Dive Brief:

• Cartesian Therapeutics on Tuesday said an experimental cell therapy it’s developing succeeded in a mid-stage clinical trial of people with the rare autoimmune condition myasthenia gravis, but shares in the biotechnology company fell by double digits nonetheless.
• According to Cartesian, 10 of the 14 participants who received its therapy and, per the study’s design, were evaluable for efficacy, had a 5-point or greater reduction on a measure of disease severity after three months of follow-up. Three of 12 placebo recipients met that mark, by comparison. Adverse events were “transient and mostly mild,” the company said.
• Cartesian claims the data support advancing the therapy, Descartes-08, into late-stage testing. Yet questions remain about the findings, as some participants were excluded from the efficacy analysis and, in the overall study population, results came closer to missing the statistical threshold for success.

Dive Insight:

Cartesian is among the leaders in a push by drugmakers to develop cell therapies for autoimmune conditions.

Like Kyverna Therapeutics, Cabaletta Bio and many others, the company aims to show that a one-time, cellular treatment can produce long-lasting remissions that free people needing other medicines. Early results from some companies have shown promise, but revealed flaws as well.

Cartesian is evaluating an mRNA-based treatment that doesn’t involve a chemotherapy conditioning regimen — a requirement of many experimental autoimmune cell therapies — and targets a different B cell protein, BCMA, than some others in development. It claims these characteristics could make its therapies more widely accessible and quicker to produce than other cell-based medicines.

The company is starting with myasthenia gravis, a disease characterized by muscle weakness that’s typically treated with immunosuppressive steroids or biologics. With the results announced Tuesday, Cartesian claims it’s now achieved “proof-of-concept” for the approach, CEO Carsten Brunn said in a statement. Notably, the company hasn’t seen any of the immune or neurological symptoms associated with cell therapies. It’s also started a test in lupus and envisions pursuing other diseases, such as rheumatoid arthritis.

Some analysts are already convinced of Descartes-08’s potential.

“These data mark a watershed moment for the field, representing the first placebo-controlled study of a CAR-T cell therapy in autoimmune disease.” wrote Thomas Smith, of the investment bank Leerink Partners, in a note to clients. The results “appear consistent” with what Cartesian reported in a separate open-label study, Smith added.

Still, there are unanswered questions, such as how long the treatment’s effects might last, how it compares to available biologics, and who will or won’t respond. There were also differences among study groups in baseline characteristics — such as how long volunteers have had their disease — that could affect the findings.

Analysts on a conference call zeroed in on a decision by the company to exclude from its efficacy analysis nine volunteers treated at community practices. Shares lost nearly a third of their value Tuesday morning.

On the call, Cartesian executives said that decision was a trade-off that lowered the study’s statistical power. But “we thought the trade-off was worth it,” said chief medical officer Milos Miljkovic, as it ensured more subjects were treated according to the trial protocol. What’s more, an analysis including patients at community sites still met statistical significance, he said.

“It really made no difference, ultimately,” Miljkovic argued. “So we’ll see for the Phase 3,” but “I don’t think there are issues administering Descartes-08 in the community.”