Full Press Release Details
Results for the Six Months Ended 30 June 2020
pipeline of next generation therapeutics and diagnostics for oncology and immune diseases of high unmet need
30 September 2020 - Tiziana Life Sciences plc ("Tiziana", AIM: TILS, NASDAQ: TLSA), a biotechnology company
that focuses on the discovery and development of novel molecules to treat human diseases in oncology, inflammation and infectious
diseases today announces its interim results for the six months ended 30 June 2020.
is a fully human engineered anti-CD3 monoclonal antibody (mAB). It was in-licensed in December 2014 from Novimmune.
the only fully human engineered human anti-CD3 mAB in clinical development, Foralumab has significant potential advantages such
as a shorter treatment duration and reduced immunogenicity. With completion of the intravenous dosing for our Phase 2a trial in
Crohn's Disease, Foralumab's ability to modulate T-cell response enables potential extension into a wide range of
other autoimmune and inflammatory diseases, such as multiple sclerosis, inflammatory bowel disease (IBD), psoriasis and rheumatoid
is being developed as both an immunosuppressive and immunomodulatory agent, with therapeutic benefits of rendering T-cells unable
to orchestrate an immune response and induction of immune tolerance via maintenance of regulatory T-cells. There is further potential
for Foralumab to be combined with the Company's TZLS-501, a fully human anti-IL-6R mAB in development to target autoimmune
and inflammatory diseases.
16 April, 2018, the Group entered into an exclusive license agreement with The Brigham and Women's Hospital, Inc. relating
to a novel formulation of Foralumab dosed in a medical device for nasal administration. An investigational new drug application
(IND) for the first-in-human evaluation of the nasal administration of Foralumab in healthy volunteers for progressive multiple
sclerosis indication was filed in the second quarter of 2018. Phase 1 clinical data demonstrated that nasally administered Foralumab,
was well-tolerated and no drug-related safety issues were reported at any of the doses. No drug-related changes were observed
in vital signs among subjects at pre-dose, during treatment and at discharge. The mean blood pressure (BP) during the 5 days of
treatment were; Cohort A (10 g/d):124/73, Cohort B (50 g/d): 119/67 and Cohort C (250 g/d):113/65 compared
to placebo:118/67). Heart rates, respiratory rates and oral temperatures were unchanged among the 3 cohorts compared to the placebo.
Nasally administered Foralumab at the 50 g dose suppressed cytotoxic CD8+ as well as perforin secreting CD8+ cells, which
have been implicated in neurodegeneration in multiple sclerosis (MS). Treatment at 50 g stimulated production of anti-inflammatory
cytokine IL-10 and suppressed production of pro-inflammatory cytokine IFN- . Taken together, the treatment showed significant
positive effects on the biomarkers for activation of mucosal immunity, which are capable of inducing site-targeted immunomodulation
to elicit anti-inflammatory effects. Based on the results we intend to conduct a Phase 2 trial in secondary progressive MS patients.
Protocol for Phase 2 nasal clinical trial is finalized. The briefing package and protocol was submitted to FDA on July 22, 2020
requesting type C meeting and FDA response expected by mid October, 2020. The trial is anticipated to begin in Q4 2020.
enteric-coated capsule formulation has been developed for oral administration of Foralumab. cGMP manufacturing of clinical trial
materials for a Phase 1 study has been completed. The Phase 1 clinical trial for Foralumab in healthy volunteers was a single-center,
single-arm, ascending dose study in which low doses (1.25, 2.5 and 5.0 mg/dose) of Foralumab and placebo were orally administered.
The primary endpoint of the Phase 1 study was safety and tolerability of oral Foralumab in humans. The Phase 1 trial was initiated
on December 2, 2019and results were reported on January 20, 2020 The proprietary oral formulation, comprising the lyophilized
and stabilized free-flowing powder of formulated Foralumab encapsulated in an enteric-coated capsule, was well-tolerated at all
doses tested and there were no drug-related safety issues even at the highest dose of 5 mg in this trial. Based on the positive
outcome of the Phase 1 trial, a Phase 2 trial in Crohn's Disease patients is expected to begin in Q2/Q3 2021.
is a fully human engineered mAb targeting the interleukin-6 receptor (IL-6R). Tiziana Life Sciences licensed the intellectual
property from Novimmune in January 2017. This fully human mAb has a unique mechanism of action that binds to both the membrane-bound
and soluble forms of the IL-6R resulting in lowering of circulating levels of IL-6 in the blood. Excessive production of IL-6
is regarded as a key driver of chronic inflammation, associated with autoimmune diseases such as multiple myeloma, oncology indications
and rheumatoid arthritis, and the Group believes that TZLS-501 may have potential therapeutic value for these indications.
preclinical studies, TZLS-501 demonstrated the potential to overcome limitations of other IL-6 blocking pathway drugs. Compared
to tocilizumab and sarilumab, while binding to the membrane-bound IL-6R complex TZLS-501 has shown a higher affinity for the soluble
IL-6 receptor as seen from the antibody binding studies conducted in cell culture. TZLS-501 also demonstrated the potential to
block or reduce IL-6 signalling in mouse models of inflammation. The soluble form of IL-6 has been implicated to have a larger
role in disease progression compared to the membrane-bound form. (Kallen, K.J. (2002). "The role of transsignalling via
the agonistic soluble IL-6 receptor in human diseases". Biochimica et Biophysica Acta. 1592 (3): 323-343.).
April 9, 2020 Tiziana announced the clinical development of anti-IL6R mAb as a treatment for "cytokine storm" induced
lung damage in COVID-19 patients. Early clinical studies conducted by doctors in China suggest that anti-IL6R mAb may
be used in clinical practice for treatment of COVID-19. Consequently, China's National Health Commission has recommended
the use of Roche's blockbuster drug, Actemra for treatment of patients infected with COVID-19, with serious lung damage and
elevated IL6 levels. Actemra was first approved by the FDA in 2010 for rheumatoid arthritis. Besides Actemra , Sanofi
and Regeneron are currently exploring Kevzara , an FDA-approved anti-IL-6 receptor therapy for rheumatoid arthritis, for treatment
of severe COVID-19. The Company believes that of TZLS-501 may have greater clinical effect than Actemra or Kevzara based
on higher binding affinity for IL6 receptor complex compared to Actemra and Kevzara . Also TZLS-501 reduces circulating
levels of IL6 via the trans-signaling pathways.
treatment utilizes a novel mode of administrationusing hand-held nebulizer to deliver aerosolized anti-IL6R mAb solution to inflamed
tissue of deep lung. On April 9,2020, Tiziana announced filing of patent application in support of treatment of COVID-19 utilizing
Anti-IL6R via inhaled delivery (Kunwar Shailubhai, inventor). Initial work on CMO selection, technology transfer and transfer
of lead cell line candidate from Novimmune to CMO initiated in April 2020. A rigorous CMO selection process was initiated in April
and STC Biologics, a boutique CMO located in Newton MA was selected as the finalist based on their ability to deliver drug substance
(DS) in approximately 10 months timeline and most competitive pricing. Tiziana shipped a lead non-clonal cell line from Novimmune
to STC Biologics in June 2020. STC Biologics is expanding the cell line, establishing monoclonality, screening for cell line stability
and antibody titer and expanding the monoclonal cell line to larger scale for development and cGMP manufacturing. Concurrently
they are purifying a batch of monoclonal antibody from the 70L Novimmune pilot batch, manufactured using the lead, non-clonal
cell line. STC's generic downstream process is being used for the purification of test article for Inhalation
Safety Toxicology studies using Cynomolgous monkeys at ITR Laboratories Canada
at Sciarra Laboratories in Hicksville, NY was initiated in May 2020, Sciarra is currently evaluating two hand-held nebulizer devices
for use in the study and characterizing physical/performance characteristics. Once a device has been selected, a few candidate
formulations of anti-IL6R mAb, from formulation development studies at STC Biologics, will be manufactured at small scale and
evaluated using the devices. Sciarra will execute cGMP manufacturing of drug product solution, packaging and ICH stability studies
July 2020, Tiziana engaged FHI clinical as CRO to conduct Phase1/2 clinical trials of TZLS-501 in for the COVID-19 indication.
FHI Clinical is a CRO specializing in infectious disease and COVID-19 clinical trials, located in Durham North Carolina. Initial
scope of work is regulatory, preparing for a FDA Type C meeting in Q4 2020. FHI will help design a multisite, Phase1/2 adaptive
trial with sites located mostly ex-US in COVID-19 hot spots to speed enrollment to start in Q1 2021
August 2020, Brand Institute was engaged for selection, qualification and Application for INN and USAN non-proprietary names for
anti-IL6R mAb (TZLS-501)
Laboratories Canada specializes in inhalation toxicology studies in primates and will start inhalation safety toxicology studies
in Cynomolgous monkeys in October 2020 using the purified, characterized anti-IL6R mAb test. Results from the study will be used
to establish dosing for the Phase 1 study in healthy volunteers.
Company is actively evaluating alternative, non-parenteral routes of monoclonal antibody (mAb) administration, namely oral, nasal
and inhalation routes, to facilitate topical or local therapeutic action.
Tiziana's lead small molecule drug, was exclusively licenced in January 2015 from Nerviano Medical Sciences. Milciclib is
an orally bioavailable, broad spectrum inhibitor of Cyclin Dependent Kinases (CDKs): 1, 2, 4, 5 and 7 and Src family kinases.
Cyclin dependent kinases are a family of highly conserved enzymes that are involved in regulating the cell cycle. Src family kinases
regulate cell growth and potential transformation of normal cells to cancer cells. A unique feature of Milciclib is its ability
to reduce microRNAs, miR- 221 and miR-222, which silence gene expression. miR-221 and miR-222 promote the formation of blood vessels
(angiogenesis) that are important for the spread of cancer cells (metastasis). Levels of these microRNAs are consistently increased
in hepatocellular carcinoma ("HCC") patients and may contribute towards resistance to treatment with Sorafenib. As
a result, the Group are investigating Milciclib both as a monotherapy and as a combination treatment with Sorafenib.
date, Milciclib has been studied in a total of eight completed and ongoing Phase 1 and 2 clinical trials in 316 patients. In these
trials, Milciclib was observed to be well-tolerated and showed initial signals of anti-tumour action.
Group initiated a Phase 2a trial (CDKO-125a-010) of Milciclib safety and tolerability as a single therapy in Sorafenib-resistant
patients with HCC in the first half of 2017. Typically, this population of patients have an advanced form of the disease with
poor prognosis and an average overall survival expectancy of 3-5 months In May 2018, the Independent Data Monitor committee (IDMC)
completed an interim analysis of tolerability data from the first eleven treated patients and recommended expansion of the initial
cohort to an additional 20 patients to complete the trial enrolment, which was completed in December 2018.
Phase 2a trial was completed in June 2019 with clinical safety and efficacy result reported in July 2019. Since overexpression
of CDKs and dysregulation in pRB pathway (regulates transcription factors critical for cell cycle progression) are prominently