bryostatin 1 (NSC 339555) / Blanchette Rockefeller Neurosciences Institute, Synaptogenix - LARVOL DELTA

Safety of Bryostatin in Patients with MS (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Robert Fox | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

Safety of Bryostatin in Patients With MS (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Robert Fox | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Multiple Sclerosis

Safety of Bryostatin in Patients With MS (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Robert Fox

New P1 trial • CNS Disorders • Multiple Sclerosis

Advanced Alzheimer's Disease Patients Show Safe, Significant, and Persistent Benefit in 6-Month Bryostatin Trial. (PubMed, J Alzheimers Dis) - "The Bryostatin-treated MMSE 10-14 patients showed no significant cognitive decline throughout the 10-month trial, versus placebo patients' decline of -12.8 SIB points."

Journal • Metastases • Alzheimer's Disease • CNS Disorders

Bryostatin-1 from Synaptogenix Shows Statistically Significant Results as an ALS Treatment in Pre-Clinical Independent Study (PRNewswire) - "Synaptogenix, Inc...today announced findings from an independent study demonstrating the potential for Bryostatin-1 as a treatment strategy for amyotrophic lateral sclerosis ('ALS'), also known as Lou Gehrig's Disease....The new article demonstrates that the gene encoding for the enzyme protein kinase C epsilon ("PKCε"), the primary initial target of Bryostatin-1, showed an expression level that was significantly reduced (p<.001, 2-tailed) in the motor cortex samples taken from a genetically identified population of ALS patients when compared to control patients. Furthermore, in pre-clinical murine motor neurons genetically engineered to model the genetic signature of these ALS patients, there was a significant (p<.001, 2-tailed) reduction in the level of activated PKCε. Bryostatin-1 treatment of these ALS motor neurons significantly reversed the PKCε deficits." "

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

The ε-Isozyme of Protein Kinase C (PKCε) Is Impaired in ALS Motor Cortex and Its Pulse Activation by Bryostatin-1 Produces Long Term Survival in Degenerating SOD1-G93A Motor Neuron-like Cells. (PubMed, Int J Mol Sci) - "We furthermore investigated the steady-state levels of both pan and phosphorylated PKCε in doxycycline-activated NSC-34 cell lines carrying the human wild-type (WT) or mutant G93A SOD1 and the biological long-term effect of its transient agonism by Bryostatin-1. Moreover, a brief pulse activation of PKCε by Bryostatin-1 produced long-term survival in activated G93A-SOD1 degenerating cells in two different cell death paradigms (serum starvation and chemokines-induced toxicity). Altogether, the data support the implication of PKCε in ALS pathophysiology and suggests its pharmacological modulation as a potential neuroprotective strategy, at least in a subgroup of sporadic ALS patients."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • PRKCE • SOD1

Synaptogenix Abstract Highlighting Bryostatin-1 Benefits in Severe Alzheimer's Disease Accepted for Presentation at 11th International Brain Research Organization World Congress of Neuroscience (PRNewswire) - P2 | N=117 | NCT04538066 | Sponsor: Neurotrope Bioscience | "Synaptogenix...announced that an abstract featuring secondary endpoint data of its National Institutes of Health (NIH) sponsored Phase 2 Bryostatin-1 trial was accepted for presentation at the 11th International Brain Research Organization (IBRO) World Congress of Neuroscience to be held in September 2023 in Spain....Data also showed statistical significance in exploratory secondary endpoints for this Severe Cohort (MMSE 10-14 stratum), and post hoc analysis was positive. Statistical significance in these analyses was measured by patients' Severe Impairment Battery* (SIB) changes from baseline for the Bryostatin-1 treatment group compared with the placebo group patients."

P2 data • Alzheimer's Disease • CNS Disorders

Bryostatin Treatment of Moderately Severe Alzheimer's Disease (clinicaltrials.gov) - P2 | N=117 | Completed | Sponsor: Neurotrope Bioscience, Inc. | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders

Modulation of CD22 Antigen Density Improves Efficacy of CD22 Chimeric Antigen Receptor (CAR) T Cells Against CD22lo B-Lineage Leukemia and Lymphoma (ASH 2017) - P1; "We further demonstrate that increased CD22 CAR affinity does not seem to improve CD22 CAR activity against CD22lo ALL. Bryostatin1-mediated CD22 modulation can improve CD22 CAR response against leukemia and lymphoma providing a potential rational combination to rescue CD22 CAR activity and remission durability."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • Biosimilar • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Indolent Lymphoma

Synaptogenix Announces Topline Results from NIH-Sponsored Phase 2 Clinical Trial of Bryostatin-1 for Advanced Alzheimer’s Disease (PRNewswire) - P2 | N=100 | NCT04538066 | Sponsor: Neurotrope Bioscience, Inc. | “Synaptogenix, Inc…announced topline data from its National Institute of Health (NIH)-sponsored Phase 2 clinical trial of Bryostatin-1 for the treatment of advanced Alzheimer's disease. The trial's primary endpoint of change from baseline in the Severe Impairment Battery (SIB) total score assessment obtained after completion of the second course of treatment (week 28) was not met with statistical significance. An average increase in the SIB total score of 1.4 points and 0.6 points was observed for the Bryostatin-1 and placebo groups, respectively, at week 28.”

P2 data • Alzheimer's Disease • CNS Disorders

Synaptogenix to Present at ThinkEquity Investor Conference on October 26, 2022 (PRNewswire) - "Synaptogenix, Inc...announced that President and Chief Scientific Officer Daniel L. Alkon, M.D. will deliver a presentation and host meetings with investors at the upcoming ThinkEquity Conference. At the conference, Dr. Alkon plans to discuss the Company's National Institutes of Health (NIH)-sponsored Phase 2 clinical trial of its lead therapeutic candidate Bryostatin-1 for the treatment of moderate to moderately severe AD. The trial is on schedule for topline data during the fourth quarter of 2022."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders

Synaptogenix Advances Dosing of First Patient in Dose Optimization Clinical Trial in Preparation for NIH-Sponsored, Phase 2 Alzheimer's Disease Trial Data (PRNewswire) - “Synaptogenix, Inc…announced today, in preparation for its next phase of Bryostatin clinical development, the dosing of its first patient in the Company's open-label dose optimization clinical trial….The Company expects to announce topline data from its National Institutes of Health ('NIH') - sponsored, Phase 2b clinical trial of Bryostatin-1 for patients suffering from advanced and moderately severe AD during the fourth quarter of 2022.”

P2b data • Trial status • Alzheimer's Disease • CNS Disorders

Synaptogenix Completes Patient Enrollment in NIH Sponsored Phase 2b Alzheimer's Disease Trial (PRNewswire) - "Synaptogenix, Inc...announced that it has completed enrolling its target of 100 patients for its ongoing National Institutes of Health ('NIH') sponsored Phase 2b clinical trial of Bryostatin-1 for patients suffering from advanced and moderately severe Alzheimer's disease ('AD'). The Company expects to announce topline data from the study during the fourth quarter of 2022."

Enrollment closed • P2b data • Alzheimer's Disease • CNS Disorders

New Peer Reviewed Article Demonstrates Extended Therapeutic Potential of Synaptogenix's Bryostatin for Alzheimer's Disease (PRNewswire) - "National Institutes of Health (NIH)-sponsored Phase 2b clinical trial of Bryostatin-1 in Alzheimer's disease (AD) patients currently underway...Synaptogenix, Inc...announced the recent publication of a collaborative peer-reviewed article in Frontiers in Aging Neuroscience. The research, led by Dr. Jarin Hongpaisan of the Kimmel Medical College of Thomas Jefferson University, resulted from a long-standing collaboration with Dr. Daniel Alkon, President and Chief Science Officer of Synaptogenix."

Enrollment status • Preclinical • Alzheimer's Disease • CNS Disorders

Bryostatin Treatment of Moderately Severe Alzheimer's Disease (clinicaltrials.gov) - P2 | N=100 | Active, not recruiting | Sponsor: Neurotrope Bioscience, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders

Synaptogenix to Present at Sachs 5th Annual Neuroscience Innovation Forum (PRNewswire) - "Synaptogenix...will present a 'Spotlight Showcase' of Synaptogenix under the title 'Regenerative Therapeutics' on Tuesday, March 22nd at 8am ET. 'Recently reported consolidated results of Synaptogenix Phase 2 clinical trial patients showed significant, persistent improvement of the cognitive psychometric Severe Impairment Battery (SIB) scores, over baseline, in a placebo-controlled publication on Bryostatin for advanced AD patients (Thompson, Tuchman, and Alkon, Journal Alzheimer's disease). We believe the persistence of the cognitive benefits for these patients is consistent with the 'rewiring' restoration of synapses demonstrated in extensive pre-clinical studies. This latest data offers encouragement for our ongoing NIH-supported, 6-month Phase 2B trial with AD patients. Clinical trials for other indications such as Fragile X syndrome and multiple sclerosis are also planned.'"

Clinical • P2 data • Trial status • Alzheimer's Disease • CNS Disorders

Synaptogenix to Present Research Highlighting Potential Broad Applicability for Lead Compound Bryostatin at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2022) (PRNewswire) - "Synaptogenix, Inc...announced today that Dr. Daniel Alkon, the Company's President and Chief Scientific Officer, will present recent clinical results today, Tuesday, March 15th, at the International Conference on Alzheimer's (AD) and Parkinson's Diseases (AD/PD 2022)...summarizes therapeutic improvement by Bryostatin for advanced AD patients in placebo-controlled trials and its potential benefits for other neurodegenerative disorders such as Parkinson's Disease....'Synaptogenix's lead compound, Bryostatin-1, is currently in an ongoing National Institutes of Health sponsored six-month trial focused on Alzheimer's disease.'"

Clinical data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

PKCε Activation Restores Loss of PKCε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, and Microvessels in Aged and Alzheimer's Disease Hippocampus. (PubMed, Front Aging Neurosci) - "The PKCε activators bryostatin and DCPLA methyl ester increased PKCε, associated with an increase in MnSOD mRNA and its protein as well as vascular endothelial growth factor (VEGF), which was inhibited by the mRNA-stabilizing HuR inhibitors...An autopsy-confirmed AD hippocampus showed a decrease in PKCε and MnSOD mRNAs and their proteins and VEGF as well as in microvascular density compared to non-AD controls. In conclusion, the PKCε activation can rescue a decrease in PKCε, MnSOD, and VEGF via posttranscription regulation and alleviate oxidative stress, and in doing so, prevent microvascular loss during aging and AD."

Journal • Alzheimer's Disease • CNS Disorders • SOD2 • VEGFA

SYNAPTIC RESTORATION FOR NEURODEGENERATIVE DISEASE (ADPD 2022) - "The persistence of the observed clinical improvement for > 30 days after the dosing regimen is consistent with restoration of synaptic networks that may enhance cognitive function in AD as well as other neurodegenerative disorders such as Parkinson’s disease, Fragile X mental retardation, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis."

Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Immunology • Inflammation • Mental Retardation • Metabolic Disorders • Movement Disorders • Multiple Sclerosis • Parkinson's Disease • BDNF

Bryostatin Placebo-Controlled Trials Indicate Cognitive Restoration Above Baseline for Advanced Alzheimer’s Disease in the Absence of Memantine1. (PubMed, J Alzheimers Dis) - "Pre-specified exploratory analyses for the individual trials and the pooled trials confirmed significant bryostatin-induced improvement over baseline (treatment p < 0.001, placebo NS)."

Journal • Alzheimer's Disease • CNS Disorders

Synaptogenix Discloses Positive Results of Further Bryostatin Trial Analyses in Presentation at Alzheimer’s Association International Conference 2021 (Yahoo Finance) - “Synaptogenix...announced that its abstract for presentation at the Alzheimer's Association International Conference (AAIC)...Analyses of treatment benefit, based on mean differences and as a function of successive dosing in the Company's two previous, separate clinical studies (#202 and #203), used each patient as his / her own control in both treatment and placebo groups. While these separate analyses showed treatment benefit, the combined groups in a pooled analysis conducted here produced a highly significant statistical separation of the Bryostatin treatment group (P<.001) from the placebo group....This integrated data analysis provides further encouragement that Bryostatin can make a clinically meaningful difference for treating the underlying pathology and cognitive deterioration of AD..."

Retrospective data • Alzheimer's Disease • CNS Disorders

Synaptogenix to Present Data at Alzheimer's Association International Conference 2021 Highlighting Bryostatin Restores Cognitive Function Above Baseline (PRNewswire) - “Synaptogenix…announced that its abstract has been accepted at the Alzheimer's Association International Conference (‘AAIC’), which will be held online and in-person July 26-30, 2021. The Company's lead drug candidate, Bryostatin-1, will be featured in a poster presentation entitled: 'Bryostatin Restores Cognitive Functions Above Baseline in Advanced Alzheimer's Disease (‘AD’) Patients: A Regenerative Therapeutic Strategy’."

Clinical • Alzheimer's Disease • CNS Disorders

Synaptogenix Announces Phase 2b NIH Sponsored Alzheimer's Disease Trial Update (PRNewswire) - P2b, N=100; "Synaptogenix...today announced an update on its ongoing National Institutes of Health ('NIH') sponsored Phase 2b clinical trial of Bryostatin-1 in patients suffering from moderately severe Alzheimer's disease ('AD'). To date, the Company has now dosed 58 of its target 100 patients. Seventeen sites continue to be live....The DSMB assessment further validates the significant safety profile of Bryostatin, as opposed to safety issues observed with other candidate Alzheimer's drugs now being developed....We are pleased that our ongoing six-month Phase 2b trial sponsored by the NIH, has also displayed signs of safety thus far, consistent with our two previous trials..."

DSMB • P2b data • Trial status • Alzheimer's Disease • CNS Disorders

Synaptogenix Announces Phase 2b Bryostatin-1 Clinical Trial Update (PRNewswire) - "Synaptogenix...today announced an update on its ongoing National Institute of Health ('NIH') sponsored Phase 2b clinical trial of Bryostatin-1 in patients suffering from moderately severe Alzheimer's disease ('AD')….To date, the Company has dosed 43 of its target 100 patients. Seventeen sites are currently live. The monitoring of the balance between the placebo group and the drug group has been completed on a blinded basis by an independent review and there have been no imbalances or safety issues referable to Bryostatin-1 reported thus far."

Trial status • Alzheimer's Disease • CNS Disorders

Synthetic Bryostatin Available to Expand Neurodegenerative Indication Trials (PRNewswire) - "Synaptogenix, Inc....announced today that it has received its first batch of synthetic Bryostatin. The Company has an exclusive licensing agreement with Stanford University ('Stanford') for synthetic Bryostatin for all neurologic indications, as well as a supply agreement in place with Bryologyx, Inc. as previously announced. To date, Synaptogenix has relied upon supply of Bryostatin, derived from natural sources...This is a milestone and building block...'Our new supply of synthetic Bryostatin allows Synaptogenix to conduct trials to potentially treat a broad range of neurodegenerative disorders including Multiple Sclerosis, Stroke, Parkinson's disease, Traumatic Brain Injury, and Fragile X / Autistic Spectrum Disorder,'..."

Commercial • Alzheimer's Disease • CNS Disorders • Depression • Fragile X Syndrome • Multiple Sclerosis • Parkinson's Disease