ImmPACT Bio’s CD19/CD20 CAR-T IMPT-514 Cleared for Phase 1 Trial in Multiple Sclerosis
The company expects to launch a study during the first half of next year.
ImmPACT Bio’s IMPT-514, an investigational bispecific CD19/CD20-directed chimeric antigen receptor T-cell (CAR-T) therapy, has received clearance of an investigational new drug (IND) application from the FDA for a phase 1 clinical trial in patients with multiple sclerosis (MS).1
The planned study will take the form of a dose escalation trial and will seek to recruit adult patients with all forms of MS whose disease is suboptimally controlled even after previous treatment with high efficacy disease-modifying therapies. IMPT-514 is intended to slow or stop progression of accumulation of disease disability and is the only CD19/CD20 CAR-T therapy in development for MS to ImmPACT Bio’s knowledge. The company expects to launch the study during the first half of next year.
“IND clearance for our bispecific CAR T-cell therapy in MS marks an exciting achievement that further expands clinical development of our autoimmune program,” Sumant Ramachandra, MD, PhD, the chief executive officer of ImmPACT Bio, said in a statement.1 “As an intended one-time treatment, IMPT-514 has the potential to reset the immune system by depleting a broad range of autoreactive immune cells implicated in the pathogenesis of MS in patients. We expect to dose the first patient in the first half of 2025.”
In addition to MS, IMPT-514 is also in development for the treatment of patients with active, refractory systemic lupus erythematosus (SLE).2 An IND application foraphase 1b/2 dose-escalation clinical trial for IMPT-514 in SLE was cleared by the FDA in August of last year.
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 2023.3,4
“The dual-targeting nature of IMPT-514 offers a unique opportunity to potentially ablate autoreactive B cells and the likely pathogenic CD20-expressing T-cells,” Jonathan Benjamin, MD, PhD, the chief medical officer of ImmPACT Bio, added to the statement.1 “Moreover, the ability of CAR T-cells to cross the blood brain barrier (BBB) could potentially overcome the limitations of current disease-modifying therapies such as antiCD20 antibodies that are not effective at crossing the BBB, where potentially pathogenic cells reside. We are pleased to receive IND clearance and further evaluate the therapeutic potential of IMPT-514 to deliver long-lasting protection against MS.”
CGTLive® previously spoke to Bruce Cree, MD, PhD, MAS, a professor of neurology and the clinical research director of the University of California San Francisco (UCSF) Multiple Sclerosis Center, about the potential of cell therapy in autoimmune disease. During the interview, Cree spoke about the potential of CAR-T in MS in general, and the rationale behind why it might be an effective approach.
“And so the concept here is with the cell-based therapy—since these are in fact the body's own T-cells that have been genetically modified—is that these cells will have access to areas of the body where there are B-cells that an antibody-based therapy can't get to,” Cree told CGTLive. “In MS, this is a very compelling story because we know when we look at the brains of multiple sclerosis patients at autopsy we do in fact see tissue-resident B-cells and T-cells within the brain, within the meninges, and in the perivascular spaces. We know that these [pathogenic B-cells] are present there and are in this privileged location where monoclonal antibodies simply can't get to—or can’t get to easily—and even if the antibody gets there, most of the antibodies kill B-cells through complement-dependent mechanisms.
