Klotho Neurosciences, Inc. (NASDAQ: KLTO) announced it is advancing manufacturing and process development for KLTO-202, its investigational gene therapy for amyotrophic lateral sclerosis (ALS). The company has licensed a unique RNA splice variant of the human alpha-Klotho gene from the Autonomous University of Barcelona, including patents and intellectual properties for developing advanced gene and cell therapies.
Novel Therapeutic Approach
The therapy targets secreted alpha-Klotho (s-KL), a protein isoform found primarily in brain and spinal cord neurons. Unlike the full-length membrane-bound Klotho protein that controls phosphate homeostasis in kidney cells, s-KL provides neuroprotective effects by minimizing oxidative stress and neuroinflammation.
Animal studies conducted over the past two years in mouse and non-human primate models have demonstrated promising results. The research, spanning models of rapid aging, Alzheimer's disease, and ALS, showed that over-expression and amplification of s-KL tissue levels using gene therapy resulted in highly favorable therapeutic outcomes across all tested models. These findings have been published in peer-reviewed scientific journals, supporting the transition to clinical development.
Manufacturing and Clinical Timeline
Klotho Neurosciences expects to complete process development and manufacturing of KLTO-202 within approximately eight months. The company plans to spend an additional four to six months conducting FDA meetings, completing mandated animal safety studies, filing an investigational new drug application (IND), and preparing clinical sites for Phase I/II studies.
Dr. Joseph Sinkule, the company's CEO and founder, stated: "With our recent fundraising success, we're moving forward with manufacturing the s-KL transgene DNA for KLTO-202. We've identified a more efficient method of producing the AAV vector to deliver the s-KL gene directly to motor neurons—the cells most affected by ALS. Our goal is to increase local s-KL protein levels to protect these neurons from the damage that leads to voluntary and involuntary muscle paralysis and ultimately death."
Addressing Critical Medical Need
ALS represents a significant unmet medical need, with the disease typically progressing rapidly. Most patients lose mobility, respiratory function, and life within just 2-3 years of diagnosis. The company's approach targets motor neurons directly, which are the primary cells affected by ALS.
Klotho Neurosciences plans to initiate single-dose gene therapy studies in ALS patients by the third quarter of next year. The company will collaborate with contract research organizations (CROs) to facilitate manufacturing and clinical trial activities while maintaining operational efficiency.
Company Focus
Klotho Neurosciences is a biogenetics company developing disease-modifying cell and gene therapies using proteins derived from the patented "anti-aging" human Klotho gene. The company's portfolio includes proprietary cell and gene therapy programs using DNA and RNA as therapeutics, along with genomics-based diagnostic assays for treating neurodegenerative and age-related disorders including ALS, Alzheimer's, and Parkinson's disease.
