Phase II Ready Assets

CSTI-500 is an oral, once-per-day serotonin, dopamine and norepinephrine reuptake inhibitor (“TRI”). It is under development for the treatment of hyperphagia in PWS, and for hypothalamic-injury induced obesity. CSTI-500 addresses the dysregulated neurotransmission in the key brain centers in PWS and hypothalamic injury-induced obesity. It is an optimally balanced triple reuptake inhibitor with unique pharmacological features that allow for predictable and safe titration to an efficacious dose tailored to the individual patient. CSTI-500 has the potential to provide a transformative therapy, not only for hyperphagia and obesity but also for many of the psychiatric co-morbidities in both diseases.

CSTI-500 was generally safe and well-tolerated and has a half-life of 50 hours in Phase I clinical trials. Also importantly, it demonstrated CNS target engagement via positron emission tomography (PET) that predicts efficacy in patients.


ConSynance holds the exclusive global rights to CSTI-500.

CSTI-100 is an oral, once-per-day, selective melanin-concentrating hormone receptor 1 (MCHR1) antagonist. MCH is a neuropeptide with a number of important physiological functions including regulating feeding behavior and sleep through the MCHR1 receptors in the brain. Orexin and MCH are the “Ying-Yang” in wake-sleep regulation. The orexin neurons fire during wakefulness and MCH neurons fire during REM sleep. The reciprocal firing patterns of orexin and MCH neuronal populations suggests a reciprocal inhibition. In narcolepsy Type I, or narcolepsy with cataplexy, orexin neurons are lost, so MCH firing is unopposed. Blocking MCH is a novel mode of action that gets to the fundamental aspect of narcolepsy previously untouched - the balance between MCH and orexin signaling. Preclinical study of an MCH antagonist SNAP 94847 in a translational narcolepsy type I model, the orexin knock-out mouse model, showed complete elimination of cataplexy, see


CSTI-100 was found to be safe and well-tolerated in Phase I studies with a 26-hour half-life. 


ConSynance holds the exclusive global rights to CSTI-100 which was discovered and developed by AMRI.