High-Throughput Phenotypic Drug Discovery
SmartCube® is a cutting-edge automated testing platform that guides mice through a series of challenges using custom hardware, integrating computer vision and artificial intelligence (AI) to extract behavioral and physiological insights. This system boasts several advantages over conventional behavioral testing methods, including:
- High-Throughput: Capable of screening tens of thousands of compounds for CNS activity, pinpointing those with phenotypic profiles reminiscent of effective treatments for neuropsychiatric disorders.
- High-Content: Collects millions of data points and thousands of features, leveraging proprietary machine learning algorithms to identify subtle phenotypic distinctions often imperceptible through standard tests.
- Unbiased: Utilizes computer vision and AI to eliminate human intervention and associated subjectivity.
Accelerating Drug Discovery
SmartCube® collects millions of data points per mouse per session, which get distilled to around 2,000 features. Machine learning classifiers that define broad classes and subclasses of marketed drugs treating a spectrum of debilitating mental illnesses have been created so that when novel compounds are screened, SmartCube® algorithms can make predictions about therapeutic utility.
SmartCube® offers various discovery approaches, from repurposing, compound screening, combination testing, and lead optimization, to whole library screening. Screening diverse chemical libraries through a target-agnostic lens has been a particularly fruitful approach.
By screening diverse libraries, PsychoGenics has amassed thousands of behaviorally active compounds, potential starting points for new discovery programs. The discovery process typically begins by seeking compound hits with desired signatures and other features. For example, a project may focus on finding compounds with antidepressant signatures that resemble certain psychedelic compounds but are devoid of 5HT2a activity.
For schizophrenia, we worked with Sumitomo Pharma to find an antipsychotic devoid of dopamine D2 receptor activity. The process began by screening a library in SmartCube® to identify compounds that resemble antipsychotics, followed by an in vitro screen to identify those compounds without dopamine D2 activity. This approach led to the discovery of ulotaront in phase III clinical trials for schizophrenia, depression, and anxiety.
This approach is highly efficient, with a potential clinical candidate often identified after screening fewer than 300 compounds in lead optimization — only a fraction of the compounds typically tested in a target-based approach. Consequently, this approach accelerates drug discovery timelines and substantially reduces costs.
Partnering with PsychoGenics
At PsychoGenics, we employ our Cube platforms with novel diverse chemical libraries to discover improved treatments for severely disabling neuropsychiatric disorders. In our quest for novel and improved treatments, we form strategic partnerships with biopharmaceutical companies. Through these collaborations, we provide access to SmartCube® and our other Cube platforms, or license our groundbreaking discoveries, to those who share our vision of a brighter tomorrow for those struggling with mental illness.
