Foralumab Nasal Spray for MS Well-tolerated in Mice for 3 Months

Foralumab, a nasal spray therapy that Tiziana Life Sciences is developing for multiple sclerosis (MS) and other disorders, was well-tolerated in mice for more than three months, according to data from a preclinical study.

Tiziana is planning to share that data in a meeting with the U.S. Food and Drug Administration (FDA) to discuss plans for a Phase 2 clinical trial testing foralumab in non-active secondary progressive multiple sclerosis (SPMS). The meeting is expected to take place before the end of the year, and the company is hoping to launch the trial next year.

“Completion of this preclinical trial is a critical milestone for Tiziana,” Gabriele Cerrone, executive chairman and interim CEO of Tiziana, said in a company press release.

“[A] mouse 13-week study is a common pre-requisite requirement needed to support an FDA Phase 2 meeting request to study investigational candidates in MS, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS) and other planned intranasal foralumab [central nervous system] studies, and we can now move forward in a number of different indications,” Cerrone said.

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Next up: testing in humans for SPMS

Foralumab is designed to reduce the activity of T-cells — a type of immune cell that plays a key role in the inflammatory attack that causes MS — by binding to a T-cell protein called CD3. According to Tiziana, the therapy has been designed for delivery via nasal spray to minimize side effects.

Because foralumab is a fully human antibody, it can only bind to the human CD3 protein, which can limit results from animal studies. Thus, the preclinical study was done in the HuGEMM CD3 transgenic mouse model — mice that have been genetically engineered to produce the human version of the CD3 protein.

“A unique scientific hurdle in studying the pre-clinical safety profile of foralumab is the fact that it is fully human,” said Matthew Davis, MD, chief medical officer of Tiziana.

“Non-human models would not be appropriate due to the specificity of foralumab to human CD3. However, by using HuGEMM CD3 transgenic mice who express human CD3, we were able to study the 13-week pre-clinical safety profile of intranasal foralumab in an elegant and validated manner,” Davis said.

Results showed that doses up to 50 micrograms (mcg) per rodent were clinically well-tolerated, with no notable changes in body weight, blood parameters, organ weight, and clinical signs. There were no treatment-related deaths.

“We are very pleased with the results and plan to include them in our request for a Phase 2 multiple sclerosis (MS) Type C meeting with the FDA before year-end, with feedback expected in the first quarter of 2023,” Davis said.

Foralumab also was recently reported to be well-tolerated among 27 healthy volunteers in another MS study. That study found no systemic side effects reported at doses up to 250 mcg.

A few patients with SPMS are being treated with the experimental therapy under expanded access programs.