Praxis Bioresearch Announces Peer-Reviewed Publication of Positive Data for Novel Prodrug Stimulant with Abuse-Deterrent Properties

MENLO PARK, Calif., March 28, 2018 -- Praxis Bioresearch, a biopharmaceutical company focused on the discovery and development of novel therapeutics for chronic neuropsychiatric and neurodegenerative disorders, today announced the peer-reviewed publication of positive results from preclinical studies of the company’s lead product candidate, PRX-P4-003, a prodrug stimulant with abuse deterrent properties.  Published data demonstrate that orally dosed prodrug PRX-P4-003 possesses the established biological activity of stimulants, while pharmacokinetically limiting the intravenous activity in preclinical models.  The findings were published in the journal Drug and Alcohol Dependence under the title “Novel prodrug PRX-P4-003, selectively activated by gut enzymes, may reduce the risk of iatrogenic addiction and abuse.”

PRX­P4­003 is a novel, abuse-deterrent dopamine norepinephrine reuptake inhibitor incorporating an active isomer of fencamfamine (FCF), a well-tolerated Schedule IV stimulant.  Fencamfamine has a long-established clinical profile following decades of therapeutic use in Europe and other countries, where it was primarily prescribed for depressive daytime fatigue, lack of concentration, and lethargy.

Unlike other stimulants, prodrug PRX­P4­003 is specifically designed to produce therapeutic stimulant activity when delivered orally but lack any such activity if illicitly injected for euphoric reasons. This 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.  Intact prodrug PRX-P4-003 lacks any stimulant activity until it is enzymatically metabolized to release the fencamfamine isomer. Translated into humans, this profile may discourage abuse and diversion while providing effective stimulant treatment by the oral route.  Additionally, the prodrug’s inherently delayed activation in the gut until it reaches the small intestine provides an added protective mechanism, minimizing the potential for its oral abuse.

Highlights of the peer-reviewed paper include:

• First demonstration of a gut-selective, lipase-based activation of a prodrug and its potential application in reducing risk of intravenous abuse.
   
• Prodrug PRX-P4-003 is a pharmacologically inactive compound, whereas its parent (-)-FCF is a dopamine reuptake inhibitor with weaker effects on norepinephrine reuptake (Ki = 0.07 & 0.80 µM, respectively).
   
• Once metabolized in the gut of rodents, orally dosed prodrug PRX-P4-003 demonstrated comparable exposure of (-)-FCF, a purified isomer of fencamfamine, as an equal oral dose of unmodified (-)-FCF, which was used as an active control.
   
• PRX-P4-003 demonstrated dose-dependent increase in spontaneous locomotor activity (SLA) in rodents compared to placebo following oral administration, which is the intended delivery route for the prodrug.  Conversely, no increase in SLA compared to placebo was seen following intravenous administration of PRX-P4-003.  This result highlights the potential of Praxis’ prodrug to prevent abuse following intravenous administration.

The published manuscript can be accessed at: https://authors.elsevier.com/a/1Wm311LiD2xqoZ. 

“We are pleased to have our novel research featured in such a highly-regarded journal in the field of substance abuse research as Drug and Alcohol Dependence.  These published findings support that the pharmacokinetic profile of prodrug PRX-P4-003 is uniquely able to offer effective stimulant therapy with a significantly reduced risk of abuse,” said Sandeep Patil, PhD, MD, chief executive officer of Praxis Bioresearch. “We look forward to continuing to advance our PRX-P4-003 program as we work to develop a novel solution that can meet the needs of patients, physicians and the broader healthcare community.”

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) 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, stimulants are classified as Schedule II controlled drugs due to a significantly high risk of addiction. Accordingly, there is a significant unmet need for effective abuse-deterrent stimulant formulations.

About Praxis Bioresearch

Praxis Bioresearch, LLC, is a biopharmaceutical company focused on the discovery and development of therapeutics for chronic neuropsychiatric and neurodegenerative disorders. Praxis’ lead development candidate is PRX-P4-003, a novel prodrug stimulant designed to offer the proven clinical activity of currently marketed stimulants while reducing risk of abuse and addiction.  PRX-P4-003 is being developed for the treatment of binge eating disorder and apathy in Alzheimer’s Disease. For more information visit: www.praxisbioresearch.com.

Contact:
Praxis Bioresearch, LLC 
Sandeep Patil, Chief Executive Officer  
650-491-4347 
[email protected]     

Vida Strategic Partners (On behalf of Praxis)
Tim Brons (media)
646-319-8981
[email protected]