iCell Presents Positive New Follow-up Clinical Data Confirming BCMA CD19 cCAR Safely Delivers Long-term Medication Free Complete Remission from Systemic Lupus Erythematosus & Lupus Nephritis at EULAR 2024

iCell Gene Therapeutics, Inc., a clinical-stage biotechnology company focused on the research and development of proprietary CAR immunotherapies for patients with unmet medical needs in autoimmune diseases and cancer, today announced new longer-term follow-up data from the Company's BCMA CD19 compound chimeric antigen receptor (cCAR) T cell immunotherapy development program. The new data were part of iCell's oral presentation regarding results of the investigator-initiated Phase 1 clinical trial of the BCMA CD19 cCAR in systemic lupus erythematosus (SLE) patients with lupus nephritis (LN) at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress taking place from June 12-15 in Vienna, Austria.

With the mean follow-up duration extended to 20 months in SLE patients (mean 16 months in LN patients), the new data presented at EULAR further confirms iCell's BCMA CD19 cCAR is well tolerated and delivers long-term, medication-free remission in SLE patients and specifically in 10 LN patients who received 3x10⁶ cCAR cells/kg:

• All elevated autoantibodies were eliminated in all 12 patients
• All 12 patients scored 0 on Physician Global Assessment
• All 12 patients are lupus medication free with no relapses
• 11 out of 12 (92%) patients now meet the DORIS criteria for complete remission (up from 9 patients meeting the criteria detailed in the manuscript published in May 2024 in the Annals of the Rheumatic Diseases)
• Renal function continues to improve in LN patients. All six patients diagnosed with LN less than 10 years ago had a complete renal response with a mean normal 24-hour protein (>90% decline from screening). Renal function improved in 2/4 LN patients diagnosed more than 10 years ago or with chronic kidney disease (CKD). The only two patients with follow-up renal biopsies show no active disease.
• cCAR treatment was well tolerated, with minimal infections (COVID-19, one grade 1 UTI), no cytokine release syndrome (CRS)>1, no CAR-T-cell-related encephalopathy syndrome (CRES), no immune effector cell-associated neurotoxicity syndrome (ICANS). Humoral immunity has now recovered in all LN patients.

"It is exciting to see the continued progress over time in patients with lupus nephritis treated with iCell's BCMA CD19 compound CAR therapy," said Yupo Ma, M.D., Ph.D., Founder and Chief Scientific Officer of iCell Gene Therapeutics. "Humoral immunity is now recovered in all LN patients. Eleven patients are in complete remission, with all elevated autoantibodies and lupus symptoms eliminated, and the ongoing improvement in kidney function and recovery from lupus renal damage in these patients is encouraging. We are excited to progress this therapy in clinical development and plan to file INDs in the United States and China soon."

"iCell's BCMA CD19 compound CAR therapy is a differentiated approach and has the most mature safety database among autoimmune cell therapy candidates," said Greg Deener, Chief Executive Officer of iCell Gene Therapeutics. "Our BCMA CD19 targeted cell therapy proof-of-concept study is the only trial of which we are aware that has demonstrated the safe elimination of all autoantibodies, delivering complete remission in the vast majority of patients. We are hopeful these results will translate into the breakthrough needed for patients with lupus and other autoimmune diseases."

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, enhance function, and to allow for cyclophosphamide-only conditioning.

The single arm investigator initiated trial (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 LN patients 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. The efficacy population is comprised of the 2 initial SLE patients and the 10 LN patients at the target dose.

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, IgA within a year and IgG is >400 mg/dL in all patients. 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 SLE 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 with 11/12 (92%) meeting the DORIS criteria for complete remission. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) reduced from 9.9 (baseline) to 2.3 at 3 months (11/12 are "0" at last follow up with one patient scoring 4 on proteinuria likely due to long-term damage as there are no signs of active disease). 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 Systemic Lupus Erythematosus (SLE) / Lupus Nephritis (LN)

SLE 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. LN 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. The DORIS task force, an international group of 60 lupus specialists who met annually from 2015 ? 2021, established criteria for complete remission in SLE to include clinical SLEDAI = 0, no serological activity, SELENA-SLEDAI Physician Global Assessment (PGA) ? 0.5, no glucocorticoids, and no immunosuppressants and / or biologics.

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/