.01), and a slowing of cognitive decline per MMSE of

50% versus placebo (p=0.01). Beyond that, diranersen was directionally favored for ADCOMS

(Alzheimer's Disease Composite Score) and Modified iADRS (Integrated Alzheimer's Disease

Rating Scale), which are composite measures of cognition, function, and disease progression.

Treatment with the low dose yielded the greatest slowing of clinical decline, with a

reduction of 23% and 30% for ADCOMS and iADRS, respectively. Notably, there was

no separation (statistically nor directionally) from placebo for ADCS-ADL-MCI (Alzheimer’s

Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment),

a measure of daily functioning. On the whole, these secondary outcome measures appear

to support an improvement in cognitive domains (e.g., memory, judgment) associated with

diranersen treatment, and we surmise that the totality of this data is what drove management's

decision to move diranersen into Phase III.

• A word on ThecaFlex DRx and the potential for its usage in diranersen delivery. Recall

that Biogen acquired Alycone in November 2025, gaining the ThecaFlex DRx drug delivery

system. ThecaFlex DRx is an implantable device designed to provide an alternative to

repeat lumbar punctures associated with IT administration of therapeutics.