Cabaletta’s CAR T-cell therapy cleared for SLE Phase 1/2 trial

Decision comes less than 6 months after CABA-201 was licensed from IASO Biotherapeutics

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by Lindsey Shapiro |

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The U.S. Food and Drug Administration (FDA) has cleared a Phase 1/2 clinical trial to test CABA-201, Cabaletta Bio’s investigational CAR T-cell therapy, in people with systemic lupus erythematosus (SLE) with or without kidney involvement.

Cabaletta asked to launch the trial in the form of an investigational new drug (IND) application. The FDA’s clearance came less than half a year after the company in-licensed the therapy from IASO Biotherapeutics last October.

“We believe the clearance of this IND application within [six] months of licensing the binder for CABA-201 is an important milestone for patients with autoimmune disease,” Steven Nichtberger, MD, CEO and co-founder of Cabaletta, said in a company press release. “By achieving a timely IND clearance, we believe we are well positioned to generate [three]-month clinical data on efficacy endpoints and tolerability for patients dosed with CABA-201 by the first half of 2024.”

Immune B-cells are responsible for producing antibodies, including the self-reactive ones that drive SLE and other autoimmune diseases.

CABA-201 is a chimeric antigen receptor (CAR) T-cell therapy designed to temporarily, but completely, deplete B-cells, thereby resetting the immune system and promoting disease remission.

With this approach, a patient’s immune T-cells are isolated and engineered in the lab to express a lab-made receptor, or CAR, that targets a specific disease-associated protein. In the case of CABA-201, CAR targets CD19, a protein on B-cells.

Following a round of chemotherapy to help reset the immune system, the therapy is given as a onetime infusion into the bloodstream. Modified T-cells will then recognize and attack CD19-positive B-cells.

Preclinical studies have indicated this approach can ease symptoms and prolong survival in SLE mouse models.

Prior to obtaining it from IASO, the treatment candidate had been evaluated as a potential therapy in about 20 people with B-cell associated cancer, in whom it was found to be well tolerated.

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Aiming for similar results with CABA-201 CAR T-cell therapy

CABA-201’s design is similar to a CD19-targeted CAR T-cell therapy developed by German researchers. That therapy was recently tested in five adults with active treatment-resistant SLE and multi-organ involvement as part of a compassionate use program.

The results, published last year in Nature Medicine, showed it safely led to disease remission for all five patients three months after infusion, allowing them to stop using immunosuppressant therapies.

Other clinical manifestations, such as kidney inflammation, arthritis, fatigue, heart problems, and lung involvement were also eliminated. The levels of SLE-associated antibodies and immune markers also dropped below clinical cutoffs.

B-cells were fully depleted two days after treatment and didn’t begin reemerging until about 3.5 months later. Even after their appearance, no patient had a clinical relapse and all remained in drug-free remission for up to 17 months, or nearly 1.5 years.

Due to that therapy’s similarities to CABA-201, Cabaletta believes its investigational therapy will similarly benefit SLE patients, including those with lupus nephritis, where the self-reactive antibodies driving SLE attack the structures in the kidneys that filter out waste.

The company has entered into a translational research partnership with the investigators from that study as they work to develop CABA-201 for SLE.

“Based on its similarity to the product used in the Nature Medicine paper, we believe CABA-201 has the potential to provide deep and durable responses for patients with SLE and possibly other autoimmune diseases where B-cells play a role to initiate or sustain disease,” Nichtberger said.

The open-label Phase 1/2 trial will involve SLE patients with active lupus nephritis as well as those with active disease, but not kidney involvement. In the dose-finding study, participants will first undergo a round of chemotherapy followed by a single CABA-201 infusion.

“The efficient clinical trial design was informed by the data package we submitted, including clinical safety data with the CABA-201 binder, our experience from prior autoimmune cell therapy IND applications and our exclusive translational research partnership with the senior author of the Nature Medicine paper,” Nichtberger said.

The trial will be the first to employ Cabaletta’s Chimeric Antigen Receptor T cells for Autoimmunity (CARTA) therapeutic development strategy.