Cartesian Therapeutics Advances mRNA CAR-T Candidate Descartes-08 into Phase 3 for Autoimmune Diseases with Favorable Safety and Durability Profile

Recently,Cartesian Therapeutics reported the Phase 2b trial data of its investigational mRNA CAR-T cell therapy, Descartes-08, for the treatment of myasthenia gravis.

In addition, Cartesian Therapeutics disclosed the Phase 3 clinical plan for Descartes-08, with the Phase 3 clinical trial AURORA expected to launch in the first half of 2025 to evaluate its use in treating myasthenia gravis.

Descartes-08 is an autologous BCMA-targeted, mRNA-engineered, autologous CAR-T cell developed for generalized myasthenia gravis (GMG) and lupus erythematosus.

Descartes-08 obtains CD8+ cells from patients, which are then modified via RNA engineering in vitro to become CAR-T cells expressing BCMA.

Traditional CAR-T cell preparation is based on DNA transduction, mRNA engineeringCAR-T cells, however, are based on RNA engineering and utilize the same steps as in mRNA vaccine engineering, including optimal 3ʹ and 5ʹ untranslated regions, Poly(A) tail length, and 5ʹ ends to enhance mRNA stability and improve translation efficiency.

mRNA CAR-T, which does not involve DNA integration, can avoid the risk of genomic integration associated with carcinogenesis that may occur with traditional CAR-T. In addition, mRNA-engineered CAR-T does not require chemotherapy pretreatment.

Currently, Descartes-08 has been granted Regenerative Medicine Advanced Therapy (RMAT) designation and Orphan Drug designation by the U.S. FDA for the treatment of MG and lupus erythematosus.

InDescartes-08In the Phase 2b trial, a total of 36 patients with MG were enrolled and randomized 1:1 to receive either Descartes-08 or placebo, with six outpatient infusions per week without pre-conditioning chemotherapy. The study met its primary clinical endpoint and supported the safety of outpatient administration of Descartes-08.

The primary efficacy dataset of the trial's follow-up portion includes the modified intention-to-treat (mITT) population of all subjects enrolled at academic medical centers who received at least one dose of Descartes-08 and completed the Month 3 MG-ADL assessment.(MG Daily Life Quality Scale, mainly used to assess the impact of MG patients' symptoms on daily life quality, thereby reflecting the severity of the disease)ScoreFollow-up Evaluation。

As of October 31, 2024, in the primary efficacy dataset, 12 participants completed the 4-month and 6-month follow-up assessments, 8 participants were available for the 9-month follow-up assessment, and 5 participants...ParticipantsThe 12-month follow-up assessment can be conducted. Two patients achieved MGC at the 3rd month.(Myasthenia Gravis Composite Scale)ResponsiveParticipantsLost to follow-up after the 3-month assessment and was not evaluated during the follow-up portion of the treatment.

The latest updated data shows:

Over time, a deepening of responses was observed, with the 12 participants showing an average MG-ADL reduction of 5.5 (±1.1) at Month 4.

In the 4th month, in patients who had not previously been exposed to biologic therapies (including complement or neonatal Fc receptor inhibitors),Participants(n=7), the average MG-ADL decreased by 6.6 (±1.5).

A deeper relief was observed at the 6th month, with 33% (4/12) ofParticipantsAnd 57% (4/7) of those previously untreated with biologic therapyParticipantsObserved the lowest symptom expression, with MG-ADL scores of 0 or 1.

The remission before the 12th month was durable, with 80% (4/5) of evaluableParticipantsMaintain clinically meaningful relief, defined as a reduction of at least 2 points in the MG-ADL score.

At the 12th month, 2 patients who had not previously been exposed to biological therapyParticipantsIn China, 2 casesParticipantsAll maintained clinically meaningful remission, with one continuing to exhibit minimal symptom expression.

In terms of safetyDescartes-08 demonstrated good tolerability, supporting outpatient administration without the need for lymphodepleting chemotherapy. Consistent with previously reported data, Descartes-08 showed good tolerability across the entire safety dataset (n=36), with adverse events being transient and mostly mild. Notably,No CRSand ICANS CasesAdditionally, no reduction in vaccine titers for common viruses was observed following Descartes-08 treatment, and it was not associated with an increased infection rate or hypogammaglobulinemia.

In addition, Cartesian announced the completion of the Phase 2a open-label portion.ParticipantsThe updated data. 2 patientsParticipateThe participant exited earlier, with rapid improvement in clinical scores and maintained minimal symptom presentation for up to a year after receiving the second treatment cycle. The third participant received a second treatment cycle, and at the participant's 2-month visit, two weeks after the final Descartes-08 infusion, the MG-ADL score decreased by 4 points and the MGC score decreased by 6 points from baseline, with no reports of CRS or ICANS. Upon re-treatment, the time course and magnitude of the therapeutic response were similar to those observed during the participant’s initial treatment. Four out of the seven remaining participants from the Phase 2a trial portion sustained a clinically meaningful response for at least one year after the initial dosing.

Based on the positive results of the Descartes-08 Phase 2 trial, Cartesian Therapeutics expects to advance to Phase 3 clinical trials in the first half of 2025.

Based on the positive results of the Descartes-08 Phase 2 trial, Cartesian Therapeutics expects to advance to Phase 3 clinical trials in the first half of 2025.This shouldYesThe fastest-progressing mRNA CAR-T cells, used forTreatment of autoimmune diseases.

Despite the advantages of Descartes-08, such as being administrable in an outpatient setting, not requiring lymphodepletion, and having low side effects, the need for six outpatient infusions per week—approximately once every day—will likely significantly reduce patient compliance. Moreover, as an autologous CAR-T therapy, the cost is also unlikely to be low.

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