Ocuphire Completes Last Clinical Trial Supporting the Planned 2022 NDA Submission of Nyxol for Reversal of Mydriasis

Ocuphire Pharma announced positive results in the MIRA-4 pediatric safety trial investigating its product candidate Nyxol for the reversal of pharmacologically-induced mydriasis (dilation of pupil). The results demonstrated that Nyxol’s efficacy and safety in pediatric subjects 3-11 years of age was consistent with that shown in previous studies conducted by Ocuphire, which enrolled both adolescents (age 12-17 years) and adults (age 18 years and older), showing a rapid reversal of pharmacologically-induced mydriasis (RM) and a favorable safety profile.

Nyxol is a proprietary, preservative-free, stable, investigational eye drop formulation of phentolamine mesylate designed to uniquely modulate the pupil size by blocking the α1 receptors found only on the iris dilator muscle without affecting the ciliary muscle. MIRA-4 is part of the comprehensive MIRA clinical program to develop Nyxol for RM. MIRA-4 enrolled 23 pediatric subjects from two sites in the U.S in 2 months. Ocuphire plans to submit an NDA that includes the results of MIRA-1, MIRA-2, MIRA-3, and MIRA-4 with the FDA in late 2022. The company is currently evaluating partnering and distribution options for an effective and cost-efficient commercial launch of Nyxol targeted for the second half of 2023, if approved.

“We are very pleased with the compelling safety results in young children from the MIRA-4 trial, marking the fourth positive data milestone in our Nyxol program in RM,” Mina Sooch, MBA, Founder and CEO of Ocuphire Pharma, said in a company news release. “These results add to our large body of clinical data demonstrating the safety and efficacy of Nyxol for RM and may potentially support a broader label to include children as young as age 3 to older adults. The rapid and large magnitude of Nyxol response of 64% in the MIRA-4 trial is consistent with that seen in the MIRA-2 (49%) and MIRA-3 (58%) trials. We remain on track for our planned NDA submission to the FDA later this year, and if approved, Ocuphire will be well positioned for a launch in the second half of 2023 for Nyxol as the only commercially-available treatment option indicated for reversing pharmacological eye dilation. We thank the study participants, physicians, study site personnel, and everyone involved in the MIRA trials for their contributions in advancing this program.”

Highlights of MIRA-4 Safety and Efficacy Results

MIRA-4 (NCT05223478) is a pediatric trial evaluating the safety and efficacy of Nyxol in healthy subjects with pharmacologically-induced mydriasis as agreed with the FDA under the Pediatric Research Equity Act. In the trial, 23 pediatric subjects (two age groups: 3 to 5 years and 6 to 11 years) were randomized to receive one drop of Nyxol (0.75% phentolamine ophthalmic solution) or placebo (Nyxol vehicle) 1 hour after receiving one of 3 mydriatic agents. The three mydriatic agents used in this trial were phenylephrine 2.5% (alpha 1 agonist targeting the iris dilator muscle), tropicamide 1% (cholinergic blocker targeting the iris sphincter muscle), and Paremyd (a combination of hydroxyamphetamine hydrobromide 1% and tropicamide 0.25%), all of which are commonly used in optometry and ophthalmology offices to dilate patients’ pupils for annual comprehensive or special eye exams as well as surgical procedures. The primary endpoint is safety with descriptive statistics for secondary efficacy endpoints.

Summary of MIRA-4 Data

Primary Safety Endpoint(s)

• The primary endpoint was met with Nyxol demonstrating a favorable safety and tolerability profile. There were no adverse events in this pediatric trial. Specifically, no complaints of headaches, redness, instillation site discomfort or pain, blurry vision, burning or stinging were reported. There was no change in vital signs.

Key Secondary Efficacy Endpoints

• At 90 minutes post-dose, 64% of Nyxol treated subjects had returned to baseline pupil diameter (PD) compared to 25% on placebo.
• At 3 hours post-dose, 82% of Nyxol treated subjects had returned to baseline PD compared to 33% on placebo.
• At 24 hours post-dose, 91% of Nyxol treated subjects had returned to baseline PD compared to 51% on placebo.
• The mean time to return to baseline PD was reduced by ~3 hours in Nyxol treated subjects compared to placebo.
• Nyxol was effective for all 3 dilating agents used and across light and dark irides.

“It is now well established that there is a notable increase in the prevalence of eye disorders such as myopia and amblyopia that require a comprehensive eye exam in children, and as a result, there is now an increased need for eye exams that require pupil dilation in children," Chris Pearson, OD, Sabal Eye Care, Florida, an investigator in the MIRA-3 and MIRA-4 clinical trials, said in a company news release. "The availability of a safe and effective pharmaceutical drop that can reverse eye dilation has the potential for broad use. Having a pediatric label would mean that children, as well as adults, could benefit.”

For more information about the MIRA-4 trial design, visit www.clinicaltrials.gov(NCT05223478). Ocuphire collaborated closely with Oculos Development Services, a Rush, NY based clinical research organization and subsidiary of Iuvo BioScience, on the execution of the MIRA-4 trial and overall MIRA program.