INTRANASAL FORALUMAB INFORM-MS KOL WEBCAST - TIZIANA LIFE SCIENCES LTD

Financial Performance:

• No specific financial metrics (revenue, earnings, cash flow, debt, or margins) were disclosed as the company is a clinical-stage biopharma firm prior to commercialization.
• Focus remains on R&D execution and capital allocation for ongoing Phase 2 trials and expansion into Phase 2b/3.

Guidance and Future Outlook:

• Alzheimer's Trial: Top-line data expected in Q1 2027 (3–4 months from call date).
• Multiple System Atrophy (MSA): Data readout anticipated within 3–4 months.
• ALS (MyMatch Consortium): Top-line data expected in 2027.
• Pivotal Strategy: Plans to hold an End-of-Phase 2 meeting with the FDA to define protocols for a pivotal, approvable trial for non-active secondary progressive MS (NASPMS).
• Next Study Design: A Phase 2b/3 trial is being planned, likely utilizing fatigue reduction (MFIS) and EDSS stabilization/improvement as primary/secondary endpoints over a 12-month duration.

Business Segments and Product Lines:

• Product: Nasal feralumab (intranasal anti-CD3 monoclonal antibody).
• Mechanism: Non-invasive delivery targeting cervical lymph nodes to induce regulatory T-cells (Tregs), which traffic to the brain to dampen microglial-driven neuroinflammation via IL-10.
• INDICATIONS:
  • NASPMS: Phase 2 results positive; drug reduces microglial activation (TSPO PET) and fatigue.
  • Alzheimer's: Phase 2 fully enrolled; early data shows reduced neuroinflammation.
  • MSA: Ongoing open-label/expanded access; data shows reduced neuroinflammation.
  • ALS: Enrolled in the ALS MyMatch consortium.
• Combination Therapy: Announced plan for a trial in Saudi Arabia combining feralumab with ocrelizumab (CD20 therapy) for relapsing-remitting MS patients who are non-responders.

Market and Competitive Landscape:

• Unmet Need: Significant gap in treatments for non-active secondary progressive MS (SPMS); existing anti-B-cell therapies (e.g., Ocrevus) fail to stop progression in ~25% of patients, particularly those with "silent" progression.
• Differentiation: First non-invasive anti-CD3 therapy shown to safely reduce microglial activation behind the blood-brain barrier; targets neuroinflammation rather than peripheral immune responses.
• Competitive Context: Cites recent failure of Sanofi's tolobrutinib (Phase 3) due to liver toxicity and lack of EDSS benefit, positioning feralumab's safety and stabilization data as superior in the progressive MS space.
• Market Trend: Increasing recognition of fatigue as a core symptom and driver of progression in MS, correlating with microglial activation.

Risks and Challenges:

• Dose Sensitivity: The 100 microgram dose showed significant fatigue reduction but failed to demonstrate statistically significant reduction in neuroinflammation (TSPO PET) compared to the 50 microgram dose; this may indicate an immunological ceiling or higher noise at higher doses.
• Trial Duration: Phase 2a was a short 3-month study; longer-term effects on EDSS and disability progression require 6–12 month follow-up (as seen in Expanded Access) and future pivotal trials.
• Sample Size Limitations: The 100 microgram arm had a small sample size (n=11), limiting statistical power for imaging endpoints.
• Regulatory Path: Need to validate clinical endpoints (fatigue vs. EDSS) with the FDA for a pivotal registration trial.

Management Commentary and Tone:

• Tone: Highly confident and enthusiastic; management characterized the results as "spectacular" and "first-of-its-kind."
• Validation: Emphasized replication of Expanded Access Program (EAP) findings in a rigorous, double-blind, placebo-controlled setting.
• Expert Consensus: Key Opinion Leaders (KOLs) unanimously agreed the results support advancing to a pivotal trial; Dr. Weiner noted the mechanism aligns with Nobel Prize-winning Treg research.
• Strategic Focus: Management is pivoting immediately to defining the pivotal trial design and exploring combination therapies to address progression-independent relapses (PIRA).

Analyst Questions and Answers:

• TSPO Imaging Noise vs. Dose: Explained that the 100mcg PET result lack of significance is likely due to low sample size and imaging variability, whereas the 50mcg dose showed robust, statistically significant (p=0.0168) reduction in global white matter inflammation.
• Fatigue Reliability: Confirmed fatigue improvements (delta ~6-7 points) are reliable and clinically meaningful (threshold >4 points), consistent with EAP data despite the smaller Phase 2 cohort.
• Correlation Analysis: Patient-level correlation between specific PET changes and fatigue improvement is ongoing and may require sub-regional brain analysis (e.g., substantia nigra/hippocampus) rather than whole-brain metrics.
• Prior Therapies: Majority of patients were on prior disease-modifying therapies (e.g., Ocrelizumab) with a standard 6-month washout for anti-CD20s and 1-2 months for oral meds; feralumab targets the "hidden" neuroinflammation that these prior therapies miss.
• Combination Strategy: Confirmed intent to combine feralumab with anti-CD20 therapies to attack both inflammatory (peripheral) and progressive (central) components of MS simultaneously.

Other Key Points:

• Safety: Drug was safe and well-tolerated at both 50mcg and 100mcg doses; no drug-related serious adverse events (SAEs) or discontinuations.
• Immunology: Confirmed mechanism of action in humans via increased regulatory T-cells, decreased cytotoxic T-cells, and reduced inflammatory markers in spinal fluid.
• Cross-Disease Mechanism: Microglial activation reduction observed in Alzheimer's and MSA suggests a broad therapeutic potential for neuroinflammatory disorders.
• Publication: Expanded Access Program data published in Neurology: Neuroimmunology & Neuroinflammation.
• Pivot to Pivotal: Management explicitly stated the data is "hot off the press" (one week old) and sufficient to move toward an FDA End-of-Phase 2 meeting.