1. What if Nature had already designed drugs… that could induce remission of rheumatoid arthritis? …..or could treat sepsis and infections caused by multi-drug resistant bacteria?

2. Orynotides™ Discovery, Design and Clinical Development of Retroevolutionary Peptide Therapeutics

3. Why are Old World monkeys so highly resistant to sepsis and other inflammatory diseases? Discovery of pleotropic cyclic peptides (theta defensins) in Old World primates, not in apes or humans Exploiting a retroevolutionary strategy, Orynotides™, derived from theta defensins from Old World monkeys are: New class of agents for treatment of infection and autoimmune/inflammatory diseases Highly active microbicides against multi-drug resistant bacteria and fungi Efficacious in rodent models of severe sepsis Rapidly arrest and induce remission in rodent models of rheumatoid arthritis Readily manufacturable, stable, safe, non- immunogenic, non-immunocompromising 18 aa cyclic peptide

4. Orynotides™: Engineered Theta-Defensins Microbicidal against MDR Bacteria and “Superbugs” Mice infected with carbapenem-resistant Klebsiella pneumoniae and treated with saline or OTP-602 Orynotides™ do not select for bacterial or fungal resistance

5. 48 h post surgical sepsis, Saline treatment only, 4 h post surgery 48 h post surgical sepsis, Single i.v. Orynotide™ treatment 4 h post surgery Single Orynotide™ treatments are effective 4 or 24 h after sepsis induction MOA is modulation of the sepsis-induced cytokine storm plus induction of bacterial clearance Orynotides™ are highly effective in rodent models of sepsis

6. The MOA of Orynotides™ Predicts Efficacy in Rheumatoid Arthritis and Related Autoimmune/Inflammatory Diseases Pristane (mineral oil) induced arthritis in rats: a robust surrogate for human RA Contact us for a link to watch this video.

7. Comparison of Orynotide™ ORTD-1 to first line RA drugs ORTD-1 (n = 16) Only ORTD-1 induces remission of disease

8. Oryn awarded first and only SBIR Direct Phase 2 Award by NIAMS (NIH) ORTD-1 highly effective in two preclinical models of RA Non-toxic: at least 50-fold safety ratio by all routes of administration Long circulating half-life: effective with q 5 day s.c. dosing in rat RA Exceedingly stable – no degradation in rat plasma for six weeks Non-immunocompromising Readily produced at scale by chemical synthesis (0.5 kg GLP ORTD-1 in hand) Non-immunogenic- no neutralizing antibodies in animals challenged daily for six weeks Oryn’s products and technologies are protected by seven issued US Patents and corresponding foreign filings ORTD-1: First-in- class Therapeutic for RA

9. $5.3 M NIH award to develop Orynotides ™ as novel agents to treat superbug infections Orynotides ™ effective in animal models of bacterial and polymicrobial sepsis Engineered Orynotides ™ are therapeutic in rodent models of carbapenem resistant bacterial infections Orynotides ™ are fungicidal against MDR fungal pathogens Highly stable and non-toxic No selection for Orynotide ™ resistance following up to 20 passages in MIC 90 peptide concentrations Orally bioavailable Engineered Orynotides™ for MDR Infections

10. Orynotides™ Revolutionary drugs designed by employing retroevolutionary concepts of immunobiology