Multiple Sclerosis

The innate immune system plays a central role in the chronic central nervous system inflammation that drives neurological disability in progressive forms of multiple sclerosis, for which there are no effective treatments. The mucosal immune system is a unique tolerogenic organ that provides a physiological approach for the induction of regulatory T cells. Nasal administration of CD3-specific antibody ameliorates disease via an IL-10-dependent effect that is mediated by the induction of regulatory T cells that share a similar transcriptional profile to Tr1 regulatory cells and that suppress the astrocyte inflammatory transcriptional program. Treatment results in an attenuated inflammatory milieu in the central nervous system, decreased microglia activation, reduced recruitment of peripheral monocytes, stabilization of the blood–brain barrier and less neurodegeneration.

Tiziana conducted a Phase 1 trial, at the Brigham and Women’s Hospital, Harvard Medical School, Boston, MA. The trial was a single-site, double-blind, placebo-controlled, dose-ranging study in healthy volunteers with nasally administered Foralumab at 10, 50 and 250 µg per day, consecutively for 5 days for the treatment of progressive multiple sclerosis (pMS). 18 subjects received Foralumab treatment, and 9 patients received placebo. All nasal doses were well tolerated. Biomarker analysis showed significant positive immune effects, that were most prominent in the 50 mg cohort with minimal immunomodulatory effects at the 10 µg and 250 µg doses.

To start with a single SPMS patient was treated with intranasal foralumab under an Expanded Access IND at the Brigham and Women’s Hospital (BWH), Harvard University, Boston, MA. Following completion of six months of treatment both biological and clinical improvements were seen in this patient which importantly overcame the challenge of delivering this antibody and then the onwards affect across the blood-brain barrier to affect immunomodulation in the brain. Foralumab administered intranasally into each nostril on a regimen of M-W-F for two weeks followed by one week off therapy for a period of six months. This regimen was well-tolerated with associated beneficial clinical and biomarker changes. Importantly, the PET imaging data indicated inhibition of microglial cell activation observed at 3 months following treatment initiation and was sustained at 6 months after treatment start. The reduction in microglial activation was seen in all parts of brain.

Consistent with clinical and PET observations, intranasally administered foralumab also downregulated serum levels of pro-inflammatory cytokines, including interferon-gamma (IFN-g), interleukin (IL-18), IL-1β and IL-6, which are associated with multiple sclerosis pathogenesis and progression. Clinical evaluation showed improvement in Timed 25-Foot Walk Test (T25FW), 9-Hole Peg Test (9HPT) and Symbol Digit Modality Test (SDMT). Other published PET studies have shown an increase in activated microglial cells (AMCs) in patients with secondary progressive MS (SPMS), and the increase in AMCs associated with higher scores on the Expanded Disability Status Scale (EDSS), a widely used scale to measure disability. Several FDA-approved drugs, such as TYSABRI®, MAYZENT® and ZEPOSIA® have been shown to suppress microglial activation and exert neuroprotective effects in the central nervous system (CNS) in animal studies but longitudinal assessment of drug effects on microglial activation in exclusive cohorts of SPMS patients are lacking.

Phase 2 Trial in na-SPMS:

The FDA has cleared the IND for foralumab to be studied in non-active secondary progressive multiple sclerosis. In December 2023 the first patient was dosed in our Phase 2a study comparing two doses of intranasal foralumab and placebo in patients with non-active secondary-progressive multiple sclerosis (na-SPMS). Six investigational centers have been recruited for this double-blind, placebo-controlled trial, with up to 18 patients per treatment arm. The primary endpoint of the trial will be the change in microglial activation based on PET scans. Clinical evaluations include the Expanded Disability Status Scale (EDSS), QoL assessments, and the Modified Fatigue Impact Scale (MFIS), which assess parameters that are essential to a patient’s everyday life. Novel immuno-biomarkers will be measured also and assessed for predictive relevance. Central review of PET scans and images is an integral component of this study.

Phase 1 Clinical Trial: Nasal Administration of Foralumab for the Treatment of Multiple Sclerosis

The completed Phase 1 clinical trial of Foralumab in healthy volunteers was a single center, single arm, ascending dose study in which low doses (10, 50 and 250 µg/dose) of Foralumab and placebo were nasally administered for 5 consecutive days. Subjects were monitored for tolerance and immunological effects. The primary endpoint of the Phase 1 study is safety, tolerability, and biomarkers of immunomodulation of clinical responses of intra nasally administered Foralumab. Interim results have indicated no drug-related safety issues so far. Topline results were reported on September 10, 2019. All nasal doses were well tolerated. Biomarker analysis showed significant positive immune effects, that were most prominent in the 50 µg cohort with minimal immunomodulatory effects at the 10 µg and 250 µg doses. These results suggested stimulation of Tregs that are needed to provide clinical benefits.

Expanded Access

At Tiziana, we’re committed to developing advancements in non-active secondary progressive Multiple Sclerosis, Alzheimer’s Disease and ALS. At times patients may wish to access investigational medicines that are not yet approved by the U.S. Food and Drug Administration (FDA) through expanded access or compassionate use programs.

In cases where enrolling in a clinical trial is not currently possible, there may be expanded access options for some patients. The criteria for these options are based on regulations governing this type of access.

Tiziana will consider each request for expanded access on a case-by-case basis when they meet the conditions below, and access is requested by a licensed practitioner in the United States who will oversee the patient’s care while using the investigational medication.

• The patient is ineligible for or otherwise unable to participate in ongoing or planned clinical trials.

• The patient is ineligible for or otherwise unable to participate in ongoing foralumab trials.
• The potential benefit to the patient should outweigh potential risks.
• All other approved treatments did not help the patient, or there is no other approved treatment option available.
• The patient meets any other relevant medical criteria for expanded access to the investigational product, as determined by Tiziana.
• There is adequate supply of the investigational product to meet the needs of the expanded access request without impacting the company’s clinical trials.

Ongoing Clinical Trials

non-active secondary progressive Multiple Sclerosis: Study Details | A Study of Nasal Foralumab in Non-Active Secondary Progressive Multiple Sclerosis Patients | ClinicalTrials.gov  (NCT06292923)

Requesting Access

To submit a request for an investigational medicine outside of a clinical trial, the treating physician can email Tiziana at the following email address, ms@tizianalifesciences.com. We will endeavor to respond to requests within ten (10) business days.