Cartesian's mRNA CAR-T achieves new primary goal in myasthenia gravis study

Cartesian Therapeutics experienced a significant decline of over 10% in premarket trading on Tuesday following the release of mid-stage results for its treatment for generalized myasthenia gravis (gMG). Despite the downturn, one analyst highlighted the study as a pivotal moment for CAR-T therapies beyond oncology. "These data signify a milestone for the field, marking the first placebo-controlled study of a CAR-T cell therapy in autoimmune diseases," noted Thomas Smith, an analyst at Leerink Partners.

The company announced that its mRNA CAR-T candidate, Descartes-08, met its primary endpoint in a Phase IIb trial, albeit a revised one. In May, Cartesian shifted the primary outcome measure from the widely used Myasthenia Gravis - Activities of Daily Living (MG-ADL) scale to the Myasthenia Gravis Composite (MGC) score. The MGC is a more comprehensive tool, comprising 10 items and 60 points that evaluate MG severity and impact. While a reduction of three points or more is generally seen as clinically significant, Cartesian set a stricter benchmark of five points based on initial clinical responses to Descartes-08.

The mid-stage study included 36 heavily pre-treated and highly symptomatic gMG patients who were randomized to receive either Descartes-08 or a placebo. The treatment was administered as six weekly outpatient infusions without the need for preconditioning chemotherapy. The primary efficacy analysis focused on a modified intent-to-treat population of 26 patients treated at academic medical centers. In this group, 71% (10/14) of patients treated with Descartes-08 achieved a ≥5-point improvement in their MGC score by the third month, compared to 25% (3/12) in the placebo group. In the per-protocol population, 69% (11/16) of Descartes-08 patients saw this level of improvement, compared to 33% (5/15) for the placebo group.

The MG-ADL scale was relegated to a secondary endpoint in this trial. Descartes-08 recipients showed a notable benefit with a -5.6 point improvement at the three-month mark. The company also observed that these improvements persisted or further improved at the four and six-month follow-up visits.

As for safety, Cartesian reported that Descartes-08's profile supported outpatient administration without lymphodepleting chemotherapy. Adverse events were described as "transient and mostly mild," with no cases of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. However, the trial did note some imbalances between the treatment groups. Specifically, five placebo patients (42%) had a diagnosis of thymoma, whereas none in the Descartes-08 group did. Additionally, more placebo patients had received prior complement inhibitors or FcRN antagonists and had undergone thymectomy.

CEO Carsten Brunn expressed optimism, stating, "We believe the positive data presented today demonstrate clinical proof-of-concept of our novel mRNA platform and highlight the potential of Descartes-08 to provide deep and durable improvements for patients with MG." Cartesian plans to hold an end-of-Phase II meeting with the FDA by the end of the year.

In other company news, Cartesian, which completed a reverse merger with Selecta Biosciences last November, announced a $130-million private placement equity financing on Tuesday.