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- A Potential Regulator of Inflammation & Pain

 

  • Chemerin, endogenous agonist of chemerin receptor ChemR23, a specific member of the G protein coupled receptor (GPCR) class, activates immune cells at the inflammation site
  • Active chemerin engages ChemR23, on circulating monocytes and macrophages recruiting these cells to the inflammation site.
  • Chemerin is further 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.
  • Urcosimod, our lead drug candidate incorporates a stable chemerin-derived 10-mer peptide as the active anti-inflammatory component of the lipidated-peptide drug structure.
  • Our lead drug candidate urcosimod consists of a 10-mer C-terminal Chemerin sequence, a linker (PEG-8), and Palmitic acid.
  • Pharmacological assessment of our drug candidate revealed high potency for ChemR23, and increased half-life.

Preclinical Data

Urcosimod Reduced Neuropathic Corneal Pain (NCP) in Mouse Model

 

Enhanced Potency<br />

 

• NCP is a severe, chronic and debilitating disease with no commercially approved topical treatments currently available for this condition.

• Urcosimod suppresses neuropathic corneal pain in a mouse model of NCP.

• Urcosimod was topically administered to mice in comparison to the positive control gabapentin which was administered via intraperitoneal injection.

• Pain relief was evaluated by an eye-wipe count, and urcosimod was shown to reduce corneal pain similar to that of gabapentin, a commonly used oral drug for neuropathic pain at day 14.

• Urcosimod had no effect on corneal epithelial integrity compared to gabapentin or BSS.

Urcosimod with Improved Potency, and Durability

*In-vitro studies

Enhanced Potency<br />
Increased Durability

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

 

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

 

Validation of Urcosimod in Pre-clinical Dry Eye Mouse Model

• Animals induced with scopolamine to generate acute DED showed a dramatic, statistically significant increase in corneal permeability relative to naïve non-stressed animals.

• The treatment with cyclosporine to scopolamine-induced DED animals showed a statistically significant reduction of permeability.

• Urcosimod demonstrated a dramatic reduction of DED-induced corneal permeability (p ≤ 0.001).

• Urcosimod’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.

Urcosimod increased mucin secreting goblet cells and reduced inflammatory CD4+ T cells

• DED typically leads to a loss of goblet cell density as was observed following induction of DED in the mice administered Vehicle

• Topical administration of urcosimod significantly rescued the DED-induced loss of Goblet Cells.

• Urcosimod 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 urcosimod treated animals were equivalent to the CD4+ T cell level observed in naïve untreated animals.