Tiziana Life Sciences Plans IND for Phase 1 Study of Intranasal Foralumab in Alzheimer Disease

Gabriele Cerrone

According to a recent announcement, Tiziana Life Sciences plans to file an investigational new drug application (IND) to the FDA for a phase 1 study to study intranasal foralumab, its human anti-CD3 monoclonal antibody, in Alzheimer disease (AD). The IND is expected to be filed by the third quarter of 2023 upon the completion of requested toxicology studies, with the phase 1 program beginning by the end of 2023.¹

The decision came after the company received an affirmative response from the FDA on a pre-investigational new drug application. Foralumab, formerly Nl-0401, has been shown to reduce release of key cytokines in healthy volunteers and in patients with Crohn disease. The company had previously submitted a patient application on the potential use of foralumab to improve the success of chimeric antigen receptor T-cells therapy for cancer and other human diseases.

"I am thrilled to see the company advancing foralumab into another promising central nervous system (CNS)-related therapeutic area with high unmet need,” Gabriele Cerrone, executive chairman and interim chief executive officer, Tiziana Life Sciences, said in a statement.¹ "Intranasal foralumab’s unique action on regulatory T-cells should allow us to study multiple CNS inflammatory pathology indications for this unique drug."

Foralumab has been assessed in several different conditions, including patients with mild to moderate COVID-19. Published in August 2021, the study featured 39 outpatients who were randomized to either control (n = 16), intranasal foralumab 100 µg/day given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n = 11), and intranasal foralumab 100 µg/day along given for 10 consecutive days (n = 12). All told, investigators observed a reduction of serum interleukin-6 and C-reactive protein in patients treated solely with foralumab vs controls or those on a combination approach. Specifically, foralumab alone resulted in a 69% reduction in IL-6 levels at day 10 (P = .031) and 85% reduction in CRP at day 10 (P = .032).²

"We have spent years studying intranasal anti-CD3, or foralumab, in inflammatory CNS-related disease models in animals,” Howard L. Weiner, MD, codirector, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, said in a statement.¹ "We look forward to evaluating intranasal foralumab in patients with early symptomatic Alzheimer’s disease, where we believe its locally acting anti-inflammatory mechanism of action will be relevant."

Under an expanded access IND, foralumab is also currently being evaluated in a small group of patients with progressive multiple sclerosis (MS). At the 2022 Consortium of Multiple Sclerosis Centers (CMSC) annual meeting, data on a single 61-year-old patient with progressive MS treated with foralumab, was presented. At the time, the patient had shown no adverse reactions, local irritation, or laboratory abnormalities, while feeling more stable and noted improvement in lower extremity strength. Using the Olink assay, measures of Th1 cytokines IFN-y and IL-18 were reduced after initiation treatment, which was consistent with preclinical models. Additionally, pro-inflammatory cytokines IL-1ß and IL-6 were reduced.³

"Tiziana strongly believes that many inflammatory CNS disease pathologies could improve with intranasally administered foralumab and as such, we hope to study additional neurological disease states over time," Matthew Davis, MD, RPh, chief scientific officer and chief medical officer, Tiziana Life Sciences, said in a statement.¹

Tanuja Chitnis, MD, an associate neurologist at Brigham and Women’s Hospital and presenter of the case study at CMSC 2022, sat down at the meeting to discuss the role of anti-CD3 therapies like foralumab in progressive MS. Watch below as she provided background on the study, and why the treatment has therapeutic potential.

REFERENCES
1. Tiziana Life Sciences plans to submit IND for phase 1 trial of intranasal foralumab in Alzheimer disease patients. News release. Tiziana Life Sciences. October 12, 2022. Accessed October 21, 2022. https://www.tizianalifesciences.com/news-item?s=2022-10-12-tiziana-life-sciences-plans-to-submit-ind-for-phase-1-trial-of-intranasal-foralumab-in-alzheimers-disease-patients
2. Moreia TG, Matos KT, De Paula G, et al. Nasal administration of anti-CD3 monoclonal antibody (foralumab) reduces lung inflammation and blood inflammatory biomarkers in mild to moderate COVID-19 patients: a pilot study. Front Immunol. Pubished online August 12, 2021. doi:10.3389/fimmu.2021.709861
3. Chitnis T, Singhal T, Zurawski J, et al. Nasal anti-CD3 monoclonal antibody (foralumab) reduces PET microglial activation and blood inflammatory biomarkers in a patient with non-active secondary progressive MS. Presented at: CMSC Annual Meeting, 2022; June 1-4; National Harbor, MD. LB