OKYO Pharma Limited has filed an application to the FDA requesting Fast Track designation (FTD) of urcosimod, its neuropathic corneal pain therapeutic (NCP).
Start with this company.
The United Kingdom-based, pre-clinical biopharmaceutical company is developing novel, targeted therapies for ocular diseases such as:
- Allergic conjunctivitis
- Dry eye disease (DED)
- NCP (our topic of choice)
- Noninfectious anterior uveitis
How it’s doing this: Via its membrane-anchored-peptide (MAP) platform—but more on that in a moment.
Talk about this NCP candidate.
The company’s lead asset, urcosimod (previously known as OK-101), is a lipid-conjugated chemerin peptide antagonist of the ChemR23 G-protein-coupled receptor (GPCR).
A couple of notes about the ChemR23 G-protein to keep in mind:
- Located on immune cells of the eye as well as on neurons and glial cells in the dorsal root ganglion
- Plays a key role in controlling inflammation and immune responses
- Encoded in humans by the chemerin chemokine-like receptor 1 (CMKLR1) gene
And an important fact to be aware of: Urcosimod was originally developed for DED.
Noted. Now explain urcosimod’s mechanism of action.
This is where OKYO’s MAP technology is instrumental.
- Using this MAP tech, the candidate was developed to produce a novel long-acting drug candidate for (as we mentioned) DED treatment.
As for its mechanism of action (MOA): Urcosimod is intended to prevent washout via a lipid “anchor” built directly into the drug molecule to—ideally and potentially—increase the amount of time it can reside within the ocular environment.
- Its mode of delivery: Topical application.
Let’s talk about its regulatory journey.
Looking specifically at this proposed NCP indication: The FDA accepted OKYO’s investigational new drug (IND) application for urcosimod (then OK-101) in February 2024.
- To note: This acceptance made OKYO the first company to have an IND app granted for NCP.
And for DED: OKYO’s investigational new drug (IND) application was accepted by the FDA in December 2022.
Now to this Fast Track designation.
To start: A company can request the FDA to grant FTD to expedite the development and review of an investigational drug intended to treat serious medical conditions and fill an unmet need (a lack of FDA-approved drugs on the market).
- In this case: NCP is considered an orphan disease—with no FDA-approved treatments currently available in the United States.
And what would this designation mean for OKYO?
As FTD is typically requested during the IND phase of drug development, OKYO noted the following advantages it would receive:
- More frequent meetings with the FDA to go over the clinical development plan for urcosimod and collect appropriate data to support its market approval
- Rolling FDA review process to expedite the regulatory pathway for urcosimod
- Quicker FDA feedback on proposed clinical trial designs and potential biomarker use
Alrighty, now let’s talk about clinical performance thus far.
We’ll focus on non-human data first.
In mouse models (DED-induced versus naïve non-stressed animals), the candidate demonstrated an ability to produce anti-inflammatory (in NCP) and pain-reducing activities (in DED).
- Specifically: Urcosimod demonstrated a “dramatic reduction of DED-induced corneal permeability (p≤ 0.001)”—and was nearly identical to the effect seen from the “cyclosporine positive control and close to the baseline corneal permeability observed in non-stressed control animals.”
- See here for more findings.
Now to human-based clinical data.
For NCP, urcosimod is currently undergoing clinical evaluation in a real-world phase 2 trial initiated in October 2024 and conducted via a clinical trial agreement with Boston-based Tufts Medical Center.
What we know about the study:
- Design: single-center, double-masked, randomized, 12-week, placebo-controlled
- Participants: 48 patients diagnosed with NCP (confirmed via confocal microscopy)
- Setup: Patients randomized into three cohorts to receive one of the following:
- Cohort 1: 0.05% urcosimod
- Cohort 2: 0.1% urcosimod
- Cohort 3: placebo
- Clinical visits: Five over a 16-week period
- Primary endpoint: Measurement of pain relief via the Visual Analog Scale (VAS)
- Duration: 9 to 12 months
So when is data expected?
The company anticipates reporting topline data by Q3 2025.
Gotcha. In the meantime, any other data on urcosimod’s performance so far?
Yes, but not for NCP. Last year, OKYO released positive results (on three separate occasions) from a first-in-human (FIH) phase 2 trial on urcosimod (dosed twice daily; BID) for DED.
The basics: 240 DED patients evaluated with a 14-week treatment period, 2-week run-in period on a placebo, and 12 weeks in a randomized portion.
Among the findings:
- Then-OK-101 demonstrated favorable safety and tolerability, with the endpoints supporting its proposed MOA demonstrated in preclinical animal models.
- OK-101 demonstrated superiority versus placebo in the sign endpoint of total conjunctival staining (measured via the Ora Calibra Staining Scale) as early as Day 29
- Statistically significant improvements observed in dry eye symptoms (stinging/burning and ocular pain)
- Reported “exceptional drop comfort,” comparable to that of artificial tear, with very good ocular tolerability and a favorable adverse event (AE) profile and no drug-related serious AEs
- A statistically significant improvement in ocular pain (also key for NCP)
And the significance of that data?
The promising results enabled “definitive phase 3 development” of the candidate—a promising sign for its proposed DED indication.