Expert Interview
A discussion of CABA-201, a Newly Designed CD19-Targeting CAR T Cell Therapy Engineered to Address a Broad Range of Autoimmune Diseases
Ticker(s): CABAInstitution: University of Erlangen-Nurember
- Professor of Translational Immunology & Senior managing physican Department of Rheumatology and Immunology at University Hospital Erlangen.
- Research focuses on the fundamentals of the immune response not only enables a better understanding of autoimmunity and inflammation, but is also the basis for the development of new and targeted therapeutic approaches for autoimmune and chronic inflammatory diseases.
- Author on Nature Medicine paper showing dramatic and durable remissions in CD19-CAR T treated systemic lupus erythematous (SLE) patients.
Cabaletta Bio has recently announced a new program for a CD-19 CAR containing a 4-1BB co-stimulatory domain and CD-3 Zeta signaling domain. This program includes a fully human CD19-binder they licensed from IASO Bio (already tested in early Phase 1 oncology studies). Assuming they were developing this to treat SLE to match the very encouraging results seen by you and your colleagues in the Nature Medicine paper, what are some of the key hurdles they face in moving this into the clinic and beyond?
What do you anticipate are some of the capabilities required to execute on this approach at scale (i.e. manufacturing specialization, storage and logistics)?
In the Nature Medicine paper, a number of caveats were discussed regarding moving this treatment modality to indications outside of SLE. Can you elaborate on which indications these caveats may refer to, and how likely, in your view, is it that these caveats may present substantial hurdles? Some examples of the caveats include:a. “This approach requires that the disease is driven by B cell activation and plasmablast generation rather than long lived plasma cells, which are usually CD19 negative”
b. “[patients] with antibodies against RNA-binding proteins may respond less well to the approach presented."
Is there any reason to believe tolerability of the therapy will be any different than CAR-T products used in oncology?
Do you believe the patients in the current NIH SLE study will eventually relapse? Why or why not?
Are you familiar with Cabaletta’s DSG-3 CAART product, and if so do you have ideas on why it hasn’t had much of an effect in Pemphigus Vulgaris to date?
Can you describe any difference in approaches between Cabaletta's SLE approach and that of Kyverna's where Dr. Schett is on the Board. Are they similar or could you clarify so we can have a better understanding.
Cabaletta's DSG-3 CAART product failed to work as mono therapy even with high doses. Do you think they will encounter this issue again in Myashthenia Gravis or other autoimmune diseases? Will there always be a need for pre-conditioning in autoimmune diseases? Your comments if you think there can be something developed without it.
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