Treatment and prevention of osteoarthritis with an intra-articular disease-modifying regenerative therapy

Abstract Osteoarthritis (OA), a degenerative joint disorder, affects nearly 10% of the US population. Costs—including loss of work, medications, hospitalization for joint replacement and/or repair surgery, and other types of therapy—are high, and consume up to 0.5% of the gross domestic product of the United States.1 Aging, genetics, prior injury, obesity, biomechanical abnormalities that accelerate joint deterioration, and inflammation play leading roles in the pathogenesis of OA, which is characterized by changes to the joint and cartilage destruction, with chondrocytes playing a central role in this process. To date, there are no therapies available that either prevent progression of OA or reverse the loss of cartilage in OA joints, short of surgical joint replacement. Regenosine is developing a first-in-class liposomal adenosine product in a proprietary, novel formulation for regenerating cartilage in joints of patients with established OA. The goal is to offer patients a novel, disease- modifying therapy with uncompromising efficacy relative to existing technologies. Through this therapy, the company hopes to significantly improve clinical outcomes and patient quality of life and reduce the total health care delivery costs associated with OA. The company demonstrated that intraarticular (IA) injections of adenosine in a liposomal formulation reverses and reduces the severity of OA in a post-traumatic OA (PTOA) model in rats and an obesity-related model in mice. Regenosine, after systematically formulating a series of candidates has now further developed and optimized RgnA09M, a shelf stable formulation of liposomal adenosine with a 15-day bioavailability. This is a significant improvement over adenosine’s half-life in whole blood and other biological fluids of 1-4 seconds, and a similar short half-life in the joint. With the NIH-NIAMS Phase II SBIR, Regenosine demonstrated the safety and efficacy of RgnA09M in pain, function, and cartilage structural change in the medial meniscal release (MR) model in dogs, considered to be the closest to a gold standard model for OA currently available in terms of anatomic similarity, disease progression, and translation of outcomes. The company was able to show that intra-articular treatments of RgnA09M significantly improved pain and function, and markedly slow the progression of OA until at least 6 months after treatment. Regenosine has conducted a technology transfer to a 3rd party contract manufacturing organization who has the necessary process, equipment, and environmental capabilities. Regenosine proposes to utilize the funds from the CRP to pursue the following aims: 1) Validation of analytical methods and cGMP process for manufacturing RgnA09M and 2) Manufacturing of a 1Liter sterile cGMP batch of RgnA09M for clinical Phase 1b/2a trial. The completion of this work will allow the company to transition into clinical trials required by the FDA before commercialization of RgnA09M.