Protagonist Therapeutics

Organization Address
521 Cottonwood Drive, Suite 100
Milpitas, CA 95035-7404

Organization Phone
(408) 649-7370



Organization Description
Protagonist is a peptide and peptidomimetic therapeutics company pursuing technology platform driven discovery and development of disulfide rich peptides (DRPs) as: New chemical entities (NCEs) against protein-protein interaction (PPI) targets translating to a distinct clinical and commercial benefit to biologics Orally active NCEs for inflammatory bowel diseases (IBD)?a feature not achieved either by biologics (lack of oral activity) or small molecules (lack of potency) Peptides are known to have poor proteolytic stability and therefore limited therapeutic utility. DRPs offer a proven but relatively unexploited solution to this problem. The Company has developed a proprietary drug discovery technology platform that enables it to identify DRP based hits and leads against almost any type of targets in a de novo manner. These DRP molecules are highly constrained and stable chemical entities that combine the beneficial features of monoclonal antibody (mAb) drugs with the desired properties of small molecule drugs. These properties include improved oral stability, reduced immunogenicity, favorable pharmacokinetics, improved distribution and tissue penetration, and delivery by injectable and/or oral routes. DRPs are ideal scaffolds for drug discovery & development as their rigid framework imparts favorable chemical and biological stability characteristics and retains the sequence flexibility which permits the introduction of new and diverse functionalities. Some of the differentiating features of Protagonist's DRPs based technology platform are as follows: DRPs are a proven chemical class of drugs with numerous examples of orally stable and injectable NCEs on the market and in various stages of clinical development DRPs offer large target scope. They can be engineered to modulate targets that are the focus of mAbs (e.g. PPIs?cytokine related targets), and can also provide scope to modulate targets that are considered difficult to approach with conventional mAbs (e.g. GPCR's, ion channels and chemokines). This is an ideal technology platform for those targets that have not responded favorably to either mAb or small molecule approaches. Protagonist pursues DRPs as a broad scaffold class, thus overcoming the typical limitations of target scope, stability characteristics and PK of a single scaffold. We have assembled a database of greater then 5000 experimentally derived structures of DRPs that represent the structural diversity and biochemical stability offered by this class of natural products. The company has a validated technology platform well suited to exploit the DRP scaffold class. It comprises: A purposefully built computational design environment (Vectrix) to select specific DRPs for targets of interest A structurally diverse screening set of 20 DRP phage libraries that randomize between 6-15 residues in discontinuous, structurally distinct and biologically relevant conformations. The selected scaffolds sample >80% of the structural diversity of known DRPs. Directed evolution approaches to prepare millions of molecules via phage libraries and identify early hits or most potent binders via deep sequencing Validated and robust medicinal chemistry type analoging and SAR development, having synthesized arrays of compounds based on >25 DRP scaffolds with multiple disulfide bonds

Clinical Development Stage