Caladrius Biosciences, Inc., a cell therapy company combining an industry-leading development and manufacturing services provider, PCT, with a select therapeutic development pipeline, announces that its product candidate CLBS03 (autologous expanded polyclonal regulatory T cells, or Tregs) was granted Fast Track designation by the US Food and Drug Administration (FDA) for the treatment of type 1 diabetes mellitus (TID), making it the first known therapeutic candidate for treatment of T1D to receive the designation.

CLBS03 has received Orphan Drug designation from the FDA as well as Advanced Therapeutic Medicinal Product (ATMP) classification from the European Medicines Agency. CLBS03 is currently being studied in a landmark phase 2 clinical trial in collaboration with Sanford Health, The Sanford Project: T-Rex Study, which is expected to complete enrollment of the first defined cohort of 18 patients in the coming weeks.

Fast Track is a process designed to facilitate the development and expedite the review of drugs, biologics or treatments for serious conditions, thereby filling unmet medical needs. Through the Fast Track program, a product may be eligible for priority review at the time of a Biologic License Application (BLA) or New Drug Application (NDA) filing and may also be eligible to submit completed sections of the BLA/NDA on a rolling basis before the complete application is submitted. These expedited processes can significantly cut down the development time and cost associated with bringing a therapy to market. Furthermore, the therapy’s sponsors are eligible for more frequent written communication and meetings with the FDA, the benefit of which may be to foster a pivotal study design which more closely meets the FDA’s needs, thereby creating a more efficient and rapid pathway to approval.

The scientific basis for treating T1D with CLBS03 derives from the use of Tregs to treat autoimmune diseases caused by T-cell imbalances in an individual’s immune system. This innovative approach seeks to restore immune balance by enhancing Treg cell number and function. Tregs are a natural part of the human immune system and regulate the activity of T effector cells, which are responsible for protecting the body from viruses and other foreign antigens. When Tregs function properly, only harmful foreign materials are attacked by T effector cells. In autoimmune diseases, deficient Treg activity permits the T effector cells to attack the body’s own beneficial cells, for example, insulin-producing pancreatic beta cells in the case of T1D.

CLBS03 is a personalized, autologous medicine consisting of each patient’s own Tregs, which have been expanded in number and functionally enhanced by a proprietary method developed by a collaboration between PCT and the University of California, San Francisco. The program is supported by promising published early clinical work conducted by respected leaders in the area of T regulatory cell science. Two phase 1 clinical trials of this technology in T1D patients demonstrated safety and tolerance, feasibility of manufacturing, infused Treg persistence and an early indication of efficacy. In particular, one of those trials provided supportive evidence of the utility of Tregs for T1D in pediatric patients 5 to 18 years of age with new onset T1D2. In that open label, randomized study, the authors reported that treatment with expanded autologous Tregs preserved function of pancreatic beta cells and reduced the need for exogenous insulin in the majority of patients treated.

“Obtaining Fast Track designation is a key milestone in our regulatory and development strategy for CLBS03. It underscores the great need for innovative treatments, such as CLBS03, in the treatment of T1D and allows for the acceleration of its development,” said David J. Mazzo, CEO of Caladrius. “We are making excellent progress advancing the US-based phase 2 clinical program of CLBS03 to treat T1D and look to complete enrollment of the first cohort of 18 patients in the coming weeks. This, coupled with our Orphan Drug and Fast Track designations, should make CLBS03 an even more attractive opportunity for a potential partner.”

The Sanford Project: T-Rex Study is a prospective, randomized, placebo-controlled, double-blind phase 2 clinical trial to evaluate the safety and efficacy of CLBS03 as a treatment for T1D with residual beta cell function in approximately 111 subjects age 12 to 17 in two cohorts (18 subjects followed by 93 subjects). The study is being conducted in collaboration with Sanford Research, a subsidiary of Sanford Health. Subjects will be randomized into one of three groups and will receive either a high dose of CLBS03, a low dose of CLBS03 or placebo. The key endpoints for the trial are the standard medical and regulatory endpoints for a T1D trial and include preservation of C-peptide, an accepted measure for pancreatic beta cell function; insulin use; severe hypoglycemic episodes; and glucose and hemoglobin A1c levels.