AstroRx (human embryonic stem cell derived astrocyte cell therapy) / Kadimastem - LARVOL DELTA

Kadimastem, NLS merge to advance ALS therapy AstroRx, other drugs (ALS News Today) - "Kadimastem...is merging with NLS Pharmaceutics to combine efforts to advance both companies’ drug portfolios. The combined company will focus on moving AstroRx and a diabetes drug being developed by Kadimastem through clinical trials. A Phase 2a study of AstroRx is planned in the U.S. after January 2025, after the agreement is finalized."

M&A • New P2a trial • Amyotrophic Lateral Sclerosis • CNS Disorders • Diabetes

Pluri’s CDMO Selected to Manufacture Kadimastem’s Novel Cell Therapy Product Candidates (GlobeNewswire) - "Leading biotechnology company Pluri Inc...today announced it has signed a tech transfer and manufacturing agreement with Kadimastem Ltd...PluriCDMO will manufacture two cell therapy product candidates for Kadimastem: AstroRx, clinical grade human astrocytes (nervous system supporting cells) for the treatment of ALS for an upcoming U.S. Food and Drug Administration (FDA) Phase 2a study; and IsletRx, clinical grade pancreatic islet cells which produce and secrete insulin and glucagon in response to blood glucose levels, for the treatment of diabetes."

Licensing / partnership • Amyotrophic Lateral Sclerosis • CNS Disorders • Diabetes • Metabolic Disorders

Kadimastem Earns FDA Approval of its IND Application For its US Multi-Site Phase IIa Clinical Trial of AstroRx to Treat ALS (Yahoo News) - neurodegenerative diseases and a potential cure for diabetes, has received FDA clearance to commence a phase IIa clinical trial in the US according to the Investigational New Drug (IND) application that was submitted in February 2023. The trial will test its lead neurological cell therapy product AstroRx® in repeated dosing of three-month intervals for the treatment of patients with ALS. The planned clinical trial follows a first in human phase I/IIa clinical trial previously conducted by the company in Israel, in which AstroRx..."

IND • New P2a trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Kadimastem Submits IND Application to the FDA for its Phase IIa Clinical Trial with AstroRx for the Treatment of ALS (Yahoo Finance) - "Kadimastem Ltd...has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) for an approval for a multi-site phase IIa clinical trial to test its lead neurological cell therapy product, AstroRx® for the treatment of patients with ALS....Pending the FDA approval of the IND submission, the planned multi-site phase IIa clinical trial intends to examine for the first time the repeated administration of AstroRx® every 3 months in order to prolong the therapeutic effect observed in the first in human phase I/IIa clinical trial conducted by the company in Israel at Ein Kerem Hadassah Hospital from 2018-2020."

IND • Amyotrophic Lateral Sclerosis • CNS Disorders

Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results. (PubMed, J Transl Med) - P1/2 | "Overall, these findings suggest that a single IT administration of AstroRx® to ALS patients at a dose of 100 × 10 or 250 × 10 cells is safe. A signal of beneficial clinical effect was observed for the first 3 months following cell injection. These results support further investigation of repeated intrathecal administrations of AstroRx®, e.g., every 3 months."

Journal • P1/2 data • Immune Modulation

Kadimastem Receives US Patent For Amyotrophic Lateral Sclerosis (ALS) Treatment (Yahoo Finance) - “The patent supports the Phase IIa study of AstroRx® for ALS planned to begin in the US in 2023….Kadimastem Ltd…has been granted a patent from the United States Patent and Trademark Office for its cell therapy technology for treating ALS and other neurodegenerative diseases….‘We are currently engaged in intensive activities to submit the IND by the end of 2022 as well as preparations for the start of a Phase IIa clinical study in 2023 in the United States.’”

IND • New P2a trial • Patent • Amyotrophic Lateral Sclerosis • CNS Disorders

Astrocytes Downregulate Inflammation in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: Applicability to COVID-19. (PubMed, Front Med (Lausanne)) - " Our results demonstrate that the immunosuppressive activity of AstroRx cells support the application of AstroRx cells as a cell therapy treatment for ARDS. The immunoregulatory activity may also be a part of the mechanism of action of AstroRx reported in the amyotrophic lateral sclerosis (ALS) neurodegenerative disease."

Journal • Acute Respiratory Distress Syndrome • Amyotrophic Lateral Sclerosis • CNS Disorders • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • CXCL1 • IL1B • IL6 • TNFA

Kadimastem Granted a Patent in Israel for the Directed Differentiation of Astrocytes from Human Pluripotent Stem Cells (AstroRx) for use in Drug Screening and the Treatment of ALS (PRNewswire) - “Kadimastem Ltd...announced that it has been granted a patent by The Israel Patent Office for its differentiated human astrocytes from human pluripotent stem cells for use in the treatment and drug screening of Amyotrophic Lateral Sclerosis (ALS).”

Patent • Amyotrophic Lateral Sclerosis • CNS Disorders

A Study to Evaluate Transplantation of Astrocytes Derived From Human Embryonic Stem Cells, in Patients With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P1/2; N=16; Completed; Sponsor: Kadimastem; Recruiting ➔ Completed; Trial completion date: Nov 2020 ➔ Jun 2020; Trial primary completion date: Nov 2020 ➔ Jun 2020

Clinical • Trial completion • Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders • Complement-mediated Rare Disorders • Transplantation

Kadimastem Announces Encouraging Results of Cohort B of its Phase 1/2a Clinical Trial of AstroRx for ALS (PRNewswire) - P1/2a, N=21; NCT03482050; Sponsor: Kadimastem; “‘The results after 6 months of follow up are encouraging, as they suggest a clinically meaningful signal of effect for a period of 3 months by a single administration of AstroRx® and confirm the safety of AstroRx®. These results support a further, 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’…"

P1/2 data • Amyotrophic Lateral Sclerosis • CNS Disorders

Kadimastem Reports Positive Interim Results of Cohort B of its AstroRx Phase 1/2a Clinical Trial in ALS (PRNewswire) - “Kadimastem…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….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.”

P1/2 data • Amyotrophic Lateral Sclerosis • CNS Disorders

"ALS Stem Cell procedure # THREE now leaving the dock. @VeteransHealth #ALS #ENDALS @alsassociation @ALSAMA @ALS @TheALSAWPA #NurOwn #AstroRX #NSI566 #missedtheboat #MND #ALS @NIHdpc @stevens_nation @ALSMNDAlliance @CureMND @mndassoc @SteveFDA https://t.co/h7HFp32bDp https://t." (@Julia70256353)

A Study to Evaluate Transplantation of Astrocytes Derived From Human Embryonic Stem Cells, in Patients With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P1/2; N=21; Recruiting; Sponsor: Kadimastem; Trial completion date: Aug 2020 ➔ Nov 2020; Trial primary completion date: Aug 2020 ➔ Nov 2020

Clinical • Trial completion date • Trial primary completion date

Kadimastem announces promising results of cohort A of its phase 1/2a clinical trial in ALS (PRNewswire) - “Kadimastem…announced promising results of cohort A of its Phase 1/2a clinical trial for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS)….findings indicate that for a period of 3-4 months following treatment the progression of the disease was reduced, providing a potentially meaningful clinical benefit to the patients….First patient has already been enrolled to cohort C…”

Enrollment status • P1/2 data

Kadimastem announces the completion of treatment for cohort B of its phase 1/2a clinical trial in ALS patients (PRNewswire) - “Kadimastem…announced that treatment with a single dose of 250x10[6] AstroRx® cells to all 5 ALS patients in cohort B has been completed….Results of cohort A and B are expected to be reported as planned and as previously announced, by the end of 2019 and during August 2020, accordingly. Results of cohort C are expected in the first half of 2021.”

P1/2 data • Trial completion

Kadimastem intends to submit an amendment of its ALS phase 1/2a clinical trial protocol following recent positive interim results (PRNewswire) - “Kadimastem…announced its intention to submit an amendment of its ongoing Phase 1/2a clinical trial for the treatment of ALS patients to the Ethics Committee and the Israeli Ministry of Health....The purpose of the amendment is to assess the safety and efficacy of a repeated low dose (100x106) administration of AstroRx® in cohort C in 2 consecutive injections separated by an interval of 2-3 months, rather than the repeated administration of the medium dose (250x106), as originally planned.”

Clinical protocol • Non-US regulatory

Kadimastem to present interim results of cohort A of its phase 1/2a clinical trial in ALS at the 7th international stem cell meeting, in Tel-Aviv, Israel (Yahoo Finance) - “Kadimastem Ltd…announced that it will present the interim results of Cohort A of its ongoing Phase 1/2a Clinical Trial in ALS (as published in Company's press release) at the 7th International Stem Cell Meeting, to be held on November 12-13 at the Dan Panorama Hotel in Tel Aviv, Israel.”

P1/2 data

Kadimastem announces promising interim results of cohort A of its phase 1/2a clinical trial in ALS (PRNewswire) - P1/2a, N=5; “Kadimastem…announced promising interim results of cohort A of its Phase 1/2a clinical trial for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS)….Final results of cohort A (total 6 months post treatment period) are expected by year-end 2019….Results of cohort B are expected in Q3, 2020.”

P1/2 data