Kadimastem Reports Positive Interim Results of Cohort B of its AstroRx® Phase 1/2a Clinical Trial in ALS

NESS ZIONA, Israel, Aug. 3, 2020 /PRNewswire/ -- Kadimastem Ltd. (TASE: KDST), a clinical-stage biotechnology company developing cell therapies for the treatment of severe debilitating diseases, announced today that its lead product, AstroRx®, showed a positive efficacy signal and a good safety profile in Cohort B of the Company's Phase 1/2a clinical trial in ALS.

"The current study results are encouraging, as they suggest a clinically meaningful signal of effect. A further randomized, parallel-controlled, clinical trial is needed to confirm these positive effects of AstroRx® in the treatment of ALS," said Dr. Marc Gotkine, Department of Neurology at Hadassah Medical Center, Jerusalem and the Principal Investigator of the Phase 1/2a clinical trial of AstroRx®. 

Kadimastem CEO Rami Epstein said, "We are excited by the positive and consistent clinical results, demonstrating both the good safety profile and therapeutic effect of AstroRx®. The comparison between the ALSFRS-R change before and after treatment convey a clinically meaningful decline of more than 50% in disease progression rate for a period of 3 months for both cohorts. The effect was even more profound in patients who deteriorate rapidly. Repeated administrations of the treatment, planned to be assessed in future clinical trials, will hopefully extend the duration of the beneficial effect. These results strengthen our commitment to bringing an innovative therapeutic treatment to ALS, a devastating disease currently having no effective treatment."

Earlier this year, due to COVID-19, the Data Safety Monitoring Board (DSMB) of the Phase 1/2a clinical trial recommended to put additional cohorts on hold to ensure the safety and well-being of the patients. Considering the ongoing situation presented by COVID-19 in Israel, the uncertainty and setbacks imposed, the Company decided to not pursue the additional cohorts of the current Phase 1/2a clinical trial.

"The positive interim results of Cohort A and B strongly support our next global clinical development stages. We are now focused on advancing strategic FDA regulatory processes that will necessitate the conduct of global multi-center clinical trials. In support, the Company is also dedicating resources to production process scale-up as well as to the development of a 2^nd generation of AstroRx® as a frozen product that will accelerate our clinical development plan to support market authorization," added Epstein.

To support these strategic processes, several senior managers with proven experience in leading such global processes have been appointed, including Dasy Mandel as Director of Business Development, Veronique Bellaiche as Director of Regulatory, and most recently Dr. Ruti Alon as the new Chairperson.

Professor Michel Revel, Kadimastem Founder and CSO added, "The strategic plan will benefit the patients and support the efforts of the medical community striving to bring a solution to this devastating disease. We value the contribution of the patients who volunteered to participate in our trial, as well as the physicians and clinical team at Hadassah Medical Center and look forward to continuing our collaboration during the next stages of global clinical trials."

Study Design

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 primary objectives of the trial were safety evaluation and tolerability of a single administration of allogeneic astrocytes derived from human Embryonic Stem Cells (hESC), administered in escalating doses. The secondary objective was to evaluate the efficacy, including ALS Functional Rating Scale-Revised (ALSFRS-R), the gold standard scale to assess ALS progression by monitoring patient muscle functions over time.

In the previously reported Cohort A, 5 patients were administered with a dose of 100X10⁶ AstroRx® cells. In Cohort B, 5 additional patients were treated with a single, higher dose of 250x10⁶ AstroRx® cells. Treatment was provided concomitantly with standard-of-care.

Primary Objective: Safety

Similarly to Cohort A, no treatment-related serious adverse events nor dose-limiting toxicities were reported and the treatment was well tolerated in the higher cell dose.

Secondary Objective: Efficacy

To identify decline in disease progression following treatment, ALSFRS-R slope analysis was performed and compared between the pre- and post-treatment periods. The starting point for the slope of the post-treatment period was referred to in the slope analysis in two ways: at first visit after treatment (Day 30, as previously published for Cohort A) and before treatment administration (Day -1). Both analyses were conducted.

• The rate of ALS disease progression in Cohort B patients, as assessed by the ALSFRS-R slope difference between pre-treatment and post-treatment (from Day -1) periods, was significantly reduced from -1.43/month during the 3-4 month run-in period before treatment to -0.78/month during 3-month follow-up after treatment, reflecting a clinically meaningful signal and statistically significant (p=0.0023) decline of 45% in disease progression rate.
• The rate of ALS disease progression in Cohort B patients, as assessed by the ALSFRS-R slope difference between pre-treatment and post-treatment (from Day 30) periods, was significantly reduced from -1.42/month in the pre-treatment period to -0.41/month in the post-treatment period (p=0.0006), reflecting a decline of 71% in disease progression rate.

• Pooling the data of the two Cohorts treated with AstroRx® (n=10, from Day -1) exhibited an even more robust and clinically meaningful effect: 
  - The ALSFRS-R slope was significantly reduced from -1.15/month in the pre-treatment period to a rate of -0.54/month post-treatment (p=0.0004). These results reflect a decline of 53% in disease progression rate.
  - Responder analysis, as assessed by the improvement of at least 25% in the ALSFRS-R rate of decline between pre-treatment and post-treatment periods, demonstrated that 70% of Cohort A & B patients treated with AstroRx® were identified as responders.

• Post-hoc efficacy (by ALSFRS-R) analysis of rapid progressors:
  Rapid progressors are defined as patients who deteriorate at least 1.1 points of ALSFRS-R per month in the run-in period.
  The treatment effect was even higher when assessing the rapid progressor subpopulation of patients from both cohorts (n=5/10, from Day -1): 
  - Slope analysis of ALSFRS-R demonstrated a reduction from -1.58/month in the run-in to -0.65/month during the post treatment, which reflects a decline of 59% in disease progression (p = 0.0003). 
  - Change from baseline in the mean decline of ALSFRS-R during the pre-treatment period in rapid progressors was -4.74 points over 90 days. In contrast, the mean decline in the post-treatment period was reduced to -2.77 over 90 days, a decline of 1.97 ALSFRS-R points per 3 months.
  - In Responder analysis, 80% of rapid progressor patients treated with AstroRx® were identified as responders.

The final results of the 6-month follow-up post-treatment for Cohort B are expected in Q4 2020.

About AstroRx®

AstroRx® is a cell therapy product developed and manufactured by Kadimastem at its GMP-compliant facility. AstroRx® contains 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 cerebrospinal cord fluid (CSF) of patients using a standard lumbar puncture procedure. The goal is to support the malfunctioning cells in the brain and spinal cord of patients suffering from Amyotrophic Lateral Sclerosis (ALS), in order to slow the progression of the disease, improve quality of life and extend life expectancy for these patients. AstroRx® has been granted orphan drug designation by the FDA for the treatment of ALS.

AstroRx® has shown to be safe and effective in preclinical trials and is now being further assessed in a Phase 1/2a open label clinical trial at Hadassah Medical Center, Ein-Kerem, Israel. The objective of the trial is to evaluate the safety, tolerability, and efficacy of escalating doses of AstroRx® cells in patients with ALS. Treatment is administered in addition to the appropriate standard-of-care.

Scientific literature indicates that astrocyte cells play a substantial role in supporting malfunctioning cells also in other neurodegenerative diseases, in addition to ALS. Accordingly, the Company is also evaluating other potential applications of the AstroRx® cell product.

About ALS 

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.

About Kadimastem

Kadimastem is a clinical stage cell therapy company, developing and manufacturing "off-the-shelf," allogeneic, proprietary cell products based on its technology platform for the expansion and differentiation of Human Embryonic Stem Cells (hESCs) into functional cells. AstroRx®, the Company's lead product, is an astrocyte cell therapy for the treatment of ALS, currently undergoing a Phase 1/2a clinical trial. IsletRx is the Company's second product in development. IsletRx is comprised of functional pancreatic islet cells intended to treat patients with insulin dependent diabetes. IsletRx demonstrated safety and efficacy in a proof of concept preclinical study. Kadimastem was founded by Professor Michel Revel, CSO of the Company and Professor Emeritus of Molecular Genetics at the Weizmann Institute of Science. Professor 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.

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Yossi Nizhar, CFO
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Marjie Hadad
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SOURCE Kadimastem

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