Advancing novel medicines for psychiatric and neurodegenerative conditions
Schizophrenia treatment still forces a tradeoff between efficacy and tolerability.
Most approved antipsychotics still work primarily through dopamine receptor blockade, a mechanism first identified decades ago. For many people living with schizophrenia, that approach falls short — whether through incomplete control of symptoms, limited impact on negative and cognitive symptoms, or side effects that make long-term treatment difficult to sustain.
Muscarinic agonism has re-emerged as a genuinely new mechanism of action for schizophrenia. But first-generation muscarinic approaches activate receptors broadly across the body, and peripheral cholinergic effects — most notably gastrointestinal discomfort — remain a real barrier to adherence and long-term use.
We think the next generation of muscarinic medicines needs to be engineered from the ground up for receptor selectivity and targeted delivery, not adapted after the fact.
Titration and food constraints
Current muscarinic therapy requires a staged dose-escalation schedule, and BID dosing without food. This delays time to therapeutic effect and adds early-treatment complexity for patients and prescribers.
Cholinergic side effects drive discontinuation
Nausea, vomiting, and GI upset are common enough that a peripheral anticholinergic (trospium) co-therapy is layered on — adding dosing complexities and adverse event burden.
Adherence
Tolerable, easily taken medicines are what make sustained treatment possible for patients and caregivers.
A structurally differentiated approach to muscarinic agonism
Three design principles guide our chemistry and our lead program, AN-113.
Receptor Selectivity
Compounds engineered for greater selectivity toward CNS-relevant muscarinic receptor subtypes, aiming to preserve central efficacy while reducing off-target activity and the need for peripheral blockade.
Targeted CNS Delivery
Materially improved DMPK properties to allow for increased receptor interaction in the brain with the potential for lower dose requirements.
Durable Receptor Engagement
Structurally optimized chemistry intended to support sustained target engagement, guided by structure-activity work across our chemical series.
AN-113 is in preclinical development. These statements describe our research approach and have not been evaluated in human clinical trials.
Company updates
Annulus Therapeutics to attend RESI Conference in Boston, MA.
Annulus Therapeutics to attend Psych Congress in New Orleans, LA.
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We're building the next generation of centrally-selective muscarinic therapeutics. Get in touch to learn more.