Key Highlights

  • Trial Success: The Phase 2a INFORM-MS trial met both dual primary endpoints for intranasal foralumab in non-active secondary progressive multiple sclerosis.
  • Brain Inflammation: Statistically significant reduction in microglial activation was observed via TSPO PET imaging in patients treated with 50 mcg foralumab versus placebo (p=0.0168).
  • Fatigue Improvement: Patients on 50 mcg foralumab showed a mean 6.17-point reduction in Modified Fatigue Impact Scale scores from baseline (p=0.035); 100 mcg patients saw a 7.18-point reduction (p=0.040).
  • Unmet Need: Non-active secondary progressive MS currently has no FDA-approved therapies specifically indicated for the condition.

Tiziana Life Sciences, Ltd.(NASDAQ:TLSA), a biotechnology company focused on immunomodulation therapies, announced that its Phase 2a INFORM-MS clinical trial of intranasal foralumab met its dual primary endpoints in patients with non-active secondary progressive multiple sclerosis — a form of the disease for which no targeted approved treatment currently exists.

Trial Design and Primary Endpoint Results

The INFORM-MS trial evaluated intranasal foralumab, a fully human anti-CD3 monoclonal antibody, in patients with non-active secondary progressive MS (na-SPMS) — a disease state characterized by the gradual accumulation of neurological disability independent of acute relapses. The dual primary endpoints required the trial to demonstrate both safety and tolerability of the treatment and a statistically significant reduction in microglial activation as measured by TSPO PET imaging.

On the imaging endpoint, patients in the 50 mcg foralumab arm showed a statistically significant reduction in microglial activation compared to the placebo group (p=0.0168). Microglial activation is a measure of neuroinflammation in the brain — an underlying process linked to disease progression in secondary progressive MS. The reduction in this biomarker in treated patients, compared to no meaningful change in placebo recipients, points to a biological effect of the drug on the central nervous system.

The safety profile met the second primary endpoint, with foralumab demonstrating tolerability at the doses studied.

Fatigue Outcomes and Secondary Findings

Beyond the primary endpoints, the trial generated notable findings on fatigue, one of the most debilitating symptoms reported by patients with progressive MS. Patients treated with 50 mcg of foralumab experienced a mean decrease of 6.17 points on the Modified Fatigue Impact Scale from their own baseline scores after 12 weeks of treatment (p=0.035). Patients in the 100 mcg group recorded a mean decrease of 7.18 points from baseline (p=0.040). The placebo group showed no significant change over the same period.

The Modified Fatigue Impact Scale measures how fatigue affects cognitive, physical, and social functioning — and a meaningful reduction in this score corresponds to a patient-perceived improvement in daily quality of life. While fatigue was a secondary rather than primary endpoint, the statistical significance of the result across both doses strengthens the overall clinical picture from the trial.

Risks

The INFORM-MS findings are from a Phase 2a trial, which is designed primarily for safety and early efficacy signal detection rather than definitive proof of effectiveness. A larger, controlled Phase 3 trial would typically be required before a regulatory submission could be made to the FDA or European regulatory authorities. Positive Phase 2a results do not guarantee that a Phase 3 trial will succeed, as the more rigorous design, larger patient population, and longer follow-up of a late-stage trial can reveal outcomes not apparent in smaller studies.

Tiziana Life Sciences is a small-cap company, and its ability to fund a Phase 3 program will depend on its financial position, access to capital markets, and potentially on partnering with a larger pharmaceutical company to share development costs. Any delays in funding or partner negotiations could slow the program's timeline.

What to Watch Next

The most important near-term question is whether Tiziana will pursue a Phase 3 trial and on what timeline. Management's statements on the regulatory path forward — including whether they will seek an FDA meeting to discuss next steps — will be central to how investors assess the program's commercial potential. Any indication of Partnership discussions with larger pharmaceutical companies would also be closely watched.

Longer-term, the durability of the microglial activation reduction and fatigue improvements beyond the 12-week trial period will need to be assessed in extended studies, as progressive MS is a chronic disease requiring long-term treatment.

Sector Context

Non-active secondary progressive MS represents a significant unmet medical need. While several approved therapies exist for relapsing forms of MS, the progressive subtypes have historically been harder to treat because the mechanisms of disability accumulation differ from those driving relapses. Immunomodulation approaches targeting brain inflammation, rather than systemic immune activity, have attracted growing interest in MS research precisely because they are better suited to the pathophysiology of progressive disease. Tiziana's anti-CD3 approach via the nasal route is designed to achieve mucosal immune tolerance — a mechanism that has generated scientific interest for its potential to modulate central nervous system inflammation without the systemic effects associated with injectable or oral immunosuppressants.