mRNA-CAR-T Descartes-08's Potential for Treating Myasthenia Gravis

Miloš Miljković, MD

Cartesian Therapeutics' Descartes-08, the company’s lead product candidate, is an autologous, BCMA-directed, mRNA-engineered chimeric antigen receptor T-cell (CAR-T) therapy currently under evaluation for the treatment of autoimmune indications including myasthenia gravis (MG) and systemic lupus erythematosus. The company presented promising data regarding the CAR-T in MG at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, MD.

Shortly before the presentation, CGTLive® interviewed Miloš Miljković, MD, the chief medical officer of Cartesian Therapeutics, to learn more. Miljković discussed the potential of mRNA-engineered CAR-T in autoimmune disease and the challenges that the company has overcome so far in bringing the modality to MG.

CGTLive: Can you give some background context for Cartesian's presentation at ASGCT?

Miloš Miljković, MD: The presentation describes 12 month follow up data for Descartes-08, which is an autologous BCMA-directed mRNA CAR-T therapy in patients with MG.

What are the key points that will be presented?

Last year, we presented early follow-up data with up to 6 months of follow-up for most patients and then we showed that patients who got 6 months weekly doses of Descartes-08 had deep responses across all 4 severity scales in MG. We will show [at this year's conference] that these patients remained in deep remission—so they still had deep responses up to 12 months of follow-up and past that. Two of the 7 patients had their response go back to baseline, so their disease went back to baseline, but 1 of the 2 was successfully retreated and had a deep response. The other patient did not receive retreatment. Then a third patient lost their response a year and a half after treatment and they were also successfully retreated.

How would you summarize the main implications that the healthcare community should take away from this?

mRNA cell therapy seems to be very clinically active in autoimmune diseases. MG is the lead indication. It's administered without lymphodepletion chemotherapy and in an outpatient setting and has a great safety profile with no cytokine release syndrome, no immune effector cell-associated neurotoxicity syndrome, and no dose-limiting toxicities across all patients who were treated under open-label.

Were there any challenges or limitations that came up in this research?

During the study covid happened, so that sort of limited the enrollment pace. But the main thing with cell therapy, as it expands in other spaces outside of oncology, is really bringing together different parts of institutions that never spoke to each other before. So here we had very experienced investigators in MG, but they had to meet with cell therapy teams, apheresis teams, sometimes under the same institution, and sometimes under a separate cancer center. That takes a lot of work to get the parties talking together, but once they do, the results are great.

Are there any future plans for further research that you can discuss a bit?

We have investigational new drug allowance for Descartes-08 for systemic lupus and we're on track to dose the first patient in the first half of this year. We're also looking at other indications in the autoimmune space. When you have a treatment that has no lymphodepletion and it's an outpatient setting you can really have a broad choice of possible indications, so we're really taking a careful look at that.

Is there anything else you want to add?

The open-label study has a randomized controlled trial extension, so we have an ongoing double-blind randomized control trial of Descartes-08 in MG, where we'll have at least 30 patients randomized 1:1 to get either Descartes-8 or placebo. This is, we believe, the first double-blind placebo control trial of any engineered cell therapy for any indication, and we are on track to get top-line data of this in the middle of this year. so that's coming soon.

This transcript has been edited for clarity.

Click here to view more coverage of the 2024 ASGCT Annual Meeting.

REFERENCES
1. Howard JF, Mozaffar T, Vu T, et al. Investigation of mRNACellTherapy as a Treatment for AutoimmuneDisease in Patients withMyastenia Gravis. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #241