Technology

OKYO’s Membrane Anchored Peptide (MAP) technology enabled the development of OK-101’s enhanced potential drug ‘residence’ time and potency at the ocular surface as well combating washout through inclusion of the lipid ‘anchor’ in the drug molecule.

Membrane Anchored Peptide (MAP) Platform

Chemerin Receptor

Chemerin, the endogenous agonist of chemerin receptor ChemR23, a specific member of the G protein coupled receptor (GPCR) class, activates immune cells at the inflammation site.
Chemerin activates ChemR23 on circulating monocytes and macrophages, recruiting these cells to the inflammation site.
Chemerin is also physiologically cleaved into smaller potent anti-inflammatory peptides that reprogram macrophages to repress inflammation inducing anti-inflammatory cytokines at the inflammatory site, thus restoring normal tissue structure and function.
OK-101, OKYO’s lead drug candidate contains a stable chemerin-derived 10-mer peptide as the active anti-inflammatory component of the drug, along with a conjugated lipid component, producing both enhanced agonist potency along with wash resistance.

OK-101 Drug Candidate

One of the major challenges with topical administration of any drug designed for treating OED is drug wash-out through natural processes of tearing and blinking, minimizing drug ‘residence’ time at the ocular site needed to provide a pharmacologic benefit.
Membrane Anchored Peptide (MAP) technology enabled the development of a long acting and stable OK-101 drug candidate.
OKYO’s lead drug candidate OK-101 consists of a 10-mer C-terminal chemerin peptide sequence, a linker component, and an anchoring lipid domain.
Unique MAP technology enabled the development of a drug with enhanced potency and the expectation of increased drug residence time on the ocular surface.

Preclinical Data

Membrane Anchoring Improves Potency, and Durability

*In-vitro studies

Enhanced Potency

Human Chemerin Receptor

Increased Durability

Human Chemerin Receptor
(Wash Resistant)

* Adapted from Doyle J et al, J. Biol. Chem. 2014

Lipidated drug candidate OK-101 showed higher potency against human chemerin receptor than the corresponding non-lipidated OK-101.
Signaling of lipidated OK-101 persisted despite serial washes, whereas activity of the non-lipidated OK-101 was markedly diminished.

Validation of OK-101 in Pre-clinical Dry Eye Mouse Model

Animals induced with scopolamine to generate acute dry eye disease (DED) showed a dramatic, statistically significant increase in corneal permeability relative to naïve non-stressed animals.
Cyclosporine, the positive control in the DED study, showed a statistically significant reduction in corneal permeability (p ≤ 0.001) in scopolamine-induced DED animals.
OK-101’s effect in reducing DED-induced corneal permeability was virtually identical to that of the cyclosporine positive control and close to the baseline corneal permeability observed in non-stressed control animals.
OK-101 demonstrated a similar reduction of DED-induced corneal permeability (p ≤ 0.001).

OK-101 increased mucin secreting goblet cells and reduced inflammatory CD4+ T cells

Dry eye disease (DED) typically leads to a loss of goblet cell density as was observed following induction of DED in mice administered no drug (control vehicle).
Topical administration of OK-101 significantly rescued the DED-induced loss of goblet cells in DED animals.
OK-101 also demonstrated a statistically significant (p ≤ 0.01) reduction in dry-eye-induced enhancement of inflammatory CD4+ T-cells. The levels of CD4+ T cells observed in OK-101 treated animals were equivalent to the CD4+ T cell level observed in naïve untreated animals.

OK-101 Reduced Neuropathic Corneal Pain (“NCP”) in Mouse Model, increased mucin secreting goblet cells and reduced inflammatory CD4+ T cells

A significant proportion of dry eye patients suffer from “neuropathic pain” with moderate to greater pain intensity.

*Ciliary Nerve Ligation Model

*Collaboration with Dr. Pedram Hamrah, Tufts Medical Center, Boston (Kenyon et al (2020) IOVS, Vol.61, 4085

OK-101 reduced corneal pain response similar to gabapentin (GBP), a commonly used drug for neuropathic pain.

Neuropathic corneal pain is a severe, chronic and debilitating disease with no commercially approved topical treatments currently available for this condition.
OK-101 suppresses neuropathic corneal pain in a mouse model of neuropathic corneal pain.
OK-101 was topically administered to mice in contrast to the positive control gabapentin which was administered via intraperitoneal injection.
Pain relief was evaluated by an eye-wipe count, and OK-101 was shown to reduce corneal pain similar to that of gabapentin, a commonly used oral drug for neuropathic pain.
OK-101 had no effect on corneal epithelial integrity compared to gabapentin or BSS.