July 2,2020

Praxis Bioresearch has been issued a new patent (US Patent 10,662,146) by the United States Patent and Trademark Office covering pharmaceutical compositions comprising fencamfamine prodrug derivatives. The patent will remain in effect until September 13, 2036. Separately, the company confirmed that it has successfully completed the key milestones of a Fast-Track Small Business Innovation Research (SBIR) grant. As a next step, it is preparing to file for an exploratory IND application for a Phase 0 “proof-of-concept” in healthy volunteers of its novel gastrointestinally-activated prodrug PRX-P4-003.

PRX-P4-003 is a new chemical entity (NCE) that incorporates an active isomer of fencamfamine, a well-tolerated Schedule IV stimulant.  Fencamfamine has a long-established clinical profile following decades of therapeutic use in Europe and other countries. PRX-P4-003 is specifically designed to deliver fencamfamine isomer selectively by the oral route. Thus, limiting its stimulant activity to oral administration and differentiating it from other marketed stimulants. The profile is made possible due to PRX-P4-003 serving as a substrate of pancreatic lipase, an enzyme whose biological activity is almost entirely restricted to the gut.

“Translated into humans, PRX-P4-003 offers a lower risk stimulant alternative that is primarily active orally and has a “built-in” pharmacokinetic barrier to abuse and diversion if attempted use by injection.” said Valentino J. Stella, distinguished professor emeritus, department of pharmaceutical chemistry at the University of Kansas and co-inventor of PRX-P4-003. “Even though the dopaminergic activity is still present orally it represents a significantly reduced risk of abuse due to favorable oral pharmacokinetics. To my knowledge, this remains the only prodrug that utilizes a gut-specific pancreatic lipase approach to limit intravenous activation by taking advantage of its asymmetric metabolism/pharmacokinetics.”

Previously, PRX-P4-003 data were presented at the annual meeting of the American College of Neuropsychopharmacology and published in the journal Drug and Alcohol Dependence. Orally dosed prodrug PRX-P4-003 possesses the established biological activity of stimulants, while pharmacokinetically limiting the potential for IV abuse in preclinical models.  Praxis plans to develop the prodrug for underserved medical needs in binge eating disorder as well as apathy in Alzheimer’s disease.

“We believe that Prodrug PRX-P4-003 mechanism elegantly taps into proven therapeutic benefit of stimulant activity with a significantly reduced abuse risk,” said Sandeep Patil, PhD, MD, chief executive officer of Praxis Bioresearch. “This is the latest accomplishment under the scientific leadership of Professor Stella, a world-recognized prodrug expert and a prolific inventor of many significant products including the solubilizer Captisol?, a key ingredient for remdesivir therapy in patients suffering from COVID-19 complications. We could not be more proud to work with such an exceptional team of core scientists.” 

Stimulants such as methylphenidate and amphetamines are among the most widely prescribed classes of medications, with an estimated 90 million annual prescriptions written for a range of central nervous system conditions including attention deficit hyperactivity disorder (ADHD), narcolepsy, and binge eating disorder. According to a report issued by Persistence Market Research, the stimulant market for ADHD alone is expected to grow to $25 billion annually in 2024. However, these two stimulants are classified as Schedule II controlled drugs due to a significantly high risk of addiction.