Cartesian Therapeutics Kicks Off Phase IIb study of rCAR-T in Autoimmune Disease

Cartesian Therapeutics dosed the first patient in a Phase IIb trial with its experimental RNA-based CAR-T treatment for the debilitating autoimmune disease, generalized Myasthenia Gravis (MG).

The Gaithersburg-based company dosed the first patient with Descartes-08, the company’s first-in-class, RNA-engineered chimeric antigen receptor T-cell therapy (rCAR-T). The placebo-controlled study, the first such trial of its kind, is expected to build on the recently-completed Phase IIa program. The study is expected to enroll 30 myasthenia patients, 15 of whom will receive a six-week course of Descartes-08 and 15 who will receive placebo.

Cartesian Therapeutics Chief Executive Officer Murat Kalayoglu expressed excitement over Descartes-08 and what its approval could potentially mean to patients with generalized MG. In patients treated to date with the autologous cell therapy, Kalayoglu said his 25-member team is “enthusiastic about the magnitude of clinical benefit and the duration of clinical benefit” in patients who have been treated with the therapeutic to date.

“This is what gets our entire team so excited, you can feel the energy in the company. It’s palpable when we’re hearing [patient] stories from our clinical sites,” Kalayoglu said.

Unlike established CAR-T therapies for cancer that use DNA-based approaches, Cartesian opted for an RNA-based approach. Cartesian Therapeutics extracts the killer T-cells from patients, engineer it with RNA, then insert the cells back into the patient. The personalized therapy is more predictable and offers controllable pharmacokinetics, Kalayoglu said. It also avoids the risk of genomic integration.

“Our mission is to unleash the potential of cell therapy through RNA engineering,” he said.

Last year, 68-year old Danny DeBerry shared his testimony at a Myasthenia conference about the benefits he has seen from treatment with Descartes-08. His worsening symptoms of muscle weakness due to the autoimmune disorder were arrested and he saw marked improvement in his life, even bicycling 10 miles per day following the six-week regimen.

DeBerry’s story is only one of numerous patients who have so far received the T-cell therapy created from his own blood. When the Phase IIb study is complete, Cartesian anticipates the positive data will allow it to move forward into a Phase III registrational study that will offer a new treatment option to MG patients.

The primary endpoint of the Phase IIb study is the proportion of participants who achieve a 6-point or greater improvement in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score at 12 weeks. Secondary endpoints include safety and other validated measures of MG disease severity. Kalayoglu said the trial includes a crossover design that will allow placebo patients to receive Descartes-08 after the six week dosing period is over.

There are approved therapies for MG, including the recently-approved Vyvgart, a neonatal Fc receptor blocker developed by Belgium-based Argenx. But, Kalayoglu believes Descartes-08 will be a welcome option for patients due to the duration of effect. Although long-term duration is not yet known, Cartesian has been following multiple patients for months after treatment. So far, none have needed additional medications, Kalayoglu said.

“This appears to be a potent and safer cell therapy,” he said. “It’s too early to say how long the benefits will last but right now, we believe the benefits are durable.”

And that durability will be additional welcome news for patients who suffer from the autoimmune disorder. Generalized MG causes disabling muscle weakness and fatigue. The cause of the autoimmune disorder is unknown but ultimately, the body attacks itself and damages the junction between the nerve cells and muscular cells. Kalayoglu said the weakness can be so bad that some patients are unable to open their eyelids. The weakness can extend across the body and in some cases, result in death due to an inability to breathe. There is no cure for MG and Kalayoglu said most treatment options require chronic immunosuppressive medicines, which have inherent risks and side effects.

Generalized MG is what Kalayoglu called a “textbook autoimmune disease.” If a treatment works in MG, it is likely to show efficacy in other autoimmune diseases. It will be something the company intends to explore in the future. In the meantime, Kalayoglu noted the company has received requests from physicians for expanded access to Descartes-08 for the treatment of other autoimmune disease.

Beyond generalized MG, Cartesian is also assessing an off-the-shelf cell therapy for multiple myeloma. The company also has preclinical programs in lymphoma, lupus and other autoimmune disorders.