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LT-NS001

LT-NS001 is the first in a family of bio-activated NSAID prodrugs. LT-NS001 is being developed to improve GI tolerability and reduce the risk of gastric ulcers in patients who require regular use of an NSAID for the treatment of diseases such as rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. LT-NS001 is pharmacologically inactive as an NSAID in the GI tract, but once absorbed into the bloodstream, it is converted rapidly and quantitatively to naproxen. Bio-activated Prodrugs are new chemical entities (NCEs) that are bio-reversible derivatives of well-known drugs.  By moving the site of activation of the drug away from the GI tract, the prodrug mitigates much of the GI injury associated with traditional NSAIDs.

 

The key clinical findings from the LT-NS001 Clinical Development Program vs Naprosyn® (naproxen):

• Endoscopy:  Relative reduction of risk for Gastric ulcer
• Knee OA Pain:  major reduction from WOMAC baseline equivalent to naproxen
• Retention on drug:  fewer withdrawaals for GI AEs than naproxen
• Tolerability:  significantly fewer episodes of moderate/severe abdominal pain
• GI Safety - only adjudicated lower GI bleed and symptomatic ulcer in naproxen pts
• Equivalent naproxen exposure at steady state vs Naprosyn 500 mg
• Less peak-to-trough fluctuation, with more patients remaining above 50 ug/mL (therapeutic threshold)
• Extremely low (ng/mL) and rare exposure to parent compound, naproxen etemesil

Clinical Development Summary

In a Phase I / II double-blind, randomized, active comparator study of LT-NS001 vs. naproxen, in volunteers 45 to 70 years of age, subjects receiving LT-NS001 experienced a significant reduction in the rate of gastric ulcers, and fewer gastric and duodenal erosions, when compared with subjects receiving Naprosyn® (naproxen).   Overall, subjects in the naproxen arm had 29 total ulcers, while only 3 ulcers were seen in the LT-NS001 arm.  Importantly, subjects dosed with LT-NS001 or naproxen twice daily for seven days had plasma concentrations of naproxen that were not different. These clinical studies confirm pre-clinical findings in rats and dogs, where LT-NS001 caused significantly less damage to the upper and lower gastrointestinal tract than equimolar doses of naproxen.

 

In 1Q2011, the Company completed a Phase 2b double-blind, double-dummy, active-comparator study of LT-NS001 versus Naprosyn®® for 12 weeks in patients aged 45-80 with osteoarthritis of the knee who are appropriate candidates for ongoing NSAID therapy.   The study confirmed that LT-NS001 (naproxen etemesil) has meaningful differences in GI toxicity vs Naprosyn®, and more over, that the product may offer highly significant safety improvements, including improved GI tolerability, for specific patient populations.

The Company is currently considering options for Phase 3 and commercial development that include a potential business transaction.  Interested partners should contact the Company's business development team.