ALKS: Top Pick – OX2R Class Could Be Big, and ALKS Has 3 of Them

Research evidence excerpt

ALKS: Top Pick – OX2R Class Could Be Big, and ALKS Has 3 of Them

Biotechnology Equity Research

ADHD Data in 4Q26 Could Broaden Enthusiasm for Ox2R Beyond Sleep

Disorders

ALKS has a pipeline of OX2R agonists behind alixorexton. Notwithstanding differences in

pharmacology with each molecule, we think this also gives ALKS an opportunity to seek differential

pricing in both rare and large indications.

Exhibit 19 - ALKS Pipeline of OX2R Agonists

Source: Company Material

Alkermes is advancing ALKS 7290, a novel OX2R agonist as a potential treatment for ADHD. ALKS

recently initiated a multi-dose Phase 1b translational study in adult ADHD patients to evaluate safety,

tolerability, and efficacy biomarkers (first patient dosed in April). Initial clinical proof-of-concept data

from this Phase 1b study are anticipated in 4Q26. In parallel, Alkermes plans to initiate a larger Phase 2

study in adult ADHD patients during the second half of 2026.

We think the PoS in ADHD and fatigue largely hinges on two questions:

1. Can orexin receptor agonists work in NT2 or IH? We are constructive as Vibrance-2 provided

some initial proof of concept despite the magnitude of efficacy falling short of expectations. We

think the Vibrance-3 Ph2 IH readout, and split dosing in particular, could add further support.

2. Can orexin receptor agonism lead to additional benefits beyond wakefulness in patients who

don't have severe orexin deficiency at baseline? We are unsure, due to the lack of data at this

point.

Point #2 is hard to answer as of yet, but ALKS did generate some preclinical data that seems

supportive.

• Alkermes conducted preclinical microdialysis studies assessing treatment-induced changes

in prefrontal cortical acetylcholine. Acetylcholine was selected given its well-established role