Development of a novel, allogeneic cell therapy for difficult to treat IBD

The National Institute of Diabetes and Digestive and Kidney Diseases awarded $356,328 to Celdara Medical, LLC on September 1, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to develop a novel allogeneic cell therapy for difficult-to-treat inflammatory bowel disease.

Celdara will develop cell-based therapeutic candidates targeting the dysregulated immune response in IBD patients who fail multiple lines of conventional therapy or experience refractory disease. The work focuses on addressing the pro-inflammatory cytokine profile (TNF-α, IL-1β, IL-6, IL-17, IL-23) and deficiency in regulatory cytokines (IL-10, TGF-β) that characterize IBD pathogenesis, particularly in the 10–20 percent of IBD sufferers classified as difficult-to-treat.

The award period runs from September 1, 2026, through August 31, 2027. Work is performed in Lebanon, New Hampshire. Celdara is a self-certified small disadvantaged business focused on cell-based and protein-engineering therapeutics across multiple therapeutic areas including cancer immunotherapy, neurological disorders, and metabolic conditions. The recipient operates exclusively as a prime on federal research grants and maintains a small federal services contract portfolio through the Small Business Administration.

Abstract

Inflammatory bowel disease (IBD), which includes crohn's disease and ulcerative colitis, represents a significant global health burden, affecting approximately 3 million adults in the U.S. Alone. IBD is characterized by chronic inflammation of the gastrointestinal tract, leading to a decreased quality of life, increased risk of infections, colorectal cancer, and mental health challenge. In 2018, IBD healthcare costs in the US totaled $8.5 billion and the prevalence of IBD continues to rise.IBD is driven by a dysregulated immune response involving pro- inflammatory cytokines TNF-α, IL-1Β, IL-6, and TH17-associated cytokines (IL-17, IL-23), along with a deficiency in the regulatory cytokines IL-10 and TGF-β. M1 macrophages polarization and compromised regulatory t cells (tregs) further perpetuate inflammation and disrupt intestinal homeostasis. Current therapies aim to reduce inflammation, manage symptoms, and maintain remission through drugs like aminosalicylates, corticosteroids, immunomodulators, biologics, small molecules, and surgery. Despite advancements in treatment options, including biologics and small molecules, there is no cure, and a substantial portion of patients have refractory disease that does not respond to multiple treatments. These "difficult to treat" patients make up 10-20% of IBD sufferers and are defined as those who fail multiple lines of therapy or experience recurrent disease complications. These patients urgently need multifaceted anti-inflammatory therapy to ameliorate their disease. Stromal cell-based therapies, such as mesenchymal stem/stromal cells (mscs), are being explored for IBD with some promise in clinical trials but face challenges related to phenotype stability, difficulty of isolation and expansion, manufacturing costs and inconsistencies, and complications with tolerability due to coagulation issues or loss of phenotype. We have developed an allogeneic lymphoid-derived stromal cell therapy, CM-AF02, using a patented manufacturing process for difficult to treat IBD.