FDA approves Phase 1 clinical trial of IMPT-514 for the treatment of difficult-to-treat MS

The U.S. Food and Drug Administration (FDA) has given Immpact Bio the green light to conduct a Phase 1 clinical trial to test IMPT-514, its experimental cell therapy, in people with multiple sclerosis (MS).

Following FDA approval of the Investigational New Drug (IND), Immpact Bio now expects to start the trial in the first half of 2025, the company said in a press release. The goal of the trial will be to test whether multiple doses of IMPT-514 can slow or stop the progression of MS-related disabilities.

The planned study can be used by people with all forms of MS whose disease is not optimally or inadequately controlled despite highly effective disease-modifying therapies.

“The IND approval of our bispecific CAR-T cell therapy in MS is an exciting achievement that further advances the clinical development of our autoimmune program,” said Sumant Ramachandra, MD, PhD, CEO of Immpact Bio. “As a planned one-time treatment, IMPT-514 has the potential to reset the immune system by targeting a broad range of autoreactive [self-reactive] Immune cells involved in the [development] of MS in patients.”

According to Ramachandra, the first participant will be treated with the drug in late June next year. Further details on the study design or location have not yet been announced.

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IMPT-514 from Immpact Bio is a CAR T cell therapy

In people with MS, the immune system mistakenly attacks the myelin sheath, a protective fatty layer around nerve fibers in the brain and/or spinal cord. Self-reactive immune B and T cells are thought to be involved in the inflammatory attacks that cause MS and other autoimmune diseases.

B cells are the immune cells responsible for producing antibodies, including the self-reactive antibodies that trigger autoimmune reactions, while T cells promote inflammatory and immune responses by also regulating the activity of other immune cells.

IMPT-514 belongs to a class of treatments known as CAR-T cell therapies, which take advantage of the biology of T cells. T cells can identify very specific molecules on the surface of cells and kill those identified cells very selectively without harming other cells.

In CAR-T cell therapies, T cells are taken from patients and modified in the laboratory so that they do not attack infectious pathogens like naturally occurring T cells, but rather recognize molecules on the surface of disease-causing immune cells and destroy these cells.

The genetically modified cells are then infused back into the patient to enhance their effect and reduce the number of disease-causing immune cells, thus alleviating symptoms and/or slowing the progression of the disease.

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Phase 1 clinical trial to test the “therapeutic potential” of IMPT-514

IMP-514, which is designed to be administered as a single dose, is a bispecific CAR T-cell therapy, meaning the genetically engineered T cells can attack two molecules at once, rather than just one. In this case, the two targets are CD19 and CD20, two proteins found primarily on the surface of B cells.

Since the presence and concentration of CD19 and CD20 on the surface of B cells change during cell development, IMPT-514 can target a wide range of B cells at different stages of maturation by specifically targeting both molecules.

In addition, CD20 is also present on the surface of a highly activated subset of T cells that produces large amounts of pro-inflammatory molecules. Previous studies have shown that CD20-positive T cells may contribute to MS activity and relapse.

“The dual targeting of IMPT-514 offers a unique opportunity to potentially remove autoreactive B cells and likely [disease-causing] CD20-expressing T cells,” said Jonathan Benjamin, MD, PhD, chief medical officer of Immpact Bio.

We are pleased with the IND approval and look forward to further evaluating the therapeutic potential of IMPT-514 to provide long-term protection against MS.

Preclinical studies have shown that IMPT-514 effectively eliminated B cells and reduced the levels of inflammatory molecules in people with autoimmune diseases who were receiving immunosuppressive treatment.

In addition, CAR-T cells can cross the blood-brain barrier (BBB), a highly selective membrane that tightly regulates which substances can pass from the bloodstream into the central nervous system (CNS), which consists of the brain and spinal cord. Crossing the BBB is often a challenge for CNS-targeted therapies, including those in MS that rely on CD20-targeted antibodies.

“We are pleased with the IND approval and continue to evaluate the therapeutic potential of IMPT-514 to provide long-term protection against MS,” said Benjamin.

Immpact Bio is also testing IMPT-514 as a potential treatment for lupus nephritis, a common kidney complication in lupus, another autoimmune disease. A Phase 1/2 trial in lupus patients is already underway.