Bristol-Myers Squibb (BMS) is paying Tranzyme Pharma $10 million up front as part of a collaboration to discover and develop novel macrocyclic compounds against multi BMS targets in different therapeutic areas. Tranzyme will also receive $3–6 million in research fees over the initial two-year term of the agreement plus development and regulatory milestones as well as sales royalties.
The company will be primarily responsible for early lead discovery, with BMS taking on much of the lead optimization activities and all preclinical product development and commercialization. The deal will focus on the use of Tranzyme’s MATCH™ (macrocyclic template chemistry) for the discovery of novel bioactive macrocyclic drugs.
MATCH compounds are designed to mimic the favorable binding characteristics of proteins and peptide, such as tight receptor binding for high potency and selectivity, while eliminating the drawbacks associated with biomolecules, including poor metabolic stability, low oral bioavailability, lack of membrane permeability, antigenicity, and high manufacturing costs. The company claims that although macrocyclic compounds from natural sources or with complex chemistries have been successfully developed as marketed drugs, its compounds represent the first completely synthetic and systematically synthesized collection.
Tranzyme is currently focused on gastrointestinal and metabolic disease targets, although Vipin K Garg Ph.D., president and CEO, claims “MATCH has broad applicability in the treatment of other diseases that involve hormones, peptides, ion channels, or protein-protein interaction pathways.”
The lead candidate in Transzyme’s in-house pipeline is TZP-101, an intravenous ghrelin agonist with potent prokinetic properties. The drug is preparing for Phase III trials against postoperative ileus. An oral ghrelin agonist, TZP-102, for gastroparesis and other gastrointestinal disorders is currently undergoing a Phase II study.
Tranzyme’s preclinical-stage candidates include the motilin antagonist, TZP-201, for the treatment of various forms of moderate-to-severe diarrhea and a ghrelin antagonist, TZP-301, for the treatment of obesity and metabolic syndrome.