SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 OR 15d-16
UNDER THE SECURITIES EXCHANGE ACT OF 1934
Commission File Number: 001-38723
Tiziana Life Sciences LTD
(Exact Name of Registrant as Specified in Its Charter)
(Address of registrant’s principal executive office)
Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.
Form 20-F ☒ Form 40-F ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐
Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐
INFORMATION CONTAINED IN THIS REPORT ON FORM 6-K
On October 25, 2022, Tiziana Life Sciences LTD (the “Company”) issued this 6K announcing the release of an updated corporate deck, that can also be found on the Tiziana Life Sciences LTD website.
The Announcement is furnished herewith as Exhibit 99.1 to this Report on Form 6-K. The information in the attached Exhibit 99.1 is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing made by the Company under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, except as otherwise set forth herein or as shall be expressly set forth by specific reference in such a filing.
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
|TIZIANA LIFE SCIENCES LTD|
|Date: October 25, 2022||By:||/s/ Keeren Shah|
|99.1||Corporate deck, dated October 25, 2022|
Enabling Breakthrough Immunomodulation Approaches to Enhance the Functionality of Treg - Based Therapies NASDAQ: TLSAx
Tiziana Life Sciences Overview | June 2022 2 Disclaimer and Forward - Looking Statement The content of this presentation has been prepared for the purpose of providing general information about, and an overview o f, the Company and its business. It is not intended to be a complete review of all matters concerning the Company and nor has it been independently verified. Whilst the presentation h as been prepared in good faith and the Company has taken all reasonable care to ensure the information and facts contained in this presentation are accurate and up - to - date, it does not mak e any representation or warranty, express or implied, as to the accuracy or completeness of any information included in this presentation. Neither the Company nor any of its directors, of fic ers, employees or agents shall be liable for any loss arising directly or indirectly from the use of or reliance upon this presentation or in relation to the adequacy, accuracy, complete nes s or reasonableness of the information it contains. All and any such liability is expressly excluded to the fullest extent permitted by law. The information in this presentation is subject to upd ating, completion, revision, further verification and amendment without notice. This presentation does not constitute or form part of any offer for sale or solicitation of any offer to buy or subscribe fo r a ny securities including ordinary shares in the Company nor does it constitute an invitation or inducement to engage in investment activity in relation to any securities, including the ordina ry shares of the Company. It does not purport to contain information that shall form the basis of or be relied upon in making such investment decisions. If you require any advice, please consult wit h a professional financial adviser. All investments are subject to risk. The value of securities may go down as well as up. Past performance cannot be relied on as a guide for future performance. This presentation may contain certain forward - looking statements concerning the financial condition, results of operations and businesses of the Company. All statements other than statements of historical fact are, or may be deemed to be, forward - looking statements. Forward - looking statements are statements of future expectations that are based on management’s current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in these statements. All forward - looking statements contained in this presentation are expressly qualified in their entirety by the cautionary statements contained or referred to in this section. You should not place undue reliance on forward - looking statements. Each forward - looking statement speaks only as of the date of this presentation. The Company does not undertake any obligation to publicly update or revise any forward - looking statement as a result of new information, future events or other information. In light of these risks, results could differ materially from those stated, implied or inferred from the forward - looking statements contained in this presentation. In the UK, this presentation has not been approved by an authorised person and is being distributed on the basis that each person in the UK to whom it is issued is reasonably believed to be such a person as is described in Article 19 (investment professionals) or Article 49 (high net worth companies, unincorporated associations etc.) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 (SI 2005/1529) or are persons to whom an invitation or inducement to engage in investment activity (within the meaning of section 21 of the Financial Services and Markets Act 2000) in connection with the issue or sale of any securities may otherwise lawfully be communicated or caused to be communicated. Persons who do not fall within such descriptions may not act upon the information contained in this presentation.
Tiziana Life Sciences Overview | June 2022 3 Investment Highlights Source: 1 Lu et al. Journal of Biomedical Science (2020) 27:1 Innovative, clinically - validated, drug delivery platform based on immunomodulating approaches Recent clinical data support the MOA Global IP protection of antibody formulation technology until 2040, can be applied across different molecules Strong IP protection for lead assets Milciclib and Foralumab Partnership with Precision Biosciences for lymphodepletion ahead of CAR - T procedures. Collaboration ongoing Targeting the global $150+ billion market for antibody treatments 1 Clinical data validate MOA for nasal administration Experienced scientific advisory board and management team that has brought four drugs to market Demonstrated Bench to market experience
Tiziana Life Sciences Overview | June 2022 4 Antibody Administration: Switching From IV and SC To Oral, Nasal And Inhaled Routes for Immunomodulating Therapies A Revolutionary Platform Benefits of non - systemic dosing • Improved patient compliance • Local activity instead of systemic distribution; may minimize side effects • Anticipated lower cost of goods and lower price of administration Today’s Options for Antibody Administration are Subcutaneous or Intravenous (IV) Foralumab Nasal administration Multiple Sclerosis Neurodegenerative diseases TZLS - 501 Anti - IL6R Direct delivery to lungs with a portable inhaler for pulmonary diseases Foralumab Oral administration For Crohn’s Disease IBD platform enables… The
Tiziana Life Sciences Overview | June 2022 5 Positive Data From Five Clinical Studies Completed Our P i p eline Subject PC IND Phase 1/IAP Phase 2 Phase 3 FORALUMAB Fully human anti - CD3 mAb Intranasal Oral Subcutaneous ANTI IL - 6 RECEPTOR Fully human mAb Inhalation Oral Progressive Multiple Sclerosis (expanded program) Enteric Coated Oral Capsules for Crohn’s Disease Ongoing IAP, 6 months data showed positive clinical response MILCICLIB Pan - CDK inhibitor Interstitial Lung Disease Milciclib + Gemcitabine in NSCLC Kras + mutants Crohn’s Disease Type 1 Diabetes Pulmonary Fibrosis
Lead Asset: Foralumab The only fully human anti - CD3 monoclonal antibody in clinical studies Non - FC binding anti - CD3 antibody mutations expected to have improved safety profile
Tiziana Life Sciences Overview | June 2022 7 OKT3 Mu r omonab * IgG2a ChAglyCD 3 Otelixizumab IgG1 N297/A (Ala - Ala) hOKT3 γ1 Teplizumab IgG2 L234/A, L235A Nuvion Visilizumab IgG2 L234/A, V237/A Foralumab IgG1 L234/A, V335E Fully M urine Chimeri c & Humani z e d Humanized Humanized Fully Human Adapted from: Kuhn, Chantal, and Howard L. Weiner. "Therapeutic anti - CD3 monoclonal antibodies: from bench to bedside." Immunotherapy 8.8 (2016): 889 - 906. Rodent Origin *Approved by the FDA for solid organ transplantation immuno - suppression CD3 - specific Monoclonal Antibodies in Clinical Development Foralumab is the Only Fully Human Anti - CD3 mAb in Clinical Trials Human Origin * Point Mutation MS IBD T1D CAR - T Rheumatoid Arthritis Lupus NASH Psoriasis
Tiziana Life Sciences Overview | June 2022 8 Our Therapeutic Approach Tregs Production and Enhance their Functionality Foralumab Facilitates Locally Targeted Immunomodulation to Improve Augment Tregs production Enhance Tregs Functionality Foralumab intranasal administration to facilitate local activity Site targeted local immunomodulation
Uptake Binding Signaling LAP induction IL - 10 TGF - b Tr1 CD8+ Treg Inhibition Effector T cell CD4 + FoxP3 + (Treg) CD4 + FoxP3 - FoxP3 induction Dendritic Cell Intranasal or Oral Foralumab Nasal or Gut Lumen gd T cell IL - 10 CD4 + LAP + (Th3) Anti - CD 3 mAb CD 3 /TCR complex Cytokines The binding of foralumab to the T - cell receptor complex, through either the nasal or oral route, results in suppression of effector T - cells involved in various inflammatory and autoimmune diseases along with a reduction in inflammatory cytokines and increase in Tregs anti - inflammatory cytokines. CD4 +
Tiziana Life Sciences Overview | June 2022 10 The First Validation That Intran asally Administered Foralumab is Well - tolerated and the Treatment Provides Clinical Benefits Results: Biomarkers measured via cytokines and C - reactive proteins Cohort Lung CT Scan Cytokine IL - 6 C - Reactive Protein Evaluable patients % Improvement % Reduction % Reduction Control, n=14 43 37 40 Foralumab + Dexa, n=12 75 41 55 Foralumab, n=10 80 69 85 Foralumab: Clinical Proof of Concept for Intranasal Delivery First Demonstrated in Mild - to - Moderate COVID - 19 - 2 Days Hospital Visit D e xa Blood and Swab Collection Medical Exam *CT Scan Blood C olle c tion Blood C olle c tion 10 Days END of T r e a tme nt 13 Hospital Visit Medical Exam *CT Scan 0 1 3 5 Foralumab treatment + P atient reported outcome CT Scan of Patients’ Lungs *Eligibility Confirmation
Tiziana Life Sciences Overview | June 2022 11 Upfront payments • Multiple payments commensurate with meeting specified successful milestones • Royalties • Additional royalty options for subsequently developed CAR - T products • Precision to be responsible for the development, commercialization and costs for use of foralumab First foralumab Program to be Tested Will be in Combination with an Anti - CD19 CAR - T Precision Biosciences (Nasdaq: DTIL) Licensing Collaboration Validates Our Technology • Exclusive agreement allowing Precision to explore Tiziana’s fully human anti - CD3 monoclonal antibody ( mAb ), foralumab, as an agent to induce tolerance of allogeneic CAR - T cells to potentially improve the clinical outcome of Precision’s CAR - T cell therapy programs • Foralumab to be used as a potential mild pre - conditioning and lymphodepleting agent to replace or reduce doses of cyclophosphamide/fludarabine (Cy/Flu)
Tiziana Life Sciences Overview | June 2022 12 LifeSci Venture Partners Provides active guidance and differentiated support to enhance portfolio companies’ probability of success Intranasal F oralumab for Treatment of Neurodegenerative Diseases (Multiple Sclerosis) Intranasal Local action with improved safety and lowered dosing Fully Human Anti - CD3 mAb
Tiziana Life Sciences Overview | June 2022 13 An Innovative Approach to Penetrate the Blood Brain Barrier (BBB) Intranasally - Administered Foralumab for Neurodegenerative Diseases
Tiziana Life Sciences Overview | June 2022 14 Intranasally Administered Foralumab in SPMS Patient: 6 - Month Treatment Data * These biomarkers are known to be associated with multiple sclerosis pathogenesis and progression Two patients were dosed with intranasal foralumab M - W - F for two weeks with a subsequent 1 - week washout period for 6 - month period. Data consistent with 3 - month period. Positive Results: The regimen was well - tolerated with associated beneficial clinical and biomarker changes PET imaging data • Indicated continued inhibition of microglial cell activation • The reduction in microglial activation was seen in all parts of brain • Suppression of microglial activation further increased after six months of treatment Clinical Results Biologic Response Biomarker changes D ownregulated serum levels of pro - inflammatory cytokines*, including: • I nterferon - gamma (IFN - g) • I nterleukin (IL) - 18 • IL - 1b • IL - 6 Clinical Test Evaluation • I mprovement in Timed 25 - Foot Walk Test (T25FW) • 9 - Hole Peg Test (9HPT) • Symbol Digit Modality Test (SDMT)
Tiziana Life Sciences Overview | June 2022 15 Assessment of Inhibition of Microglial Activation by PET Imaging Following Treatment with Nasally Administered Foralumab in First SPMS Patient
Tiziana Life Sciences Overview | June 2022 16 Graph Depicting Microglial Activation PET Signal in Different Regions of the Brain at Various Time Points
Tiziana Life Sciences Overview | June 2022 17 Intranasally Administered Foralumab in SPMS Patient: 6 - Month Treatment Data *Percent reduction is based on changes from baseline in SUVR - 1, a surrogate index for PET binding potential. SUVR=Standardized U ptake Value Ratio, calculated with reference to a pseudo reference region in cerebral white matter that showed minimal change in PET SUV, across time points. WHOLE BRAIN CEREBRAL CORTEX THALAMUS WHITE MATTER CEREBELLUM 3 mon3 MONTHS3 month - 23% - 23% - 20% - 25% - 22% 6 MONTHS - 38% - 38% - 50% - 36% - 38% Percent Reduction* in Microglial PET Signal After Starting Intranasal Foralumab as Compared to Baseline, in Whole Brain and Selected Brain Regions The clinical data from the second patient is consistent with clinical data from the first patient. These results confirm that intranasally administered foralumab produces positive clinical responses 3 months 6 months WHOLE BRAIN CEREBRAL CORTEX THALAMUS WHITE MATTER CEREBELLUM - 23% - 38% - 23% - 38% - 20% - 50% - 36% - 25% - 22% - 38%
Tiziana Life Sciences Overview | June 2022 18 LifeSci Venture Partners Provides active guidance and differentiated support to enhance portfolio companies’ probability of success Other Potential CNS - related Indications (Alzheimer’s and ALS) Intranasal anti - CD3 provides a unique approach for treating progressive neurologic diseases by modulating microglial cells. The intranasal route of immunotherapy has minimal toxicity and induces regulatory T cells locally, that then migrate to the brain to dampen brain inflammation.
Tiziana Life Sciences Overview | June 2022 19 Study Presented at the Alzheimer’s Association International Conference® (AAIC®) Proof - of - Concept Demonstrated in Alzheimer’s Disease In this study animal models of Alzheimer’s disease (AD) demonstrated that microglia activity was restored and cognition was improved following the dosing of intranasal anti - CD3 monoclonal antibody. • Clinical measures were assessed in the mouse models using the Y - maze and Morris water maze tests which showed improvements in cognition. Biological improvements were also observed based on restoration of genetic phenotypes as measured by the presence of homeostatic microglia genes detected by Nanostring . In addition, it was found that intranasal anti - CD3 induced the migration of regulatory T cells (Tregs) to the brain which then interacted with microglia. • Alzheimer’s is another potentially valuable application of anti - CD3 based on its ability to stimulate the immune system to promote homeostatic microglial cells while decreasing degenerative microglial cells in the brain. “Treatment of Alzheimer’s disease by modulation of microglial neuroinflammation by nasal anti - CD3 mAb ” (presented by Weiner, M.D., Co - Director of the Ann Romney Center for Neurologic Disease at the Brigham and Women’s Hospital (BWH) and Chairman of Tiziana's Scientific Advisory Board)
Tiziana Life Sciences Overview | June 2022 20 IND for Intranasal Foralumab in Alzheimer’s Planned Submission Q2/Q3 2023 Receive an affirmative written response from the FDA on a Pre - Investigational New Drug Application (PIND) Submit an Investigational New Drug Application (IND) to conduct a Phase 1 study intranasal foralumab in Alzheimer's disease patients Planned IND filing by Q3 2023 upon the completion of requested toxicology studies Start Phase 1 program in 2H of 2023
Tiziana Life Sciences Overview | June 2022 21 Intranasal Foralumab in Amyotrophic Lateral Sclerosis (ALS) • In September, a Lawrence & Isabel Barnett Drug Development Program Grant was awarded to the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH) by the ALS Association • This prestigious research grant supports the study of an intranasal anti - CD3 monoclonal antibody ( mAb ) in an animal model of Amyotrophic Lateral Sclerosis (ALS). • The grant will allow further study the role of intranasal anti - CD3 mAb in dampening the microglial activation which amplifies ALS disease progression. ALS patients have limited therapeutic options and high unmet need “We have now seen the potential of intranasal foralumab to dampen microglial activation in three major neuroinflammatory - related diseases, which creates significant optionality for exploring its benefits in some of the most important and burdensome medical conditions of our time.”
Tiziana Life Sciences Overview | June 2022 22 LifeSci Venture Partners Provides active guidance and differentiated support to enhance portfolio companies’ probability of success Oral Foralumab for Inflammatory Bowel Diseases (Crohn’s Disease) Oral capsules Foralumab , a fully human anti - CD3 mAb
Tiziana Life Sciences Overview | June 2022 23 Orally - Administered Foralumab in Phase 1a Trial in Healthy Volunteers Clinical results Single ascending dose, double - blind, placebo - controlled study in healthy subjects Foralumab administered at 1.25, 2.5 and 5.0 mg/dose in enteric - coated capsules Well - tolerated at all doses tested and no drug - related safety issues observed No systemic absorption of orally administered foralumab Capsule ta k en o r ally
Tiziana Life Sciences Overview | June 2022 24 Oral Foralumab Dosing (n=8) Phase 1B Study Design in Crohn’s Disease Primary Endpoints Safety Tolerability Clinical and immune signal responses 2 nd Review by Safety Monitoring Committee Dosing period 2.5mg daily One week break Follow up period Day 0 N=6 foralumab N=2 placebo Day 5 Day 12 Day 28 Final Evaluation If safety issues arise, reduce dose to 1.25 mg and continue dose through day 28 Dose increase to 5.0 mg 2.5 mg or 5 mg Stool calprotectin biomarker assessed for clinical response 1 st Review by Safety Monitoring Committee Continue dose through day 28 *
Tiziana Life Sciences Overview | June 2022 25 * Boden, E. K., Canavan, J. B., Moran, C. J., McCann, K., Dunn, W. A., Farraye, F. A., Ananthakrishnan, A. N., Yajnik, V., Gandhi, R., Nguyen, D. D., Bhan, Aantibodies. K., Weiner, H. L., Korzenik, J. R., Snapper, S. B. Immunologic alterations associated with oral delivery of anti - CD3 (OKT3) monoclonal in patients with moderate - to - severe ulcerative colitis. Crohn's & Colitis 360 (2019). 183: 240 - 246. in Ulcerative Colitis Validated Proof of Concept for Oral Administration of OKT3, an Anti - CD3 mAb OKT3 was approved for renal transplantation patients but is now off the market due to toxicity concerns Prof. Snapper, et al., of Harvard Medical School conducted an exploratory study with oral OKT3 treatment in patients with ulcerative colitis, an inflammatory bowel disease Key Findings • Biologic response of increased proliferation and anti - inflammatory gene expression profile in peripheral blood mononuclear cells • 3 of 6 patients had a clinical response including one patient in clinical remission • Treatment was well - tolerated with no serious treatment - related adverse events • Patients with moderate - to - severe ulcerative colitis received oral OKT3, a fully - murine anti - CD3 mAb once daily for 30 days
Tiziana Life Sciences Overview | June 2022 26 LifeSci Venture Partners Provides active guidance and differentiated support to enhance portfolio companies’ probability of success Oral Milciclib for NSCLC Broad - spectrum inhibitory activities of milciclib on CDKs are favorable Milciclib CDK 5 CDK2 CDK1 CDK 4 CDK7 S p ecific ally downregulates miR - 221/miR - 222 pair and c - myc .
Tiziana Life Sciences Overview | June 2022 27 Phase 1 Study of Milciclib + Gemcitabine in Refractory Solid Tumors Trial Design 16 Patients with refractory solid tumors Treated with oral milciclib at three dose levels (45, 60, and 80 mg/m 2 /day) With a fixed dose of IV gemcitabine (1000 mg/m 2 /day) Milciclib was well - tolerated with manageable side effects Overall response rate was 36% Clinical activity was observed in patients with variety of solid cancers who were non - responders to all existing chemo therapy Recommended Phase 2 dose (RPD) found to be 80mg/m 2 /day Results Swimmer plot showing treatment duration. Tumor type was indicated for patients having a prolonged stable disease or a partial response. M = milciclib G = gemcitabine Cancer Chemotherapy and Pharmacology , June 2017, 79(6), 1257 - 1265
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