Commercialization of Macrocyclic Peptide Triazoles
Irwin Chaiken, PhD, Biochemistry & Molecular Biology
Adel Ahmed, PhD, Biochemistry & Molecular Biology
Dong Lee, MD, Medicine: Division of Infectious Diseases & HIV Medicine
Protagonist Therapeutics, Inc., Small Business Partner
A prevention or cure for HIV/AIDS is an unmet global need, and emerging drug resistant and more virulent forms of HIV pose a continuing threat. We discovered a class of small cyclic peptide triazoles (cPTs) that target HIV surface glycoproteins (Env) to block virus from immune cell entry and infection. Functional advantages of cPTs include (a) simultaneous blockade of Env attachment to both cellular CD4 and co- receptors, (b) triggering of gp120 irreversible shedding from Env, leaving non-infectious naked virions, and (c) inactivation of Env expressed on the surface of infected cells. cPTs, including the lead compound AAR029N2, have good aqueous solubility, metabolic stability and promising pharmacokinetics (PK). Recent data with liposomal encapsulation of cPTs and nanoparticle surface display demonstrate the potential to target both virus and HIV infected cell reservoirs, thus endowing cPTs with unique advantages for treatment and eradication vs. current anti-HIV drugs. The combined functional properties of “Blocking & Inactivation”, potency and drug-like characteristics of AAR029N2 make it an attractive candidate as an anti-HIV agent. We have formed a translational development research team to establish AAR029N2 and potentially other advanced cPT class variants with sufficient efficacy, stability and synthetic scalability to drive towards next-round formulation, advanced animal models and clinical development.