PLL Therapeutics has announced the commencement of a Phase I/II clinical trial in Australia to evaluate PLL001, a novel therapeutic approach for Amyotrophic Lateral Sclerosis (ALS). The trial, approved by Australia’s Human Research Ethics Committees (HREC), will assess the safety, tolerability, efficacy, and pharmacodynamics of PLL001 in patients with ALS. PLL001 aims to address the underlying causes of ALS by restoring microbiome balance and preventing gut leakage, a departure from treatments focused solely on symptom management.
The Phase I/II trial is designed as a multi-center, randomized, double-blind, placebo-controlled study, with an optional open-label extension. Monash Health, a major public hospital in Melbourne, will serve as the lead clinical site, enrolling 12 patients in Phase I and 140 in Phase II. Results from the trial are expected within 18 months, with a six-month milestone assessment.
PLL001: Targeting the Root Cause of ALS
PLL Therapeutics' lead candidate, PLL001, is derived from the company's polypeptide delivery platform. It is designed to restore the permeability of the gut and Blood-Brain Barrier (BBB) by replenishing a critical compound in the microbiome. This mechanism aims to prevent the leakage of contaminants into the brain, which are believed to initiate neurodegenerative processes. According to Jean-Pascal Zambaux, co-founder and CEO of PLL Therapeutics, this approach targets the triggers underlying gut and BBB leaks, rather than merely addressing the symptoms of ALS.
Advancing Early-Stage Diagnostics for ALS
In conjunction with the PLL001 trial, PLL Therapeutics will evaluate its early-stage diagnostic tool for ALS. This diagnostic kit utilizes serum antibodies to detect neurodegenerative pathologies, offering a potentially faster and simpler method compared to the ALSFRS-R Score, a questionnaire-based scale currently used to track physical function in ALS patients. The company aims to demonstrate the advantages of combining early diagnostics with therapeutic intervention, enabling detection and treatment at the onset of the disease, before irreversible damage occurs.
ALS: A Devastating Neurodegenerative Disease
ALS, also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder affecting motor neurons. Approximately 140,000 new cases are diagnosed worldwide each year. The disease leads to respiratory failure and death, typically within three to five years of symptom onset.
Trial Collaborations and Future Plans
PLL Therapeutics is collaborating with Alithia Lifesciences, an Australian Contract Research Organization, and Copexis, a Swiss consultancy firm, for this Phase I/II study. Patient enrollment is anticipated to be completed by the end of 2024. PLL001 consists of several Active Pharmaceutical Ingredient (API) molecules designed to restore the microbiome and prevent gut leakage. It utilizes PLL Therapeutics’ patented Poly-L-Lysine technology to deliver Small Chain Fatty Acids (SCFAs) to the epithelium gut cells and the BBB.
