Pipeline

Foralumab

Multiple administration routes of a proven systemic anti-inflammatory, patent protected until 2040

Indication
Preclinical
IND
Phase 1
Phase 2
Phase 3

Non-active SPMS*

Phase 2a began in 3Q 2023*Non-Active Secondary Progressive Multiple Sclerosis (expanded access program; n=10).

Phase 2

Alzheimer's

IND clearance received in 3Q 2023

Phase 1

Long COVID

IND planned

IND

Early Onset Type 1 DM

IND

ALS*

* Grant from Amyotrophic Lateral Sclerosis Association for development

Preclinical

Intracerebral Hemorrhage (ICH)

Preclinical

Foralumab

Subcutaneous
Indication
Preclinical
IND
Phase 1
Phase 2
Phase 3

Diabetes

Deprioritized

Phase 1

Foralumab

Oral
Indication
Preclinical
IND
Phase 1
Phase 2
Phase 3

Crohn's Disease

Deprioritized

Phase 1
Foralumab

Overview

Foralumab is a fully human anti-CD3 monoclonal antibody (mAb) for the treatment of Crohn’s and neurodegenerative diseases. We have recently completed two Phase 1 clinical trials: one for progressive MS indication with nasal administration and the other for Crohn’s disease indication, with enteric coated capsules administered orally. We also completed a Phase 2 trial treating mild to moderate non-hospitalized COVID-19 patients in Brazil with intranasal foralumab with positive results1. Currently, Six secondary progressive MS patients are being treated at Brigham and Women’s Hospital, Boston MA, with intranasal foralumab under Expanded Access INDs with signs of clinical benefit. EA1 has completed Twenty months of treatment and the EA2 has completed Thirteen months. Foralumab has demonstrated ability to activate regulatory T cells that systemically circulate to elicit targeted immunomodulation providing therapeutic benefit to patients.

Tiziana has submitted a patent application on potential use of Foralumab, to improve success of chimeric antigen receptor T cells (CAR-T) therapy for cancer and other human diseases. The patent application covers inventions related to improving CAR-T expansion and/or survival. Foralumab administered alone or co-administered in combination with co-stimulatory molecules, such as an anti-IL-6 receptor monoclonal antibody, an anti-CD28 monoclonal antibody or specific inhibitors of signaling pathways of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), or mammalian target to improve success of CAR-T therapy.

References

1. Moreira, T. G., et al. (2021) Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study. Front Immunol 12, 709861

Foralumab

Clinical trials

Completed Phase 1 Clinical Trial: Nasal Administration of Foralumab for the Treatment of Multiple Sclerosis

The completed Phase 1 clinical trial of Foralumab in healthy volunteers was a single center, single arm, ascending dose study in which low doses (10, 50 and 250 µg/dose) of Foralumab and placebo were nasally administered for 5 consecutive days. Subjects were monitored for tolerance and immunological effects. The primary endpoint of the Phase 1 study is safety, tolerability and biomarkers of immunomodulation of clinical responses of intra nasally administered Foralumab. Interim results have indicated no drug-related safety issues so far. Topline results were reported on September 10, 2019. All nasal doses were well tolerated. Biomarker analysis showed significant positive immune effects, that were most prominent in the 50 µg cohort with minimal immunomodulatory effects at the 10 µg and 250 µg doses. These results suggested stimulation of Tregs that are needed to provide clinical benefits.

Completed Phase 1 Clinical Trial: Oral Administration of Foralumab in Healthy Volunteers

An enteric-coated capsule formulation has been developed for oral administration of Foralumab. cGMP manufacturing of clinical trial materials for a Phase 1 study has been completed. The Phase 1 clinical trial for Foralumab in healthy volunteers is a single-center, single-arm, ascending dose study in which low doses (1.25, 2.5 and 5.0 mg/dose) of Foralumab and placebo were orally administered. The primary endpoint of the Phase 1 study was safety and tolerability of oral Foralumab in humans. A Phase 1 trial of the oral, enteric capsule formulation of Foralumab in healthy subjects was initiated on December 2, 2019. Results of the Phase 1 Trial were reported on January 20, 2020 The proprietary oral formulation, comprising the lyophilized and stabilized free-flowing powder of formulated Foralumab encapsulated in an enteric-coated capsule, was well-tolerated at all doses tested and there were no drug-related safety issues even at the highest dose of 5 mg in this trial.

Prior Novimmune Clinical Trials using Intravenous Foralumab

Intravenous Foralumab has been studied in one Phase 1 and two Phase 2 clinical trials (Crohn’s disease https://clinicaltrials.gov/ct2/show/NCT00630643 and patients With Acute Renal Allograft Rejection https://clinicaltrials.gov/ct2/show/NCT00805909) conducted by Novimmune. A total of 68 patients were administered Foralumab:

  • The short-term tolerability profile of Foralumab was very similar to those reported with other anti-CD3 antibodies and no new emerging concerns have been identified.
  • Total daily doses of up to 1mg (~ 500 µg/m2) per patient were generally well tolerated without corticosteroid premedication with reduction in the Crohn’s Disease Activity Index (CDAI) scores in patients.
  • The most common adverse events following exposure to Foralumab were Infusion Related Reactions (IRRs).
  • A clear reduction of IRRs was observed with steroid pre-medication up to 2.5 mg/dose for 5 consecutive days.
  • Therefore, usage of steroid pre-medication allows the administration of higher doses.
  • Both the magnitude and duration of CD3 modulation increased in a dose related manner.
  • No anti-drug antibodies were detected.

Expanded Access

At Tiziana, we’re committed to developing advancements in non-active secondary progressive Multiple Sclerosis, Alzheimer’s Disease and ALS. At times patients may wish to access investigational medicines that are not yet approved by the U.S. Food and Drug Administration (FDA) through expanded access or compassionate use programs.

In cases where enrolling in a clinical trial is not currently possible, there may be expanded access options for some patients. The criteria for these options are based on regulations governing this type of access.

Tiziana will consider each request for expanded access on a case-by-case basis when they meet the conditions below, and access is requested by a licensed practitioner in the United States who will oversee the patient’s care while using the investigational medication.

• The patient is ineligible for or otherwise unable to participate in ongoing or planned clinical trials.

• The patient is ineligible for or otherwise unable to participate in ongoing foralumab trials.
• The potential benefit to the patient should outweigh potential risks.
• All other approved treatments did not help the patient, or there is no other approved treatment option available.
• The patient meets any other relevant medical criteria for expanded access to the investigational product, as determined by Tiziana.
• There is adequate supply of the investigational product to meet the needs of the expanded access request without impacting the company’s clinical trials.

Ongoing Clinical Trials

non-active secondary progressive Multiple Sclerosis: Study Details | A Study of Nasal Foralumab in Non-Active Secondary Progressive Multiple Sclerosis Patients | ClinicalTrials.gov  (NCT06292923)

Requesting Access

To submit a request for an investigational medicine outside of a clinical trial, the treating physician can email Tiziana at the following email address, ms@tizianalifesciences.com. We will endeavor to respond to requests within ten (10) business days.