foralumab intravenous (TZLS-401 IV) / Tiziana Life Sci, Light Chain Biosci, Precision BioSci - LARVOL DELTA

Monoclonal Antibodies as Therapeutic Agents in Autoimmune and Neurodegenerative Diseases of the Central Nervous System: Current Evidence on Molecular Mechanisms and Future Directions. (PubMed, Int J Mol Sci) - "Similarly, novel agents under investigation, such as frexalimab and foralumab, modulate T and B cell interactions and regulatory immunity. The evolving armamentarium of mAbs reflects a paradigm shift toward personalized neuroimmunology and neurodegeneration-targeted treatments, based on ongoing clarification of molecular and neuroinflammatory mechanisms. In this context, the present review summarizes current evidence on mAbs used in CNS disorders, with an emphasis on their pathophysiological targets, molecular mechanisms, clinical efficacy, and safety."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Immunology • Inflammation • Movement Disorders • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Parkinson's Disease • Rare Diseases • CD20 • CD52 • IL6

Development of In Vivo CAR T Cell Therapy Using Nanoparticle and RNA-Based Gene Delivery Systems (ASGCT 2025) - "In this study, we applied the GrAb approach by fusing ApoA1 to the Fc domain of a CD3 antibody (Foralumab) or a CD5 antibody (5D7)... We generated modified nucleoside-containing mRNA encoding a CAR targeting CD19 (a marker of B cells) and encapsulated it in CD3- or CD5-targeted GrAb-LNPs (hereafter referred to as aCD3LNP or aCD5LNP, collectively T-LNP) (Fig. 1A). As a proof-of-concept experiment, we incubated NBD-PE-labeled T-LNPs with freshly isolated human Peripheral Blood Mononuclear Cells (hPBMCs) in vitro."

CAR T-Cell Therapy • IO biomarker • Preclinical • Hematological Malignancies • Leukemia • Lymphoma • Oncology • APOA1 • CD19 • CD5

Novel Therapeutic Strategy to Modulate CNS Neuroinflammation and Promote Functional recovery in Traumatic Brain Injury (NCS 2024) - "Our studies have immediate translational possibilities for treating TBI patients given that a fully humanized anti-CD3 mAb (Foralumab) has been given to healthy volunteers and has shown positive effects in a pilot study of subjects suffering from COVID-19. The content to be presented in this talk has been supported by an NCS Research Training Fellowship."

CNS Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Vascular Neurology

Treatment of six non-active secondary progressive MS patients with nasal anti-CD3 monoclonal antibody (Foralumab): safety, biomarker, and disability outcomes (MSMilan 2023) - "Nasal Foralumab is a novel, non-toxic immunomodulatory treatment for non-active SPMS. Two patients completed over 12 months of therapy with no severe TRAEs and experienced improved clinical, imaging, and immune biomarkers. 10 patients in total will be treated under the expanded access program and a multi-center placebo controlled double blind trial is planned."

Biomarker • Clinical • Immune Modulation • Inflammation • Multiple Sclerosis • Novel Coronavirus Disease • Pneumonia • IFNG • IL18 • IL6 • NKG7 • TGFB1

Comparative analysis of humanized and mouse anti-CD3 antibodies conjugated with amine-slica and amine-dextran coated magnetic nanoparticles for immunotherapy (ACS-Fall 2023) - "An optimal Fc-directed conjugate of a humanized monoclonal anti-CD3 antibody (Foralumab mAb) for COVID-19 immunotherapy and amine-silica coated magnetic nanoparticles (MNPs) with an average particle diameter of 35 nm was prepared...In addition, we confirmed the therapeutic effect by injecting the conjugated mAb-MNPs into the tail vein and the back of mouse with increased inflammation through a microneedle. These results are expected to be used as an immunotherapeutic agent for suppressing cytokine storm based on the characteristics of MNPs that enable drug delivery and target induction."

Preclinical • Infectious Disease • Inflammation • Novel Coronavirus Disease

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Review

Tiziana Life Sciences Ltd Reports Annual Results for the Twelve Months Ended December 31, 2022, and Corporate Update (GlobeNewswire) - "Tiziana Life Sciences, Ltd...announced financial results for the twelve months ended December 31, 2022, and provided a corporate update on its lead programs in development....Research and development (R&D) expenses decreased to $13.0 million compared to $13.2 million in the twelve months ended 31 December 2021. The decrease is primarily related to the focus on the Company’s proprietary programs, foralumab and to a lower extent, IL6-R."

Commercial • Alzheimer's Disease • CNS Disorders • Crohn's disease • Immunology • Inflammatory Bowel Disease

"@TizianaLS advances foralumab into human testing for hemorrhagic stroke. $TLSA PR: https://t.co/hGoqIveavE" (@vanjohn10)

Cardiovascular • Cerebral Hemorrhage • Hematological Disorders

Nasal administration of anti-CD3 mAb (Foralumab) downregulates NKG7 and increases TGFB1 and GIMAP7 expression in T cells in subjects with COVID-19. (PubMed, Proc Natl Acad Sci U S A) - "TGFB1, GIMAP7, and NKG7 transcriptomic changes observed in Foralumab-treated COVID-19 subjects were also observed in healthy volunteers, MS subjects, and mice treated with nasal anti-CD3. Our findings demonstrate that nasal Foralumab modulates the inflammatory response in COVID-19 and provides a novel avenue to treat the disease."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CCL4 • CRP • GZMA • GZMB • IL32 • IL6 • PRF1 • TGFB1

"Thank you @IJMSCtweets for sharing. $TLSA #SPMS #foralumab" (@TizianaLS)

Multiple Sclerosis

Flow Characteristics of the Conjugate of Anti-CD3 Monoclonal Antibodies and Magnetic Nanoparticle in PBS and Blood Vessels. (PubMed, Adv Exp Med Biol) - "The experimental conditions for optimal liquid production are derived from the Fc-directed conjugation of anti-CD3 foralumab antibodies and magnetic nanoparticles (Ab-MNPs)...This implies that MNPs with CD3 antibodies attached to the surface through biocompatible ligand functional groups has better fluidity in PBS. Afterwards, a non-clinical animal testing for the flow characteristics of Ab-MNPs inside a blood vessel is carried out to observe the effects of Ab-MNP delivery through intravenous injection."

Journal

Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects. (PubMed, Front Immunol) - "Parenteral anti-CD3 Mab (OKT3) has been used to treat transplant rejection and parental administration of a humanized anti-CD3 Mab (Teplizumab) showed positive effects in diabetes. No side effects were observed, and no subjects developed human anti-mouse antibodies. 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."

IO biomarker • Journal • CNS Disorders • Diabetes • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Transplant Rejection • Transplantation • CD4 • CD8 • CTLA4 • GZMB • IFNG • IL17A • KIR3DL2 • KLRG1 • PRF1 • TGFB1 • TIGIT • TNFA

"$TLSA @TizianaLS Foralumab for Alzheimer's @adnewstoday #Alzheimers" (@AshfordPlumber)

Alzheimer's Disease • CNS Disorders

"$TLSA @TizianaLS foralumab pipeline." (@AshfordPlumber)

"$TLSA @TizianaLS #TILS Foralumab" (@AshfordPlumber)

Nasal anti-CD3 monoclonal antibody (Foralumab) reduces PET microglial activation and blood inflammatory biomarkers in two patients with non-active secondary progressive MS (ECTRIMS 2022) - "EA1 is a 61-year-old male diagnosed for over 20 years and EA2 is a 42-year-old male diagnosed for 8 years, both last treated with ocrelizumab for 3 years. Nasal Foralumab in non-active SPMS patients treated for at least 3 months reduced microglial activation, decreased levels of proinflammatory cytokines, and had positive clinical effects."

Biomarker • Clinical • Immunology • Inflammation • Multiple Sclerosis • Novel Coronavirus Disease • Pneumonia • CD8 • IFNG • IL18 • IL6

"Just gone online. Another peer review coming from @NaturePortfolio on Foralumab from @TizianaLS $TLSA #TILS #COVID19" (@AshfordPlumber)

Review • Infectious Disease • Novel Coronavirus Disease

"#MultipleSclerosis #foralumab 👇👇 https://t.co/vYf9QZTlm9" (@TinaMey90814508)

CNS Disorders • Multiple Sclerosis

Injection Effect of Anti-CD3 Monoclonal Antibody on Primo Vessel in Lymph Vessel of Rabbit with Lipopolysaccharide-Induced Inflammation. (PubMed, J Acupunct Meridian Stud) - "By injecting Foralumab into lymph nodes of rabbits with lipopolysaccharide-induced inflammation, the floating primo vessel in the lymph vessel appeared thicker and was distinctly visible. The observation of the primo vessel post-treated with Foralumab in the inflamed lymphatic system suggests the possibility of a functional role of the primo vascular circulatory system in pathophysiological conditions."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

"Foralumab game changer/blockbuster #tils #tlsa @TizianaLS https://t.co/y52Pc297G5" (@yodahanforce)

"Game changer/blockbuster Foralumab #tlsa @TizianaLS https://t.co/zq21KMqoWB" (@yodahanforce)

"#tlsa @TizianaLS foralumab game changer/blockbuster #agl @Parsortix changes how they diagnose & treat cancer forever #lnd @landore_plc gold, nickle, copper, cobalt, iron safe jurisdiction Canada #tgr @Tirupatiuk Graphite" (@yodahanforce)

Oncology

"Foralumab game changer/blockbuster #tlsa @TizianaLS" (@yodahanforce)

"Game changer/blockbuster Foralumab #tlsa @TizianaLS https://t.co/sNdVIHy9jK" (@yodahanforce)

Tiziana to Host Investor Call to Discuss Exclusive License Agreement to Evaluate Foralumab, a Novel, Fully Human Anti-CD3 Monoclonal Antibody, in Conjunction with Allogeneic CAR T Candidates for Cancer Treatment (GlobeNewswire) - "Tiziana Life Sciences plc...will host a conference call and audio webcast on Wednesday, September 8, at 4:15 p.m. ET to discuss its recently announced exclusive license agreement to evaluate Foralumab, the Company’s novel, fully human anti-CD3 monoclonal antibody, in conjunction with allogenic CAR T candidates for cancer treatment."

Licensing / partnership • Oncology