Our Science
CURE-PROs: Next Generation Protein Degraders
A Proprietary Solution to Address the Limitations of First-Generation Targeted Protein Degraders
Targeted Protein Degradation (TPD) is a rapidly emerging field of drug development exploiting a cell’s own destruction machinery to tackle disease-causing proteins that have historically been undruggable or highly challenging to target with conventional therapies. TPD therapies are designed to eliminate (rather than temporarily interrupt) target proteins. However, several significant limitations have emerged with first generation TPDs, primarily that they are large & complex, with challenging drug-like properties (high molecular weight, poor solubility, low permeability, difficulty to deliver orally, difficulty crossing the blood brain barrier). Furthermore, the E3 ligase partners used in early TPDs have been restricted to two out of >600, limiting potential targets.
Based on over 10 years of research in Professor Francis Barany’s lab at Weill Cornell Medicine, Chiara is pioneering an approach to revolutionize TPDs usings its novel, differentiated, and proprietary platform. CURE-PROs (Combinatorial Ubiquitination REal-time PROteolysis ) are small-molecule degraders designed to self-assemble inside cells using proprietary linker chemistry.
CURE-PROs address the limitations of first-generation TPDs in multiple ways:
2-3X smaller than PROTACs: they can easily enter target cells/tissues, be administered orally, and penetrate the central nervous system
They do not exhibit the “hook effect”: resulting in larger therapeutic windows
Expands E3 ligase partners: Their smaller size enables Chiara to add many more E3 ligase partners, exponentially expanding the number of CURE-PRO combinations.
Rational Design: They are relatively easy, fast, and cost-effective to design and synthesize.
Discovery & Screening Platform
Chiara has developed a unique high-throughput TPD platform: reusable libraries of target protein engagers and E3 ligase engagers. With this platform, CURE-PROs can be combined to create exponentially greater numbers of pairs, allowing for the rapid and simultaneous identification of hits. As an example, combining 100 target protein engagers and 100 E3 ligase partners will enable testing of 10,000 CURE-PRO pairs in one experiment, making this highly capital efficient and ultra-rapid to identify potential lead pairs.
Our platform is being used to develop Chiara’s own internal pipeline and can be used by in collaboration with others for strategic design of CURE-PROs against targets of choice.
Pipeline
We are advancing a pipeline of diverse and promising therapeutic candidates in areas of high unmet need where protein degradation has the potential to provide transformative results.
| Program | Target Identification | Discovery | Preclinical | Early Clinical | |
|---|---|---|---|---|---|
| Oncology | Multiple Undisclosed Targets | ||||
| Other Disease Areas | Undisclosed | ||||
| Platform Development | Novel E3 ligases | ||||