IMPT-514 Receives Investigational New Drug Clearance From the FDA

The investigational new drug application (IND) for IMPT-514 (ImmPACT Bio), a CD19/CD20 bispecific chimeric antigen receptor (CAR) T-cell therapy for the treatment of adult patients with multiple sclerosis (MS), received FDA clearance. The decision advances clinical development of treatment for patients who have suboptimal disease control despite prior treatment.

IMPT-514 utilizes a bispecific CAR and a 4-1BB costimulatory domain to target CD19 and CD20. Image Credit: © SewcreamStudio- stock.adobe.com

MS is a neurodegenerative disease characterized by the demyelination of the central nervous system that results in permanent damage of the myelin sheathes around nerve fibers, affecting cognitive, emotional, motor, sensory, and visual functions. This can include weakness or numbness in the limbs, vision loss, mood disturbances, lack of coordination, or an inability to walk.^1,2

According to the World Health Organization, MS affects approximately 1.8 million individuals around the world. Despite its prevalence, it is difficult to diagnose in its early stages and has limited treatment options, emphasizing the unmet needs of this patient population. CAR T-cell therapy is gaining attention as a potential treatment for MS, and the development of the IMPT-514 bispecific CAR targeting CD19/CD20 marks a significant advancement towards expanding therapeutic options for patients.³

"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, chief medical officer of ImmPACT Bio, said in a news release. “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 anti-CD20 antibodies that are not effective at crossing the BBB, where potentially pathogenic cells reside.”⁴

IMPT-514 utilizes a bispecific CAR and a 4-1BB costimulatory domain to target CD19 and CD20, which research indicate plays a significant role in disease progression in MS. In preclinical studies, IMPT-514 was successfully manufactured from immunosuppressed patients across multiple autoimmune disease and demonstrated significant elimination of autologous B-cells and a moderate cytokine profile.^4,5

The decision marks a crucial advancement in the development of treatment options for patients with MS. The company plans to initiate a phase 1 dose escalation focusing on patients with suboptimal disease control despite prior treatment with the intent to slow or stop the progression of disability accumulation.⁴

"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, CEO of ImmPACT Bio, said in a news release. "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."⁴

REFERENCES

1. Machine learning models may predict disease progression in patients with multiple sclerosis. Pharmacy Times. August 14, 2024. August 21, 2024. https://www.pharmacytimes.com/view/machine-learning-models-may-predict-disease-progression-in-patients-with-multiple-sclerosis

2. Researchers identify a potential therapeutic target for multiple sclerosis. Pharmacy Times. August 2, 2024. Accessed August 21, 2024. https://www.pharmacytimes.com/view/researchers-identify-a-potential-therapeutic-target-for-multiple-sclerosis

3. Multiple sclerosis. World Health Organization. August 7, 2023. Accessed August 1, 2024. https://www.who.int/news-room/fact-sheets/detail/multiple-sclerosis

4. Immpact bio announces fda clearance of ind application for cd19/cd20 bispecific car-t cell therapy in multiple sclerosis. PR Newswire. August 21, 2024. Accessed August 21, 2024. https://prnmedia.prnewswire.com/news-releases/immpact-bio-announces-fda-clearance-of-ind-application-for-cd19cd20-bispecific-car-t-cell-therapy-in-multiple-sclerosis-302226926.html

5. Chen D, Ireland S, Davis L, et al. Autoreactive cd19+cd20− plasma cells contribute to disease severity of experimental autoimmune encephalomyelitis. J Immunol. February 15, 2016. doi:10.4049/jimmunol.1501376