PPI-1011 / Med-Life Discoveries - LARVOL DELTA

First-In-Human Safety, Tolerability, and Pharmacokinetics of PPI-1011, a Synthetic Plasmalogen Precursor. (PubMed, Clin Transl Sci) - "PK analysis confirmed that both single (25, 50, 75 and 100 mg/kg) and multiple-dose (75 and 100 mg/kg, once daily) administration of PPI-1011 significantly increased serum levels of the target plasmalogen (PlsEtn 16:0/22:6). With a once-daily regimen, PPI-1011 administration resulted in a sustained increase of PlsEtn 16:0/22:6 serum concentrations in healthy participants over a duration of 14 days and beyond."

Clinical • Journal • P1 data • PK/PD data • Gastrointestinal Disorder • Genetic Disorders

NONCLINICAL AND CLINICAL DEVELOPMENT OF PPI-1011, AN ORAL PLASMALOGEN PRECURSOR, AS A TREATMENT FOR ALZHEIMER'S DISEASE (ADPD 2024) - "PPI-1011 is well-tolerated in both animals and humans, representing a novel treatment modality to address the plasmalogen deficiency observed in AD. A Phase 2 clinical protocol is under development to evaluate the effects of PPI-1011 on cognitive decline in AD patients."

Clinical • Alzheimer's Disease • Cardiovascular • CNS Disorders

DEVELOPMENT OF A NOVEL ALZHEIMER'S DISEASE MOUSE MODEL BASED ON CHRONIC PLASMALOGEN DEFICIENCY IN ADULTHOOD (ADPD 2024) - "Following tamoxifen treatment, the animals were characterized by functional assessments (open field, sleep monitoring, and nerve conduction), neuroimaging (anatomical MRI and mass spectrometry imaging (MSI), and for neuroinflammatory markers (NfL)...Preliminary results following treatment with PPI-1011, an oral plasmalogen therapeutic precursor, showed normalization of brain structure and lipid composition. Our Gnpat conditional mouse model confirms for the first time that plasmalogen reductions in adulthood, comparable to the chronic situation observed in individuals with AD, are sufficient to impair function, alter sleep architecture, increase neuroinflammatory markers and reduce brain volumes. This model therefore represents a critical tool in the evaluation of future plasmalogen-targeted therapeutics."

Preclinical • Alzheimer's Disease • CNS Disorders

A First-in-Human Phase 1 Study of Plasmalogen Precursor PPI-1011 in Healthy Adult Volunteers to Assess Safety, Tolerability, and Pharmacokinetics (clinicaltrials.gov) - P1 | N=56 | Recruiting | Sponsor: MED-LIFE DISCOVERIES LP

New P1 trial

Pharmacokinetics, Mass Balance, Excretion, and Tissue Distribution of Plasmalogen Precursor PPI-1011. (PubMed, Front Cell Dev Biol) - "Uptake to the brain was also definitively confirmed, proving PPI-1011's ability to cross the blood-brain barrier. In conclusion, our results suggest that oral administration of PPI-1011 results in high uptake across the body, and that repeated dosing over time represents a viable therapeutic strategy for treating plasmalogen deficiencies."

Journal • PK/PD data

Neuroprotection and immunomodulation in the gut of parkinsonian mice with a plasmalogen precursor. (PubMed, Brain Res) - "The protective effects of PPI-1011 were observed regardless of whether it was administered pre- or post- MPTP treatment. These results suggest that PPI-1011 has neuroprotective and anti-inflammatory properties in the gut and indicate its potential utility as a treatment for both early and more advanced stages of PD."

Journal • Preclinical • CNS Disorders • Immune Modulation • Immunology • Inflammation • Movement Disorders • Parkinson's Disease