NSI-566 / Palisade Bio, Korea Kolmar - LARVOL DELTA

Current status of neural progenitor/stem cells for spinal cord injury: fundamental research and clinical trials. (PubMed, Front Neurol) - "Subsequently, we systematically analyze 19 clinical trials of NPC/NSC-based products conducted in 10 countries, covering HuCNS-SC, LCTOPC1, NSI-566, hESC-OPC, and the emerging iPSC-derived product XS228. No NPC product has yet achieved regulatory approval, reflecting persistent challenges in cell source optimization, safety control, graft survival, in vivo tracking, and trial design. Nevertheless, by integrating rigorous cell source selection, rational gene modification, advanced delivery systems, and well-designed clinical trials targeting carefully defined patient populations, NPCs are expected to achieve meaningful-and potentially transformative-clinical benefits for individuals with SCI in the future."

Journal • Review • CNS Disorders • Oncology • Orthopedics • Transplantation

Long-term safety and clinical outcomes from a single-site phase 1 study of neural stem cell transplantation for chronic cervical spinal cord injury. (PubMed, Stem Cell Reports) - "In this phase 1 trial, we investigate the long-term outcomes of cervical spinal cord implantation of NSI-566, a human spinal cord-derived neural stem cell line...Subclinical neurophysiological changes and limited functional gains were observed, although interpretation is constrained by the absence of a control group and the confounding effects of post-operative rehabilitation. These findings support the feasibility of intraparenchymal stem cell delivery for chronic SCI and underscore the need for larger, controlled trials to clarify efficacy and optimize therapeutic parameters."

Clinical data • Journal • P1 data • CNS Disorders • Musculoskeletal Diseases • Oncology • Orthopedics • Transplantation

Intraparenchymal stem cell transplantation for spinal cord injury: a review of clinical trials. (PubMed, Regen Med) - "This review synthesizes early-phase clinical trials from the United States, Canada, Europe, and Australia, evaluating five major cell platforms: autologous olfactory-ensheathing-cells (OECs), fetal-derived neural stem cells (HuCNS-SC), embryonic stem cell derived oligodendrocyte progenitors (OPC1), fetal spinal cord derived neural progenitor cells (NSI-566), and autologous Schwann cells (ahSCs)...These findings support biological activity but insufficient functional efficacy under current trial designs. Future progress will require controlled efficacy studies with standardized endpoints, optimized timing and dosing, and rehabilitation or neuromodulatory integration."

Journal • Review • CNS Disorders • Oncology • Orthopedics • Solid Tumor • Transplantation

Human Neural Stem Cell Line NSI-566 Provides Years of Stable Motor Gain from Chronic Hemiparesis due to Ischemic Stroke (ISC 2026) - "Altogether 19 patients received a single dose of NSI-566 of whom 18 completed at least 12 months of follow-up. The degree of motor improvement by FMMS highly correlated with the degree of stroke cavity filling by new tissue from the 566 transplantation. Eight 566 patients showed no filling of the cavity in MRI and no significant change in FMMMS scores for the entire duration."

Preclinical • Cardiovascular • Ischemic stroke

Long-term clinical and safety outcomes from a single-site phase 1 study of neural stem cell transplantation for chronic thoracic spinal cord injury. (PubMed, Cell Rep Med) - P1 | "The primary outcome of the trial was to test the feasibility and safety of human spinal cord-derived neural stem cell (NSI-566) transplantation for the treatment of chronic spinal cord injury in four subjects with thoracic two to thoracic twelve spinal cord injury. Here, we report that all four subjects tolerated the stem cell implantation procedure well, and two subjects had durable electromyography-quantifiable evidence of neurological improvement as well as increased neurological motor and sensory scores at five years post-transplantation."

Journal • P1 data • Bone Marrow Transplantation • CNS Disorders • Orthopedics • Transplantation

Stable Intracerebral Transplantation of Neural Stem Cells for the Treatment of Paralysis Due to Ischemic Stroke. (PubMed, Stem Cells Transl Med) - "NSI-566 is a stable, primary adherent neural stem cell line derived from a single human fetal spinal cord and expanded epigenetically with no genetic modification...Immunosuppression therapy with tacrolimus was maintained for 28 days...Although this was a small, one-arm study of feasibility, the results are encouraging to warrant further studies. Stem Cells Translational Medicine 2019."

Journal • Amyotrophic Lateral Sclerosis • Cardiovascular • Complement-mediated Rare Disorders • Ischemic stroke • Reperfusion Injury • Transplantation

Seneca Biopharma reports 2020 first quarter results (PRNewswire) - “Completion of the Company's stem cell manufacturing facility in Suzhou, China which will be used to manufacture NSI-566 for clinical trials within China.”

Commercial • 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)

Seneca Biopharma announces results of meeting with FDA Regarding the design of phase 3 trial for NSI-566 in ALS (PRNewswire) - “Seneca Biopharma…announced that the company held a Type C meeting with the Office of Tissues and Advanced Therapies at the FDA on March 10, 2020 to discuss future clinical development plans for NSI-566…As a result of the discussion and feedback received from the FDA, Seneca believes that the existing phase 1 and 2 trial results support moving into a phase 3 clinical study for ALS.”

Clinical • FDA event

Seneca Biopharma, Inc. reports year end 2019 fiscal results (Herald-Mail Media) - "The Company received approximately $6.8 million in net proceeds....'With the proceeds from the January 2020 transaction, we have the capital to build out our management team and continue our initiative of evaluating new therapeutic products for development as well as seeking partners for our promising neural stem-cell therapeutic NSI-566...'"

Financing

Form 8-K Seneca Biopharma, Inc. for: Feb 20 (Streetinsider.com) - "...Seneca Biopharma...commenced an outreach process focused on out licensing its stem cell asset, NSI-566. Filed herewith as Exhibit 99.01 through 99.02 are the materials being used in such outreach."

Licensing / partnership

Seneca Biopharma rockets 129% on cell therapy promise (SeekingAlpha) - “Thinly traded nano cap Seneca Biopharma (SNCA +129%) (formerly Neuralstem) has annihilated short sellers on a whopping 90x surge in volume….The presentation focused on three potential indications of lead candidate NSI-566, a spinal cord-derived stem cell therapy, for amyotrophic lateral sclerosis (ALS), chronic stroke and chronic spinal cord injury.”

Stock price

A First-in-Human, Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury. (PubMed, Cell Stem Cell) - "Our results support the safety of NSI-566 transplantation into the SCI site and early signs of potential efficacy in three of the subjects warrant further exploration of NSI-566 cells in dose escalation studies. Despite these encouraging secondary data, we emphasize that this safety trial lacks statistical power or a control group needed to evaluate functional changes resulting from cell grafting."

Journal • P1 data

First Human Trial of Stem Cell Transplantation in Complex Arrays for Stroke Patients Using the Intracerebral Microinjection Instrument. (PubMed, Oper Neurosurg (Hagerstown)) - "IMI technology permits unprecedented numbers of injections to be tactically placed in 3-dimensional arrays safely and reliably in human subjects.This advanced methodology can optimize the benefits of novel therapeutics by enabling versatile 3-dimensional intracerebral targeting."

Clinical • Journal