Clinical Development Plan

Ocuphire’s pipeline currently includes two small molecular product candidates targeting front and back of the eye indications. Our lead candidate Nyxol® is being developed for dim or night vision disturbances (NVD), reversal of pharmacologically-induced mydriasis, and presbyopia. Our second product candidate, APX3330, is being developed for diabetic retinopathy (DR) and diabetic macular edema (DME).

Lead Product Candidate Nyxol® is Phase 3 Ready in Multiple Indications

Ocuphire believes that results from Nyxol’s Phase 1 and Phase 2 trials, including the results from ORION-1 and MIRA-1 which were Phase 2b trials that were successfully completed in 2019, support its current development plan focused on NVD, reversal of mydriasis, and presbyopia patients. Specifically, patients treated with Nyxol were observed to have significantly decreased pupil diameter and improved low contrast visual acuity.

In the fourth quarter of 2020 through first quarter of 2021, Ocuphire plans to initiate three clinical trials for Nyxol® Eye Drops, including a Phase 3 trial in NVD (LYNX-1), a Phase 3 trial in RM (MIRA-2), and a Phase 2 POC trial in Presbyopia (Nyxol with low dose pilocarpine, VEGA-1). Pending the results of these clinical trials and on regulatory feedback, Ocuphire expects, alone or with a partner, to file an NDA for Nyxol® with the FDA under the 505(b)(2) drug approval pathway, and in parallel make additional international filings.

Secondary Product Candidate APX3330 to Initiate Phase 2 Clinical Development

Ocuphire’s second product candidate, APX3330, is a twice-a-day oral tablet designed to target multiple pathways relevant to retinal and choroidal vascular diseases such as DR and DME. Prior to Ocuphire’s in-licensing of the product candidate, APX3330 had been studied in six Phase 1 and five Phase 2 clinical trials totaling over 440 patients, for inflammatory and oncology indications, and had demonstrated promising evidence of target engagement, tolerability, pharmacokinetics, and durability.

In the first quarter of 2021, Ocuphire plans to initiate ZETA-1, a Phase 2 trial for APX3330 for the treatment of moderately severe non-proliferative DR (NPDR) and mild proliferative DR (PDR), as well as patients with DME without loss of central vision (ZETA-1). Ocuphire anticipates advancing APX3330 towards an NDA in the future.

2019 Completed Trials

ORION-1 was a multi-center, randomized, double-masked, placebo-controlled, multiple-dose Phase 2b study in 39 subjects (average age 60) with elevated intraocular pressure, evaluating for changes in IOP, safety pupil reduction, and vision performance following once daily evening 1% Nyxol drop dosing for 14 days. Study results were presented at ARVO 2020. ORION-1 results provide insights into our Phase 2 presbyopia trial (VEGA-1) and our Phase 3 dim light or night vision disturbance trials (LYNX-1).

MIRA-1 was a multi-center, randomized, double-masked, placebo-controlled, crossover, single-dose Phase 2b trial with 32 healthy subjects to study 1% Nyxol’s safety and efficacy in reducing pharmacologically induced mydriasis (dilation of pupil for eye exams). Study results were presented at ARVO 2020. MIRA-1 results provide the foundation for moving into similar Phase 3 reversal of mydriasis trials (MIRA-2).

APX_CLN-0001 (NCT03375086) was a multi-center, open-label, dose-escalation Phase 1 oncology study of APX3330 in patients with advanced solid tumors in early 2018 that established tolerability, pharmacokinetics, and pharmacodynamic effects. Nineteen patients received APX3330 in escalating doses from 240 mg/d dose to 720 mg/d in increments of 120mg/d. Ocuphire believes that the APX CLN 0001 results provide sufficient evidence of safety and tolerability to move forwards in Phase 2 ocular indications.