Terran Biosciences Develops TerXT for Schizophrenia, Seeks Accelerated Approval

Terran Biosciences Inc., a biotech firm specializing in treatments for neuropsychiatric conditions, has introduced TerXT—a novel combination of prodrugs of xanomeline and trospium. These prodrugs are crafted to provide long-acting solutions for schizophrenia. Terran has also received notice from the United States Patent and Trademark Office (USPTO) confirming the patentability of these new compounds.

In its effort to develop TerXT, Terran tackled the inherent pharmacokinetic and physical limitations associated with xanomeline and trospium. Issues such as poor colonic absorption and high aqueous solubility were addressed through a groundbreaking prodrug strategy. The result is TerXT, which supports fixed-dose combinations for once-daily oral intake and long-acting intramuscular injections lasting for several months. This innovation enables Terran to pursue accelerated development and regulatory pathways, including the FDA's 505(b)(2) approval route.

Recent clinical trials of a twice-daily, fixed-dose oral combination of xanomeline (developed in the 1990s) and trospium (from the 1960s) have shown promising results in treating schizophrenia. This combination has been submitted to the FDA under the 505(b)(1) approval process and is currently under review, with a decision anticipated by September. Should the FDA approve this combination, Terran aims to expedite the approval process for TerXT and its long-acting variant through the 505(b)(2) pathway. This could significantly shorten the timeline for bringing these next-generation treatments to market, potentially within five years, leveraging pharmacokinetic bridging studies and existing clinical data to enhance patient access, usability, and affordability.

To overcome the pharmacokinetic challenges of xanomeline and trospium, Terran assembled a team of leading experts in medicinal chemistry. This effort led to the creation of over 10,000 new prodrug designs. Terran's pharmacokinetic modeling team developed a comprehensive predictive model to determine the optimal formulations and release profiles for these compounds. The team synthesized over 500 prodrugs, which then underwent extensive preclinical testing, including 285 in vitro and 365 in vivo studies.

Sam Clark, MD, PhD, founder and CEO of Terran, emphasized the significance of this prodrug approach. He noted that while long-acting formulations of antipsychotics like Aristada®, Haldol® Decanoate, and Invega Hafyera® have greatly benefited patients, these advancements often came many years—sometimes decades—after the initial compounds were approved. Terran aims to accelerate this timeline, ensuring that patients gain quicker access to improved treatments.

Terran Biosciences is focused on developing a range of therapeutics and technologies targeting neurological and psychiatric disorders. The company has built a tech-enabled drug development platform centered on central nervous system (CNS) diseases. This platform includes late-stage therapeutics for schizophrenia, an FDA-cleared neuroimaging software tool, and a drug design engine that has produced cutting-edge psychedelic-based treatments and innovative prodrugs optimized for patient use.