Palisades Therapeutics’ PT150 Emerges as First‑in‑Class 'Metabolic Setpoint Modifier' to Lock In GLP‑1 Weight Loss

Ph 2-ready oral PT150 reduces post semaglutide weight regain in preclinical models with no meaningful drug interaction risk, enabling rapid combination trials

CLIFFSIDE PARK, NJ, UNITED STATES, April 9, 2026 /EINPresswire.com/ -- Pop Test Oncology LLC, operating as Palisades Therapeutics, today announced the posting to bioRxiv of a preclinical study showing that the investigational Ph2-oral therapeutic PT150 reduces weight regain after GLP-1 treatment.

Selective glucocorticoid receptor modulator PT150, combined with semaglutide, reduces weight rebound in obesity models without added safety or drug-drug interaction concerns, supporting immediate progression to Phase 2 trials. These findings highlight a potential new strategy to help patients keep weight off after stopping GLP-1 injections, a major unmet need in current obesity care.

The new manuscript on bioRxiv describes how the selective glucocorticoid receptor antagonist PT150, when combined with the GLP‑1 receptor agonist semaglutide, markedly reduced post‑treatment weight regain in diet‑induced obesity mouse models compared with semaglutide alone. The findings support PT150 as a first‑in‑class “metabolic setpoint modifier” designed to be given as a short‑course adjunct at the end of GLP‑1 therapy to stabilize body‑weight regulation.

In the study, diet‑induced obese mice received four weeks of treatment with vehicle, PT150, semaglutide, or the PT150–semaglutide combination, followed by a 20-day drug‑free washout period. Animals treated with PT150 plus semaglutide experienced robust weight loss during active treatment comparable to controls, but showed significantly less weight regain after treatment cessation. The combination did not produce sustained differences in cumulative food intake or pancreatic immune‑cell infiltration, suggesting a central, setpoint‑related mechanism rather than simple appetite suppression..

The preprint is available on bioRxiv at this link: https://www.biorxiv.org/content/10.64898/2026.04.06.712688v1

“GLP‑1 drugs have transformed obesity care, but once treatment stops, many patients see the weight start to come back,” said Dr. Mehboob A. Hussain, a board-certified UCI Health endocrinologist who specializes in diabetes, metabolic disorders and diseases of the endocrine system. “The GLP‑1 era has shown that people will understandably do almost anything to feel better about their weight and health. Our goal is to support those efforts with approaches that respect both biology and long term well being. However, the field has focused on goals that don’t necessarily protect patients from the metabolic snap‑back that follows discontinuation of GLP-1 medications. PT150 opens the next chapter in this by helping the brain defend a healthier body‑weight setpoint.”

Principal investigator perspective

The bioRxiv manuscript is led by Estefania P. Azevedo, PhD, Assistant Professor of Neuroscience at the Medical University of South Carolina and principal investigator of the study. Dr. Azevedo’s laboratory focuses on the neurobiology of behavior, stress, and energy balance, providing a translational framework for testing PT150 as a modulator of hypothalamic circuits that govern defended body‑weight setpoint.

“We designed this study to ask a very simple but clinically relevant question: can we make GLP‑1 weight loss stick after the injections stop?” said Dr. Azevedo. “Our preclinical data suggest that short‑course PT150, layered on top of semaglutide, helps animals maintain much more of their weight loss during washout without obvious safety trade‑offs. The next step is to test whether this ‘setpoint‑support’ strategy translates to people living with obesity.”

Clean drug-drug interaction profile and Phase 2‑ready status

PT150 is a selective glucocorticoid receptor modulator with an extensive clinical safety database across Phase I and Phase II studies in other indications, including more than 900 subjects treated at doses up to 900 mg per day for up to four weeks. A recently updated clinical interaction report concludes that no clinically meaningful pharmacokinetic or pharmacodynamic drug-drug interactions are expected between PT150 and GLP‑1 agonists such as semaglutide, tirzepatide, or liraglutide. The assessment is supported by:

• Non‑overlapping metabolic pathways for PT150 (CYP‑mediated) and GLP‑1 agonists (proteolytic clearance rather than CYP metabolism).
• A human “cocktail” study demonstrating minimal in‑vivo inhibition across six major CYP isoforms and P‑gp at the maximum planned clinical dose of PT150.
• Two dedicated Phase I ethanol interaction studies showing no significant changes in PT150 or ethanol pharmacokinetics, vital signs, ECGs, or safety parameters during co‑administration.

Based on these data, Palisades Therapeutics considers oral dosed-PT150 Phase 2‑ready for use as adjunctive therapy initiated shortly after GLP‑1 discontinuation in patients with obesity. In parallel, the company is advancing PT157, a rationally designed dimer within the same PT platform, intended to extend intellectual‑property life and potentially further optimize pharmacokinetics and clinical durability in future studies. Together, PT150 and PT157 form the core of Palisades Therapeutics’ PT platform, aimed at delivering durable, physiology based weight maintenance solutions after GLP-1 therapy.

Intellectual property and exclusivity

PT150 and its dimer PT157 are protected by issued and pending composition‑of‑matter and method‑of‑use patents across the United States and key ex‑US markets, with coverage extending into the 2040s.

We are actively seeking strategic pharmaceutical partners to advance PT150 and PT157 into combination development and registrational programs. We welcome licensing discussions, combination‑collaboration inquiries, and data‑package requests from‑focused BD and clinical teams - please reach out to Randi@PopTestLLC.com.

We are particularly interested in partnering with leading global organizations to accelerate PT150/PT157 into registration‑enabling programs.

@Pfizer @Bristol Myers Squibb @Astellas Pharma @AstraZeneca @Johnson & Johnson @Novo Nordisk @Eli Lilly and Company

#obesity, #weightloss, #biotech, #GLP1

Forward‑Looking Statements
This press release contains forward‑looking statements regarding the development of PT150 and PT157. PT150 and PT157 have not been approved by any regulatory authority.

Randi Altschul
Pop Test Oncology/Palisades Therapeutics
randi@poptestllc.com
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