World Lupus Day 2024: Looking Back at a Year of New Cell Therapy IND Clearances

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In observance of World Lupus Day, held annually on May 10, we took a look back at a year of progress in bringing CAR-T to this autoimmune disease.

Over the past year or so, an explosion of interest has taken place across industry and academia in bringing advanced cell therapy modalities such as chimeric antigen receptor T-cell (CAR-T) therapy to the field of autoimmune disease. Many institutions have launched their efforts by targeting systemic lupus erythematosus (SLE) and lupus nephritis (LN), and between 2023 and 2024 an unprecedented number of investigational new drug (IND) application clearances were secured from the FDA for cell therapy candidates in these indications.

For World Lupus Day, observed annually on May 10 by the patient and clinician communities, CGTLive® is taking a look back at these and other milestones in the development of cell therapy products for lupus that have occurred over the past year. Click the "READ MORE" buttons for more details and information about each item.

Caribou Biosciences Cleared to Evaluate Allogeneic CAR-T CB-010 in Lupus

April 8, 2024 — In light of the IND clearance, Caribou stated that it anticipates initiating its planned phase 1 GALLOP clinical trial (NCT identifier pending) for CB-010 in patients with LN and ERL by the end of 2024. The open-label, multicenter study will evaluate a single dose level of CB-010, which will be delivered as a single infusion following a cyclophosphamide and fludarabine conditioning regimen. Notably, participants will receive CB-010 manufactured from donors with partial human leukocyte antigen (HLA) matching, with the intention of achieving better clinical outcomes.

Synthekine Cleared to Tackle Lupus With CAR-T and IL-2 Combination Therapy in US Clinical Trial

March 27, 2024 — Notably, the combination therapy, which is based on the company’s proprietary orthoIL-2 technology, will be administered without the use of lymphodepletion. In the planned multicenter, dose-escalation study, SYNCAR-001 will be administered as a one-time, fixed dose. On the other hand, patients will receive a limited course of STK-009 administered by subcutaneous injection each week. Synthekine anticipates enrollment of the first patient in the trial to take place in the second half of this year.

Atara Biotherapeutics Joins Lupus CAR-T Race With Allogeneic Candidate ATA3219

March 12, 2024 — Atara is planning to conduct a phase 1 clinical trial for ATA3219 that will treat patients with SLE and LN. The multicenter, open-label, dose-escalation trial will utilize 3 different dose levels: 40x106 CAR+ T-cells, 80x106 CAR+ T-cells, and 160x106 CAR+ T-cells, with a group of 3 to 6 patients to be assigned to each dose level. The company anticipates that the first participant will be enrolled during the second half of this year. Participants will receive ATA3219 as a 1-time infusion after lymphodepletion. Atara expects to announce initial data from the trial in the first half of 2025.

Gracell’s CAR T-Cell Therapy to be Evaluated in Lupus

November 28, 2023 — Gracell plans to initiate the phase 1 portion of the trial in 2024. This initial part of the trial will evaluate the safety and tolerability of the GC012F, determine the recommended phase 2 dose, and characterize pharmacokinetics in patients with rSLE. SLE is a B-cell-mediated autoimmune disease and immunosuppressants are used as the current standard of care.

Nkarta Enters the Lupus Nephritis CAR Cell Therapy Race With NKX019 IND Clearance

October 19, 2023 — In light of the IND clearance, Nkarta intends to evaluate NKX019 in an open-label, multicenter, dose escalation clinical trial that will recruit up to 12 patients with refractory LN. The trial, which is expected to enroll its first participant in the first half of next year, will administer the NK cell therapy over the course of 3 doses set at either 1 billion or 1.5 billion cells per dose. The doses will be given on days 0, 7, and 14 after lymphodepletion, which will be conducted with the use of cyclophosphamide.

Kyverna Makes Progress Evaluating Lupus Nephritis Cell Therapy in US, Germany

September 2, 2023 — Kyverna Therapeutics has received regulatory clearance in Germany to initiate a phase 1/2 clinical trial of KYV-101 CAR T-cell therapy in patients with LN. The announcement follows Kyverna’s June update that its US phase 1/2 trial (NCT05938725) of KYV-101 for the same indication dosed its first patient with LN. KYV-101 is a CD19-targeted CAR T-cell therapy designed to treat B cell-driven autoimmune diseases. It has previously been evaluated in a phase 1 clinical trial (NCT02659943) in 20 patients with B-cell lymphomas and chronic lymphocytic leukemia sponsored by the National Cancer Institute.

Artiva Biotherapeutics’ NK Cell Therapy AlloNK Cleared for Trial in Systemic Lupus Erythematosus

August 19, 2023 — AlloNK, which is intended to heighten the effect of rituximab via antibody-dependent cellular cytotoxicity (ADCC), is unengineered and derived from cord blood units selected for the high affinity variant of the CD16 receptor and the KIR-B haplotype. Artiva noted that no allogeneic NK or CAR-T therapy has previously received IND clearance for evaluation in an autoimmune disease indication.

ImmPACT Bio’s Systemic Lupus Erythematosus CAR-T Cleared for US Trial

August 17, 2023 — IMPT-514 makes use of a 4-1BB costimulatory domain and consists of the same CAR construct used in ImmPACT Bio’s investigational CAR-T IMPT-314, which is currently being evaluated in an investigator-led phase 1 clinical trial (NCT04007029) at University of California, Los Angeles (UCLA), in patients with non-Hodgkin lymphoma. ImmPACT Bio also received IND clearance to evaluate IMPT-314 in a larger multicenter phase 1/2 clinical trial (NCT05826535) in patients with aggressive non-Hodgkin lymphoma in January 2023, but as of May 2023 the first patient in that trial had not yet been dosed.

Systemic Lupus Erythematosus CAR-T Gets FDA Fast Track Designation

May 4, 2023 — CABA-201 contains a 4-1BB costimulatory domain and is intended to deplete B-cells in order to “reset” the immune systems of patients. In March 2023, Cabaletta Bio received clearance of its IND application for the therapy from the FDA. The company is planning to initiate a phase 1/2 clinical trial which will seek to enroll a cohort of 6 patients with SLE with active LN and a separate cohort of 6 patients with SLE whose disease has no renal involvement. Both cohorts will be treated with a dose of 1x106 CAR-T cells/kg.

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