FDA OKs Phase 1 clinical trial of IMPT-514 for hard-to-treat MS
Trial testing Immpact Bio cell therapy candidate expected to launch in 2025
The U.S. Food and Drug Administration (FDA) has given the green light to Immpact Bio to conduct a Phase 1 clinical trial to test IMPT-514, its experimental cell therapy, in people with multiple sclerosis (MS).
With the investigational new drug (IND) clearance by the FDA, Immpact Bio now expects to launch the study in the first half of 2025, the company said in a press release. Its goal will be to evaluate whether several doses of IMPT-514 can slow or stop the accumulation of MS-related disability.
The planned trial will be open to individuals with all forms of MS who have suboptimal or poor disease control despite having received high-efficacy disease-modifying therapies.
“IND clearance of our bispecific CAR T-cell therapy in MS marks an exciting achievement that further expands clinical development of our autoimmune program,” said Sumant Ramachandra, MD, PhD, CEO of Immpact Bio. “As an intended one-time treatment, IMPT-514 has the potential to reset the immune system by depleting a broad range of autoreactive [self-reactive] immune cells implicated in the [development] of MS in patients.”
The trial is expected to dose its first participant by the end of June of next year, Ramachandra said. No further details on the study’s design or location were disclosed at this time.
Immpact Bio’s IMPT-514 is a CAR T-cell therapy
In people with MS, the immune system mistakenly attacks the myelin sheath, a protective fatty coating around nerve fibers, in the brain and/or spinal cord. Self-reactive immune B-cells and T-cells are thought to participate in the inflammatory attacks that drive 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 also by regulating the activity of other immune cells.
IMPT-514 belongs to a class of treatment 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 these identified cells in a very selective manner, without harming other cells.
CAR T-cell therapies involve collecting T-cells from patients and modifying them in the lab so that instead of targeting infectious agents like naturally occurring T cells, they recognize molecules at the surface of disease-causing immune cells and destroy those cells.
The engineered cells are then infused back into the patient to promote their effects and help reduce the number of disease-causing immune cells, easing symptoms and/or slowing disease progression.
Phase 1 clinical trial to test ‘therapeutic potential’ of IMPT-514
IMP-514, intended to be administered as a one-time dose, is a bispecific CAR T-cell therapy, meaning that the engineered T-cells can simultaneously target two molecules instead of only one. In this case, the two targets are CD19 and CD20, two proteins primarily found on the surface of B-cells.
Given that the presence and levels of CD19 and CD20 at B-cells’ surface change throughout the cells’ development, by targeting both molecules, IMPT-514 can act on a wide range of B-cells at different stages of maturation.
Additionally, CD20 is present also at 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 nature of IMPT-514 offers a unique opportunity to potentially ablate autoreactive B cells and the likely [disease-causing] CD20-expressing T-cells,” said Jonathan Benjamin, MD, PhD, chief medical officer of Immpact Bio.
We are pleased to receive IND clearance and further evaluate the therapeutic potential of IMPT-514 to deliver long-lasting protection against MS.
Preclinical studies showed that IMPT-514 effectively eliminated B-cells and reduced levels of inflammatory molecules in people with autoimmune diseases who were on immunosuppressive treatments.
Moreover, CAR T-cells can cross the blood-brain barrier (BBB), a highly selective membrane that tightly regulates what substances from the bloodstream can access the central nervous system (CNS) which is comprised of the brain and spinal cord. Crossing the BBB is often a challenge for CNS-targeting therapies, including those in MS that are based on CD20-targeting antibodies.
“We are pleased to receive IND clearance and further evaluate the therapeutic potential of IMPT-514 to deliver long-lasting protection against MS,” Benjamin said.
Immpact Bio also is testing IMPT-514 as a potential treatment for lupus nephritis, a common kidney complication of lupus, another autoimmune disease, with a Phase 1/2 trial involving lupus patients already ongoing.
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