iCell Gene Therapeutics Announces Positive Clinical Data from Investigator Initiated Phase 1 Trial Evaluating BCMA-CD19 Compound CAR in Patients with Systemic Lupus Erythematosus/Lupus Nephritis Published in Annals of the Rheumatic Diseases
23 Mayo 2024 - 6:00AM
Business Wire
– BCMA-CD19 compound CAR (cCAR) therapy was
safe and well tolerated and achieved proof of concept of complete
humoral reset delivering long-term medication-free remission –
– iCell’s BCMA-CD19 cCAR was the first CAR T
evaluated in autoimmune disease with first SLE patient treated
September 2019 –
– Based on successful IIT study, iCell plans to
file INDs in U.S. and China –
iCell Gene Therapeutics, a clinical stage biopharmaceutical
company focused on immunotherapies for autoimmune disorders and
cancer, today announced the publication in Annals of the Rheumatic
Diseases of positive results of an investigator initiated clinical
trial (IIT) for its BCMA-CD19 compound chimeric antigen receptor
(cCAR) T cell immunotherapy.
The clinical trial evaluated the safety and efficacy of a
complete humoral reset of both long-lived plasma cells and B cells
in 13 systemic lupus erythematosus (SLE) patients treated with
iCell’s cCAR, including 11 patients with SLE and lupus nephritis
(LN). All patients (12/13) who received an initial dose of 3x106
cCAR cells/kg were negative for all autoantibodies, including those
derived from long-lived plasma cells, 3-months post-cCAR, and the
complement returned to normal levels. These patients achieved
symptom-free and medication-free remission (MFR), with post-cCAR
follow-up to 46 months. cCAR therapy was well tolerated with mild
cytokine-release syndrome (no CRS >1). iCell considers this IIT
to be a successful proof of concept; the Company plans to file an
investigational new drug application (IND) for its BCMA-CD19 cCAR
in the United States and China.
iCell’s cCAR, with two independently functioning CARs in a
single construct targeting the B cell CD19 and the plasma cell BCMA
surface antigens, is uniquely designed to completely reset humoral
immunity and address the underlying cause of SLE/LN through the
elimination of all elevated autoantibodies including those produced
by long-lived plasma cells.
Unique armoring of iCell’s cCAR allows for safe pretreatment
conditioning with cyclophosphamide only (no fludarabine was used in
LN patients), and patients in the study discontinued all lupus
medications, including glucocorticoids and immunosuppressants,
prior to cCAR treatment and remained lupus medication-free
post-infusion. There are currently no approved therapies that
deliver MFR in SLE/LN patients who are at high risk of long-term
organ damage and kidney transplant.
“This study demonstrates that the complete reset of humoral
immunity results in elimination of all elevated autoantibodies,
that long term medication free remission is achievable, and that
treatment with a BCMA-CD19 compound CAR is well-tolerated in
patients suffering from lupus nephritis. The data show humoral
immunity recovering, a low rate of infections, no CRS greater than
1, and no ICANS observed to date,” said Yupo Ma, M.D., Ph.D., Chief
Scientific Officer and Founder of iCell. “iCell now has the largest
clinical dataset of autoimmune patients receiving CAR therapy, and
we are excited to continue the advancement of our BCMA-CD19
cCAR.”
“iCell first envisioned the potential for CAR treatments in
autoimmune diseases more than 10 years ago and subsequently became
the first to patent a BCMA-CD19 compound CAR. Nearly five years
ago, we were the first company worldwide to treat an autoimmune
patient with a CAR, and we are delighted to see that this patient
continues to do well,” said Greg Deener, Chief Executive Officer of
iCell. "We look forward to receiving further follow up data
confirming the promising results to date, and we plan to present
this data on June 12th at the European Alliance of Associations for
Rheumatology (EULAR) 2024 Congress.”
Study Details:
iCell designed its cCAR T Cell immunotherapy to express two
distinct and fully functional CAR molecules in a single construct,
one that targets the molecule CD19 present on B cells and one that
targets BCMA present on plasma cells. Targeting both B cells and
long-lived plasma cells is needed to eliminate all elevated
autoantibodies, given they have separate and redundant memory.
iCell’s cCAR is armored to safely promote T cell survival and
function and to allow for cyclophosphamide-only conditioning.
The single arm IIT evaluating iCell’s BCMA-CD19 cCAR was
conducted in two leading centers in China, Zhongshan People’s
Hospital and Peking University Shenzhen Hospital. Initially two
patients with SLE and comorbid localized lymphoma were treated with
the BCMA-CD19 cCAR (the first in September 2019); 11 patients with
LN with biopsy-confirmed active disease (Class III-V) and
inadequate response to at least two lines of therapies were
subsequently enrolled into the study and treated between June 2022
and February 2023. Ten LN patients received the target single cCAR
dose of 3x106/kg.
Overall, the cCAR therapy was found to be generally safe and
well-tolerated. The 10 LN patients receiving the target dose
achieved depletion of B cells from peripheral blood within 10 days
post-cCAR treatment and depletion of immunoglobulin within 42 days,
and complete recovery of B cells and IgM was seen within 2-6 months
post-cCAR. Excluding COVID-19, the only infection reported was a
grade 1 urinary tract infection. In iCell’s overall cCAR safety
database of 18 patients with autoimmune diseases (including the 13
patients with SLE or LN), there have been no CRS >1 and no ICANS
or CRES.
All lupus patients (12/13) who received the target dose were
negative for all autoantibodies, including those derived from
long-lived plasma cells, 3-months post-cCAR, and the complement
returned to normal levels. Patients achieved symptom-free and
medication-free remission (MFR), with post-cCAR follow-up to
46-months. Mean Systemic Lupus Erythematosus SLE Disease Activity
Index 2000 (SLEDAI-2K) reduced from 9.9 (baseline) to 2.3 (3
months), and mean renal function significantly improved in the 10
LN patients ≤90 days post-cCAR. The data suggest that cCAR therapy
was safe and effective in inducing MFR and depleting
disease-causing autoantibodies in SLE and LN patients.
About SLE/LN
Systemic lupus erythematosus is an antibody-mediated autoimmune
disease, in which autoantibodies attack the body’s own tissues,
resulting in widespread damage in affected organs including
kidneys, lungs, joints, brain and blood vessels. According to the
Lupus Foundation of America, an estimated 1.5 million Americans,
and at least five million people worldwide, have SLE/LN. Lupus
nephritis affects ~40% of SLE patients and disproportionately
burdens nonwhite women from lower socioeconomic groups. LN patients
have a 6-fold higher risk of mortality with 1 in 4 progressing to
end stage renal disease There are currently no treatments targeting
the underlying causes of the disease delivering MFR. Standard of
care LN treatments have substantial side effects. Prolonged
immunosuppression increases the risk of serious infections and
cancers. Glucocorticoid associated adverse effects include
osteoporotic fractures, avascular necrosis, diabetes mellitus,
cataracts, glaucoma, and premature mortality.
About iCell Gene Therapeutics
iCell Gene Therapeutics is a clinical-stage biopharmaceutical
company developing chimeric antigen receptor (CAR) immunotherapies
designed to be innovative, first-in-class and lifesaving. iCell is
focused on developing treatments for diseases where no treatment
options exist and where dramatic improvements in quality and
duration of life are needed, including autoimmune disorders, AML,
and T-cell malignancies. The company is currently conducting
clinical trials in the U.S. and China utilizing its CARvac, T-cell
targeted CARs, compound CARs and non-gene edited universal CARs
engineered as treatments for autoimmune diseases, cancer, and organ
rejections. For more information, please visit
http://icellgene.com/
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Investor Contact: Greg Deener, CEO greg.deener@icellgene.com
Media Contact: Argot Partners icellgene@argotpartners.com