Tiziana Reports Data Indicating Significant Immunomodulation effects on Immune and Inflammatory Biomarkers with Nasally Administered Foralumab in Healthy Volunteers

Rhea-AI Summary

Tiziana Life Sciences (NASDAQ: TLSA) announced positive results from its Phase 1 trial of nasally administered Foralumab, showing significant immunomodulatory effects. Conducted at Brigham and Women’s Hospital, the study demonstrated that a 50 mcg/day dose led to favorable changes in cytotoxic T-cell subsets and inflammatory biomarkers without severe toxicity. These findings support further clinical development, primarily targeting progressive MS. Tiziana's innovative approach may enhance treatment outcomes for neurodegenerative diseases.

Positive

• Statistically significant immunomodulatory effects observed at the 50 mcg/day dose in T-cell subsets.
• No severe toxicity or adverse effects reported during the trial.
• Potential for nasally administered Foralumab to treat progressive MS and other neurodegenerative diseases.

Negative

• None.

NEW YORK and LONDON, May 26, 2021 (GLOBE NEWSWIRE) -- Tiziana Life Sciences plc (NASDAQ: TLSA, LSE: TILS) (“Tiziana” or the “Company”), a biotechnology company focused on innovative therapeutics for inflammatory diseases and cancers, today provided an update on further analysis of lymphocyte subsets from blood samples from a Phase 1 study with nasally administered Foralumab in healthy volunteers. Results exhibiting statistically significant immunomodulatory effects on CD8 cytotoxic T-lymphocytes and other inflammatory biomarkers were observed. This Phase 1 trial, conducted at the Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, was a single-site, double-blind, placebo-controlled, dose-ranging study with nasally administered Foralumab at 10, 50 and 250 mcg per day, consecutively for 5 days in healthy volunteers. The treatment was well-tolerated at all doses and there were no apparent symptoms of severe toxicity. Importantly, the treatment showed significant positive effects at 50 mcg/day dose (compared to other dose and placebo groups) on T-cell subsets and inflammatory biomarkers. These data support other clinical and pre-clinical studies showing that this route of administration is capable of inducing site-targeted immunomodulation and anti-inflammatory effects. Furthermore these pharmacodynamic data point to a clinical dose range that Tiziana intends to test in further clinical development among MS patients.

Highlights of clinical and immunologic data

• Nasally administered Foralumab was well tolerated and there were no apparent symptoms of severe toxicity or cytokine release syndrome.
• Systemic levels of Foralumab were below the lower quantitation limit of 8 ng/mL suggesting that nasally administered Foralumab appears to exert its effects via nasal epithelium utilizing local and lymphatic immune systems directly.
• Most prominent effects among cytotoxic T-cell subsets were observed in the 50mcg group compared to 10mcg, 250mcg and placebo groups.
• The observed effects in the 50mcg dose group were the following:
  1. Statistically significant reductions from baseline in CD8_Tem cytotoxic T-cell subset through 14 days and CD8_TEMRA, CD8_GranzymeB, CD8_Perforin subsets through 21 days
  2. Statistically significant increase from baseline in CD8_naive subset through day 21
  3. Statistically significant stimulation in production of anti-inflammatory cytokine IL-10 along with suppressed production of pro-inflammatory cytokine IFN-γ, suggested a positive trend for immunomodulation and anti-inflammatory effect.
     

These observed clinical responses on biomarkers, indicative of immunomodulation and anti-inflammatory, are consistent with the positive clinical data observed with nasally administered Foralumab in COVID-19 patients in Brazil. Results from this clinical study demonstrated that nasally administered Foralumab at 100 mcg/day for 10 consecutive days was not only well-tolerated but it also showed significant reduction of lung inflammation along with statistically reduced levels of interleukin-6 (IL-6) and C-reactive protein (CRP), in the blood samples taken from patients (https://www.tizianalifesciences.com/news-item?s=2021-02-02-tiziana-reports-positive-data-from-the-clinical-study-of-nasal-administration-with-foralumab-its-proprietary-fully-human-anti-cd3-monoclonal-antibody-in-covid-19-patients-in-brazil).

“Nasal administration of Foralumab is a unique approach to treat patients with neurodegenerative diseases such as progressive MS, amyotrophic lateral sclerosis (ALS) and Alzheimer’s Disease (AD). This study demonstrates for the first-time that nasally administered Foralumab, at the identified optimal dose of 50 mcg/day, induces immunomodulatory effects capable of providing clinical benefit to treated subjects. These data along with results from our recently completed trial in COVID-19 patients in Brazil suggest a dose-range of 50 mcg-150 mcg could be used for future clinical development of nasally administered Foralumab. This is a major accomplishment providing the scientific rationale to move forward with further clinical development of nasally administered Foralumab in patients with neurodegenerative diseases,” commented Dr. Howard L. Weiner, Chair of the Scientific Advisory Board of Tiziana Life Sciences and Professor of Neurology at Harvard Medical School. He added that “both oral and nasal administration routes are physiologic approaches to stimulate the mucosal immune system to induce disease modifying immunomodulation. Our immediate focus is on developing Foralumab for treatment of progressive MS.”

“The demonstration of the positive immunomodulatory effects providing a recommended dose-range is important to move forward with further studies in the progressive MS population,” stated Dr. Tanuja Chitnis, the study PI at the Brigham and Women’s Hospital.

The person who arranged for the release of this announcement on behalf of the Company was Dr Kunwar Shailubhai, CEO & CSO of Tiziana.

THIS ANNOUNCEMENT CONTAINS INSIDE INFORMATION FOR THE PURPOSES OF ARTICLE 7 OF REGULATION 2014/596/EU (WHICH FORMS PART OF DOMESTIC UK LAW PURSUANT TO THE EUROPEAN UNION (WITHDRAWAL) ACT 2018) ("UK MAR"). UPON THE PUBLICATION OF THIS ANNOUNCEMENT, THIS INSIDE INFORMATION (AS DEFINED IN UK MAR) IS NOW CONSIDERED TO BE IN THE PUBLIC DOMAIN.

About Foralumab

Foralumab (formerly NI-0401), the only entirely human anti-CD3 mAb, shows reduced release of cytokines after IV administration in patients with Crohn's disease with decreases in the classic side effects of cytokine release syndrome (CRS) and improves the overall safety profile of Foralumab. 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 the T cells, enhances Tregs and thus provides therapeutic benefit in

FAQ

What were the results of the Phase 1 trial for Foralumab conducted by Tiziana Life Sciences?

The Phase 1 trial showed statistically significant immunomodulatory effects on T-cell subsets at a 50 mcg/day dose without severe toxicity.

What is the significance of the 50 mcg/day dose in the Foralumab study?

The 50 mcg/day dose demonstrated the most prominent effects on immunomodulation and inflammatory biomarkers.

What future plans does Tiziana Life Sciences have for Foralumab?

Tiziana intends to further develop Foralumab for clinical trials focusing on progressive MS and potentially other neurodegenerative diseases.

How was the tolerability of Foralumab in the Phase 1 trial?

Foralumab was well tolerated across all dosing groups with no apparent severe toxicity or cytokine release syndrome.

What does the Phase 1 trial's outcome indicate for Tiziana Life Sciences' stock TLSA?

The positive results from the trial may enhance investor confidence and interest in Tiziana's future clinical developments, potentially impacting TLSA stock performance.