Disease progression was reduced in the first 3 months post-treatment period compared to the 3 months pre-treatment period, this preliminary result demonstrates statistically significant decline in disease progression (p=0.0023)
No treatment-related serious adverse events nor dose-limiting toxicities were reported
Final results of cohort A expected by year-end 2019; results of cohort B are expected in Q3 2020
NESS ZIONA, ISRAEL – September 24, 2019 – Kadimastem Ltd. (TASE: KDST), a clinical stage cell therapy company, today announced promising interim results of cohort A of its Phase 1/2a clinical trial for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS). The primary objective of the trial is to evaluate the safety of injecting AstroRx®, an "off-the-shelf" clinical-grade astrocyte cell product, developed and manufactured by the Company, into the spinal cord fluid of ALS patients. A secondary objective of the trial includes preliminary efficacy.
An interim analysis to explore possible efficacy was initiated and conducted after all 5 patients in cohort A completed 3 months post treatment visits. No serious adverse events (SAE) nor dose-limiting toxicities were reported, and statistically significant preliminary efficacy was observed.
The 5 patients included in cohort A received the lowest dose of AstroRx® (100x106 cells).
Preliminary efficacy assessment was based on ALS Functional Rating Scale-Revised (ALS-FRS-R), the gold standard criteria to assess ALS progression by monitoring patient muscle functions over time. During the 3 months pre-treatment period, the ALS-FRS-R decreased at an average rate of (-0.87) per month. This rate of decrease is similar to that reported in the scientific literature. The average ALS-FRS-R change in the 3 months post-treatment was (+0.26) per month.
These results demonstrate a statistically significant difference between the slope in the pre-treatment period and the slope in the first 3 months post-treatment period (p=0.0023). This indicates that the progression of the disease was reduced in the first post-treatment period compared to the pre-treatment period. Preliminary and interim results of Cohort A will be presented at the prestigious annual NEALS meeting to be held in Florida, US at the beginning of October 2019. Final results of cohort A (total 6 months post treatment period) are expected by year-end 2019.
Following the recommendation of the trial's independent Data & Safety Monitoring Board (DSMB) and the approval of the Israeli Ministry of Health, all 5 patients of cohort B who will receive a higher dose of AstroRx® cells (250x106) were recruited. Results of cohort B are expected in Q3, 2020.
"ALS is a devastating disease and there is a critical need for new treatments to more effectively slow down or halt its rapid progression", stated Dr. Marc Gotkine, Department of Neurology at Hadassah Medical Center, Jerusalem, and the Principal Investigator of the trial. "These preliminary results on a small subset of patients are encouraging, as the treatment seems to be safe, at this lower dose. Initial data analysis presented to us, appears to demonstrate a slowing down of the reported ALSFRS-r deterioration rate over the 3-months following treatment. The trial is now continuing with higher doses and repeated injections".
Rami Epstein, CEO of Kadimastem, commented: "To the best of our knowledge, Kadimastem is the only company developing astrocyte-based cell therapy for the treatment of ALS, which may become a breakthrough in ALS treatment. "These results are not only an important milestone in our quest to bring treatment to ALS patients, but also serve as a validation of our unique technology platform and ability to develop and manufacture clinical grade cells in our GMP compliant facilities."
Prof. Michel Revel, Founder and CSO of the Company, stated, “These interim results show that our AstroRx® cell product, even at the lowest dose, has therapeutic effects. The scientific literature indicates that astrocyte cells play a substantial role in supporting malfunctioning cells also in other neurodegenerative diseases in addition to ALS. Therefore, we intend to study the potential therapeutic effect of our AstroRx® cells in additional neurodegenerative diseases.”
About the Phase 1/2a ALS Clinical Trial
The Phase 1/2a trial is an open label, dose escalating clinical study to evaluate the safety, tolerability and preliminary efficacy of AstroRx® cells in patients with ALS. The trial is expected to include 21 patients and is being conducted at the Hadassah Medical Center, Jerusalem, Israel. The primary endpoints of the trial are safety evaluation and tolerability of a single administration of allogeneic astrocytes derived from human Embryonic Stem Cells (hESC), administered in escalating low, medium and high doses (100x106, 250x106, and 500x106 cells, respectively). The medium dose will also be administered in 2 consecutive injections separated by an interval of 60 days. Secondary end points include efficacy evaluation and measurements. Treatment is administered in addition to the appropriate standard-of-care.
AstroRx® is a clinical grade cell therapy product developed and manufactured by Kadimastem in its GMP-compliant facility, containing functional healthy astrocytes (nervous system support cells) derived from human Embryonic Stem Cells (hESC) that aim to protect diseased motor neurons through several mechanisms of action. The Company's technology enables the injection of AstroRx® cells into the spinal cord fluid of patients suffering from Amyotrophic Lateral Sclerosis (ALS) with the goal of supporting the malfunctioning cells in the brain and spinal cord, in order to slow the progression of the disease and improve patients’ quality of life and life expectancy. AstroRx® has been shown to be safe and effective in preclinical studies. AstroRx® has been granted orphan drug designation by the FDA.
Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease causing dysfunction in the upper and lower motor nerves that control muscle function. ALS leads to muscle weakness, loss of motor function, paralysis, breathing problems, and eventually death. The average life expectancy of ALS patients is 2-5 years. According to the ALS Therapy Development Institute, it is estimated that there are approximately 450,000 ALS patients worldwide of which 30,000 reside in the US. According to the ALS Foundation for Life, the annual average healthcare costs of an ALS patient in the US are estimated at US$ 200,000. Thus, the annual healthcare costs of ALS patients in the US alone amount to US$ 6 Billion.
Kadimastem is a clinical stage cell therapy company, developing and manufacturing "off-the-shelf" allogeneic proprietary cell products based on its platform technology for the expansion and differentiation of Human Embryonic Stem Cells (hESCs) into clinical grade functional cells. AstroRx®, the Company's lead program, is a clinical-grade astrocyte cell therapy for the treatment of ALS, currently undergoing a Phase 1/2a clinical trial. In addition, preclinical trials are ongoing with the Company’s IsletsRx pancreatic functional islet cells for the treatment of insulin dependent diabetes. Kadimastem was founded by Prof. Michel Revel, CSO of the Company and Professor Emeritus of Molecular Genetics at the Weizmann Institute of Science. Prof. Revel received the Israel Prize for the invention and development of Rebif®, a multiple sclerosis blockbuster drug sold worldwide. Kadimastem is traded on the Tel Aviv Stock Exchange (TASE: KDST).
Forward Looking Statement
This document may include forward-looking information as defined in the Securities Law, 5728 – 1968. Forward-looking information is uncertain and mostly is not under the Company’s control and the realization or non-realization of forward-looking information will be affected, among other things, by the risk factors characterizing the Company’s activity, as well as developments in the general environment and external factors affecting the Company’s activity. The Company’s results and achievements in the future may differ materially from any presented herein and the Company makes no undertaking to update or revise such projection or estimate and does not undertake to update this document. This document does not constitute a proposal to purchase the Company’s securities or an invitation to receive such offers. Investment in securities in general and in the Company in particular, bears risks. One should take into account that past performance does not necessarily indicate performance in the future.
Yossi Nizhar, CFO