Tiziana Life Sciences Announces Discovery of New Immune Biomarkers in Multiple Sclerosis Patients Treated with Nasal Foralumab
Tiziana Life Sciences (NASDAQ: TLSA) has announced the discovery of new immune biomarkers in patients with non-active secondary progressive multiple sclerosis (na-SPMS) treated with nasal foralumab. The findings were observed in their ongoing ISPPEA expanded access program through single-cell RNA sequencing of blood samples taken before, three, and six months after drug administration.
The study identified key gene expression changes in several immune cell types, including FoxP3 T regulatory cells, CD4+ and CD8+ central memory T cells, CD14+ and CD14- monocytes, and Naïve B cells. These changes were associated with a reduction in microglial brain inflammation, as measured by advanced PET scans.
The company's intranasal foralumab, a fully human anti-CD3 monoclonal antibody, is currently in Phase 2 trials. The biomarker discoveries are expected to help monitor treatment efficacy and patient response in future trials.
Tiziana Life Sciences (NASDAQ: TLSA) ha annunciato la scoperta di nuovi biomarcatori immunitari nei pazienti con sclerosi multipla secondaria progressiva non attiva (na-SPMS) trattati con foralumab nasale. I risultati sono stati osservati nel loro ongoing ISPPEA programma di accesso espanso attraverso il sequenziamento dell'RNA a singola cellula di campioni di sangue prelevati prima, tre e sei mesi dopo la somministrazione del farmaco.
Lo studio ha identificato importanti cambiamenti nell'espressione genica in diversi tipi di cellule immunitarie, tra cui cellule T regolatorie FoxP3, cellule T della memoria centrale CD4+ e CD8+, monociti CD14+ e CD14-, e cellule B naive. Questi cambiamenti erano associati a una riduzione dell'infiammazione microgliale nel cervello, misurata attraverso scansioni PET avanzate.
Il foralumab intranasale dell'azienda, un anticorpo monoclonale anti-CD3 completamente umano, è attualmente in fase 2 di sperimentazione. Le scoperte sui biomarcatori sono destinate ad aiutare a monitorare l'efficacia del trattamento e la risposta del paziente nei futuri studi.
Tiziana Life Sciences (NASDAQ: TLSA) ha anunciado el descubrimiento de nuevos biomarcadores inmunitarios en pacientes con esclerosis múltiple secundaria progresiva no activa (na-SPMS) tratados con foralumab nasal. Los hallazgos se observaron en su programa de acceso expandido ISPPEA a través de la secuenciación de ARN de una sola célula de muestras de sangre tomadas antes, a los tres y seis meses después de la administración del fármaco.
El estudio identificó cambios clave en la expresión génica en varios tipos de células inmunitarias, incluyendo células T reguladoras FoxP3, células T de memoria central CD4+ y CD8+, monocitos CD14+ y CD14-, y células B naïve. Estos cambios estaban asociados con una reducción de la inflamación microglial en el cerebro, medida mediante exploraciones PET avanzadas.
El foralumab intranasal de la empresa, un anticuerpo monoclonal anti-CD3 completamente humano, se encuentra actualmente en ensayos de fase 2. Se espera que los descubrimientos de biomarcadores ayuden a monitorear la eficacia del tratamiento y la respuesta del paciente en ensayos futuros.
티지안나 생명과학 (NASDAQ: TLSA)는 비활성 이차 진행성 다발성 경화증 (na-SPMS) 환자들을 대상으로 비강 포랄루맙을 치료함으로써 새로운 면역 바이오마커를 발견했다고 발표했다. 이 연구 결과는 약물 투여 전, 3개월 후, 6개월 후에 채혈한 샘플의 단일 세포 RNA 시퀀싱을 통해 진행 중인 ISPPEA 확대 접근 프로그램에서 관찰되었다.
연구는 FoxP3 T 조절 세포, CD4+ 및 CD8+ 중앙 기억 T 세포, CD14+ 및 CD14- 단핵구, 및 Naïve B 세포를 포함한 여러 면역 세포 유형에서 중요한 유전자 발현 변화를 확인했다. 이러한 변화는 고급 PET 스캔으로 측정된 미세아교세포 뇌 염증의 감소와 관련이 있었다.
회사의 비강 포랄루맙은 완전 인간 anti-CD3 단클론 항체로 현재 2상 임상 시험 중이다. 바이오마커 발견은 향후 연구에서 치료 효능 및 환자 반응을 모니터링하는 데 도움이 될 것으로 예상된다.
Tiziana Life Sciences (NASDAQ: TLSA) a annoncé la découverte de nouveaux biomarqueurs immunitaires chez des patients présentant une sclérose en plaques secondaire progressive non active (na-SPMS) traités avec du foralumab nasal. Les résultats ont été observés dans leur programme d'accès élargi ISPPEA à travers le séquençage de l'ARN à cellule unique d'échantillons de sang prélevés avant, trois et six mois après l'administration du médicament.
Cette étude a identifié des changements clés dans l'expression génique de plusieurs types de cellules immunitaires, notamment les cellules T régulatrices FoxP3, les cellules T mémoires centrales CD4+ et CD8+, les monocytes CD14+ et CD14-, et les cellules B naïves. Ces changements étaient associés à une réduction de l'inflammation microgliale dans le cerveau, mesurée par des scans PET avancés.
Le foralumab intranasal de l'entreprise, un anticorps monoclonal anti-CD3 entièrement humain, est actuellement en phase 2 d'essai clinique. Les découvertes de biomarqueurs devraient aider à surveiller l'efficacité du traitement et la réponse des patients lors des futures études.
Tiziana Life Sciences (NASDAQ: TLSA) hat die Entdeckung neuer Immunbiomarker bei Patienten mit nicht aktiver sekundärer progressiver Multipler Sklerose (na-SPMS) bekannt gegeben, die mit nasalem Foralumab behandelt wurden. Die Ergebnisse wurden in ihrem laufenden ISPPEA-Programm zur erweiterten Zugänglichkeit durch Einzelzell-RNA-Sequenzierung von Blutproben beobachtet, die vor der Verabreichung des Arzneimittels sowie drei und sechs Monate danach entnommen wurden.
Die Studie identifizierte wichtige Veränderungen in der Genexpressionsmuster verschiedener Immunzelltypen, einschließlich FoxP3 T-regulatorischer Zellen, CD4+ und CD8+ zentralen Gedächtnis-T-Zellen, CD14+ und CD14- Monozyten sowie Naïve B-Zellen. Diese Veränderungen waren mit einer Verringerung der mikroglialen Entzündung im Gehirn assoziiert, wie durch fortgeschrittene PET-Scans gemessen.
Das intranasale Foralumab des Unternehmens, ein vollständig humanisiertes anti-CD3 monoklonales Antikörper, befindet sich derzeit in Phase 2 der klinischen Studien. Die Entdeckungen der Biomarker sollen helfen, die Wirksamkeit der Behandlung und die Patientenreaktion in zukünftigen Studien zu überwachen.
- Discovery of new immune biomarkers validates treatment mechanism
- Clinical data shows reduction in brain inflammation via PET scans
- Treatment demonstrates modulation of multiple immune cell pathways
- Drug currently advancing in Phase 2 trials
- None.
Insights
A groundbreaking discovery in Tiziana's multiple sclerosis (MS) research program has revealed specific biological markers that demonstrate how their nasal foralumab drug affects the immune system. In simple terms, imagine these biomarkers as molecular 'fingerprints' that prove the drug is working as intended, similar to how a thermostat shows that your heating system is functioning correctly.
The findings are particularly valuable for three key reasons:
- Validation of Mechanism: The discovery confirms that foralumab is effectively modulating the immune system in MS patients, specifically targeting important immune cells like T-cells and monocytes. This provides concrete evidence of the drug's biological activity.
- Treatment Monitoring: These biomarkers could serve as early indicators of treatment effectiveness, potentially allowing doctors to determine if a patient is responding to the therapy within three months, rather than waiting for clinical symptoms to change.
- Development Acceleration: Having clear, measurable biomarkers could expedite future clinical trials and regulatory submissions by providing objective evidence of the drug's effects.
From an investor perspective, this development strengthens Tiziana's position in the competitive MS drug market, estimated at over
The use of advanced technologies like single-cell RNA sequencing also demonstrates Tiziana's sophisticated research capabilities and commitment to developing personalized medicine approaches. This could make the company an attractive partner for larger pharmaceutical companies looking to expand their neurology portfolios.
NEW YORK, Jan. 22, 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 the discovery of new immune biomarkers in patients with non-active secondary progressive multiple sclerosis (na-SPMS) treated with nasal foralumab. We believe these findings contribute substantially to our understanding of the immune mechanisms underlying the effects of nasal foralumab.
The study identified gene expression changes which were detected beginning three months after intranasal dosing of foralumab in our ongoing ISPPEA (or expanded access program). Key findings include modulation of:
- FoxP3 T regulatory cells (Tregs)
- CD4+ and CD8+ central memory T cells
- CD14+ and CD14- monocytes
- Naïve B cells
These pathways are known to be associated with antigen presentation, interferon responses, and other regulatory immune mechanisms.
In this study, single-cell RNA sequencing (scRNAseq) of peripheral blood samples taken before and at three and six months after drug administration has revealed relevant gene expression changes associated with nasal foralumab, which has been associated with a reduction in microglial brain inflammation, as measured by advanced microglial PET scans in these same patients.
“We are excited to announce this breakthrough in understanding how nasal foralumab induces immune modulation in Secondary Progressive MS patients,” said Dr. 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. “These findings highlight the potential of nasal foralumab in modulating critical immune pathways and offer new insights into its clinical effects. This discovery represents a pivotal step toward personalized treatment strategies for MS. We look forward to submitting these data to a peer reviewed journal.”
“The observed clinical stabilization and microglial PET findings are supported by these new biomarker discoveries, providing compelling evidence of nasal foralumab's biological effects,” said Dr. Howard Weiner, Chairman of Tiziana’s Scientific Advisory Board and co-director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, a founding member of Mass General Brigham healthcare system. “The identification of these biomarkers not only strengthens our understanding of the treatment’s mechanism but also establishes a framework for monitoring its efficacy in future trials and may establish a framework for monitoring a patient’s response to foralumab treatment.”
“This data, and its implications, underscores our commitment to advancing innovative therapies for neurodegenerative diseases,” commented Ivor Elrifi, CEO of Tiziana Life Sciences. “Foralumab, the first fully human anti-CD3 monoclonal antibody, is in a Phase 2 trial as a groundbreaking immunomodulatory therapy with applications in autoimmune and neurodegenerative diseases. These findings further confirm its potential and set the stage for broader clinical exploration.”
The FDA defines a biomarker as a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention, including therapeutic interventions. Molecular, histologic, radiographic, or physiologic characteristics are types of biomarkers. A biomarker is not an assessment of how an individual feels, functions, or survives.
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 with either an improvement or stability of disease seen within 6 months in all patients. The FDA has recently allowed an additional 20 patients to be enrolled in this EA program. 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).
Activated T cells play an important role in the inflammatory process. Foralumab, the only fully human anti-CD3 monoclonal antibody (mAb) currently in clinical development, binds to the T cell receptor and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets. This effect has been observed in patients with COVID and with multiple sclerosis, as well as in healthy normal subjects. The non-active SPMS intranasal foralumab Phase 2 trial (NCT06292923) began screening patients in November of 2023. Immunomodulation by nasal anti-CD3 mAb represents a novel avenue for 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
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[1] https://www.pnas.org/doi/10.1073/pnas.2220272120
[2] https://www.pnas.org/doi/10.1073/pnas.2309221120
FAQ
What new biomarkers did Tiziana (TLSA) discover in MS patients treated with nasal foralumab?
How does nasal foralumab affect brain inflammation in TLSA's MS treatment?
What is the current development stage of TLSA's nasal foralumab?
When did TLSA observe the biomarker changes in MS patients?
How will TLSA's biomarker discovery impact future MS treatment?
