Tiziana Advances Phase 2 Site Selection For Its Lead Clinical Program In Non-Active Secondary Progressive Multiple Sclerosis (SPMS) And The Company Prepares For Six-Month Clinical Data Update

Tiziana Life Sciences Ltd. TLSA recently announced the Company has initiated site selection for its lead intranasal anti-CD3 monoclonal antibody drug candidate “foralumab” program entering Phase 2a clinical testing in non-active Secondary Progressive Multiple Sclerosis (na-SPMS) patients. In total, the multi-center clinical trial will have six to ten new clinical trial sites across the US. 

According to the Company, another key data milestone is expected soon at the ECTRIMS conference, which will detail the results from the expanded access program after six months of treatment. Investors should take note, as this is a significant event for the company through providing six-month clinical results on the second cohort of four patients (numbers 3-6), and also providing a PET scan which shows neuroinflammation in the brain (microglia). ECTRIMS is the world’s largest research meeting in multiple sclerosis and will be held October 11-13 in Milan, Italy. 

Tiziana also recently announced the acceptance of a publication in the prestigious journal Proceedings of the National Academy of Sciences (PNAS) of its study validating the mechanism of action (MoA) using intranasally administered foralumab in Alzheimer’s disease (AD). The published study concluded that “nasal anti-CD3 has the potential to be a non-toxic novel immunotherapeutic approach for the treatment of Alzheimer’s disease (AD)”, which further supports the Company’s hypothesis for the use of foralumab in neurodegenerative disease. Key highlights from the Journal included:  

 

• The authors conclude that “nasal anti-CD3 has the potential to be a non-toxic novel immunotherapeutic approach for the treatment of Alzheimer’s disease (AD)”

• FDA has cleared the IND for intranasal foralumab, a fully human anti-CD3 monoclonal antibody, for human study in mild to moderate Alzheimer’s Disease

• The publication shows anti-CD3 monoclonal antibody (mAb) administered intranasally, ameliorates disease in a 3xTg model of Alzheimer’s disease by targeting microglial activation in the brain, while expanding regulatory T cells in the periphery

• Remarkably, this reduced microglial activation and improved cognition occurs independent of amyloid beta disposition.

• The full publication can be found HERE 

 

Tiziana’s Foralumab Is A Promising  Treatment With Potential To Treat Multiple Neurological Diseases

“The anti-CD3 target is established and it’s validated,” said Tiziana COO and CMO Mathew Davis at a recent conference. “We are the only company that is delivering this intranasally. We are the only company that is in the clinic with a fully human anti-CD3 antibody.”

The anti-CD3 monoclonal antibody used in Tiziana’s Foralumab binds to the CD3 receptor on the surface of T cells, typically used as a way to suppress the immune system to prevent transplant rejection or treat autoimmune disease. 

The challenge in treating these kinds of conditions has long been finding the balance between suppressing the immune response to protect the patient without harming the body’s ability to fight off actual threats like viral infections and bacteria. 

However, research shows that anti-CD3 antibodies can do just that. They are able to selectively dampen the autoimmune response – when the dysregulated immune system attacks the body’s own cells and tissue – without limiting its ability to detect and respond to external threats.  

The promising new treatment approach has already sparked interest from pharmaceutical industry leaders like Sanofi SA SNY, which just acquired an anti-CD3 therapy being developed for type 1 diabetes in a $2.9 billion acquisition of Provention Bio, Inc. 

Tiziana’s Foralumab is the only anti-CD3 monoclonal antibody treatment in clinical trials that is fully human — a significant differentiator as these tend to come with fewer adverse reactions than those that are genetically engineered.

It’s also the only one that’s delivered via an intranasal spray, making it less invasive than an infusion and allowing it to travel directly to the T cells in the patient’s lymph nodes. 

In the neurological diseases that Tiziana is focused on, this formulation has allowed its lead drug candidate to bind to regulatory T cells, then these T cells activate and create Tregs which are specifically tasked with maintaining homeostasis and preventing the immune system from attacking itself. Once Foralumab creates these Tregs, they can cross through the blood-brain barrier and help fight neuroinflammation at its source. 

Tiziana Highlights Past Results And Upcoming Milestones Across Foralumab Clinical Trials

During a recent investor conference, Davis focused on the exciting results Tiziana has seen so far from its clinical trials and highlighted some of the upcoming milestones and plans for the year ahead. 

Its lead program is in non-active secondary progressive multiple sclerosis (SPMS), a more severe stage of the debilitating disease that currently has no FDA-approved treatment. Instead, the standard of care typically involves treating the patient with Ocrelizumab, an anti-CD20 monoclonal antibody sold under the brand name Ocrevus by Genentech, a subsidiary of Hoffmann-La Roche AG RHHBY. But the drug is not always as effective for SPMS patients as it is for other forms of MS. 

In fact, Davis noted that all of the patients in its clinical trials had previously tried Ocrelizumab and discontinued it when their symptoms continued to progress. In its ongoing expanded access program, for example, the Tiziana COO and CMO spoke about a patient who had discontinued the anti-CD20 treatment in 2021 when his condition had become so bad that he could no longer walk more than 100 feet without assistance. 

The non-active SPMS patient enrolled in Tiziana’s expanded access program in January 2022. “By the end of 2022, he was able to walk without assistance,” Davis said. “He’s back in his job and, as of this recording, he continues to walk without assistance.”

In the biopharma’s most recent data readout, other patients from the expanded access program started to show similar improvement. Three of the four patients currently enrolled saw their fatigue scores decrease after three months. Meanwhile, a phase 1 trial found that microglia – a part of the innate immune system inside the brain – had significantly decreased activation in the brains of 5 out of 6 treated patients after three months.

Davis said another data readout is expected soon, detailing the results from the expanded access program after six months of treatment. Tiziana has begun clinical site selection and plans to start a phase 2a trial in non-active SPMS before the end of this year with topline data expected by the end of 2024. 

The clinical-stage biopharma is also investigating Foralumab for Alzheimer’s disease (AD), another progressive neurological disease with an urgent need for better treatment options. Tiziana just received FDA approval to begin a phase 2 study in AD, and the company plans to launch that trial in the first half of next year. A press release on the acceptance from the Proceedings of the National Academy of Sciences (PNAS) can be found HERE along with the full publication HERE titled “Nasal Administration of anti-CD3 monoclonal antibody (mAb) ameliorates disease in a mouse model of Alzheimer’s disease”.

To learn more about Tiziana, click HERE

Featured photo by Jesse Orrico on Unsplash.

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