PLL Therapeutics, a biopharmaceutical company developing a groundbreaking polypeptide delivery platform to treat the root cause of autoimmune and neurodegenerative diseases, has announced positive results in the first stage of its phase I/II clinical trial in amyotrophic lateral sclerosis (ALS), demonstrating a favourable safety and tolerability profile for its investigational therapy, PLL001.
The administration of a single ascending dose in the first stage of PLL Therapeutics’ phase I/II study successfully met its primary objectives of showing safety and tolerability in 12 ALS patients.
The study, led by Susan Mathers, lead investigator, was conducted across multiple sites in Australia: Alfred Health, Calvary Health Care and Wesley Research Institute. It was designed to evaluate the safety and tolerability of single ascending doses of PLL001, in which patients were assigned to one of three dose cohorts during the first seven days, with a single administration of PLL001 or placebo in a double-blind manner.
The first stage of the study demonstrated a favourable safety and tolerability profile, with no serious adverse events (SAE) reported and no treatment emergent adverse event (TEAEs) resulting in study discontinuation.
“We are very encouraged by the phase I results in the 12 patients with ALS, which validate the safety profile of PLL001,” said Jean-Pascal Zambaux, co-founder and CEO of PLL Therapeutics.
“This is a critical step forward in our mission to restore the intestinal epithelium barrier, thereby treating the root cause of ALS – a disease linked to the dysbiosis of the gut. Our teams in Australia, New Zealand and France are diligently advancing this program into phase II.”
The successful completion of this clinical phase paves the way for a second-stage trial, involving 140 ALS patients in Australia and New Zealand, to test the efficacy of PLL001, and for future ‘compassionate use’ programmes. This next phase, due to start in Q2 of 2026, is scheduled to run for one year, during which patients will receive a daily injection of either PLL001 or a placebo over a six-month treatment period.
PLL001 is designed to address ALS at its onset and slow or halt disease progression. It is derived from PLL Therapeutics’ polypeptide delivery platform that leverages a poly-L-lysine conjugate, a peptide chain engineered to extend the in vivo half-life of active compounds. PLL001 aims to restore the intestinal epithelium barrier through the delivery of targeted small-chain fatty acids (SCFAs) to gut epithelial cells and the blood-brain barrier (BBB), helping restore the normal function of cells lining the gut, as well as the BBB. Tightening the junctions between cells, sealing the gut lining to prevent leakage of harmful substances into the bloodstream and central nervous system, helps reduce inflammation.
Although ALS is classified as a rare disease, research findings indicate it will impact a growing proportion of the global population over the coming decades. There are approximately between four and eight people per 100,000 living with ALS worldwide, with its prevalence projected to increase by 30% across multiple countries by 2040, when considering aging populations and improved survival rates.