Kadimastem and iTolerance Work to Bring Immunosuppression-Free Diabetes Cell Therapy to Trials


Kadimasem’s lead clinical candidate, AstroRx, was recently cleared for trials in the US for people with ALS.

Kadimastem and iTolerance have requested an INTERACT meeting with the FDA to discuss their preclinical joint cell therapy in development for the potential treatment of diabetes, iTOL-102.1

“The INTERACT meeting is an important step forward for this development program. We are dedicated to advancing this program and providing diabetic patients with a potential solution to live without the need for insulin injections,” Asaf Shiloni, Chief Executive Officer, Kadimastem, said in a statement.1

Kadimastem and iTolerance signed a collaboration agreement in May 2023 for the development of a diabetes cell therapy that would not require chronic immunosuppression and received a grant of about 1 million dollars from the Binational Israel-U.S. Industrial R&D (BIRD) Foundation to pursue the research. With the grant, the companies are advancing development of iTOL-102, which combines Kadmastem’s Islet Rx cell technology with iTolerance’s iTOL-100 immunomodulatory technology. IsletRx consists of insulin-secreting, human pancreatic islet-like cell clusters, and iTOL-100 is designed to enable tissue mismatched, allogeneic cell transplantation without the need for chronic immunosuppression.

The INTERACT meeting represents the first step to bringing iTOL-102 to clinical trials, and would be followed by submitting a pre-investigational new drug (IND) application based on feedback from INTERACT and then an IND application before opening clinical trials.

READ MORE: Vertex Pauses Diabetes Cell Therapy Trial After Unrelated Patient Deaths

“We are pleased with the continued progress of our research collaboration with Kadimastem and look forward to meeting with the FDA. We believe that this collaboration has the potential to provide a much-needed, innovative cure for patients with Type 1 Diabetes and look forward to building on our continued momentum,” Anthony Japour, MD, Chief Executive Officer, iTolerance, added.1

Kadimastem’s lead clinical candidate is the AstroRx cell therapy, which the company is investigating for the treatment of amyotrophic lateral sclerosis (ALS). The FDA cleared the IND for AstroRx in March 2023 but the therapy is already being assessed in a clinical trial (NCT03482050) in Israel.2

The therapy had a manageable safety profile, with no clinically significant changes in lab assessments, vital signs, physical examinations, or ECG results, or central nervous system tumor formations. The most common treatment-emergent adverse events (AEs) were post-lumbar puncture headache (50%) and injection site pain (10%). AEs related to immunosuppression were all mild to moderate and resolved. There were 3 deaths after treatment related to disease progression.3

Investigators observed an attenuation in rate of decline in ALSFRS-R scores in the first 3 months after treatment which was not maintained after this point. Mean decline attenuated from –0.88 per month in group A to –0.3 per month after 3 months (P = .039) for a 66% attenuation rate. This rate became -0.76 per month and -0.82 per month at months 6 and 12, respectively. Mean decline attenuated from –1.43 per month in group B to –0.78 per month at 3 months (P = .002) for a 45% attenuation rate. These rates were –1.59 per month and –1.29 per month at months 6 and 12. Combined, groups A and B had an attenuation rate of 53% in the first 3 months after AstroRx treatment (P <.001). Change in decline was also analyzed superficially in a subpopulation of 5 rapid progressors from both groups, whose rate of attenuation was 58% from –1.58 per month to –0.65 per month (P <. 001).3

“These results support a further need for a randomized-controlled, clinical trial with repeated doses of AstroRx® in patients with ALS, in order to prolong the clinical effect observed by a single dose," principal investigator Marc Gotkine, MD, Head, ALS Clinic, Department of Neurology, Hadassah Medical Center, Jerusalem, said in a statement about the data.4

1. Kadimastem and iTolerance Submit Initial Targeted Engagement for Regulatory Advice on CBER Products (INTERACT) Meeting Request with FDA for Potential Cure for Type 1 Diabetes. News release. Kadimastem. November 7, 2023. https://finance.yahoo.com/news/kadimastem-itolerance-submit-initial-targeted-120000679.html
2. Kadimastem earns FDA IND approval for its US phase IIa clinical trial with AstroRx® to treat ALS. News release. Kadimastem. March 19, 2023. https://www.kadimastem.com/post/kadimastem-earns-fda-ind-approval-for-its-us-phase-iia-clinical-trial-with-astrorx-to-treat-als
3. Gotkine M, Caraco Y, Lerner Y, et al. Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results. J Transl Med 21, 122 (2023). doi: 10.1186/s12967-023-03903-3
4. Kadimastem's clinical trial in ALS Patients was publicized in the Journal of Translational Medicine. News release. Kadimastem. February 15, 2023. https://finance.yahoo.com/news/kadimastems-clinical-trial-als-patients-120937753.html
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