I3*
MenoFitX - Post-Menopausal Obesity Treatment for Healthy Aging
Dr Lenka Maletinska, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences; Dr Sonia Cantel, University of Montpellier, IBMM, CNRS; Dr Jan Skace, IOCB Tech - PharmTheon; Dr Katarina Psenakova, IOCB Tech - PharmTheon
IOCB Tech
Challenge
Postmenopausal women face a dual burden of obesity and osteoporosis driven by estrogen deficiency and worsened by energy-rich diets. Current anti-obesity therapies fail to address bone marrow adiposity and bone fragility, while osteoporosis treatments do not correct systemic metabolic dysfunction. There is a critical unmet need for mechanism-based therapies that concurrently target adiposity, inflammation, and bone loss, enabling healthy aging in a large and underserved population.
Technology
We are developing non-peptidic small-molecule modulators of a GHSR with high constitutive activity, where inverse agonism suppresses basal signaling independently of ligand levels. Following menopause, declining estrogen levels are associated with increased basal GHSR signaling, driving white adipose tissue (WAT) accumulation, obesity, and expansion of bone marrow adipose tissue (BMAT), which contributes to osteoporosis. Our approach aims to reduce WAT and BMAT, enhance thermogenesis, attenuate inflammation, and indirectly protect bone integrity. Therapeutic efficacy is evaluated in ovariectomized, diet-induced obese (OVX-DIO) mice, a clinically relevant model of postmenopausal obesity and osteoporosis.
Commercial Opportunity
The global markets for obesity, metabolic disease, and osteoporosis exceed USD 100B annually, with postmenopausal women representing a large, underserved patient segment. A proposed first-in-class inverse agonist offering dual metabolic and bone benefits could be positioned as: • a standalone therapy for postmenopausal obesity, • a disease-modifying adjunct to GLP-1–based treatments, • or a differentiated metabolic-bone franchise asset. The small-molecule nature supports oral dosing, scalability, and combination strategies, aligning well with pharma pipelines.
Development Status
• Potent non-peptidic GHSR inverse agonists identified with strong suppression of constitutive receptor activity
• Demonstrated in vitro inverse agonism and ex vivo metabolic effects
• In vivo proof-of-concept for appetite and metabolic modulation established in rodents
• Ongoing/prepared studies: chronic dosing in OVX-DIO mice, with endpoints including body weight, WAT and BMAT biochemical analysis, thermogenesis, metabolic phenotyping, inflammatory markers, and bone pathology
• Lead optimization and translational biomarker strategy in progress
Patent Situation
Patent protection has not yet been filed. The project has identified a novel chemical series of the GPCR target inverse agonists with well-defined structure-activity relationships, providing a strong basis for composition-of-matter and therapeutic-use patent filings. The series is considered patentable, with scope for further optimization and IP expansion prior to filing.
Further Reading
Ali et al., 2022; Hardouin et al., 2016; Kim et al., 2024; Maletínská et al., 2011; Rosen & Bouxsein, 2006
