NASDAQ:TLSA | LSE:TILS
Today, Tiziana Life Sciences (NASDAQ:TLSA) (LSE:TILS) reported positive topline results from its COVID-19 clinical study of Foralumab in Brazil. Foralumab is the first monoclonal antibody formulated for nasal administration for use in this groundbreaking trial. The study was a 39-subject, exploratory trial comparing the use of Foralumab in mild to moderate patients with COVID-19 who are not yet hospitalized. The objectives of the trial were to assess safety and to assess if the treatment may be able to delay the progression of the disease to reduce hospitalization. The three cohorts include a control arm, a Foralumab arm and a Foralumab + Dexamethasone arm. The drug was dosed once per day over 10 days of treatment.
Exhibit I – Phase I Foralumab Trial Arms (1)
Comparing the Foralumab arm with the control arm, the investigational drug was able to achieve a 39 percentage point improvement in lung inflammation, a 32 percentage point improvement in interleukin (IL)-6 reduction and a 44 percentage point improvement in reducing C-Reactive Protein (CRP). The favorable data suggest that Foralumab may downregulate inflammation and inflammatory biomarkers and temper an overreaction of the immune system in patients with COVID-19. This is the first study to evaluate if modulation of human immune system by nasally administered Foralumab may be able to fight against the virus. The positive results reported this morning suggest that this approach was indeed successful. This is important because the scientific concept underlying this therapeutic approach may be useful for treatment of Covid-19 and its newly identified variants in UK, South Africa and Brazil.
Exhibit II – Summary of Clinical Data (2)
While the beneficial effects of the treatment are exciting, the primary endpoint for this trial was safety and tolerability. On this metric, all treatments were well tolerated and there were no grade 3 or grade 4 serious adverse events (SAEs) in any of the cohorts. Additional information on secondary endpoints including pharmacokinetics (PK), immunological biomarkers, stimulation of T regulatory cells, reduction in the use of ventilators and anti-drug antibodies will be reported later.
Investigators found that patients treated with Foralumab regained their sense of taste and smell more quickly than those in the control group.
Key Takeaways:
‣ The anti-inflammatory effect of Foralumab may be useful for multiple COVID-19 variants and other viruses such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS) that cause an aggressive inflammatory response
‣ Direct delivery of Foralumab to the nasal passages and respiratory tract has a rapid impact on inflammation, as evidenced by CT Scans
‣ Foralumab-treated patients indicated an improved sense of smell and taste, suggesting suppression of inflammation in nasal mucosa caused by COVID-19 virus
‣ Multiple pro-inflammatory biomarkers including IL-6 and CRP were reduced in Foralumab-treated patients
Foralumab
Foralumab is a fully human anti-CD3 mAb that has been in-licensed from Novimmune SA. The fully-human IgG1 antibody has been reconstituted into a lyophilized powder that can be manufactured into a pill or solution form. The drug has been investigated in Phase I and Phase II trials by Novimmune and in Phase I trials by Tiziana for Multiple Sclerosis, Crohn’s Disease and most recently COVID-19 using an intranasal administration approach.
Most mAbs are administered via intravenous (IV) infusion; however, there are disadvantages to this approach such as the need for hospital visits, fluid overload, infusion complications (extravasations or air emboli, local infections, hematoma) and allergic reactions including anaphylaxis. Tiziana has overcome this limitation by manufacturing lyophilized and stabilized free flowing powder that can be used in oral and stabilized solution forms. In the COVID-19 study, the stabilized solution form of Foralumab was used for direct delivery via nostrils, which provides for rapid delivery to the nasal mucosa, airway and lungs, precisely the area where it may reduce inflammation by direct application.
Nasal administration allows the biologic to more easily transit the nasal passages to the lungs where it can impact localized inflammation. Anti-CD3 epsilon (ε) chain binding suppresses the immune system by reducing the number of effector T cells and inducing the development of adaptive T regulatory cells, which can suppress immune response. This feature was hypothesized to be particularly valuable in COVID patients who in the worst cases have an overactive immune response and suffer from severe respiratory distress.
Exhibit III – Foralumab, Fully Human Anti-CD3 (3)
COVID Spread and Mutation
Since the start of the COVID-19 pandemic a year ago, the SARS-CoV-2 virus has mutated leading to several other strains that have proven to be more transmissible and lead to more severe reactions in those contracting it. Populations in the U.K., South Africa and Brazil have all been exposed to a new classification of COVID-19 that appears to have more aggressive characteristics. One strain in particular, designated the P.1 coronavirus variant, has spread throughout Brazil and was first detected in the Brazilian city of Manaus. Not only does this variant appear to be more transmissible than its predecessor, but may also be infecting individuals previously sick with SARS-CoV-2.
Several vaccines have been made available and individuals throughout the Americas, Europe and Asia have begun receiving vaccinations. However, large portions of the global population are not protected against the virus and it appears that some individuals may not have lasting immunity following their recovery from SARS-CoV-2. This highlights the importance for a treatment that can address an overactive immune response to the virus. Foralumab has taken the first step in clinical trials to demonstrate safety and effectiveness to address the worldwide pandemic.
Tiziana Life Sciences
Tiziana Life Sciences is a UK and US headquartered biotechnology company developing therapies for a portfolio of indications including Multiple Sclerosis, Crohn’s Disease, COVID-19 and various cancers. Two Phase II trials investigating Foralumab are expected to be launched in the second quarter of this year in Multiple Sclerosis and Crohn’s Disease. Another Phase II trial for hepatocellular carcinoma (HCC) is targeting launch by the third quarter of 2021 with the investigational drug Milciclib.
Exhibit IV – Tiziana Pipeline (4)
Summary
Tiziana Life Sciences reported positive topline data from its COVID-19 study with Foralumab. This fully-human anti-CD3 mAb demonstrated safety and effectiveness in an exploratory trial conducted in Brazil. Data from the study suggest that Foralumab is safe and can favorably impact lung inflammation and levels of inflammatory biomarkers in the blood, including IL-6 and CRP. While it was not powered for statistical analysis, there were material improvements in several secondary endpoints, which merits further analysis. We expect to see additional data on trial endpoints in a few weeks.
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1. Source: Tiziana Life Sciences Press Release Dated February 2, 2021
2. Source: Tiziana Life Sciences Press Release Dated February 2, 2021
3. Source: Tiziana Life Sciences January 2021 Corporate Presentation
4. Source: Tiziana Life Sciences January 2021 Corporate Presentation