Weizmann Institute-Born Cell Therapy Technology In Clinical Trials for ALS Patients

Weizmann Institute-Born Cell Therapy Technology In Clinical Trials for ALS Patients

Kadimastem, an Israeli biopharma venture, recently declared it was hoping to discuss with the U.S. Food and Drug Administration (FDA) its AstroRX cells experimental therapy, after demonstrating promising results with cohort AM of its Phase I/IIa clinical trials for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS).

TrialSite News probes this news coming out of Israel via the Jerusalem Post. ALS is a deadly disease that afflicts about 450,000 worldwide according to the ALS Therapy Development Institute.

Known as  Lou Gehrig’s disease the disease causes the death of neurons controlling voluntary muscles. Some also use the term motor neuron disease for a group of conditions of which ALS is the most common.

What is Kadimastem’s AstroRX?

AstroRX is a stem cell therapy developed by Kadimastem. The U.S. FDA granted the experimental cell therapy orphan drug status for the treatment of ALS in November 2018.

Astrocytes are star-shaped cells of the central nervous system that play a key role in maintaining a healthy brain environment. It has been evidenced that malfunctioning astrocytes play a key role in ALS disease progression. One study, conducted by Nagoya University, Japan is listed here

AstroRX is derived from human embryonic stem cells that are made to develop into specialized cells tagged astrocyte progenitor cells (APCs), reports ALS News Today. It turns out these APCs are allowed by researchers to mature into astrocytes. So essentially, the researchers have developed a way to produce astrocytes, which are then directly injected, along with a variety of neurogenic and neuroprotective factors into the spinal fluid of the ALS patient. Apparently, these healthy astrocytes can compensate for the bad or malfunctioning astrocytes thus leading to the prevention of loss of motor neurons—the hypothesis: actually slow the progress of ALS.

The Study Discussion

This dose-escalating, four subject -group clinical study includes a single treatment administration of AstroRX, administered in an escalating low, medium and high dose of two consecutive administrations of the medium dose separated by an interval. AstroRX is administered by intrathecal (spinal) injection to patients with ALS at the early disease stage. The study commenced April 2018 and runs till August, 2020. Conducted at Hadassah Ein Kerem Medical Center, the study is led by Principal Investigator Marc Gotkine, MD and the protocol identifies 21 patients for inclusion.

Results Thus Far

The Israeli sponsors report that cohort A of the Phase I/II clinical trial included five patients, each of which received a dose of 100×106 AstroRX cells developed by the company and who then completed the six month program of post-treatment checkups and monitoring. According to the sponsor’s CEO, Rami Epstein, the results thus far are revealing that “our treatment is effective” in the support of the malfunctioning cells in the brain and spinal cord—with the goal of slowing the progression of the disease and improve overall patient quality of life not to mention life expectancy. Epstein noted that the study protocol included the ALS Functional Rating Scale-Revised (ALSFRS-R) or “the gold standard criteria” to asses ALS progression.

Some Measurements & Observations

According to ALS News Today, the results thus far as measured by average ALSFRS-R change in the three months post-treatment was a positive +0.26 which contracts with the three months previous to the study which showed an average rate of -0.87. CEO Epstein notes, “These results demonstrate a statistically significant difference between the slope in the pre-treatment period and the slope in the three month post-treatment period.” Moreover, it is reported that the fourth month of the post treatment period evidenced improvements—however, there have not been improvements in month five and six, which according to Epstein in ALS News Today, is because it “indicates a higher dose and/or repeated administrations may achieve prolonged efficacy, both of which will be tested in the coming months among cohorts B and C of this trial.” To date, there are no treatment-related serious adverse events or dose-limiting toxicities occurring during the six-month post-treatment follow up term of cohort A patients.

Obviously, this cell therapy based trial for ALS is not complete—TrialSite News will continue to monitor for material information.

Who is Kadimastem?

Kadimastem was founded in 2009 and is based in Israel. It is a biopharma company devoted to industrial applications of human embryonic stem (hES) cells, and other pluripotent stem cells, such as iPS cells. They are developing the use of pluripotent cells for manufacturing specific human tissues for two separate purposes (using different ES cell lines) including 1) Therapeutic applications in regenerative medicine and 2) Pharmaceutical R&D applications for drug screening.

These technologies were originally developed in the laboratory of Prof. Michel Revel at the Weizmann Institute of Science (Rehovot, Israel) and Kadimastem has an exclusive license from Yeda R&D (the TTO of the Weizmann Institute, Israel) for their commercialization. Kadimastem is developing these technologies in its state of the art 1,000 m2 facility in Nes Ziona, Israel, for controlled production under best industrial practices.

They employ between 25 and 50 employees.

Business & Finance

The company floated an IPO in 2013. At $48.10 per share, their current market capitalization is $49.3 million with a forecast loss of approximately $25 million. Since the IPO the company has been thinly capitalized and has had to execute on ongoing financings, this represents a high risk, thinly capitalized emerging biopharma asset. Can they stabilize financing to execute ongoing?

Lead Research/Investigator

Marc Gotkine, MD