Penn cell therapy spinoff Cabaletta Bio of Radnor raises $38 million 

Cabaletta Bio Inc., a biopharmaceutical startup spun out of the University of Pennsylvania, has raised $38 million in an equity financing and signed an exclusive license agreement with Penn related to T cell therapy.

In addition, the Radnor-based company has entered into two multiyear sponsored research agreements with Penn for the discovery and development of engineered T cell therapy products for B cell-mediated autoimmune diseases.

The engineered T cell technology uses what are known as chimeric autoantibody receptors (CAARs) to bind and destroy only disease-causing B cells — while sparing the healthy B cells.

Cabaletta has also entered into a master services agreement with Penn that will allow it to enter into agreements for scientific, clinical and manufacturing expertise to develop a first CAAR product targeting mucosal pemphigus vulgaris, a rare skin disorder characterized by skin blistering. Penn researchers have produced what the company described as “compelling” proof of concept data on the use of CAARs to treat the condition.

Cabaletta’s $38 million Series A financing was led by 5AM Ventures, with participation from the founding investors Adage Capital Management and Penn.

Funds from the private stock sale will allow Cabaletta to advance the experimental treatment, called DSG3-CAART, into clinical development.

Cabaletta is led by Dr. Steven Nichtberger, the company’s co-founder, chairman and CEO. A former executive with Merck, Nichtberger was also the founding CEO of Tengion, a regenerative medicine company previously based in East Norriton. He is also chairman of Control Rad, a medical-device company also based in Radnor that is focused on radiation safety.

“During the past 18 months, Cabaletta has advanced a series of CAAR T cell therapy products, licensed foundational intellectual property and assembled leading scientists, clinicians and experts in the discovery, development, manufacturing and regulatory approval of cell therapy products to accelerate development of highly specific CAAR T cell therapies that may offer a potential one-time cure for certain B cell-mediated autoimmune diseases,” Nichtberger said “CAAR T cells are engineered T cells that build on the revolutionary chimeric antigen receptor (CAR) T cell technology developed at Penn, which is FDA approved for the treatment of certain B cell-mediated cancers.

Nichtberger said Cabaletta believes the success of CAR T in B cell-mediated cancers reduces the risk profile of our CAAR T programs in B cell-mediated autoimmune diseases, where chronic and broadly immunosuppressive therapies are typically used despite short-term effectiveness and significant adverse effects.

Cabaletta’s foundational platform and lead asset are based on early work conducted at Penn by Drs. Michael Milone and Aimee Payne, both of whom are co-founders of the company.

Milone, an associate professor of pathology and laboratory medicine and member of the Center for Cellular Immunotherapy since inception at Penn, is a co-inventor of Kymriah, the CAR-T cell therapy developed at Penn and now marketed as a cancer treatment by Novartis.

“The work that we at Penn, and investigators at other organizations, have completed has clinically proven the value of CAR T therapies to treat other serious malignant diseases,” Milone said. “Through continued work at our institution, we have shown that this core platform can be slightly modified and directed toward B cell-mediated autoimmune diseases. Cabaletta was founded with the objective of expediting this important work and finding new and better solutions for patients who suffer from these debilitating diseases.”

Payne is an associate professor of dermatology and lead physician in the Autoimmune Blistering Clinic at Penn. Her research focus is on understanding how autoimmunity occurs in pemphigus, the skin blistering B cell-mediated autoimmune disease that is the target of Cabaletta’s lead asset, DSG3-CAART. Payne’s laboratory conducted the preclinical proof-of-concept work that demonstrated that DSG3 CAAR T cells could “robustly” control mucosal pemphigus vulgaris in animal models.

“Mucosal pemphigus vulgaris is a rare autoimmune disease that causes painful blisters on mucous membranes and increases risk of serious infections,” Payne said. “Current treatments, primarily immunosuppressants, are reasonably effective but can have very serious side effects. The highly targeted nature of CAAR T cells suggests that pathogenic B cells could be eliminated without impacting normal B cell function, a potentially ideal combination of efficacy and safety. We look forward to moving this program into the clinic in the near-term.”