Tiziana Files Annual Safety Report for Intranasal Foralumab with FDA

Rhea-AI Summary

Tiziana (NASDAQ: TLSA) submitted its seventh annual Development Safety Update Report to the FDA covering Sept 21, 2024–Sept 2, 2025, reporting a cumulative 37.4 patient-years of intranasal foralumab exposure with no drug-related serious adverse events.

Key exposures: 14 naSPMS patients in Expanded Access (50 µg dose) contributed 30.7 patient-years; the TILS-021 randomized trial plus TILS-022 extension added ~5.2 patient-years; one AD patient added 0.5 patient-years. No new risks or safety actions were identified and nasal delivery showed improved tolerability versus prior IV foralumab reports. The company noted an FDA Dec 23, 2025 complete response letter denying approval of Sanofi’s tolebrutinib for nrSPMS and said its Phase 2 naSPMS readout is expected in 2026.

Positive

• 37.4 patient-years cumulative intranasal exposure with no drug-related serious adverse events
• Expanded Access: 14 naSPMS patients contributed 30.7 patient-years
• TILS-021/TILS-022 added ~5.2 patient-years of trial exposure
• Nasal delivery showed improved tolerability versus IV administration

Negative

• None.

Key Figures

Cumulative exposure 37.4 patient-years Total intranasal foralumab exposure across CNS indications in DSUR period

naSPMS patients 14 patients Expanded Access Program for intranasal foralumab

Dose level 50 micrograms Nasal foralumab dose per administration in Expanded Access and AD case

Dosing schedule 6 days per 3-week cycle Intranasal foralumab regimen in Expanded Access naSPMS patients

Exposure range 23 weeks to 3.5 years Duration of treatment in naSPMS Expanded Access patients

EAP exposure 30.7 patient-years Cumulative intranasal foralumab exposure from naSPMS Expanded Access Program

Trial exposure 5.2 patient-years Exposure from TILS-021 randomized trial and TILS-022 open-label extension

AD case exposure 0.5 patient-years Single moderate Alzheimer’s patient treated 28 weeks at 50 micrograms

Market Reality Check

$1.60 Last Close

Volume Volume 101,503 vs 20-day average 415,069 (relative volume 0.24) indicates subdued trading interest before this update. low

Technical Price $1.48 trading below the 200-day MA at $1.64, reflecting a weaker longer-term trend into the news.

Peers on Argus 1 Up 1 Down

Biotech peers showed mixed moves, with examples like SLS up 4.18% and TRDA down 2.98%. Momentum scanner names were split (VOR down 4.82%, SLS up 4.18%), suggesting this TLSA move was more stock-specific than part of a broad sector swing.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 19	Insider share purchase	Positive	+5.6%	Executive Chairman increased holdings by 97,687 shares, signaling insider confidence.
Dec 17	Corporate milestone	Positive	-5.8%	Nasdaq Closing Bell event celebrating progress of intranasal foralumab pipeline.
Dec 17	Clinical trial update	Positive	-5.8%	First patient dosed in Phase 2 Alzheimer’s trial of intranasal foralumab.
Dec 15	Insider share purchase	Positive	-10.7%	CEO bought 163,400 shares in open market, expanding personal stake in TLSA.
Dec 15	Offering withdrawn	Neutral	-10.7%	Withdrawal of proposed public offering of common shares due to market conditions.

Pattern Detected

Recent TLSA news often coincided with negative price reactions, even on seemingly positive items like insider buying and clinical progress, indicating a tendency toward selling into good news.

Recent Company History

Over the last months, Tiziana highlighted insider share purchases, with the Executive Chairman acquiring 97,687 shares on Dec 19, 2025 and the CEO adding 163,400 shares on Dec 15, 2025. The company also advanced intranasal foralumab, dosing the first patient in a Phase 2 Alzheimer’s trial on Dec 17, 2025, and began ringing the Nasdaq Closing Bell to showcase progress. Despite these milestones and a withdrawn public offering, share reactions frequently skewed negative, framing today’s safety-focused update within a backdrop of cautious trading.

Market Pulse Summary

This announcement highlights intranasal foralumab’s safety, with 37.4 patient-years of cumulative exposure across CNS indications and no drug-related serious adverse events reported. It builds on recent milestones, including Phase 2 Alzheimer’s trial initiation, and contrasts nasal delivery with issues seen for some intravenous anti-CD3 antibodies. Investors may watch for future efficacy readouts, regulatory feedback on ongoing programs, and additional clinical exposure that further clarifies long-term risk–benefit in neuroinflammatory diseases.

Key Terms

development safety update report regulatory

"announces the submission of its seventh annual Development Safety Update Report (DSUR)"

A development safety update report is a periodic summary that gathers new safety information about an experimental drug or medical product while it is being tested. It tells regulators and investors whether any new risks, side effects, or patterns have emerged — like a regular health check that flags changes — and matters to investors because it can affect trial timelines, regulatory approval chances, and the financial outlook of the program.

dsur regulatory

"This DSUR (September 21, 2024, to September 2, 2025), reports no drug-related"

A Development Safety Update Report (DSUR) is an annual regulatory filing that compiles new safety information from a company’s ongoing clinical trials for an investigational drug, summarizing adverse events, safety trends, and the company’s assessment of risks. Like an annual vehicle safety inspection, a DSUR helps investors judge whether a drug’s development is proceeding without worrying safety signals that could prompt regulatory action, delays, or extra costs.

u.s. food and drug administration regulatory

"Development Safety Update Report (DSUR) to the U.S. Food and Drug Administration (FDA)."

The U.S. Food and Drug Administration is the federal agency that evaluates and enforces safety, effectiveness and labeling standards for medicines, medical devices, vaccines, food and related products before they reach consumers. For investors it matters because FDA approvals, warnings or recalls determine whether a product can be sold, how quickly it reaches the market and how costly compliance will be—changes that directly affect a company’s revenue, costs and stock value.

fda regulatory

"Report for Intranasal Foralumab with FDA"

The FDA is the U.S. federal agency that evaluates and approves medical drugs, devices, biological therapies and certain foods; think of it as the gatekeeper that decides whether a medical product is safe and effective for patients. For investors, FDA decisions determine whether a company can sell a product, affect expected revenue and introduce regulatory risk, so approvals, rejections or safety warnings can quickly move a company's valuation and stock price.

complete response letter regulatory

"The FDA’s December 23, 2025 complete response letter denying approval of Sanofi’s"

A complete response letter is an official communication from a drug or medical-device regulator, such as the U.S. Food and Drug Administration (FDA), telling a company that a marketing application cannot be approved in its current form and listing the specific deficiencies to be fixed. For investors it matters because it pauses or delays a product’s path to market—like a building inspector issuing a list of repairs before a certificate of occupancy—affecting revenue timing, costs and stock value.

anti-cd3 monoclonal antibody medical

"foralumab, a fully human, anti-CD3 monoclonal antibody, announces the submission"

A lab-made antibody engineered to attach to CD3, a protein found on T cells, so it can change how those immune cells behave. Investors care because these drugs can act like a targeted brake on an overactive immune system—useful for autoimmune disease, transplant rejection or as part of cancer therapies—but they also carry clinical trial, safety and regulatory risks that determine commercial success.

expanded access program regulatory

"Key highlights from the submission include: Expanded Access Program: Fourteen naSPMS patients"

A program that allows patients with serious or life‑threatening conditions to receive an experimental drug or therapy before it is fully approved by regulators, when they cannot join clinical trials. Investors care because expanded access can change a treatment’s market perception, create early real‑world safety or demand signals, and affect regulatory timelines and potential revenue — like a pre‑order system that also reveals how the product performs outside controlled testing.

open-label extension medical

"TILS-021 Randomized Trial and TILS-022 Open-Label Extension: In our naSPMS study"

An open-label extension is a continuation of a clinical trial where all participants and researchers know which treatment is being given, often after an initial blinded phase. It allows further study of a drug's long-term safety and effectiveness. For investors, it can indicate ongoing interest and confidence in a product's potential, influencing perceptions of its future value.

AI-generated analysis. Not financial advice.

• Tiziana reports excellent safety profile with intranasal foralumab after 37.4 patient-years cumulative exposure
• FDA denial of Sanofi’s tolebrutinib for nrSPMS shows need for safe therapy

BOSTON, Dec. 29, 2025 (GLOBE NEWSWIRE) -- Tiziana Life Sciences, Ltd. (Nasdaq: TLSA) (“Tiziana”), a biotechnology company developing its lead candidate, intranasal foralumab, a fully human, anti-CD3 monoclonal antibody, announces the submission of its seventh annual Development Safety Update Report (DSUR) to the U.S. Food and Drug Administration (FDA). This DSUR (September 21, 2024, to September 2, 2025), reports no drug-related serious adverse events after a cumulative exposure of 37.4 patient-years, highlighting the safety and tolerability data profile of intranasal foralumab in treating neuroinflammatory diseases, including non-active secondary progressive multiple sclerosis (naSPMS), multiple system atrophy and Alzheimer’s Disease (AD).

“The FDA’s December 23, 2025 complete response letter denying approval of Sanofi’s tolebrutinib for nrSPMS, based on toxicity, highlights the need for a safe therapy for untreated neuroinflammatory disorders,” said Ivor Elrifi, Chief Executive Officer of Tiziana. “We have seen 37.4 patient-years of cumulative foralumab exposure with no study drug-related serious adverse events, a milestone that reinforces the safety of our intranasal approach. Our Phase 2 foralumab trial in naSPMS will read out in 2026.”

Key highlights from the submission include:

• Expanded Access Program: Fourteen naSPMS patients received nasal foralumab at 50 micrograms per dose (6 days per three-week cycle) for durations from 23 weeks to 3.5 years, contributing 30.7 patient-years of exposure.
• TILS-021 Randomized Trial and TILS-022 Open-Label Extension: In our naSPMS study and its extension, patients have received foralumab (50 or 100 microgram doses), for about 5.2 patient-years of exposure.
• Single-Patient Expanded Access for AD (IND 172400): One patient with moderate Alzheimer’s Disease completed 28 weeks of treatment at 50 micrograms, adding 0.5 patient-years.
  

This cumulative exposure of 37.4 patient-years underscores the significant clinical experience gained with intranasal foralumab in CNS indications. Notably, no serious adverse events have been attributed to the study drug in these nasal administration studies. Adverse events reported during the period were consistent in type and frequency with previous reports. No new risks were identified that necessitated significant protocol modifications.

The safety profile of intranasal foralumab aligns with prior studies of foralumab administered intravenously (IV) in healthy volunteers, patients with Crohn’s disease, and kidney transplant recipients. Unlike IV administration, which has been linked to infusion-related reactions seen with other anti-CD3 monoclonal antibodies, nasal delivery of foralumab has shown vastly improved tolerability, with no such issues observed. No new actions are required to address foralumab safety based on this update.

About Foralumab

Foralumab, a fully human anti-CD3 monoclonal antibody, is a biologic candidate that has been shown to stimulate T regulatory cells when dosed intranasally. Currently, 14 patients with Non-Active Secondary Progressive Multiple Sclerosis (naSPMS) 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. Immunomodulation by intranasal foralumab represents a novel avenue for the treatment of neuroinflammatory and neurodegenerative human diseases.^[1],[2]

About Tiziana Life Sciences

Tiziana 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 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 Tiziana'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 Tiziana's control, are difficult to predict, and could cause actual results to differ materially from those expressed or forecasted in the forward-looking statements. Tiziana cautions security holders and prospective security holders not to place undue reliance on these forward-looking statements, which reflect the view of Tiziana 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, 2024, 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. Tiziana 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 safety findings did Tiziana report for intranasal foralumab in the Dec 29, 2025 DSUR?

The DSUR reported 37.4 patient-years of exposure with no drug-related serious adverse events and no new safety risks identified.

How much exposure did the Expanded Access program provide for TLSA's intranasal foralumab?

The Expanded Access program enrolled 14 naSPMS patients at 50 µg, contributing 30.7 patient-years of exposure.

What clinical exposure came from TILS-021 and TILS-022 trials for TLSA?

The TILS-021 randomized trial and TILS-022 open-label extension together contributed approximately 5.2 patient-years of exposure.

Did Tiziana identify any new safety actions or protocol changes in the DSUR?

No new risks were identified and no significant protocol modifications or new safety actions were required.

How does nasal foralumab tolerability compare to IV foralumab according to the report?

The report states nasal delivery has vastly improved tolerability versus IV administration, with no infusion‑related reactions observed.

When is TLSA's Phase 2 naSPMS trial readout expected after the Dec 29, 2025 DSUR?

The company expects the Phase 2 naSPMS trial readout in 2026.