TerXT is a combination of xanomeline and trospium prodrugs for the treatment of schizophrenia, and intends to pursue accelerated 505(b)(2) approval pathway
Miami, FL – May 20, 2024 – Terran Biosciences Inc. (“Terran”), a biotech platform company developing therapeutics and technologies for patients with neuropsychiatric illnesses, has announced the development of TerXT, a combination of novel prodrugs of xanomeline and trospium designed to be long-acting treatments for schizophrenia. Terran has received notice of patent claims found to be allowable from the United States Patent and Trademark Office (USPTO) for the composition of matter for the world’s first prodrugs of xanomeline.
To develop TerXT, Terran sought to overcome inherent pharmacokinetic and physical property limitations of the compounds xanomeline and trospium, such as poor colonic absorption and high aqueous solubility, by utilizing a novel prodrug strategy. These prodrugs were designed to enable fixed-dose combinations for once-daily oral administration (“TerXT”) and long-acting intramuscular injection with multi-month duration (“TerXT LAI”). These new forms could potentially allow Terran to pursue accelerated development and regulatory strategies such as the FDA 505(b)(2) approval pathway.
Recent clinical trials of an oral, twice-daily, fixed-dose combination of xanomeline, a compound invented in the 1990s, and trospium, invented in the 1960s, have demonstrated safety and efficacy in treating schizophrenia. This combination has been submitted to the FDA for approval on the 505(b)(1) path and is currently undergoing FDA review, with a decision expected by September this year. If the FDA approves the xanomeline/trospium combination, Terran plans to pursue the rapid 505(b)(2) approval pathway for TerXT and TerXT LAI. This regulatory pathway could potentially enable Terran to use pharmacokinetic bridging studies and leverage existing safety and efficacy data from completed trials to bring Terran’s next-generation therapeutics to market approximately five years after the first xanomeline/trospium approval, helping to broaden access for patients, improve the use profile, and increase affordability.
In order to successfully overcome the pharmacokinetic limitations of xanomeline and trospium, Terran assembled a team of the world’s experts in medicinal chemistry, resulting in over 10,000 new prodrugs designs. Terran’s PK modeling team developed a predictive model of both xanomeline and trospium across a vast spectrum of different formulation designs and release profiles to determine the optimal pharmacokinetic parameters and ratios. Terran utilized a team of 200 chemists to synthesize over 500 prodrugs, which then underwent preclinical testing, including 285 in vitro and 365 in vivo studies.
“We’ve seen the prodrug approach significantly improve long-acting formulations of some of the most effective antipsychotics to date, including Aristada®, Haldol® Decanoate, and Invega Hafyera®, to the great benefit of patients,” said Sam Clark, MD, PhD, Terran’s founder and CEO, and inventor on the patent. “However, these improved forms were not developed until many years after the original compounds were first approved; in some cases, decades later. At Terran, we believe patients shouldn’t have to wait for the latest technology and we believe that our prodrugs of xanomeline and trospium will enable improvements in ease of use and quality of life on a much more rapid timescale than has historically been achieved.”
Terran Biosciences is a biotech platform company developing a portfolio of therapeutics and technologies for patients with neurological and psychiatric diseases. Terran has built a CNS-focused, tech-enabled drug development platform and is rapidly advancing a number of assets that include late-stage therapeutics for schizophrenia, an FDA-cleared neuroimaging software platform, and a drug design engine that has generated first-in-class and best-in-class psychedelic-based therapeutics and novel prodrugs optimized for patient use. Follow us on LinkedIn and X.