FDA Grants Orphan Drug Designation to KLTO-202 Gene Therapy for ALS Treatment

The FDA has granted orphan drug designation to Klotho Neurosciences’ experimental gene therapy candidate, KLTO‑202, for the treatment of amyotrophic lateral sclerosis (ALS).

Orphan drug designation is intended to encourage the development of therapies for rare diseases affecting fewer than 200,000 people in the U.S. The designation provides benefits including exemption from certain fees, tax credits for clinical trials, and seven years of market exclusivity if the therapy is approved.

“Receiving the orphan drug designation for [KLTO‑202] for the early treatment of ALS underscores the importance of bringing new treatment options to patients suffering from this rare, universally fatal disease,” Joseph Sinkule, Klotho’s CEO, said in a company press release.

KLTO‑202 is designed to protect nerve cells by delivering the genetic instructions for producing secreted alpha-Klotho (s-KL), a protein found at reduced levels in the muscles and spinal cord of ALS mouse models. This protein is thought to lower inflammation and oxidative stress (an imbalance between the production and clearance of harmful oxygen-containing molecules).

The therapy uses an adeno-associated virus (AAV) vector—modified to be harmless—to deliver the gene encoding s-KL. The gene is engineered to be active primarily in neuromuscular junctions, where nerves and muscles interact. This targeted delivery is intended to promote muscle repair or regeneration (myoregenerative properties), potentially addressing muscle weakening caused by nerve cell loss.

In preclinical ALS models, gene therapy delivering s-KL has shown several therapeutic effects, including:

• Reduced inflammation
• Improved muscle strength and coordination
• Delayed symptom onset and progression
• Extended survival

Klotho Neurosciences is completing studies assessing KLTO‑202 in two animal models of ALS and has initiated manufacturing of the therapy. The company says they are preparing for discussions with U.S. and European regulatory agencies regarding the clinical development pathway, with plans to begin a first-in-human, single-dose trial for ALS patients by the third quarter of next year.