Cartesian launching 2 clinical trials testing Descartes-08 in MG

Cartesian Therapeutics is gearing up for two clinical trials of its cell therapy Descartes-08: the first, a Phase 3 study, will enroll adults with myasthenia gravis (MG), while the second, a Phase 2 basket trial, will test the treatment candidate in children with juvenile MG and other autoimmune diseases.

The Phase 3 study, called AURORA (NCT06799247), is on track to be initiated by the end of June, according to a company press release. A placebo-controlled trial, it’s expected to involve 100 people with generalized MG, known as gMG, which is characterized by widespread muscle weakness.

The Phase 2 study is a pediatric basket trial — meaning it will investigate one drug in different pediatric populations that share similar characteristics — that is slated to start before the end of the year.

“We look forward to commencing our Phase 3 AURORA trial by the end of this quarter,” said Carsten Brunn, PhD, president and CEO of Cartesian, noting that the company is “off to a strong start in what we expect to be a productive year.”

Per Brunn: “Progress continues across the balance of our pipeline, with … the initiation of a pediatric basket trial in select autoimmune diseases expected in the second half of this year.”

Descartes-08 designed to not require prior chemotherapy

An autoimmune disease, MG is caused by self-reactive antibodies that disrupt the communication between nerve and muscle cells, ultimately leading to symptoms of muscle weakness and fatigue. Antibodies are immune proteins made by specialized immune cells called B-cells.

Cartesian’s therapy candidate is designed to treat MG by lowering the number of B-cells, which is expected to also lower the levels of disease-driving antibodies.

Descartes-08 is a CAR T-cell therapy. With this type of treatment, other immune cells called T-cells are collected from a patient and then engineered to carry a chimeric antigen receptor, or CAR. In Descartes-08, T-cells are specifically equipped with a CAR that targets B-cell maturation antigen, a protein found on B-cells. This enables the modified T-cells to specifically recognize and kill B-cells once they are infused back into the patient.

Standard CAR T-cell treatments often require patients to undergo a process called preconditioning, in which a person is given chemotherapy to wipe out existing immune cells before the modified CAR T-cells are infused. Descartes-08 is notably designed not to require preconditioning.

We observed deep and sustained benefits at month 12 following a single course of therapy, particularly in participants without exposure to prior biologic therapies. … [Descartes-08 may] truly transform the current treatment paradigm.

Recent data from a Phase 2b clinical trial, called MG-001 (NCT04146051), indicated that six weekly infusions of Descartes-08 led to reductions in MG severity that were still seen at one year.

“We observed deep and sustained benefits at month 12 following a single course of therapy, particularly in participants without exposure to prior biologic therapies,” Brunn said.

Those findings “underscore the potential of Descartes-08,” Brunn said, noting that the treatment “is designed to be dosed conveniently in an outpatient setting without the need for preconditioning chemotherapy.”

According to Brunn, the therapy candidate may “truly transform the current treatment paradigm.”

A Phase 3 study, AURORA will involve people with MG who are positive for antibodies against acetylcholine receptor, or AChR — the most common type of MG-causing antibody. Participants will receive weekly infusions of Descartes-08 or a placebo for six weeks.

The study’s main goal will be to assess how the cell therapy affects the scores of the MG Activities of Daily Living (MG-ADL) scale, a standardized tool that assesses the extent to which MG symptoms cause problems for patients in day-to-day life. Specifically, the goal is to determine the proportion of patients seeing their MG-ADL scores improve by at least three points after four months of Descartes-08 treatment compared with those on the placebo.

Meanwhile, Cartesian is planning to launch a Phase 2 basket trial that will test Descartes-08 in children with several different autoimmune conditions, including juvenile MG. The company said the trial is expected to launch later this year, but did not give further details about its design.

Unlike traditional trials that focus on specific diseases, a pediatric basket trial tests whether a therapy can be effective across multiple conditions affecting children.