A Phase 1, Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetic (PK) Profile of Single and Repeat Oral Doses of CAD-1883 in Healthy Subjects

Cadent Therapeutics, Inc. is developing CAD-1883 for the treatment of
spinocerebellar ataxia (SCA) and essential tremor (ET).

CAD-1883 is a novel small molecule positive allosteric modulator of SK channels
that has been shown to regulate Purkinje cell firing in cerebellar brain
slices. It furthermore reduced measures of ataxic gait in mouse models of
autosomal-dominant hereditary ataxia and reduced tremor in the rat harmaline
tremor model.

The proposed study is intended to assess the safety, tolerability and
pharmacokinetic (PK) profile of single and repeated oral doses of CAD-1883 in
healthy subjects. In particular, this clinical trial will evaluate the safety
and tolerability of escalating single oral doses of CAD-1883 in healthy male
subjects, evaluate PK of a single oral dose of CAD-1883 and the effect of food
on the PK of CAD-1883 in healthy female subjects, and evaluate the safety and
tolerability of escalating multiple oral doses of CAD-1883 in healthy male
subjects. The safety, tolerability, and pharmacokinetics of CAD-1883 observed
in this study are intended to inform the design of subsequent Phase 1 studies
in SCA and ET patients.

Primary objectives
Part 1:
* To evaluate the safety and tolerability of escalating single oral doses of
CAD-1883 in healthy male subjects.
Part 2:
* To determine the effect of food on the PK profile of a single oral dose of
CAD-1883 in healthy female subjects.
Part 3:
* To evaluate the safety and tolerability of escalating multiple oral doses of
CAD-1883 in healthy male subjects.

Part 1:
* Cohort 1:1 to 1:4 and cohort 1:6: To determine the PK profile of single oral
doses of CAD-1883 in healthy male subjects.
* Cohort 1:5 only: To determine the PK profile of a twice daily oral dose
of CAD-1883 in healthy male subjects.
* Cohort 1:6 only: To correlate CAD-1883 exposure in CSF with plasma exposure
in healthy male subjects.

Part 2:
* To determine the effect of food on the safety and tolerability of CAD-1883 in
healthy female subjects.

Part 3:
* To determine the PK profile of multiple oral doses of CAD-1883 in healthy
male subjects.

This study is a randomized, placebo-controlled phase 1 study in three parts:
single ascending doses or two doses administered 12 hours apart in males (Part
1), food effect in females (Part 2), and multiple ascending doses in males
(Part 3). Parts 1 and 3 are double-blind, Part 2 is both double-blind (Period
3) and open-label (Period 1 and Period 2).

CAD-1883
Matching placebo

This study is being conducted in healthy volunteers. There are no anticipated
benefits of the IMP. Please see the IMP information (IB) for further
information.