Executive Summary

We are focused on developing and commercializing first-in-class musculoskeletal regenerative therapies for osteoarthritis. Our proprietary platform technology harnesses the healing potential of the purinergic system which plays a critical role in maintaining cartilage homeostasis. Our lead product is a proprietary formulation for regenerating cartilage in joints with established osteoarthritis, targeting a rapidly growing joint preservation market. Our goal is to offer a disease modifying therapy with uncompromising efficacy relative to existing technologies. By developing this disease modifying therapy, we will significantly improve clinical outcomes and patient quality of life, and reduce the total health care delivery costs associated with osteoarthritis.

The purinergic system plays a critical role in maintaining cartilage homeostasis. We found that lack of adenosine A2a receptor can cause spontaneous osteoarthritis (OA) in mice, and that chondrocytes in OA patients generate much less adenosine than normal chondrocytes. Adenosine has an extremely short half-life in biological fluids (1-2 seconds). A key aspect of the intellectual property lies in the formulation of the two assets in our development pipeline which prolong the activity of adenosine. These formulations were tested for efficacy with intra-articular injections in two models simulating the most common causes of OA: a rat model with established OA following ACL rupture, and a model where mice develop OA due to weight gain. In both models, we demonstrated that restoring adenosine levels in affected joints prevented the progression of OA, reversed cartilage degradation and restored cartilage thickness in the treated joints. The treatment also reduces joint pain and progressively reduces joint inflammation. It activates the TGF-beta signaling associated with chondrocyte proliferation & maturation, and downregulates factors leading to cell death. 

Intraarticular injection of liposomal adenosine reduces cartilage damage in established murine and rat models of osteoarthritis. Scientific Reports 2020 Aug 10;10(1):13477. Link

Adenosine A2A receptor (A2AR) stimulation enhances mitochondrial metabolism and mitigates reactive oxygen species-mediated mitochondrial injury. FASEB J. 2020 Apr;34(4):5027-5045. Link

Endogenous adenosine maintains cartilage homeostasis and exogenous adenosine inhibits osteoarthritis progression. Nature Communications 2017 May 11;8:15019. Link

Adenosine-Functionalized Biodegradable PLA-b-PEG Nanoparticles Ameliorate Osteoarthritis in Rats. Scientific Reports 2019 May 15;9(1):7430. Link

Adenosine metabolism, immunity and joint health. Biochemical Pharmacology 2018 May;151:307-313. Link

The Role of Adenosine Receptor Activation in Attenuating Cartilaginous Inflammation. Inflammation 2018 Aug;41(4):1135-1141. Link

Regulation of bone and cartilage by adenosine signaling. Purinergic Signal 2016 Dec;12(4):583-593. Link