Pipeline
Foralumab
Multiple administration routes of a proven systemic anti-inflammatory, patent protected until 2040
Non-active SPMS*
Phase 2a began in 3Q 2023*Non-Active Secondary Progressive Multiple Sclerosis (expanded access program; n=10).
Alzheimer's
IND clearance received in 3Q 2023
Long COVID
IND planned
Early Onset Type 1 DM
ALS*
* Grant from Amyotrophic Lateral Sclerosis Association for preclinical development
Intracerebral Hemorrhage (ICH)
Foralumab
Diabetes
Deprioritized
Foralumab
Crohn's Disease
Deprioritized
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.
Early (Expanded) Access Policy
Tiziana Life Sciences is dedicated to developing new therapies that have a positive impact on patient health, and to serving patients, patient families and patient communities through education, empathy, and awareness.
Consistent with Tiziana Life Sciences’ mission to bring innovative medicines to patients with serious or life-threatening illnesses or conditions, we are focused on enrolling and conducting the clinical trials necessary to gain regulatory approvals to make our medicines available broadly to patients as quickly as possible. We are privileged to collaborate with clinical investigators and with patients who participate in our studies to develop new, safe and effective therapies. We believe this approach will serve patients who could be helped by the therapies we are developing. At the same time, we understand that there are seriously ill patients who will not be eligible for our clinical trials and may not have options for alternative therapies, including investigational therapies in trials being conducted by other sponsors. In these circumstances, Tiziana Life Sciences will consider providing a requesting physician with pre-approval access to a specific Tiziana Life Sciences investigational drug, for the treatment of an individual patient outside of a clinical trial, when certain conditions are met. These conditions include the following:
- The patient has a serious or life-threatening illness or condition and is either no longer responsive to or no longer able to tolerate any available treatment option;
- The investigational drug is in active clinical development with sufficient data available to determine an appropriate dose and schedule for the patient’s specific condition;
- A benefit-risk analysis, based on both the available clinical data as well as the requesting physician’s assessment of the individual patient’s condition and history, supports making the investigational drug available;
- Making the investigational drug available will not negatively impact or delay the conduct of clinical trials or regulatory review or approval of the investigational drug for broader patient access; and
- Adequate supply of the investigational drug is available.
We continually evaluate the benefit-risk profile of each of our investigational drugs based on evolving clinical data. Each compound under development is different and the fact that one investigational drug is made available for the treatment of a particular patient does not mean it will be made available in response to other requests on behalf of other patients whose circumstances and medical histories may be different, or that a different investigational drug will be made available under our policy. Requests will be considered on a case-by-case basis.
Tiziana Life Sciences is committed to evaluating all requests in a fair and equitable manner. All requests must be submitted by the patient’s treating physician; Tiziana Life Sciences may require more detailed information in order to fully evaluate a request. The requesting physician must agree to obtain appropriate regulatory and ethics committee approvals and comply with regulatory obligations, including obtaining patient consent, patient monitoring and safety reporting. Each request will be given careful consideration by Tiziana Life Sciences, whose decisions are final.
Physicians seeking pre-approval access for patients with no alternative treatment options should submit their requests to ea@tizianalifesciences.com. We regularly monitor this mailbox and will use our best efforts to acknowledge each submitted request within 5 business days after receipt.