Protollin / NovaBridge Biosciences, Jiangsu NHWA Pharma - LARVOL DELTA

Efficacy of Immunostimulatory Adjuvants and Nano-Adjuvants in Current SARS-CoV-2 Vaccines: A Comprehensive Review. (PubMed, Health Sci Rep) - "Narrative review of preclinical and clinical evidence on alum, emulsions (MF59, AS01/AS03), Montanide ISA-51, delta inulin, TLR agonists (e.g., CpG, TLR3), rOv-ASP-1, and nano/mucosal platforms (liposomes, polymeric or metal nanoparticles, Protollin) for SARS-CoV-2 and related coronaviruses...Immunostimulatory and nano-adjuvants substantially strengthen SARS-CoV-2 vaccine immunogenicity, support antigen-sparing, and favor balanced (often Th1-biased) protection. Prudent adjuvant selection and integration of conventional and nanotechnology-derived platforms are key to achieving safe, durable, and broadly protective COVID-19 vaccines."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • TLR3

Nasal Protollin in Early Symptomatic Alzheimer's Disease (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Brigham and Women's Hospital

New P1 trial • Alzheimer's Disease • CNS Disorders

INDUCTION OF AMYLOID CLEARING MONOCTYTES WITH NASAL PROTOLLIN AND MICROGLIAL DAMPENING TREGS WITH NASAL FORALUMAB TO TREAT ALZHEIMER'S DISEASE (ADPD 2025) - "Nasal Foralumab could be a treatment for ARIA. Phase 2 placebo controlled trials of nasal Protollin and nasal Foralumab in early AD are being undertaken."

IO biomarker • Alzheimer's Disease • CNS Disorders • Hematological Disorders • Multiple Sclerosis • IL10 • NKG7 • TGFB1

NASAL PROTOLLIN MODULATES PERIPHERAL MONOCYTES THAT PROMOTE INCREASED CLEARANCE OF BRAIN AMYLOID BETA IN APPPS1 MICE (ADPD 2024) - "Our data demonstrate that nasal Protollin 1) induces transcriptional changes in peripheral monocytes that migrate to the brain promoting Abeta clearance and improving cognitive deficits and 2) generates unique brain cell subsets promoting neuronal growth and function. Protollin is a novel immunologic approach and it is currently being tested in human trials."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

NASAL IMMUNOTHERAPY OF THE MONOCTYE-MICROGLIAL AXIS TO TREAT ALZHEIMER'S DISEASE (ADPD 2024) - "Nasal Protollin and nasal Foralumab had positive immunologic and clinical effects in humans and are novel immunotherapeutic approaches to target monocytes and microglia to treatment AD and can be given in combination with anti-amyloid drugs. Phase 2 placebo controlled clinical trials of nasal Protollin and Foralumab in subjects with early AD are currently being undertaken."

IO biomarker • Alzheimer's Disease • CNS Disorders • Hematological Disorders • Inflammation • Multiple Sclerosis • HIF1A • IL10 • IL12A • IL4

Treatment of early symptomatic Alzheimer's disease with nasal Protollin to activate monocytes and clear amyloid beta (CTAD 2023) - "Nasal Protollin is safe in early AD subjects and induces immune changes in monocytes, B cells and T cells. Protollin is a novel peripheral immunomodulatory approach for the treatment of AD by inducing monocytes to clear amyloid in the brain."

Alzheimer's Disease • CNS Disorders • Otorhinolaryngology • CD4 • CD8 • HIF1A • IFNG • IL12A • IL4 • TLR2 • TLR4 • TNFA

IMMUNOTHERAPY OF ALZHEIMER'S DISEASE BY MODULATION OF INNATE IMMUNITY (ADPD 2023) - "Our studies identify novel therapeutic approaches to target both the central and peripheral innate immunity for the treatment of AD. Clinical trials of Protollin in AD are in progress and trials of nasal-anti-CD3 are planned."

Alzheimer's Disease • CNS Disorders • Immunology • Inflammation • IL10

MODULATION OF PERIPHERAL MONOCYTES BY A PROTEOSOME-BASED ADJUVANT (PROTOLLIN) FOR THE TREATMENT OF ALZHEIMER’S DISEASE. (CTAD 2022) - "Background : Amyloid beta (Aβ) accumulation is considered the primary initiating event in Alzheimer’s disease (AD) pathogenesis. Our data demonstrate that nasal Protollin induces: 1) tissue-specific transcriptional changes in peripheral monocytes which infiltrate in the brains of APP/PS1 mice promoting Aβ clearance and improving cognitive deficits; 2) generation of unique glial and choroid plexus epithelial cell subsets promoting neuronal growth and function in the cortex of Protollin-treated APP/PS1 mice and 3) an increase in the phagocytic ability of blood CD14+ monocytes against Aβ1- 42 from nasal Protollin-treated AD patients plus alterations in the transcriptional profile of blood monocytes. A phase 1 single ascending dose trial of nasal Protollin in early AD is in progress. Given its safety profile and immune effects in both animal models and human AD subjects, Protollin represents a novel immunologic approach for the treatment of AD."

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Immunology • CD14 • TLR2 • TLR4

Could a Vaccine for Alzheimer’s Be on the Horizon? - "Jeffrey Cummings...goes as far as to say, 'It just feels like we have turned a corner.'"

Media quote • Alzheimer's Disease

I-Mab Announces First Patient Dosed in U.S. Phase 1 Study of Protollin for the Treatment of Alzheimer’s Disease (PRNewswire) - "I-Mab...today announced that the first patient had been dosed in the I-Mab and Nhwa-sponsored U.S. Phase I study of Protollin, an investigational drug being co-developed to treat Alzheimer's disease. The Phase I trial conducted by Brigham and Women's Hospital is a randomized, double-blinded ascending dose study of the safety, tolerability, and immune effects of Protollin in patients with early symptomatic Alzheimer's disease."

Trial status • Alzheimer's Disease • CNS Disorders

First human trial of Alzheimer's disease nasal vaccine to begin at Boston hospital (CBSNews) - “Brigham and Women's Hospital will test the safety and efficacy of a nasal vaccine aimed at preventing and slowing Alzheimer's disease, the Boston hospital announced Tuesday. The start of the small, Phase I clinical trial…The trial will include 16 participants between the ages of 60 and 85, all with early symptomatic Alzheimer's but otherwise generally healthy….A Phase I clinical trial is designed to establish the safety and dosage for a potential new medication. If it goes well, a much larger trial would be needed to test its effectiveness….The vaccine uses a substance called Protollin, which stimulates the immune system.”

New P1 trial • Alzheimer's Disease • CNS Disorders

Treatment of Alzheimer’s disease by a proteosome-based adjuvant (Protollin) that modulates both peripheral monocytes and disease-associated microglia (CTAD 2021) - "Our data demonstrate that nasal Protollin induces: 1) tissue-specific transcriptional changes in peripheral Ly6Chigh monocytes which are recruited in the brains of APP/PS1 mice; 2) downregulation of microglial DAM/MGnD-related genes and 3) activation of a transcriptional signature that reprograms human CD14+ monocytes towards a phagocytic phenotype leading to increased Aβ uptake in vitro. Given its safety profile and effect on both animal models of AD and human monocytes, a phase 1 single ascending dose trial of nasal Protollin in early AD is planned for the fall of 2021. Protollin represents a novel immunologic approach to clear Aβ in AD."

Clinical • Alzheimer's Disease • CNS Disorders • Immunology • APOE • AXL • CD14 • CSF1 • TLR4

I-Mab Announces IND Approval by FDA to Initiate Phase 1 Study for Protollin for the Treatment of Alzheimer’s Disease (PRNewswire) - "I-Mab...announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) submission for Protollin, an investigational drug to treat Alzheimer's disease, enabling a Phase 1 clinical trial to be initiated."

IND • New P1 trial • Alzheimer's Disease