ST-905

Syremis is developing ST-905, a potent M1/M4 preferential muscarinic agonist for the treatment of Schizophrenia.

ST-905 is an investigational drug that has not been previously approved 
for commercial distribution.

Schizophrenia is a chronic and debilitating disorder with onset typically occurring in late-teens / early adulthood. An estimated 2.7 million people live with Schizophrenia in the U.S., and more than 24 million worldwide

It is characterized by positive (psychotic) symptoms including hallucinations, delusions, disorganized speech and behavior, as well as negative symptoms such as diminished emotional expression and inability or lack of energy to engage in routine activities.  Schizophrenia can also lead to some degree of cognitive impairment, including poor executive function and impaired memory and attention.

Despite advancements in treatment, many people with Schizophrenia do not fully respond to their medication: 50% experience only partial improvement in positive symptoms or unacceptable adverse effects​. Current antipsychotic medications treat positive symptoms, but do not treat negative symptoms well.

Scientific aspects

ST-905 targets M1/M4 receptors in the brain: M1 and M4 muscarinic receptors are expressed in brain regions linked to schizophrenia symptoms: the associative and limbic striatum (positive symptoms) and the prefrontal cortex (negative and cognitive symptoms).

Agonism of these receptors modulates neurotransmitters like acetylcholine, dopamine, GABA, and glutamate, potentially improving positive, negative, and cognitive symptoms of schizophrenia.

 

Dual M1/M4 agonism has clinical potential across multiple neuropsychiatric indications and symptom domains.

  • M4 receptors are located at both ends of the mesostriatal dopamine pathways which play a central role in psychosis, and their activation reduces dopamine release.
  • Activating prefrontal cortex M1 receptors is expected to increase dopaminergic activity locally while reducing cortical stimulation of mesostriatal dopamine activity, potentially treating non-positive symptoms and further reducing psychosis.
  • Mechanism of dual agonism of M1/M4 receptors is under development research, with one product being recently approved by FDA for schizophrenia.

 

ST-905 is currently in early stages of clinical development.

 

Paul et al. 2024 Muscarinic Receptor Activators as Novel Treatments for Schizophrenia, Biol Psychiatry. 2024 Mar 25:S0006-3223(24)01173-9.
Yohn et al. 2022 Muscarinic acetylcholine receptors for psychotic disorders: bench-side to clinic, Trends Pharmacol Sci. 2022 Dec;43(12):1098-1112
American Psychiatric Association. (2022). Diagnostic and statistical manual of mental disorders (5th ed., text rev.)
Reid Huber PhD
Partner, Third Rock Ventures

Reid Huber joined Third Rock in 2018 as a Partner, bringing more than 25 years of leadership and experience to the role. He focuses on the formation, development, and strategy of Third Rock’s portfolio companies. Reid served as Interim CEO of MOMA Therapeutics until the appointment of Dr. Asit Parikh in Spring of 2021, of Rapport Therapeutics until the appointment of Abe Ceesay in the Spring of 2023, and of Merida Biosciences until the appointment of Adam Townsend in the Spring of 2025.


Reid joined TRV from Incyte, where he was a member of the founding scientific team and most recently served as executive vice president and chief scientific officer. At Incyte, he held roles of increasing responsibility across multiple therapeutic areas in both drug discovery and clinical development. In 2011, he assumed responsibility for the company’s research and early development activities. Before joining Incyte, Reid held scientific research positions at DuPont Pharmaceuticals and Bristol-Myers Squibb from 1998 to 2002.


He received his Ph.D. in molecular genetics from the Washington University School of Medicine and held predoctoral and postdoctoral fellowships at the National Institutes 
of Health.


Reid is a board director at Rapport Therapeutics, Merida Biosciences, Terremoto, Synnovation Therapeutics, MOMA Therapeutics, Asher Biotherapeutics, and a board observer at insitro.