Arthrofibrosis control using small molecule inhibitors of interleukin-11

The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded Novomedix LLC $314,362 on September 22, 2025, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) to develop and commercialize a novel therapy for arthrofibrosis using small-molecule inhibitors of interleukin-11.

The project aims to develop Novomedix small-molecule anti-inflammatory and antifibrotic drug candidates (NMX) for local application to reduce and potentially reverse fibrous tissue deposition in joint structures, reduce pain and stiffness, and improve range of motion. Arthrofibrosis occurs in end-stage osteoarthritis around joint replacement surgery, prolonged immobilization following skeletal injury, and after anterior cruciate ligament repair; current treatments such as manipulation under anesthesia and invasive arthrolysis are not always completely effective.

The work will be performed in California. The Marrero Laboratory will execute the proposed approach using its orthopedic resources and experience with disease and surgical rodent models. Specific aims include assessing the effectiveness of ten different NMX analogs in reducing fibrotic characteristics in fibrotic synovial cells, confirming efficacy in cultured osteoarthritis patient-derived synovial cells, and selecting three drug candidates for animal testing.

The award period runs through August 31, 2027. Novomedix LLC is a woman-owned small business based in San Diego, California, specializing in developing novel small-molecule therapeutics for complex medical conditions.

Abstract

This program aims to develop and commercialize a novel, safe, and effective therapy for arthrofibrosis (AF) to reduce and potentially reverse fibrous tissue deposition, reduce pain and stiffness, and improve the range of motion in affected joints. AF is characterized by the excessive buildup of fibrous collagen within joint structures such as the synovium. IT often occurs in end-stage osteoarthritis (OA) around joint replacement surgery, prolonged immobilization following skeletal injury, and after anterior cruciate ligament repair. Current treatment methods, such as manipulation under anesthesia and invasive arthrolysis, are not always completely effective in relieving the pain and limited movement associated with AF. To address this issue, we propose to investigate a new therapeutic approach for AF that involves local application of novomedix small-molecule anti-inflammatory and antifibrotic drug candidates (NMX), which have been recently found to reverse differentiation of myofibroblasts and prevent their abnormal deposition of collagen during idiopathic pulmonary fibrosis (IPF). Based on successful studies in IPF models, we anticipate that NMX can minimize AF in fibroblastic synovial cells derived from OA patients and in a RAT model of AF following acute joint injury with prolonged immobilization. The marrero laboratory is poised to execute the proposed approach because of its orthopedic resources and extensive participation in select projects involving disease and surgical rodent models of arthritis, limb amputation, and studies requiring rodent arthrotomy and joint repair. The specific aims for this project are: 1) assess the effectiveness of 10 different NMX analogs in reducing fibrotic characteristics in fibrotic synovial cells, confirm efficacy in cultured osteoarthritis patient-derived synovial cells, and select 3 drug candidates for testing in animals, and 2) test the effectiveness of intra-articular NMX on improvement in joint movement and reduced fibrous tissue in a RAT model of post-traumatic immobilization-induced AF. This will allow US to select a drug candidate to move into IND-enabling studies to conduct a phase 1 clinical trial.