vandefitemcel (SB623) / SanBio - LARVOL DELTA

Relationship Between Location of Cell Transplantation and Recovery for Intracerebral Stem Cell Transplantation for Chronic Traumatic Brain Injury: Post-hoc Analysis of STEMTRA Trial. (PubMed, Neurotrauma Rep) - "Intracerebral transplantation of allogeneic mesenchymal stem cells, specifically SB623, has shown promise in achieving better neurological recovery compared with a sham surgery group in the STEMTRA trial...A moderate to strong trend of correlations was observed, suggesting that a shorter distance is preferable for the motor cortex group, while a greater distance is preferable for the DWM group. The optimal site for stem cell transplantation may be different from the damaged site of the patient; however, a further large number cohort is necessary to elucidate this hypothesis."

Journal • Retrospective data • Bone Marrow Transplantation • CNS Disorders • Transplantation • Vascular Neurology

Therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) with voluntary and forced exercise in a rat model of ischemic stroke. (PubMed, Exp Neurol) - "The SB623 + V-Ex group was most effective in alleviating depression-like behavior. Future research should optimize these exercise protocols and elucidate the underlying mechanisms to develop tailored rehabilitation strategies for stroke patients."

Journal • Preclinical • Cardiovascular • CNS Disorders • Depression • Ischemic stroke • Psychiatry • Transplantation

Modified human mesenchymal stromal/stem cells restore cortical excitability after focal ischemic stroke in rats. (PubMed, Mol Ther) - "Our findings demonstrate that intra-cortical transplants of hMSC-SB623 cells correct stroke-induced circuit disruptions even at the chronic stage, suggesting broad utility as a therapeutic for neurological conditions with network hyperexcitability. Additionally, the transplanted cells exert far-reaching immunomodulatory effects whose therapeutic impact remains to be explored."

Journal • Preclinical • Stroma • Cardiovascular • CNS Disorders • Ischemic stroke • Transplantation • Vascular Neurology

Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial. (PubMed, Neurology) - P2 | "Intraparenchymal implantation of SB623 cells was safe and significantly improved motor status at 24 weeks in participants with chronic motor deficits after TBI, with continued improvement of function and ADL at 48 weeks. Cell therapy can modify chronic neurologic deficits after TBI."

Clinical • Journal • Retrospective data • Stroma • CNS Disorders • Vascular Neurology

Mesenchymal Stem Cells Promote an Increase in Neuronal Oscillation via Glutamate Tonic Release. (PubMed, Neuroscience) - "We investigated the effects of SB623 cells (Notch-1 intracellular domain-transfected MSCs) and parental MSCs on human induced pluripotent stem cell (iPSC)-derived neurons using multi-electrode arrays...Glutamate release was further implicated by the reduced excitability in co-cultures with astrocytes, known glutamate scavengers. Our findings reveal a novel mechanism for MSCs: promoting neuronal activity and network formation through tonic glutamate release, with potential implications for MSC-based therapies."

Journal • CNS Disorders • NOTCH1

Notch Signaling-Modified Mesenchymal Stem Cell Patch Improves Left Ventricular Function via Arteriogenesis Induction in a Rat Myocardial Infarction Model. (PubMed, Cell Transplant) - "Moreover, rat cardiomyocytes treated with SB623 cell patch transplantation showed upregulation of ephrin-B2 (P = 0.03) and EphB4 (P = 0.01) gene expression, indicating arteriogenesis induction. In conclusion, SB623 cell patch transplantation improved LV function by inducing angiogenesis and arteriogenesis in a rat ICM model."

Journal • Preclinical • Cardiomyopathy • Cardiovascular • Gene Therapies • Myocardial Infarction • Transplantation • EPHB4

Synergistic therapeutic effects of intracerebral transplantation of human modified bone marrow-derived stromal cells (SB623) and voluntary exercise with running wheel in a rat model of ischemic stroke. (PubMed, Stem Cell Res Ther) - "This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF."

Journal • Preclinical • Stroma • Cardiovascular • Ischemic stroke • Transplantation • BDNF

SanBio's Sakigake Approval for SB623 Has Been Further Deferred, and Production-Related Issues Are Materializing [Google translation] (Nikkei) - "SanBio announced on October 20, 2022 that the cell medicine SB623, which the company applied to the Ministry of Health, Labor and Welfare for approval as a treatment for chronic traumatic brain injury (TBI), will not receive approval during FY01/23. announced a forecast. The reason for this is that 'our response to production-related inspections has become more specific, and we have learned that it will take more time.'"

Japanese regulatory • CNS Disorders

Transplantation of modified human bone marrow-derived stromal cells affords therapeutic effects on cerebral ischemia in rats. (PubMed, CNS Neurosci Ther) - "SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell-cell interaction as primarily mediating the cells' functional benefits in ischemic stroke."

Journal • Preclinical • Cardiovascular • CNS Disorders • Ischemic stroke • Transplantation • NICD • NOTCH1

SanBio, Domestic SB623 Chronic Traumatic Brain Injury Program Manufacturing and Marketing Approval Status [Google translation] (Nikkei) - "The Ministry of Health, Labor and Welfare announced on July 20 that the Pharmaceutical Affairs and Food Sanitation Council's Regenerative Medicine Products and Biological Technology Subcommittee...will be held on August 3, but it was designated as a pioneer examination. Our developed SB623, which has been approved for treatment of traumatic brain injury within the framework of the system, was not included in the agenda. Since the approval period has not been decided by us, we have not disclosed it, but based on the public information on the pioneering examination designation system, patients who are expected to obtain approval by September....We have determined that SB623 will not be approved until September as it was not included in the agenda of the Headquarters meeting held on August 3. We are working as one on a daily basis to respond to the approval review of our first and unprecedented therapeutic drug, and we will survive the approval review phase as quickly as possible."

Japanese regulatory • CNS Disorders

SanBio : Consolidated Financial Results for the Three Months Ended April 30, 2022 (Market Screener) - "Under these circumstances, during the three months ended April 30, 2022, the Company recorded ¥1,370 million in research and development expenses mainly consisting of manufacturing-related costs incurred in applying for approval with respect to the SB623 development program for treatment of chronic traumatic brain injury. As a result, operating loss was ¥1,844 million (operating loss of ¥1,540 million for the same period in the previous fiscal year)."

Commercial • CNS Disorders

SB623 Demonstrated Sustained Improvement in Motor Impairment up to 48 Weeks and Associated with Improvement in Function and Activities of Daily Living in Patients with Chronic Traumatic Brain Injury (Businesswire) - P2 | N=63 | STEMTRA (NCT02416492) | Sponsor: SanBio, Inc. | "The SanBio Group...announced that SB623 met the primary endpoint and demonstrated a trend toward maintaining the improvement of function and activities of daily living in the final, one-year analysis of the Phase 2 STEMTRA trial, which evaluated the efficacy and safety of SB623 compared to sham surgery in patients with chronic motor deficit from traumatic brain injury (TBI). These results will be presented in an oral plenary session at the American Academy of Neurology (AAN) Annual Meeting, taking place on April 5, 2022, in Seattle, Washington, USA....SanBio is preparing to initiate a Phase 3 trial for SB623 in the United States, where many traumatic brain injury patients currently live."

P2 data • CNS Disorders

SanBio: Notice Regarding Completion of Approval Filing for Japan SB623 Chronic TBI Program (Businesswire) - "The SanBio Group...announces the completion of an application filing today with Japan’s Ministry of Health, Labour, and Welfare (MHLW) for manufacture and marketing approval as a regenerative medicine product for the investigational product SB623, as a treatment for chronic motor deficit from traumatic brain injury (TBI). This application for approval is based on efficacy and safety results from the US-Japan global Phase 2 clinical trial (Study of Modified Stem Cells in Traumatic Brain Injury, or STEMTRA)."

Japanese regulatory • CNS Disorders

Efficacy and Safety Outcomes in Patients with Chronic Traumatic Brain Injury: Final Analysis of the Phase 2 Stemtra Trial (AAN 2022) - P2 | "SB623 cell implantation appeared to be safe and well tolerated, was associated with statistically significant improvement of motor impairment in the primary efficacy endpoint at 24 weeks, and a trend toward maintaining this improvement of function and activities of daily living at 48 weeks."

Clinical • P2 data • CNS Disorders • Immunology • Vascular Neurology

Efficacy and Safety Outcomes in Patients with Chronic Traumatic Brain Injury: Final Analysis of the Phase 2 Stemtra Trial (AAN 2022) - P2 | "SB623 cell implantation appeared to be safe and well tolerated, was associated with statistically significant improvement of motor impairment in the primary efficacy endpoint at 24 weeks, and a trend toward maintaining this improvement of function and activities of daily living at 48 weeks."

Clinical • P2 data • CNS Disorders • Immunology • Vascular Neurology

Pharmaceutical industry Today's news summary reading (February 10, 2022) [Google translation] (AnswersNews) - "SanBio announced on February 10 that it is expected to apply for the indication of chronic traumatic brain injury next month for the regenerative medicine product 'SB623', which is the target item of the pioneering examination designation system. The pioneering comprehensive evaluation consultation with the Pharmaceuticals and Medical Devices Agency (PMDA) has been completed, and application preparations have begun. The company expects to apply in about a month in the future. In principle, the pioneering examination designation system is approved within 6 months from the application."

Japanese regulatory • CNS Disorders

SanBio Joins the Newly Formed National TBI Registry Coalition (NTRC) as a Founding Member Organization (GlobeNewswire) - "...We are currently preparing to file a Biologics License Application for potential approval in Japan for our lead asset, SB623, for the treatment of chronic motor deficits resulting from TBI.”"

Japanese regulatory • CNS Disorders

SanBio answers zero questions to SB623 approval application (Nikkei) - "SanBio...held an online financial results briefing for the second quarter of the fiscal year ending January 2022 on September 16, 2021. The company has postponed the domestic approval application for chronic traumatic brain injury (TBI) of SB623, which is the core pipeline, twice so far, and an early application is expected."

Japanese regulatory • CNS Disorders • Ischemic stroke

Determining Minimally Clinically Important Differences for Outcome Measures in Patients with Chronic Motor Deficits Secondary to Traumatic Brain Injury. (PubMed, Expert Rev Neurother) - P2 | "Retrospective analysis from the 1-year, double-blind, randomized, surgical sham-controlled, Phase 2 STEMTRA trial (NCT02416492), in which patients with chronic motor deficits secondary to TBI (N=61) underwent intracerebral stereotactic implantation of modified bone marrow-derived mesenchymal stromal (SB623) cells...For the first time in the setting of patients with chronic motor deficits secondary to TBI, this study reports triangulated MCIDs for: 1) DRS, a measure of global outcome; and 2) FM-UE, FM-LE, and FMMS, measures of motor impairment. These findings guide the use of DRS and Fugl-Meyer Scales in the assessment of global disability outcome and motor impairment in future TBI clinical trials."

Clinical • Journal • CNS Disorders • Vascular Neurology

Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model. (PubMed, Sci Rep) - "Furthermore, rat muscle treated with SB623 cells showed a trend for higher ephrin-B2 and significantly higher EphB4 expression, which are known as arteriogenic markers. In the hindlimb ischemia model, SB623 cells improved tissue perfusion by inducing arteriogenesis, suggesting a promising cell source for treatment of CLTI."

Journal • Cardiovascular • Ischemic stroke • EPHB4

Cell Therapy for Chronic TBI: Interim Analysis of the Randomized Controlled STEMTRA Trial. (PubMed, Neurology) - P2 | "SB623 cell implantation appeared to be safe and well tolerated, and patients implanted with SB623 experienced significant improvement from baseline motor status at 6 months compared to controls."

Clinical • Journal • CNS Disorders • Immunology • Vascular Neurology

[VIRTUAL] Building New Arteriogenic Therapy for Ischemic Cardiomyopathyusing Notch-induced Mesenchymal Stem Cell Patch (AHA 2020) - "SB623 patch transplantation induces arteriogenesis with functional recovery via Notch signaling in rat myocardial infarction model, proposing a new strategy for the treatment of ischemic cardiomyopathy."

Atherosclerosis • Cardiomyopathy • Cardiovascular • Dyslipidemia • Fibrosis • Immunology • Myocardial Infarction • Transplantation • EPHB4

ACTIsSIMA: Study of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke (clinicaltrials.gov) - P2b; N=163; Completed; Sponsor: SanBio, Inc.; N=302 ➔ 163

Clinical • Enrollment change • Cardiovascular • Ischemic stroke

Neurodegenerative disease treatments by direct TNF reduction, SB623 cells, maraviroc and irisin and MCC950, from an inflammatory perspective - a Commentary. (PubMed, Expert Rev Neurother) - "We include the therapeutic outcomes with etanercept (a widely used specific anti-TNF biological), XPro1595 (a new double negative TNF inhibitor), 3,6-dithiothalidomide, implanted SB623 stem cells, maraviroc (a CCR5 inhibitor used to treat AIDS), MCC950 (an NLRP3 inhibitor), and changes in the hormone irisin. With regard to developments demonstrated by MCC950, we note that DAMPs and PAMPs recognize and activate both TLRs and inflammasomes in these disease states. Here, as in other illnesses, data suggests that preventing a pathogenic interaction could be achieved through shutting down either of these arms of innate immunity."

Journal • CNS Disorders • Human Immunodeficiency Virus

ACTIsSIMA: Study of Modified Stem Cells (SB623) in Patients With Chronic Motor Deficit From Ischemic Stroke (clinicaltrials.gov) - P2b; N=302; Completed; Sponsor: SanBio, Inc.; N=163 ➔ 302

Clinical • Enrollment change • Cardiovascular • Hematological Disorders • Ischemic stroke • Reperfusion Injury