March 27, 2026 —
Celosia Therapeutics has announced the first patient has been dosed in the Phase 1b KOANEWA clinical trial, evaluating CTx1000, an investigational AAV9-based gene therapy designed to target pathological forms of the TDP-43 protein in patients with amyotrophic lateral sclerosis (ALS).
The KOANEWA trial is a first-in-human, open-label Phase 1b study being conducted at the Neurology Department of Macquarie University Hospital in Sydney, Australia. The trial is designed to evaluate the safety and tolerability of a single administration of CTx1000 in individuals diagnosed with ALS, also known as motor neuron disease (MND).
In addition to safety endpoints, the study will also explore biomarkers and clinical outcomes, including changes in disease progression measures such as the ALS Functional Rating Scale–Revised (ALSFRS-R). Participants will be monitored for up to one year for primary safety outcomes, with extended follow-up planned for up to three years to evaluate long-term safety and clinical signals.
CTx1000 is a novel adeno-associated virus serotype 9 (AAV9) gene therapy designed to directly target the pathological accumulation of TDP-43, a protein that plays a central role in the biology of ALS. Under normal conditions, TDP-43 resides within the cell nucleus and helps regulate gene expression. However, in many ALS cases, the protein becomes mislocalized and forms toxic aggregates outside the nucleus, contributing to neuronal dysfunction and disease progression.
The therapy builds on research led by Professors Lars Ittner and Yazi Ke, whose work was published in the journal Neuron and later licensed to Celosia Therapeutics. Their discovery identified a specific binding region from the 14-3-3 protein that selectively interacts with abnormal forms of TDP-43.
CTx1000 delivers a gene encoding this 14-3-3 binding fragment fused to a degradation tag, enabling cells to produce a molecule capable of recognizing and binding toxic TDP-43 aggregates and targeting them for cellular degradation. In multiple preclinical ALS models, this approach was shown to halt disease progression and, in some cases, partially reverse disease symptoms.
The therapeutic gene is delivered using an AAV9 vector, a widely used platform for neurological gene therapies due to its ability to efficiently transduce neurons. In the KOANEWA trial, CTx1000 is administered through an injection into the cisterna magna, a cerebrospinal fluid space at the base of the brain, enabling broad delivery of the AAV9 vector to the central nervous system.
ALS is a progressive and ultimately fatal neurodegenerative disorder characterized by the degeneration of motor neurons, leading to progressive muscle weakness, paralysis, and respiratory failure. Current treatments provide only modest benefits, and there remains a significant need for therapies that can modify the underlying disease process.
The KOANEWA study is enrolling patients whose first ALS symptoms began within the past two years, with participants continuing standard-of-care ALS treatments during the trial. All participants will receive the therapy as part of the open-label design.
If successful, CTx1000 could represent a first-in-class AAV gene therapy targeting the core molecular pathology of ALS, potentially offering a disease-modifying approach for a condition that currently has limited therapeutic options.
