Tiziana Life Sciences Announces Comprehensive Positive Results from Study of Nasal Foralumab in Patients with Multiple Sclerosis

Rhea-AI Summary

Tiziana Life Sciences (NASDAQ: TLSA) has announced positive results from a clinical study of nasal foralumab in treating non-active secondary progressive multiple sclerosis (na-SPMS). The study involved 10 patients who were treated for a minimum of six months, with key findings including:

- No serious treatment-related adverse events reported
- Stabilization of Expanded Disability Status Scale (EDSS) scores in all patients
- Improvement in fatigue symptoms in 6 out of 10 patients
- Significant reductions in microglial activation at six months (p<0.05)
- No new T2 lesions observed on MRI
- Increased regulatory T cells and TGFβ expression

The company has initiated a randomized, double-blind, placebo-controlled Phase 2 clinical trial with expected top-line data by the end of 2025. The treatment represents a novel approach for na-SPMS patients who currently have limited treatment options.

Positive

• Successful safety profile with no serious treatment-related adverse events
• Clinical efficacy demonstrated through stabilization of EDSS scores in all patients
• Significant reduction in microglial activation at 6 months (p<0.05)
• Fatigue improvement in 60% of patients
• Phase 2 clinical trial already initiated for larger patient cohort

Negative

• Small sample size of only 10 patients in the study
• Open-label study design limits interpretation of results
• Results pending peer review

Insights

Neurology Specialist

Tiziana's nasal foralumab shows promising results in progressive MS, stabilizing disability and reducing neuroinflammation with potential quality-of-life improvements.

The clinical findings for nasal foralumab represent a potentially significant advancement for non-active secondary progressive MS (na-SPMS), a condition with few effective treatments. The most clinically relevant outcomes include stabilization of disability scores in all ten patients, with three of four patients treated for 12 months showing actual improvement. This is remarkable since na-SPMS typically follows a relentless progression pattern.

The significant reduction in microglial activation (p<0.05) demonstrated via TSPO-PET imaging addresses the central pathological mechanism in progressive MS. Current MS therapies primarily target peripheral immune cells and have limited efficacy once progression begins. By contrast, foralumab's mechanism leverages the nasal route to induce regulatory T cells and modulate central nervous system inflammation without causing systemic immunosuppression.

The improvement in fatigue scores in 60% of patients is particularly meaningful for patients' daily functioning. Fatigue represents one of the most debilitating yet difficult-to-treat MS symptoms, often persisting despite disease-modifying therapies.

The absence of new T2 lesions and the favorable safety profile further support this approach. However, important limitations include the study's small sample size, open-label design, and relatively short duration. The upcoming randomized controlled Phase 2 trial will be crucial to confirm these promising signals and establish foralumab's place in the MS treatment landscape.

Biotechnology Analyst

Tiziana's novel nasal anti-CD3 therapy shows promising early results in progressive MS, addressing a major market gap with a differentiated approach.

Tiziana's positive clinical data represents a potential breakthrough in addressing the significant unmet need in progressive multiple sclerosis. The results targeting non-active secondary progressive MS (na-SPMS) are particularly noteworthy because this patient population has limited treatment options once they enter the progressive phase of the disease.

The nasal administration route offers several compelling advantages: non-invasive delivery, potential for self-administration, and a mechanism that modulates central nervous system inflammation without the systemic immunosuppression seen with intravenous therapies. This differentiated approach could position foralumab uniquely in the MS treatment landscape.

The clinical endpoints showing stabilization of EDSS scores and improvement in fatigue address core progressive MS symptoms. The reduction in microglial activation validated through advanced imaging (TSPO-PET, p<0.05) provides mechanistic support for the clinical observations.

Tiziana has established a clear development timeline with the Phase 2 randomized controlled trial expected to deliver results by end of 2025. The company's interest in expanding to other neurodegenerative conditions like Alzheimer's and ALS could significantly expand the market opportunity, though these applications would require separate clinical validation.

While these early results are encouraging, they come from a small (n=10), open-label study. The upcoming Phase 2 blinded, placebo-controlled trial will be the critical test for this novel therapeutic approach and its market potential.

• Meaningful Fatigue score reduction seen in study is a critically important quality of life (QoL) measure for Multiple Sclerosis patients.
• All patients experienced stabilization of Expanded Disability Status Scale (EDSS) scores.
• TSPO-PET imaging showed significant reductions in microglial activation at six months (p<0.05).
  

NEW YORK, May 06, 2025 (GLOBE NEWSWIRE) -- Tiziana Life Sciences, Ltd. (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company developing breakthrough immunomodulation therapies with its lead development candidate, intranasal foralumab, a fully human, anti-CD3 monoclonal antibody, today announced promising results from an open-label clinical study evaluating nasal foralumab, the world’s only fully human anti-CD3 monoclonal antibody administered intranasally, for the treatment of non-active secondary progressive multiple sclerosis (na-SPMS). This comprehensive study demonstrated that nasal foralumab was safe, induced potent regulatory immune responses, reduced microglial activation, and stabilized clinical progression in patients suffering from progression independent of relapse activity (PIRA)—a major unmet need in the treatment of MS, and a key disease endpoint for intranasal foralumab development. The article is titled “Nasal foralumab treatment of PIRA induces regulatory immunity, dampens microglial activation and stabilizes clinical progression in non-active secondary progressive MS.” This study is the first to integrate, F18TSPO PET, Proteomics, and Clinical assessments in na-SPMS. These findings in MFIS score reduction are a critically important Quality of Life (QoL) measure for patients with MS.

Study Highlights:

• Ten patients with na-SPMS, who continued to progress despite B-cell therapy, were treated with nasal foralumab for a minimum of six months.
  
• No serious or severe treatment-related adverse events were reported.
  
• All patients experienced stabilization of their Expanded Disability Status Scale (EDSS) scores; three of four patients that were treated continuously for 12 months showed improvement.
  
• Fatigue, a major symptom burden in MS, improved in six out of ten patients, as measured by the Modified Fatigue Impact Scale (MFIS).
  
• Total MFIS scores correlated strongly with mGALP scores in the hippocampus (r=0.89, p=0.007) at baseline.
  
• No new T2 lesions were observed on MRI.
  
• TSPO-PET imaging showed significant reductions in microglial activation at six months (p<0.05).
  
• Single-cell RNA sequencing revealed early and sustained changes in peripheral immune cells, including increased regulatory T cells (Tregs) and expression of TGFβ across multiple cell types.
  

“Our findings mark a significant advancement for patients living with non-active Secondary Progressive MS, who currently have very limited treatment options,” said Tanuja Chitnis, M.D., Principal Investigator and Professor of Neurology at Harvard Medical School and senior neurologist at Brigham and Women’s Hospital, a founding member of Mass General Brigham Healthcare System. “Nasal administration of foralumab represents a novel, non-invasive approach that not only induces regulatory immunity but also reduces harmful CNS inflammation.”

PIRA and progressive forms of MS are characterized by central nervous system-centric inflammation driven by microglial activation, processes not adequately addressed by existing therapies. Traditional MS treatments targeting B-cells and cell trafficking have limited efficacy in managing progression behind the blood-brain barrier.

Nasal foralumab leverages the mucosal immune system to induce regulatory immune responses, offering a novel mechanism to suppress CNS inflammation without the systemic immunosuppression seen with intravenous therapies. Previous studies showed that nasal anti-CD3 could treat progressive MS in animal models by expanding LAP+ and IL-10+ Tregs, providing the scientific rationale for this human study.

In parallel with these encouraging results, Tiziana Life Sciences has initiated a randomized, double-blind, placebo-controlled Phase 2 clinical trial to further assess the efficacy and safety of nasal foralumab in a larger cohort of patients with na-SPMS. This trial is expected to reach top line data read out at the end of 2025.

“We are incredibly excited by these results, which validate the potential of nasal foralumab to fundamentally shift the treatment paradigm for progressive MS,” said Ivor Elrifi, Chief Executive Officer of Tiziana Life Sciences. “We are also committed to advancing this promising therapy into other larger clinical studies, such as Alzheimer’s Disease and ALS as quickly as possible.”

This article has been submitted for peer review, and the full preprint is available here: https://www.medrxiv.org/content/10.1101/2025.04.30.25326602v1

About Foralumab

Foralumab, a fully human anti-CD3 monoclonal antibody, is a biological drug candidate that has been shown to stimulate T regulatory cells when dosed intranasally. At present, 10 patients with Non-Active Secondary Progressive Multiple Sclerosis (na-SPMS) have been dosed in an open-label intermediate sized Expanded Access (EA) Program (NCT06802328) with either an improvement or stability of disease seen within 6 months in all patients. In addition, intranasal foralumab is currently being studied in a Phase 2a, randomized, double-blind, placebo-controlled, multicenter, dose-ranging trial in patients with non-active secondary progressive multiple sclerosis (NCT06292923).

Foralumab is the only fully human anti-CD3 monoclonal antibody (mAb) currently in clinical development. The non-active SPMS intranasal foralumab Phase 2 trial (NCT06292923) began screening patients in November of 2023. Immunomodulation by intranasal foralumab represents a novel avenue for the treatment of neuroinflammatory and neurodegenerative human diseases.^[1],[2]

About Tiziana Life Sciences

Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy. Tiziana’s innovative nasal approach has the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s lead candidate, intranasal foralumab, which is the only fully human anti-CD3 mAb currently in clinical development, has 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 more information about Tiziana Life Sciences and its innovative pipeline of therapies, please visit www.tizianalifesciences.com.

Forward-Looking Statements

Certain statements made in this announcement are forward-looking statements. These forward-looking statements are not historical facts but rather are based on the Company’s current expectations, estimates, and projections about its industry, its beliefs, and assumptions. Words such as ‘anticipates,’ ‘expects,’ ‘intends,’ ‘plans,’ ‘believes,’ ‘seeks,’ ‘estimates,’ and similar expressions are intended to identify forward-looking statements. These statements are not guarantees of future performance and are subject to known and unknown risks, uncertainties, and other factors, some of which are beyond the Company’s control, are difficult to predict, and could cause actual results to differ materially from those expressed or forecasted in the forward-looking statements. The Company cautions security holders and prospective security holders not to place undue reliance on these forward-looking statements, which reflect the view of the Company only as of the date of this announcement. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties related to market conditions and other factors described more fully in the section entitled ‘Risk Factors’ in Tiziana’s Annual Report on Form 20-F for the year ended December 31, 2023, and other periodic reports filed with the Securities and Exchange Commission. The forward-looking statements made in this announcement relate only to events as of the date on which the statements are made. The Company will not undertake any obligation to release publicly any revisions or updates to these forward-looking statements to reflect events, circumstances, or unanticipated events occurring after the date of this announcement except as required by law or by any appropriate regulatory authority.

For further inquiries:

Tiziana Life Sciences Ltd
Paul Spencer, Business Development, and Investor Relations
+44 (0) 207 495 2379
email: info@tizianalifesciences.com

[1] https://www.pnas.org/doi/10.1073/pnas.2220272120

[2] https://www.pnas.org/doi/10.1073/pnas.2309221120

FAQ

What are the main results of TLSA's nasal foralumab study in Multiple Sclerosis?

The study showed stabilization of EDSS scores in all patients, fatigue improvement in 60% of patients, significant reduction in microglial activation, and no serious adverse events. The treatment demonstrated safety and efficacy in non-active secondary progressive MS patients.

How many patients were involved in Tiziana's MS treatment study?

The study included 10 patients with non-active secondary progressive multiple sclerosis (na-SPMS) who were treated with nasal foralumab for a minimum of six months.

What is the next step for Tiziana's nasal foralumab MS treatment?

Tiziana has initiated a randomized, double-blind, placebo-controlled Phase 2 clinical trial to further assess efficacy and safety in a larger patient cohort, with top-line data expected by the end of 2025.

What makes TLSA's nasal foralumab treatment different from other MS treatments?

Nasal foralumab is the world's only fully human anti-CD3 monoclonal antibody administered intranasally. It uses the mucosal immune system to induce regulatory immune responses without systemic immunosuppression, unlike traditional MS treatments.

What safety data was reported for Tiziana's MS treatment?

The study reported no serious or severe treatment-related adverse events, and no new T2 lesions were observed on MRI scans during the treatment period.