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Principal Investigator: Benjamin Goldman Cooper
Organization: ORTHOLEVO, INC.
Fiscal Year: 2024
Award: $504,965
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
PROJECT SUMMARY/ABSTRACT
Shoulder contracture or “arthrofibrosis” is a painful and gradual loss of shoulder motion caused by trauma,
surgical procedures, inflammation, prolonged joint immobilization, or for no clear cause (i.e. idiopathically), as is
the case in “frozen shoulder”. Shoulder arthrofibrosis occurs in 9 million individuals in the United States with
more than 1.6 million seeking surgical remedies each year. Current treatment options, including intra-articular
corticosteroid injections, NSAIDs, and nerve blockers, provide only marginal and temporary relief of patient
symptoms and do not address the underlying cause of the disease—the accumulation of fibrotic collagenous
tissue. Surgical interventions are used in more severe cases, but these procedures are fraught with complica-
tions and can further aggravate symptoms. Ortholevo is developing a local injectable polymeric microparticle
sustained release formulation of relaxin-2 for the treatment of shoulder arthrofibrosis. Relaxin-2 (RLX) is a 6-kDa
naturally-occurring peptide hormone that is present in males and females but is especially known for temporally
downregulating collagen production and upregulating matrix metalloproteases to loosen pelvic ligaments prior to
childbirth. Using this peptide therapeutic for the treatment of arthrofibrosis provides an unprecedented
opportunity to treat this disease with a first of its kind therapy and a resulting paradigm shift in the
treatment of shoulder arthrofibrosis.
Ortholevo proposes to advance its technology down the path of commercialization by the completion of the
following late-stage product development proposed aims: 1) Perform pilot scale production of IND-enabling re-
laxin (RLX) drug substance for use in late stage drug product development; 2) Complete late-stage manufactur-
ing activities and sterilization development of sustained-release relaxin (SR-RLX) drug product, resulting in a tox
batch for IND-enabling studies; 3) Conduct key rat GLP acute local toxicology studies to demonstrate a wide
therapeutic window; and 4) Execute FDA regulatory strategy in support of pre-IND meeting and IND submission.
To accomplish these aims, we have collected key preliminary data demonstrating efficacy using a relaxin-2
loaded microparticle formulation as well as assembled a team with expertise in science/engineering/medicine
(e.g., protein therapeutics, microparticles, biomechanics, and clinical joint contracture) and translation and com-
mercialization (e.g., management, regulatory, manufacturing, and marketing). With the successful completion of
the specific aims in this CRP proposal, the next commercialization steps include completing remaining IND-
enabling studies, producing clinical trial drug product, obtaining IND approval, and initiating clinical investigation.
Achievement of these goals will lead to the first standard of care treatment for shoulder arthrofibrosis based on
reversing the underlying and abnormal accumulation of fibrotic collagenous tissue that delivers the therapeutic
in a sustained and controlled manner to the site of disease while keeping systemic exposure to a minimum.
Terms: <Abbreviations><Achievement><Achievement Attainment><Acute><Address><Adrenal Cortex Hormones><Anesthesia><Anesthesia procedures><Ankle><Articular Range of Motion><Biodistribution><Biomechanics><Body Tissues><Capital Financing><Capital Funding><Childbirth><Clinical><Clinical Research><Clinical Study><Clinical Trials><Collagen><Common Rat Strains><Contracting Opportunities><Contracts><Contracture><Corticoids><Corticosteroids><Data><Development><Disease><Disorder><Dosage Forms><Drug Delivery><Drug Delivery Systems><Drugs><Effectiveness><Elbow><Encapsulated><Endocrine Gland Secretion><Engineering><Evaluation><Experimental Designs><Exposure to><Female><Fibroblasts><Fibrosis><Formulation><Freezing><Frequencies><General Population><General Public><Goals><Histologic><Histologically><Hormones><Human><Immobilization><In Vitro><Incidence><Individual><Inflammation><Injectable><Injections><Joint Range of Motion><Joints><Knee><Laboratories><Ligaments><Manufactured form><Manufacturer><Marketing><Medication><Medicine><Metallopeptidases><Metalloproteases><Metalloproteinases><Microbeads><Microspheres><Modeling><Modern Man><Motion><Motivation><Musculoskeletal><NSAIDs><Nerve><Non-Steroidal Anti-Inflammatory Agents><Operative Procedures><Operative Surgical Procedures><Orthopedic><Orthopedic Surgical Profession><Orthopedics><Pain><Painful><Patients><Pelvic><Pelvic Region><Pelvis><Peptide Hormone Gene><Peptide-based drug><Peptides><Pharmaceutical Preparations><Phase><Physiatric Procedure><Physical Medicine Procedure><Physical Therapeutics><Physical therapy><Physiotherapy><Polymers><Pre IND FDA meeting><Pre-IND mtg><Privatization><Procedures><Process><Production><Proteins><Rat><Rats Mammals><Rattus><Regio tarsalis><Relaxin><Risk><SBIR><Safety><Science><Shoulder><Site><Small Business Innovation Research><Small Business Innovation Research Grant><Specific qualifier value><Specified><Sterilization><Surgical><Surgical Interventions><Surgical Procedure><Symptoms><System><Technology><Testing><Therapeutic><Therapeutic Hormone><Time><Tissues><Toxicology><Translations><Trauma><United States><Work><Writing><alleviate symptom><ameliorating symptom><biomechanical><child birth><clinical investigation><commercialization><customized therapy><customized treatment><decrease symptom><developmental><diabetic><drug/agent><efficacy validation><experience><fewer symptoms><improved><in vivo><individualized medicine><individualized patient treatment><individualized therapeutic strategy><individualized therapy><individualized treatment><joint function><male><manufacture><meeting><meetings><native protein drug><non-steroidal anti-inflammatory drugs><orthopedic freezing><particle><patient specific therapies><patient specific treatment><peptide drug><peptide hormone><pharmaceutical protein><polymer><polymeric><pre-IND consultation><pre-IND discussion><pre-IND meeting><pre-Investigational New Drug meeting><product development><protein drug agent><protein-based drug><range of motion><reduce symptoms><relieves symptoms><residence><residential building><residential site><restoration><stability testing><standard of care><substance use><substance using><surgery><symptom alleviation><symptom reduction><symptom relief><tailored medical treatment><tailored therapy><tailored treatment><therapeutic peptide><therapeutic protein><translation><unique treatment><validate efficacy>