Cabaletta Bio Receives Orphan Drug Designation for DSG3-CAART 

Cabaletta Bio, Inc. recently announced that the US FDA has granted Orphan Drug Designation for the company’s lead product candidate, DSG3-CAART, for the treatment of pemphigus vulgaris (PV). DSG3-CAART is designed to target the cause of mucosal PV (mPV), B cells that express pathogenic autoantibodies directed against the DSG3 protein, while preserving normal B cell immune function.

“Mucosal pemphigus vulgaris is a rare and potentially fatal, chronic autoimmune disease characterized by the loss of adhesion between cells of mucous membranes, resulting in widespread damage, painful blisters of the mucosal membranes, and increased susceptibility to life-threatening systemic infections,” said David Chang, MD, Chief Medical Officer of Cabaletta. “For affected patients, despite current treatment options, there is an urgent unmet need for more effective and durable therapies that can provide reliable, complete, and persistent remission from the disease beyond general immune suppression and B cell depletion provided by current treatment options. Orphan Drug Designation is an important recognition for investigational therapies for rare diseases and provides us with potentially valuable benefits as we prepare to initiate the DesCAARTes trial to generate and then report acute safety data from the first cohort of patients by the end of 2020.”

The FDA grants Orphan Drug Designation to drugs or biologics intended to treat or prevent rare diseases or conditions that affect fewer than 200,000 individuals in the US. This designation qualifies Cabaletta for certain incentives, which may include partial tax credit for clinical trial expenditures, waived user fees and potential eligibility for seven years of marketing exclusivity.

PV is a rare autoimmune blistering disease that is characterized by painful blisters and an increased risk of life-threatening infections due to 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 by scientists 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 patients with 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 by scientists at the University of Pennsylvania that resulted in the first commercially available CAR T cell products for the treatment of B cell cancers. 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 in a Phase 1 clinical trial as a potential treatment for a prototypical B cell-mediated autoimmune disease, mucosal pemphigus vulgaris. For more information, visit www.cabalettabio.com.