Cartesian Data Advances CAR-T in Autoimmune Disease

Cartesian Therapeutics recently announced progress with its experimental cell therapy, Descartes-08, during a mid-stage clinical trial for myasthenia gravis, a rare autoimmune disorder. Despite these promising results, Cartesian's stock price dropped significantly. The trial demonstrated that 10 out of 14 participants who received the therapy showed a 5-point or greater reduction in disease severity after three months, compared to 3 out of 12 participants who received a placebo. The adverse events reported were mostly mild and transient.

Cartesian is now looking to advance Descartes-08 to late-stage trials, although some questions remain about the exclusion of certain participants from the efficacy analysis, which nearly affected the statistical success threshold. Cartesian is one of several companies exploring cell therapies for autoimmune diseases, aiming for long-term remissions with a one-time treatment. This approach is different from traditional methods that often require continuous medication.

The company's unique method involves an mRNA-based treatment that doesn't need a chemotherapy conditioning regimen. This strategy targets a different B cell protein, BCMA, which may make the therapy more accessible and quicker to produce compared to other cell-based treatments. Cartesian's initial focus is on myasthenia gravis, which causes muscle weakness and is typically managed with immunosuppressive steroids or biologics. CEO Carsten Brunn emphasized that the recent results establish proof-of-concept for this approach, noting the absence of immune or neurological side effects commonly associated with cell therapies.

In addition to myasthenia gravis, Cartesian has begun testing the therapy in lupus and is considering other autoimmune diseases like rheumatoid arthritis. Some analysts are optimistic about Descartes-08's potential. Thomas Smith, from Leerink Partners, highlighted the significance of this placebo-controlled study, noting its consistency with previous open-label study results.

Despite the positive outcomes, several key questions remain, such as the duration of the treatment's effects, its effectiveness compared to existing biologics, and the variability in patient responses. Differences in baseline characteristics among study groups, like disease duration, could also influence the results. During a recent conference call, analysts questioned the company's decision to exclude nine volunteers treated at community practices from the efficacy analysis. This decision was explained as a necessary trade-off to ensure that more subjects adhered to the trial protocol, although it did reduce the study's statistical power.

Chief Medical Officer Milos Miljkovic defended this decision, stating that including community site patients in the analysis still met statistical significance, indicating that the treatment's efficacy wasn't compromised. Miljkovic expressed confidence that there wouldn’t be issues administering Descartes-08 in community settings for Phase 3 trials.

Nonetheless, the company's stock suffered a nearly one-third drop following the announcement. This decline reflects the market's cautious stance, possibly due to the unanswered questions and the complexities involved in developing new therapies for autoimmune diseases. The upcoming late-stage trials will be crucial in determining Descartes-08's long-term viability and its potential impact on the treatment landscape for myasthenia gravis and other autoimmune conditions.