Platform to target small-molecule therapeutics to bone – Novel prodrugs to selectively deliver therapeutics to bone

Challenge: Musculoskeletal diseases represent the second largest contributor to disability worldwide (WHO). Despite efforts made in the past few years, drugs development in bone therapy is challenging. Indeed, bone is a difficult tissue to drug due to its material properties and limited vascularity, requiring high drug doses and frequent administration to achieve efficacy. Most FDA approved bone therapeutics are focused on reducing bone resorption and the few approved bone-anabolic drugs are associated with significant side effects which limit their duration of use (1-2 years). Thus, a bone anabolic drug that could increase bone mass and reverse osteoporotic bone loss without side effects would address an important unmet medical need.

Solution: The team has developed a small molecule-based platform allowing for selective accumulation of drug within bone tissue through a targeted prodrug delivery technology. By doing so, they aim to increase drug selectivity and mitigate systemic adverse effects. The first class of compounds developed by the team with this technology is a bone building drug (C3) that incorporates a prostaglandin EP4 receptor agonist payload. In this project, the team will complete preclinical studies in order to validate the pharmacology and safety profile of their lead compound and complete a 28-day GLP toxicology study in one animal species.

Expected achievements/Impact: This new technology aims to overcome several existing limitations, with respect to bone anabolic therapies. The completion of this project will validate a technology with vast potential in multiple indications. It could first lead to the development of new therapeutics for the treatment of underserved bone diseases. It will also support the broader use of this platform which can be tailored to deliver a variety of cargos (small molecules, biologics, etc.). Upon completion, this project will strengthen Mesentech competitiveness and bring commercial value to their newly developed platform

Principal Investigator:

Tully Michael Underhill


Robert Young 


Ongoing Project
$ 3,318,194 / 2 years


Supported by CQDM through:
• Merck Canada
• BL-NCEAnd by co-funding partner
• Mesentech