Nasal administration of anti-CD3 mAb (Foralumab) downregulates NKG7 and increases TGFB1 and GIMAP7 expression in T cells in subjects with COVID-19 

Activated T cells play an important role in the complications following COVID-19 infection. Anti-CD3 monoclonal antibody (mAb) binds to the T cell receptor and dampens inflammation by modulating T cell function. We show here that nasal administration of a fully human anti-CD3 Mab (Foralumab) modulates T cell inflammatory responses in COVID-19 by suppressing effector features in multiple T cell subsets, an effect also seen in subjects with multiple sclerosis. Immunomodulation by nasal anti-CD3 mAb represents a novel avenue for treatment of inflammatory human diseases.


Nasal administration of anti-CD3 monoclonal antibody ameliorates disease in a mouse model of Alzheimer’s disease

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques, neurofibrillary tangles, and microglial activation. Therapies targeting amyloid beta have shown positive effects in subjects with AD. Nasal anti-CD3 has been shown to treat animals with a progressive form of experimental autoimmune encephalomyelitis, a model for multiple sclerosis, by inducing regulatory T cells that dampen microglial inflammation in the brain. Here, we show that nasal anti-CD3 also ameliorates disease in a murine model of AD by targeting microglial activation in the brain independent of amyloid beta deposition. These studies identify a unique approach to treat Alzheimer’s disease that could also be given in combination with anti amyloid therapy.


Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects


These findings demonstrate that nasal Foralumab is safe and immunologically active in humans and presents a new avenue for the treatment of autoimmune and CNS diseases. 


Treatment of six non-active secondary progressive MS with nasal anti-CD3 monoclonal
antibody (foralumab): safety, biomarker, and disability outcomes

Nasal foralumab is a novel, non-toxic immunomodulatory treatment for non-active SPMS. We report a total of 6 patients on foralumab: 2 patients completed over 12 months
of therapy, and an additional 4 patients were treated for 6 months with no severe TRAEs. All 6 patients experienced improvement in at last one clinical measure (EDSS,
pyramidal score or MFIS), and 5/6 showed improvement on microglial PET imaging at 6 months. 10 patients in total will be treated under the expanded access program and
a multi-center placebo controlled double-blind phase 2 trial is underway.