Tiziana Life Sciences PLC (NASDAQ:TLSA) reported new data from its ongoing non-active secondary progressive multiple sclerosis (na-SPMS) expanded access (EA) trial. Details of the new data were provided in a press release and in a webinar made available on June 5th. The call featured Dr. Howard Weiner, M.D., Principal Investigator for the EA trial, acting CEO Gabriele Cerrone and Chief Medical Officer Matthew Davis, M.D.
The agenda for the program began with introductions and a discussion of the development history of intranasal foralumab for treatment of neurodegenerative disease. It continued with an update on the EA trial and observations addressing the six patients enrolled to date. The next segment addressed the upcoming Phase IIa trial, how it will be structured and other details. The last part of the presentation provided an opportunity for analysts and investors to ask questions and receive answers from the management team and Dr. Weiner.
Some of the near-term milestones announced during the event by acting CEO, Gabriele Cerrone, include the receipt of grant funding for ALS, advancement of foralumab in intracerebral hemorrhage and expectation of investigational new drug (IND) application submission for Alzheimer’s disease (AD).
Dr. Weiner began his portion of the webinar with a review of microglial cells and how they are regulated by nasal anti-CD3. In many neurodegenerative diseases, the microglial cells in the brain can become inflamed triggered by a number of factors including injury, infection or disease. Nasal anti-CD3 has been administered to both animals and humans, and demonstrated that the microglial inflammation can be reduced. In support of this assertion, Dr. Weiner cited the research provided in a recent Proceedings of the National Academy of Sciences (PNAS) publication. The research examined the effect of the drug in COVID, multiple sclerosis (MS) and healthy subjects.
Tiziana’s anti-CD3, nasal foralumab, provides a mechanism of action that supports it use in many other indications besides COVID and MS as demonstrated in animal models. This includes Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Type 1 diabetes and intracerebral hemorrhage among others.
Patient Progress
In the next segment, management reviewed patient progress in the EA group. A slide was presented with PET imaging, capturing microglial activation at baseline and at waypoints during the trial. The first and second patients both showed improvement and a halt to MS progression in their subsequent PET imaging. In all, five of six patients, showed a decrease in microglial activation in PET scans and achieved improvements in disability.
Phase II Trial
A double blind and placebo-controlled Phase II trial is planned for later this year. Two doses will be evaluated, a 50 mcg and 100 mcg dose administered weekly, with a two-on, one-off weekly schedule. 54 patients will be randomized in a 1:1:1 ratio in the 50/100/placebo groups. Endpoints will be measured at three months and include microglial activation as measured through a PET scan, MRI, biomarkers and a clinical evaluation. Depending on the success of the trial, it may be extended, expedited treatment may be pursued or a Phase III may be planned. The magnitude of the unmet need supports the use of Fast Track and Accelerated Approval if the data are supportive.
Analyst Questions
Analyst and investor questions were wide ranging and addressed speed of action, dosing objectives, partnership seeking efforts and pipeline priority. One important transaction that was highlighted by Tiziana was the Provention Bio acquisition for $2.9 billion. Sanofi bought the company for its TZIELD anti-CD3 asset for Type 1 Diabetes. Management also highlighted some expected milestones including a near term submission of the AD IND and start of a trial this year and results from both the Phase II in na-SPMS and AD in 2024.
Follow up Press Release
The KOL event was followed by a press release on June 15th reiterating the findings presented in the webinar. The much-heralded Phase II trial remains on track to begin in 3Q:23. Non-active SPMS (na-SPMS) is a result of microglial activation and inflammation, conditions which destroy the myelin, the protective sheath covering of nerve fibers. The disease also contributes to the formation of MS lesions. The absence of approved treatment for na-SPMS supports the advancement of intranasal foralumab for these patients. The reduction in microglial activation in five of six expanded access patients is another column of support for the proof-of-concept trial. Other anticipated clinical work revolves around the Alzheimer’s disease (AD) investigational new drug application (IND). The submission of the IND is expected in the very near term, and if cleared will support the start of the AD program. The Long COVID program is the subject of an IND planned for 4Q:23.
Dr. Matthew Davis Assumes Additional Responsibility
Tiziana’s Chief Medical Officer, Dr. Matthew Davis added a new title to his name with the addition of Chief Operating Officer (COO) as described in a June 13th press release. Dr. Davis’ new responsibilities will include overseeing Tiziana’s daily operations, including R&D, manufacturing, clinical trials and commercialization efforts.
Intracerebral Hemorrhage
Building on its work in other indications for its anti-CD3 franchise, Tiziana has conducted preclinical work that supports further clinical efforts in hemorrhagic stroke. The monoclonal antibody has shown promise in mice, improving motor and cognitive outcomes after a month of treatment. The mechanism of action for the nasally administered anti-CD3 induces FoxP3+ T regs and interleukin (IL)-10 producing FoxP3+ T regs in the brain.
An abstract was put forward at the American Academy of Neurology annual meeting by Dr. Saef Izzy et al. The research demonstrated that the intranasally administered anti-CD3 reduced microglial activation and lesion volume after intracerebral hemorrhage. Further observations found that treatment improved behavioral outcomes, including motor, spatial learning and hippocampal-dependent working memory functions.
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1. Source: Corporate presentation, KOL Webinar, June 5, 2023.
