Orynotides are based on nature’s endogenous anti-inflammatory molecules which regulate host responses to infection, inflammation, and harmful autoimmune reactions. Orynotides are pleotropic biomolecules that regulate critical pathways involved in exaggerated and harmful immune responses, while also targeting microbial pathogens. Among the first therapeutic applications of Orynotides is as a first-in-class drug for treatment of RA. Based on our understanding of Orynotide mode of action, it is likely that these peptides will be effective in the treatment of other inflammatory diseases such as inflammatory bowel disease, psoriatic arthritis, juvenile idiopathic arthritis, cystic fibrosis, and more.
A new era: First-in-class drug for treatment of rheumatoid arthritis
None of the currently approved RA drugs induce remission of disease. In fact, about a third of all RA patients receive little or no benefit from any combination of approved drugs. Moreover, many of the current RA drugs have “black box” warnings due to often serious side effects including increased risk for tuberculosis and certain cancers. To date, no such immune-compromising side effects have been detected with long term administration of Orynotides.
ORYNOTIDE ARRESTS AND REVERSES EXPERIMENTAL RA
Left panels: rat with pristine-induced arthritis (PIA). Upper left panel shows profound swelling of ankles and paws. Lower left panel shows joint changes in tissue sections from ankle joint. Invasive synovial pannus (solid arrow), a prominent feature of RA, erodes the joint surface and invades bone (hollow arrow) like a local tumor. Right panels: ankles, paws, and tissue sections from a PIA rat that was treated with Orynotide. Swelling and redness completely resolved in less than two weeks and tissue sections of previously arthritic joints show normal architecture indicative of disease remission and healing.
ORYNOTIDE TREATMENT OF RAT ARTHRITIS IS RAPID AND INDUCES REMISSION
Immune arthritis was induced in rats by intradermal injective with pristane (mineral oil). After disease was established (typically within 2 weeks), animals were randomized to receive saline (control) or Orynotide subcutaneous injections. Significant reductions in arthritis severity were observed within 3 days of the first Orynotide treatment and remission was apparent by day 11.
The promise of Orynotides for multiple autoimmune and inflammatory diseases
Numerous animal studies demonstrate the speed, efficacy, stability, and safety of Orynotides in animal models or RA. Oryn plans to file an IND and proceed to a Phase I clinical trial for the RA application in 2016. Ongoing studies are evaluating engineered Orynotides as therapeutics for inflammatory bowel disease, septic arthritis, and cystic fibrosis.