Otelixizumab

Advancing pipeline of next generation therapeutics and diagnostics for oncology and immune diseases of high unmet needLONDON, Dec. 27, 2022 (GLOBE NEWSWIRE) -- Tiziana Life Sciences Ltd (“Tiziana”, NASDAQ: TLSA), a biotechnology company focused on innovative therapeutics for oncology, inflammation, and infectious diseases today announces its interim results for the six months ended 30 June 2022. Highlights during the period: CLINICAL and NON-CLINICAL PROGRAMMES ForalumabTZLS-401​ Announced FDA approval for enrollment of a second, Secondary Progressive Multiple Sclerosis (SPMS) patient in under the Individual Patient Expanded Access (EA) Program following favorable clinical results after 6 months of treatment of the first patient in the EA program.Announced initiation of phase 1b clinical trial in Crohn’s disease patients to evaluate oral capsules of foralumab, a fully human anti-cd3 monoclonal antibody. The revised protocol allows for the study of a broader patient population and a shorter dosing period. These protocol amendments or revisions are intended to expedite patient enrollment with study completion targeted for the fourth quarter of 2022. This study is the first multiple-dose study with orally administered enteric-coated capsules of foralumab in patients with CD. This study will initiate soon with patient enrollment in the second quarter of 2022. Enteric-coated capsules, containing doses up to 5 mg of foralumab, will be administered once-daily for five consecutive days to patients with mild-to-moderately active CD. While the primary objective is safety and tolerability, additional endpoints are to assess clinical and immune signal responses, including calprotectin measurements in stool. Blood samples will be collected to evaluate pharmacokinetics, including the rate and extent of systemic absorption. The presence of anti-drug antibodies (ADAs) will also be determined.Announced that FDA granted permission to enroll up to 8 additional (SPMS) patients in the expanded access program with intranasal foralumab. The safety, tolerability, and clinical responses from the first two SPMS patients were submitted to the FDA to seek permission to treat up to an additional eight SPMS patients with the goal of obtaining more clinical data to assess robustness of the clinical responses. As part of the original treatment plan, the foralumab dose will remain 50 mcg three times a week (MWF), which is the same dose administered previously to the first two SPMS patients. The dosing regimen in this IND also has a provision for dose escalation up to 100 mcg three times a week (MWF) as an option to improve clinical benefit, if needed.Announced that data from a Secondary Progressive Multiple Sclerosis patient treated with intranasal treatment with foralumab will be presented at the consortium of multiple sclerosis centers (CMSC) 2022 annual meeting. Dr. Tanuja Chitnis, MD, Professor of Neurology and the Principal investigator of the clinical study at the at the Brigham and Women’s Hospital (BWH), Boston, MA., presented a poster discussing clinical data from a patient with secondary progressive Multiple Sclerosis (SPMS), who was treated with intranasal foralumab for six months. Announced positive clinical results in the second patient with secondary progressive multiple sclerosis (SPMS) following three months of dosing with intranasal foralumab. These results confirm the previously reported data, from the first SPMS patient after three months of treatment of the first SPMS patient. The treatment with foralumab, a fully human anti-CD3 monoclonal antibody, was well-tolerated and improved clinical and PET imaging analyses.The second patient, a young male in his 40s, was diagnosed with SPMS in 2014. Since then, the disease has been progressive, resulting in an accumulation of disability. Following completion of three months of treatment with intranasal foralumab (50 mcg; three times a week for two weeks, followed by one week off treatment), the patient showed improvement as measured by PET imaging, to assess inhibition of microglial activation, and by neurologic examination. Approximately 10-30% reduction in PET signal was seen across brain regions (including cortex, thalamus, white matter, and cerebellum) in the second SPMS patient, which is comparable to the PET changes seen in the first SPMS patient following three months of treatment with intranasal foralumab. Clinically, the Timed 25-Foot Walk test and neurologic exam were also improved. Initiated five GLP safety toxicology studies of foralumab administered intranasally and subcutaneously in HuGEMM CD3 transgenic mice. Three intranasal toxicology studies of 14 days, 13 weeks and 26 weeks dosing duration and two subcutaneous safety toxicology studies of 14 days and 28 days dosing duration were initiated.Completed manufacturing of clinical supplies of foralumab solution for subcutaneous injection at Frontage Laboratories and initiated ICH stability studiesCompleted compatibility, stability and characterization studies of foralumab nasal solution in Aptar Unidose device for nasal administration Anti IL-6R mAbTZLS-501, formerly NI-1201​ Filed IND for Phase 1 Clinical Trial in Healthy Subjects for treatment of interstitial lung disease associated with systemic scleroderma (SSc ILD). Initiated effector function studies at STC Biologics Milciclib TZLS-201 ​ Completed manufacturing of clinical supplies, milciclib capsules, and initiated ICH stability program. Intellectual Property As of September 2022, the Company has a total of 298 granted patents. New appointments Appointed Dr Matthew Davis, MD, RPh as Chief Medical Officer. Resignations and interim arrangements Announced the resignation of Kunwar Shailubhai, PhD, CEO, CSO and the appointment of Gabriele Cerrone as interim CEO Deaths Announced death of Executive Board Director, Thomas Adams, PhD Highlights post period end: On September 20, 2022, Tiziana announced that the second patient (“EA2”) with non-active secondary progressive multiple sclerosis (SPMS) receiving intranasal foralumab had shown additional clinical improvements as measured by the Expanded Disability Status Scale (EDSS), a standard clinical assessment.On October 12, 2022, Tiziana announced that it planned to submit an Investigational New Drug Application (IND) for a Phase 1 Trial of intranasal foralumab in Alzheimer's disease patients after receiving an affirmative written response from the FDA on a Pre-Investigational New Drug Application (PIND). Tiziana plans on filing the IND for Alzheimer’s disease by the third quarter of 2023 upon the completion of requested toxicology studies, then starting its Phase 1 program by the end of 2023.On November 2, 2022, Tiziana announced the completion of enrollment of the first patient cohort in its Intermediate Size Patient Population Expanded Access Program to evaluate foralumab in non-active Secondary Progressive Multiple Sclerosis (SPMS) patients. On November 10, 2022, Tiziana announced its near-term focus on developing intranasal foralumab for inflammatory diseases of the Central Nervous System (CNS) such as non-active secondary-progressive Multiple Sclerosis (SPMS), Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).On December 15, 2022, Tiziana filed an IND with the FDA pertaining to a phase 2 study of milciclib in combination with gemcitabine for NSCLC indication. FINANCIAL For the six months to 30 June 2022 the consolidated Group made a loss of $8.3m (six months to 30 June 2021: $17.0m).The Group ended the period with $26.5m cash as at 30 June 2022 (31 December 2021: $42.2m). Research and development (R&D) expenses increased to $7.5m compared to $5.6m in the first half of 2021. The increase is primarily expenses related to the advancement of our proprietary programs, TZLS-401 and TZLS-501. The Company continues to carefully manage its working capital position and continues the process, as referred to below, to evaluate opportunities to raise further funds through the issue of additional equity capital. Contacts: Tiziana Life Sciences LtdGabriele Cerrone, Chairman and founder+44 (0)20 7495 2379 About Tiziana Life Sciences Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough immunomodulation therapies via novel routes of drug delivery. Tiziana’s innovative nasal, oral and inhalation approaches in development have the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s two lead candidates, intranasal foralumab, the only fully human anti-CD3 mAb, and milciclib, a pan-CDK inhibitor, have both demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications.

Third-party research conducted by leading U.S. academic institutions published in a peer reviewed journal Frontiers in Immunology shows a favorable safety profile for intranasally administered foralumab and immunological activity in humans Finding supports Tiziana’s intranasal foralumab monoclonal antibody platform as a new modality for the treatment of autoimmune and CNS diseasesTiziana’s fully human foralumab is the first anti-CD3 mAb which has not shown an anti-drug antibody (immune reaction) in humans NEW YORK, Nov. 23, 2022 (GLOBE NEWSWIRE) -- Tiziana Life Sciences Ltd. (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company enabling breakthrough CNS immunomodulation approaches to enhance the functionality of Treg-based therapies, announces publication of a scientific article in the peer-reviewed journal Frontiers in Immunology entitled “Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects”(1) . The study was completed by researchers at the Brigham and Womens Hospital (BWH) and Harvard Medical School. The goal of the study was to assess safety and the immune effects of an entirely human, previously uncharacterized nasal anti-CD3 mAb (foralumab) in humans and its in vitro stimulatory properties. The findings support Tiziana’s intranasal foralumab platform as a new modality for the treatment of autoimmune and CNS diseases. About the Study The study evaluated 27 healthy volunteers (nine per group) who received either intranasal foralumab at a dose of 10ug, 50ug, or 250ug daily for 5 days or placebo. Safety was assessed and immune parameters were measured on day one (pre-treatment), and days 7, 14, and 30 by Fluorescence-Activated single Cell Sorting (FACS) and by Single-cell RNA sequencings (cRNAseq). No adverse events or safety signals were found when foralumab was dosed at the amounts of 10ug, 50ug and 250ug given for 5 consecutive days. Immunomodulatory effects were predominantly observed at the 50ug dose. At the 50ug dose a reduction of CD8+ effector memory cells, an increase in naive CD8+ and CD4+ T cells, and reduced CD8+ T cell granzyme B and perforin expression were observed. A dose effect with 50ug being more immunomodulatory than 250ug is consistent with previously conducted animal studies of mucosal tolerance in which higher doses do not induce immune regulation. This is likely due to the partial signaling that occurs at intermediate doses which favors the induction of regulatory cells. No anti-drug antibodies in humans were detected. ConclusionWhen intranasal foralumab was dosed in humans at the above levels, immunological activity and a favorable safety profile were observed. The findings present a new modality for the treatment of autoimmune and CNS diseases. Tiziana’s intranasal monoclonal antibody (mAb) technology is applicable to marketed mAbs which are currently available only through IV & SC administration, addressing enourmous market potential. A notable finding from this research is that the biologic effect of intranasal anti-CD3 is different from IV anti-CD3. IV anti-CD3 is associated with modulation of CD3 from the cell surface, a decrease in CD3 cells and with side effects that include cytokine release syndrome and in some instances activation of EBV(2). EBV reactivation was observed with IV foralumab at the 500ug and 1000ug doses. In contrast, intranasal foralumab did not show EBV activation at any of the doses or modulation of CD3 from the cell surface and the researchers did not find foralumab in the bloodstream. From these results it can be concluded thar nasal foralumab acts locally while IV administered anti-CD3 acts systemically. Confirming these findings, in animal studies, it was observed that nasal anti-CD3 localized to the cervical lymph nodes and as with human studies, nasal anti-CD3 was not observed in the bloodstream of animals. This article provides a wealth of scientifically rigorous immunologic data on intranasal foralumab,” said Matthew Davis, MD, RPh, Chief Medical Officer of Tiziana. “The finding that the immune effects were predominately observed at the 50ug dose rather than the lower and higher doses studied was intriguing. Our current study in non-active Secondary Progressive Multiple Sclerosis is using a 50ug dose and our planned Phase 2 multicentered placebo-controlled dose-ranging study will also include a 50ug dosing arm.” To view the online publication, please click here: https://www.frontiersin.org/articles/10.3389/fimmu.2022.956907/full Cited References: (1)Chitnis T, Kaskow BJ, Case J, Hanus K, Li Z, Varghese JF, Healy BC, Gauthier C, Saraceno TJ, Saxena S, Lokhande H, Moreira TG, Zurawski J, Roditi RE, Bergmark RW, Giovannoni F, Torti MF, Li Z, Quintana F, Clementi WA, Shailubhai K, Weiner HL and Baecher-Allan CM (2022) Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects. Front. Immunol. 13:956907. doi: 10.3389/fimmu.2022.956907 (2)Kuhn C, Weiner HL. Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside. Immunotherapy (2016) 8(8):889–906. doi: 10.2217/imt-2016- 0049 About Foralumab Foralumab, the only entirely human anti-CD3 mAb, has shown reduced release of cytokines after intravenous (IV) administration in healthy volunteers and in patients with Crohn's disease. In a humanized mouse model (NOD/SCID IL2γc-/-), it was shown that while targeting the T-cell receptor, orally administered foralumab modulates immune responses of T-cells and enhances regulatory T-cells (Tregs), thereby providing therapeutic benefit in treating inflammatory and autoimmune diseases without the occurrence of potential adverse events usually associated with parenterally-administered mAb therapy. Once-a-day treatment for 10 consecutive days with intranasal foralumab was both well tolerated and produced clinical responses in COVID-19 patients. Based on these studies, the intranasal and oral administration of foralumab offers the potential to become a well-tolerated immunotherapy for autoimmune and inflammatory diseases by the induction of Tregs. About Tiziana Life Sciences Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough immunomodulation therapies via novel routes of drug delivery. Tiziana’s innovative nasal, oral and inhalation approaches in development have the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s two lead candidates, intranasal foralumab, the only fully human anti-CD3 mAb, and milciclib, a pan-CDK inhibitor, have both demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications. For further inquiries: Tiziana Life Sciences Ltd Hana Malik, Business Development, and Investor Relations Manager+44 (0) 207 495 2379email: info@tizianalifesciences.com Investors:Irina KofflerLifeSci Advisors, LLC646.970.4681ikoffler@lifesciadvisors.com