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.

Grant Number: 5SB1AR084381-02
NIH Institute/Center: NIH
Principal Investigator: Siddhesh Angle