TG Therapeutics advancing CAR T-cell therapy toward Phase 1 trial
Developer using MaxCyte’s tech to manufacture azer-cel for progressive MS
In a new deal, TG Therapeutics will use MaxCyte’s engineering technology to develop and manufacture its off-the-shelf CAR T-cell therapy candidate azercabtagene zapreleucel — azer-cel for short — for adults with progressive forms of multiple sclerosis (MS).
The experimental treatment is being advanced toward a Phase 1 clinical trial expected to enroll more than 30 MS patients in the U.S.
The two companies are partnering through a strategic platform license, meaning that TG Therapeutics will have access to MaxCyte’s flow electroporation technology and ExPERT platform in exchange for yearly fees and earnings. This tech will allow the developer to engineer immune T-cells and scale up production for clinical applications.
“By leveraging our commercially validated cell-engineering platform and optimized T cell manufacturing workflow, TG Therapeutics is advancing toward their Phase 1 clinical trial for the application of azer-cel in progressive forms of MS,” Maher Masoud, MaxCyte’s president and CEO, said in a company press release.
MaxCyte tech will allow developer to scale up production of CAR T-cell therapy
Early last year, TG Therapeutics acquired azer-cel’s development and commercialization rights from Precision BioSciences for the treatment of autoimmune diseases, including MS, and indications other than cancer. The company was later cleared by the U.S. Food and Drug Administration to begin clinical testing of the CAR T-cell therapy in adults with progressive forms of MS.
“Our technology … was efficiently transferred from Precision BioSciences when TG Therapeutics obtained global rights for azer-cel for autoimmune diseases in January 2024,” Masoud said. “With our new partnership, we will continue to support the development of azer-cel to expand the application to autoimmune diseases.”
MS is caused by self-reactive antibodies that promote an immune attack against the myelin sheath that covers nerve cells, triggering inflammation and damage that builds up over time. Antibodies, including self-reactive ones, are produced by immune cells called B-cells.
A CAR T-cell therapy takes advantage of T-cells’ ability to promote immune attacks against specific cells, resulting in the cells’ death. Such treatments involve the modification of T-cells in the lab to harbor a chimeric antigen receptor, or CAR, that binds to specific proteins at the surface of target cells.
Unlike other CAR T-cell therapies that use T-cells from the patient themselves, azer-cel collects T-cells from healthy donors. These donor-derived T-cells are modified in the lab to produce a CAR that targets CD19, a protein found on B-cells, and then are grown in number before being infused into patients.
By targeting and killing B-cells, azer-cel is expected to reduce the production of MS-driving self-reactive antibodies and ease disease symptoms. According to the company, azer-cel is also designed to avoid graft-versus-host disease, a complication that occurs when donor-derived T-cells view the body’s healthy cells as a threat.
Our technology … was efficiently transferred … when TG Therapeutics obtained global rights for azer-cel for autoimmune diseases in January 2024. … With our new partnership, we will continue to support the development of azer-cel to expand the application to autoimmune diseases.
The Phase 1 trial (NCT06680037), sponsored by TG Therapeutics, aims to determine the recommended dose of azer-cel for Phase 2 clinical testing.
The study plans to enroll up to 32 people, ages 18-60, with progressive forms of MS, such as primary progressive MS and secondary progressive MS. The study may already be recruiting at a site in Lexington, Kentucky.
Participants will receive a single intravenous, or into-the-vein, infusion of azer-cel at different dose levels. The study’s main goal is to evaluate the number of patients experiencing dose-limiting toxicities over 28 days, or about a month. Such toxicities are side effects that are serious enough to prevent an increase in dose to the next level.
Over a period of up to about two years, researchers will continue to monitor the occurrence of adverse events, and assess azer-cel’s pharmacokinetics — its movement into, through, and out of the body — as well as its pharmacodynamics, or its effects in the body. Other secondary goals include time to disability progression and brain changes detected by MRI scans. Top-line data are expected next year.
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