A Randomised, Double-blind, Placebo-controlled Phase 2a Pilot Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ONP-002 in Adults With Mild Traumatic Brain Injury

Up to 40 participants will be randomized 1:1 to receive either ONP-002 or placebo, using a block randomization algorithm.

• Control Arm: Placebo
• Interventional Arm: 8 mg BID ONP-002 (a demethylated analogue of the enantiomer of progesterone) Intranasal Participants will receive BID doses of 8 mg ONP-002 or placebo for 5 consecutive days with a total of up to 9 doses, through IN administration.

If participants receive their first dose on the morning of Day1, they will receive a total of 9 doses. If participants receive their first dose on the evening of Day 1, they will receive a total of 8 doses. The last dose of study drug for all participants will be administered in the morning on Day 5.

Objectives Endpoints To determine the feasibility of administering ONP-002 in acute mTBI patients within 12 hours of injury. • Time to enrolment post injury and first treatment with ONP-002 To investigate the safety and tolerability of multiple IN doses of ONP-002 in patients with mTBI. • Incidence and severity of AEs

• Changes in vital sign measurements
• Changes in clinical laboratory results
• Changes in ECG parameters
• Change from baseline in macroscopic nasal examination findings To measure levels of ONP-002 in plasma following multiple IN doses in patients with mTBI. • Plasma concentrations of ONP-002
• Accumulation ratio (RAUC, and RCmax) To establish POC that IN ONP-002 administration within 12 hours of injury results in blood biomarker/functional changes consistent with the proposed mechanism of action. • Changes in blood biomarker and functional scores (clinical improvement over time) from baseline in ONP-002 treated participants compared to placebo.