Expert Interview
Discussing the potential of CD19 targeted therapies in systemic lupus erythematosus (SLE)
Ticker(s): AMGN, CGEM, ELYM, CABAInstitution: University College Hospital, London
- Emeritus Professor of Rheumatology at University College London
- Chairs Lupus UK Research Committee, and founding member and Chair of BILAG and SLICC lupus study groups
- Published over 600 original articles and over 300 reviews, chapters and written and/or edited 20 books
What are the limitations of a low fucosylation antibody (TNT119 fka DIB4) vs a fully afucosylated antibody (inebilizumab)?
How do you view the translatability of CART which includes lymphodepletion to bispecific therapy that will not have lymphodepleting regimens?
What SLE endpoints/subscales (skin/heme/etc) have traditionally been more responsive to B-cell depleters?
CD19 Readthroughs
CART to antibody
Blinatuomomab (RA) to CLN-978 (SLE)
lymphoma data to SLE (best CD19 lymphoma drug = best in SLE?)
Uplizna (MG, NMO, Igg4) to SLE - How can low igg reduction (vs. FcRn) w/CD20,19 translate to efficacy?
CD19 antibody structures (monoclonal constructs vs TCE) - ROCHE/BIIB's CD20xCD3 in SLE?
Rituximab limitations (tissue penetration, CD20 expression) solved by CD19?
Novel targets? RNAC?
What is NVS (Richard Siegel) thinking?
Can you provide some perspective for challenges of enrolling SLE patients in clinical trials? Does the depletive nature of these antibodies add extra hurdles?
Can you contextualize the patient profile that would likely be a candidate for a TCE or CAR-T therapy?
Mechanistic advantage of CD19 vs. CD20 vs. BAFF/APRIL (and even BCMA)?
CD20: Do you use rituximab off label in SLE patients? If so, what's your experience with it? Why no benefit for rituximab vs. pbo in Ph3 EXPLORER and LUNAR studies? Due to mechanism, background therapy, clinical endpoints, etc.? Views on whether obintuzumab for SLE?
CD19 CART: Views on Schett SLE data (Nature Medicine, 2022)? Looking at baseline characteristics, how representative were the five patients to the SLE population you treat and those SLE pts in clinical trials? Experience treating SLE pts with cyclophophamide and their clinical response? With current SOC, how often do patients achieve remission criteria according to DORIS? What are your views on current data (SLEDAI-2k reductions and B cell response) from CABA-201? If data holds, who is the pt profile for CART in SLE?
CD-19 TCE (blinatumumab) data in RA: Views on data? Read-through to SLE?
CD19 MOA in lupus nephritis: Expectations for this mechanism to work in pts w/ renal involvement? Do autoantibodies play a larger/smaller/similar role vs. extra-renal lupus?
Current unmet need in SLE: real-world efficacy with Benlysta and where does it fall short? Could CD19 directed therapy prevent proteinuria and progression to renal involvement?
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