Oryn is developing therapeutics based on Orynotides — macrocyclic peptide biomolecules inspired by theta defensins, circular peptides that occur naturally in Old World monkeys. In addition to their demonstrated efficacy in preclinical models of several human diseases, Orynotides are highly stable, have excellent bioavailability, low toxicity and low immunogenicity, and are readily producible at commercial scale.
Oryn sought to develop a therapeutic targeting rheumatoid arthritis (RA) due to an unmet need in this and other autoimmune diseases. Despite the success of anti-TNF biologics, many patients do not adequately respond to these agents, and they can also lose efficacy in many patients who initially respond.
Additionally, treatment with RA biologics is associated with often serious side effects, and consequently many products carry black box warnings about risks of severe adverse side effects.
The immunomodulating properties of Orynotides are predicted to make them effective in treatment of cancer. In recent studies the company identified Orynotides that are effective in preclinical models of melanoma and colon adenocarcinoma, and a lead compound has been identified for further development.
ORYN 1053 is in IND-enabling development for the treatment of cancer in combination with a PD-1 or PD-L1 inhibitor. Results of nonclinical efficacy studies of combination therapy of ORYN 1053 with immune checkpoint inhibitors in nonclinical cancer disease models suggest an important potential role for ORYN 1053 in enhancing and extending the efficacy and indication range of checkpoint inhibitor drugs. In combination with a PD-1 inhibitor, ORYN 1053 significantly enhances anti-PD-1 mediated tumor suppression in mouse models of melanoma, colon cancer (MC38), and pancreatic cancer (PAN02). Significantly enhanced survival is induced with both standard and reduced doses of the PD-1 inhibitor when combined with ORYN 1053. In mice, in which complete regressions are induced, tumor immunity is seen in long-term survivors. Additional studies are underway to replicate and extend these results by evaluating additional tumor cell lines.
Although safety studies are still underway (MTD and repeat dose at various levels), a wide safety margin has already been established, with the toxic dose substantially higher than the doses necessary for efficacy.
The multicomponent mode of action by which ORYN 1053 enhances the anticancer effectiveness of a PD-1 inhibitor includes the following:
The growing threat of antibiotic resistant bacterial and fungal pathogens requires new paradigms to address the worldwide risk of “superbugs.” These infectious agents have adapted to acquire resistance, in some cases, to all known antibiotics, opening up the real possibility of devastating epidemics.
Multi-drug resistant (MDR) pathogens represent an immediate danger to individuals and populations. A number of studies indicate that antimicrobial resistance will cause more deaths worldwide than cancer by 2050.
MDR fungal infections
Infections cause by fungal pathogens are becoming increasingly resistant to currently available antifungal drugs, of which only three classes exist. Oryn has identified several Orynotides that are effective in treating drug sensitive and drug resistant fungal infections in mouse models. Funded in part by an NIH SBIR Fast-Track award, Oryn is developing a novel approach for treatment of systemic fungal infections for which no effective agent is currently available.
MDR bacterial infections
The company has identified and produced Orynotides that are highly effective in preclinical models of MDR bacterial infections mediated by pathogens that are resistant to nearly all known antibiotics. A lead Orynotide is being developed for treatment of systemic infections caused by MDR gram-negative bacteria.
