CSTI-100 / HBS-102
Overview
In 2021 ConSynance reached an asset purchase agreement with Harmony Biosciences (HMBY) for an early clinical asset, CSTI-100, now renamed HBS-102. Harmony is currently evaluating the potential of HBS-102, a first-in-class MCHR1 antagonist, in a variety of rare neurological areas.
Harmony Biosciences holds the full development and commercialization rights globally, with the exception of Greater China. ConSynance holds the development and commercialization rights in Greater China.
For further information please refer to Harmony’s website: www.harmonybiosciences.com
Mechanism of Action
Tunable & Personalized Dosing
Illustrative representation of CSTI-500 brain occupancy vs plasma concentration at steady state in healthy humans
What does "tunable" mean?
SERT engagement predominates at lower exposures, while DAT and predicted NET engagement increase as exposure rises.
What is the supporting evidence?
Human PK/PET studies established exposure–occupancy relationships for SERT and DAT.
Why does the profile matter?
At lower exposures, CSTI-500 pharmacology is dominated by SERT engagement, modulating serotonin pathways associated with emotional regulation, behavioral flexibility, and compulsivity. As exposure rises, DAT and predicted NET engagement increase, adding modulation of dopamine pathways associated with food-related reward and motivation and norepinephrine pathways associated with arousal and attention.
This concentration-dependent profile provides the rationale for PK-guided dose titration across behavioral and feeding-related symptom domains in PWS. Whether this mechanistic rationale translates into clinical benefit remains to be established in clinical trials.
How is this applied clinically?
In the ongoing U.S. Phase 2 study in PWS, measured plasma concentrations guide dose titration toward predefined target-exposure ranges. Brain occupancy is not directly measured in study participants.
This quantitative approach supports individualized dose selection while safety, tolerability, pharmacokinetics, and preliminary clinical activity are evaluated.
Clinical Development Status
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Generally safe and well-tolerated in Phase 1 studies in healthy volunteers (n = 87)
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Demonstrated CNS target engagement via Positron Emission Tomography (PET) imaging
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Phase 1 in PWS patients completed (n = 10), confirming PK and tolerability in the target population
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Phase 2 clinical trial currently recruiting (NCT07348601)