Tris Pharma Announces Development of a Very Low Sodium and Once-Nightly Oxybate Formulation

• First oxybate product to provide both once a night dosing and very low sodium
• Novel formulation developed using Tris's proprietary RaftWorks™ and LiquiXR® Technology

MONMOUTH JUNCTION, N.J., July 27, 2022 /PRNewswire/ -- Tris Pharma, Inc. ("Tris"), a fully integrated pharmaceutical company with a robust portfolio of CNS products announced today that it has successfully developed an oxybate formulation for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy that has the potential to be significantly advantageous to existing approved therapies, such as Jazz Pharmaceuticals' blockbuster XYWAV® and XYREM® franchise. The Tris oxybate formulation is believed to provide an advantage over approved therapies by utilizing Tris's proprietary LiquiXR technology platform and our newly developed RaftWorks design to provide a unique oxybate formulation offering both once-nightly dosing, and very low sodium content. The Tris oxybate formulation is investigational and not yet approved by any regulatory agency.

Both XYWAV® and XYREM® require twice a night dosing – once at bedtime and again 2.5 to 4 hours later for the second dose. Further, XYREM contains an express warning based on its high sodium content and associated risk to patients with heart failure, hypertension or impaired renal function. The Tris oxybate formulation seeks to improve on existing therapies by providing convenient once per night dosing, and significantly reduced sodium content such that it will contain less than 100 mg of sodium per 9.0 gm of maximum sodium oxybate equivalent dose. Based on the significant potential advantage the Tris oxybate formulation could provide over existing available therapies, Tris is pursuing an Orphan Drug Designation for its unique oxybate formulation.

In a human clinical study, Tris established about 100% bioavailability for one dose of its formulation against two doses of XYREM at 4.5 gm each, equivalent to the 9.0 gm maximum dose of sodium oxybate. If approved, the Tris product will provide significant advantages in that patients will not have to wake up in the middle of the night to take a second dose and will have all the benefits of a very low sodium product.

The Tris oxybate product achieved its clinical objectives by combining two distinct proprietary Tris technologies: the LiquiXR platform, and the newly developed RaftWorks design. Working together, these unique formulation platforms provide an interpenetrating network raft in-situ, in which sodium-free drug particles are entrapped in a raft that allows for extended release of the active ingredient. Many drugs, such as oxybate, are poorly absorbed because they have a narrow window of absorption within the human gastro-intestinal tract. The RaftWorks approach permits a slow and extended release of oxybate from a floating raft in-situ, thereby facilitating absorption of the active ingredient within the targeted area in the gastro-intestinal tract. Further, the raft disintegrates at a predetermined time due to the trigger mechanism that is built into the formulation.

"This unique formulation design by Tris scientists potentially achieves drug delivery capabilities that have never previously been achieved within our industry", said Ketan Mehta, Founder and Chief Executive Officer of Tris. "We are looking to build on this approach and develop extended-release formulations for other drugs that are limited by their narrow window of absorption."

Narcolepsy, a chronic and disabling neurological disorder that affects the stability of sleep and wakefulness, is characterized primarily by excessive daytime sleepiness, with or without episodic loss of muscle tone usually triggered by strong emotions during wakefulness (cataplexy) ^1-4. Additional symptoms can vary by person and may include disrupted nighttime sleep, and REM-sleep phenomena (sleep paralysis, hallucinations). The exact number of individuals with narcolepsy in the United States is unknown. Several studies have estimated the prevalence of narcolepsy in the United States to be approximately 1 (range: 0.6 to 1.6) in 2,000 people ^2,4-6. There is currently no cure for narcolepsy; treatment of symptoms includes medications and lifestyle modifications ¹. 

Tris is a fully integrated, innovation-driven CNS company that provides a differentiated approach to target unmet medical needs, including the application of novel technologies designed to enhance patient benefits across therapeutic categories. Tris's CNS portfolio includes treatments for pain; addiction; spasticity in multiple sclerosis, cerebral palsy; narcolepsy; and ADHD. For more information, please visit www.trispharma.com and www.trismedical.com.

1. Barker EC, Flygare J, Paruthi S, Sharkey KM. Living with Narcolepsy: Current Management Strategies, Future Prospects, and Overlooked Real-Life Concerns. Nat Sci Sleep. 2020;12:453-466. doi:10.2147/NSS.S162762
2. Longstreth WT, Jr., Ton TG, Koepsell T, Gersuk VH, Hendrickson A, Velde S. Prevalence of narcolepsy in King County, Washington, USA. Sleep Med. Apr 2009;10(4):422-6. doi:10.1016/j.sleep.2008.05.009
3. Medicine AAoS. International Classification of Sleep Disorders. 3rd ed.
4. Scheer D, Schwartz SW, Parr M, Zgibor J, Sanchez-Anguiano A, Rajaram L. Prevalence and incidence of narcolepsy in a US health care claims database, 2008-2010. Sleep. Jul 8 2019;42(7)doi:10.1093/sleep/zsz091
5. Acquavella J, Mehra R, Bron M, Suomi JM, Hess GP. Prevalence of narcolepsy and other sleep disorders and frequency of diagnostic tests from 2013-2016 in insured patients actively seeking care. J Clin Sleep Med. Aug 15 2020;16(8):1255-1263. doi:10.5664/jcsm.8482
6. Silber MH, Krahn LE, Olson EJ, Pankratz VS. The epidemiology of narcolepsy in Olmsted County, Minnesota: a population-based study. Sleep. Mar 15 2002;25(2):197-202. doi:10.1093/sleep/25.2.197

Both Xyrem® and Xywav® are registered trademarks of Jazz Pharmaceuticals. LiquiXR® is a registered trademark of Tris Pharma.

SOURCE Tris Pharma, Inc.