TLSA: Six Month SPMS Results
NASDAQ:TLSA
In a series of press releases released over the first half of October, Tiziana Life Sciences PLC (NASDAQ:TLSA) announced impressive results for its expanded access (EA) cohort of six patients who were receiving intranasal foralumab to treat non-active Secondary Progressive Multiple Sclerosis (na-SPMS). The six-month results span multiple parameters and demonstrated a positive result in five of the six subjects. Parallel work on these subjects showed an improvement in microglial activation as measured in Positron Emission Tomography (PET) scans. The achievements in the EA program provide additional validation for the start of a Phase IIa clinical trial of intranasal foralumab in na-SPMS subjects. Tiziana announced the initiation of the study in late September which is expected to enroll its first subjects before year end. The FDA has allowed at-home dosing of intranasal foralumab for MS subjects, which should dramatically simplify treatment for the autoimmune disorder and reduce the burden on enrollees. In parallel with the work being done in na-SPMS, Tiziana continues to report results from its Alzheimer’s disease (AD) programs including publication of study results in the journal Proceedings of the National Academy of Sciences (PNAS). Finally, Tiziana announced that it has appointed William A Clementi as Chief Development Officer who will oversee pipeline development.
Six Month Data for SPMS
In a series of press releases published in mid-October, Tiziana updated stakeholders on the results from its six-patient EA study in na-SPMS at the six-month mark. Trial participants had been nasally administered the anti-CD3 monoclonal antibody foralumab over a six-month period. The first update identified a qualitative reduction in microglia activation while the second identified overall improvements in the enrolled patients’ measures for multiple sclerosis (MS).
Five of six patients evinced a reduction in microglial activation as measured by positron emission tomography (PET) scans over a six-month period. Activated microglia are thought to contribute to the pathogenesis of neuroinflammatory and neurodegenerative diseases such as MS, AD and amyotrophic lateral sclerosis (ALS). Three of the four most recently added patients dosed in the program produced scans that suggest a qualitative reduction in the microglial PET signal. This helps to confirm the assessment that foralumab produced an improvement in microglial activation for the first two EA subjects. The results further confirm the trend observed in the three-month PET scan and continue to support the start of the Phase II study. Tiziana provided PET imaging of the last enrolled subject at baseline, three months and six months showing the reduction in microglial activation over the period. See the following exhibit for an illustration of this progress.
Additional work with the EA subjects produced favorable results at the six-month mark. Several metrics were used to evaluate the condition of the na-SPMS patients and compare their status over the course of the study. The measures used include Expanded Disability Status Scale (EDSS), Pyramidal Scores, Timed 25-Foot Walk Test (T25FW) and Modified Fatigue Impact Scale. Each factor was directionally measured for the six subjects evaluated. Notable is that na-SPMS is a degenerative disease which worsens over time and stabilization is considered to be a favorable outcome. The clinical trial managers compiled a matrix that depicts the data for each of the patients which we include below. A dash (-) indicates stability over the six-month period while a down arrow (↓) denotes improvement.
Of the four measures, fatigue (MFIS) improved for the largest number of subjects (4/6) compared to the other metrics. This debilitating symptom of MS is a result of damage to the central nervous system and can dramatically impact a person’s quality of life.
While the results from the PET scans and the various MS-related metrics were supportive for additional clinical work, the much-heralded Phase II clinical trial was initiated in September. Initial work with the expanded access patients took place at the Brigham and Women’s Hospital, which will continue to be used for the Phase IIa as well as six to ten new clinical sites.
Poster na-SPMS Expanded Access Trial Outcomes
A poster was developed to summarize the results from the non-active secondary progressive MS (SPMS) expanded access (EA) trial that recently produced favorable data. It was presented at the 39th Congress of the European Committee for Treatment and Research of Multiple Sclerosis (ECTRIMS) that was held in Milan, Italy, from October 11th to 13th, 2023. The title of the piece is Treatment of six non-active secondary progressive MS with nasal anti-CD3 monoclonal antibody (foralumab): safety, biomarker, and disability outcomes. It summarizes the results of the trial discussed above that examined three female and three male na-SPMS patients who were administered a two week on / one week off treatment cycle of 50 μg/day of nasal foralumab, three times per week.
The poster summarized study results finding that there were no severe treatment related adverse events (TRAEs), that all six patients experienced improvement in at least one metric (see Exhibit II) and five of six showed improvement in microglial activation as shown in the baseline to six month PET scan.
At Home Dosing
One of the primary difficulties of administering monoclonal antibodies is that they are usually infused, which requires a trip to the hospital or clinic for the drug to be administered. The requirement to go on site also means that patients with severe mobility problems must enter into densely populated areas multiple times per week to receive their therapy. Limited mobility is a common hardship for severe MS patients.
Tiziana overcame the first hurdle related to infusion and was able to develop a nasally administered formulation of foralumab; however, for the clinical trial, it remained necessary for the drug to be administered by a clinic-based provider due to the lack of safety data for the drug. The protocol for the na-SPMS trial required that the drug be administered three times per week at the MS clinic at Mass Brigham, which placed a large burden on patients and caregivers.
In an October 18th press release, Tiziana announced that the FDA will allow a protocol change to allow for at-home dosing now that nasal foralumab is better understood. Some initial training is required for patient administration; however, the shift to at-home treatment is a significant improvement in accessibility and convenience. Previously, those in the EA program were required to visit the hospital three times per week. Under the new protocol, they will only be required to visit the clinic one time every three weeks. At-home administration will also be used for the upcoming Phase IIa study which is expected to start in November.
Start of Phase IIa
Tiziana announced on September 26th that it had initiated its Phase IIa clinical trial evaluating intranasal foralumab for na-SPMS. The company held an investigators’ meeting and began work to add six to ten new trial sites in addition to the original site at Brigham and Women’s Hospital to recruit patients. Site initiation visits have begun. Proposed endpoints are PET imaging and likely other metrics similar to what was used in the EA program. This included fatigue, disability status, 25-foot walk test and pyramidal scores. For the Phase IIa, the FDA will allow for at-home administration of nasal foralumab, which should dramatically improve the burden of the trial on enrollees.
Addition to the Team
In late August, Tiziana announced that it had appointed William A. Clementi as Chief Development Officer. Dr. Clementi will oversee the company’s development strategies and aid in the advancement of the pipeline of therapeutic candidates. His background is as director of marketing at Lorex Pharmaceuticals and he has provided consulting services to drug, biologic, cell-based therapy and other development projects. He has also completed National Institute of Health (NIH) Training Fellowship in drug metabolism and vascular smooth muscle relaxation. Academic credentials include degrees from Boston University and the University of Texas.
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1. Tiziana press release, October 13, 2023. Tiziana Announces Positive Qualitative Six-Month PET Scan Results With Intranasal Foralumab Treating Multiple Sclerosis Patients Diagnosed With Non-Active Secondary Progressive MS (na-SPMS)
2. Tiziana Press Release, October 16, 2023. Tiziana Life Sciences Announces Positive Six-Month Clinical Results in Multiple Sclerosis Patients Treated with Intranasal Foralumab.
