Cabaletta Bio Receives IND Clearance From FDA to Initiate First Clinical Trial

Cabaletta Bio, Inc. recently announced it has received clearance of its IND application from the US FDA to initiate a first-in-human clinical trial of desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) in patients with mucosal pemphigus vulgaris (mPV) to assess the safety and tolerability of DSG3-CAART in these patients. The Company anticipates enrolling the first patient in 2020.

“The FDA’s clearance of our IND for DSG3-CAART is an important milestone for patients with mPV and the first IND clearance for a product candidate from our Cabaletta Approach to selective B cell Ablation (CABA) platform,” said Steven Nichtberger, MD, Chief Executive Officer and Co-Founder of Cabaletta Bio. “DSG3-CAART is the first of several CAAR T cell product candidates in our announced pipeline, which includes product candidates targeting patients with MuSK myasthenia gravis, the mucocutaneous form of pemphigus vulgaris (PV), and hemophilia A patients with inhibitors to factor VIII therapy.”

mPV is a potentially fatal, B cell-mediated chronic, rare autoimmune disease that causes painful blisters and sores on mucous membranes of affected patients, leading to severe and sometimes debilitating and life-altering effects. DSG3-CAART is designed to selectively target and eliminate B cells expressing autoantibodies specific for DSG3 that are the cause of mPV while preserving healthy B cell immune function. DSG3-CAART has the potential to generate persistent complete remission off therapy while avoiding the adverse effects of chronic and generalized immunosuppression. Currently available treatment options induce broad immunosuppression, which put the patient at risk of infection and often provide only transient complete remission with subsequent relapses for patients with moderate to severe mPV. Approximately 4,250 patients suffer from mPV in the United States and 6,250 patients in Europe, which accounts for approximately 25% of all PV cases.

PV is a rare autoimmune blistering disease that is characterized by the loss of adhesion between cells of the skin or mucous membranes. PV is caused by the production of autoantibodies that disrupt structural proteins within the skin and/or mucosa that connect with other proteins to enable the skin and/or mucosal cells to connect with each other. The autoantibodies can target desmoglein 3 (DSG3) and/or desmoglein 1 (DSG1), which are primarily expressed in the mucosal membranes and skin, respectively. mPV is characterized by autoantibodies against DSG3 only whereas mucocutaneous PV (mcPV) is characterized by autoantibodies against DSG3 and DSG1.

Chimeric AutoAntibody Receptor (CAAR) T cells are designed to selectively bind and eliminate only disease-causing B cells, while sparing the normal B cells that are essential for human health. CAAR T cells are based on the chimeric antigen receptor (CAR) T cell technology developed at the University of Pennsylvania. While CAR T cells typically contain a CD19-targeting molecule, CAAR T cells express an autoantibody-targeted antigen on their surface. The co-stimulatory domain and the signaling domain of both a CAR T cell and a CAAR T cell carry out the same activation and cytotoxic functions. Thus, Cabaletta’s CAARs are designed to direct the patient’s T cells to kill only the pathogenic cells that express disease-causing autoantibodies on their surface, potentially leading to complete and durable remission of disease while sparing all other B cell populations that provide beneficial immunity from infection.

Cabaletta Bio is a clinical-stage biotechnology company focused on the discovery and development of engineered T cell therapies for B cell-mediated autoimmune diseases. The Cabaletta Approach to selective B cell Ablation (CABA) platform, in combination with Cabaletta’s proprietary technology, utilizes Chimeric AutoAntibody Receptor (CAAR) T cells that are designed to selectively bind and eliminate only specific autoantibody-producing B cells while sparing normal antibody-producing B cells, which are essential for human health. Cabaletta’s lead product candidate is based on the Chimeric Antigen Receptor (CAR) T cell technology developed at the University of Pennsylvania (Penn) that resulted in one of the first commercially-available CAR T cell products for the treatment of B cell cancers. Cabaletta was founded by Penn physician/scientists Michael Milone, M.D., Ph.D., and Aimee Payne, M.D., Ph.D., who serve as co-chairs of Cabaletta’s Scientific Advisory Board, and Steven Nichtberger, M.D., CEO of Cabaletta. Cabaletta has an exclusive global licensing agreement and multiple sponsored research agreements with the University of Pennsylvania to develop the CAAR T technology to treat B cell-mediated autoimmune diseases. The Company’s lead product candidate is being studied as a potential treatment for a prototypical B cell-mediated autoimmune disease, mucosal pemphigus vulgaris (mPV). For more information, visit www.cabalettabio.com.