Cabaletta Bio, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted separate Fast Track Designations to CABA-201, an investigational 4-1BB-containing fully human CD19-CAR T cell therapy, for the treatment of patients with dermatomyositis to improve disease activity and for the treatment of patients with systemic sclerosis (SSc) to improve associated organ dysfunction. To date, Cabaletta has received clearance from the FDA for Investigational New Drug (IND) applications for CABA-201 in multiple autoimmune conditions including systemic lupus erythematosus (SLE), myositis, SSc and generalized myasthenia gravis (gMG). Cabaletta is conducting four Phase 1/2 clinical trials with a total of nine cohorts that can advance simultaneously, employing a similar parallel cohort design and starting dose of 1 x 106 cells/kg without a dose escalation requirement.

The FDA?s Fast Track process is intended to facilitate the expedited development and review of therapeutics intended to treat serious or life-threatening conditions and to address unmet medical needs. Companies that receive Fast Track Designation are eligible for several potential benefits, including the opportunity for more frequent meetings and interactions with the FDA during clinical development as well as eligibility for accelerated approval and/or priority review, if relevant criteria are met. Companies may also be allowed to submit sections of their Biologics License Application on a rolling basis.

Dermatomyositis (DM) is an autoimmune disease that can lead to severe functional impairment that may be life-threatening despite best available standard of care. It is characterized by a skin rash along with muscle inflammation and weakness. Although the pathophysiology of DM is not well understood, it is thought to be a subtype of myositis that is driven by B cells.

DM affects approximately 43,000 patients in the U.S. alone, and typically affects middle-aged individuals, particularly women. Current treatment typically involves medications to suppress the immune system and/or chronic intensive therapies such as intravenous immunoglobulin, or IVIg. Despite these therapies, a significant portion of DM patients have disease that remains refractory to existing medications.

SSc is a rare and potentially fatal chronic autoimmune disease characterized by progressive skin and internal organ fibrosis that can be life-threatening, including interstitial lung disease, pulmonary hypertension, and scleroderma renal crisis. Although the etiology of SSc is not well understood, the pathogenic role of autoantibodies and B cells in SSc provides a rationale for studying CAR T therapy in this population. SSc affects approximately 88,000 patients in the U.S., and typically affects middle-aged individuals, particularly women.

Standard treatment options, which have modest effects, include generalized immunosuppressive agents or drugs targeted to specific symptomatic manifestations. Autologous hematopoietic stem cell transplant may provide some benefits in organ involvement, but carries significant risks, including mortality, infertility, and secondary autoimmune disease, limiting its potential to be applied broadly. Due to the lack of adequate treatments, the risk of mortality in systemic sclerosis remains high, with an average survival of approximately 12 years following diagnosis.