Kymera Therapeutics

Our Powerful Engine to Naturally Destroy Disease-Causing Proteins

Protein degradation is a natural process by which our body’s cellular machinery – the ubiquitin proteasome system (UPS) – breaks down or degrades unwanted proteins. The UPS comprises a series of finely orchestrated sequences involving critical enzymes called E3 ubiquitin ligases (E3 ligases) which direct the “tagging” of unwanted proteins with a molecule called ubiquitin. Tagged proteins are then recognized and degraded by a protein complex called the proteasome.

Targeted protein degradation (TPD) is a new modality that co-opts this innate cellular process to direct the degradation of specific disease-causing proteins and has the potential to overcome challenges associated with existing modalities like monoclonal antibodies, RNAi, and other oligo-based therapies. The core of TPD relies on the design of small molecules with two actives ends: one that binds to a target protein of interest and the other to a specific E3 ligase. These heterobifunctional degrader molecules are capable of mediating the interaction of the E3 ligase and the disease-causing protein, resulting in tagging and subsequent degradation of the unwanted protein.

Kymera is working at the forefront of TPD to invent new medicines for difficult-to-treat cancers and immune-inflammation diseases. Our proprietary Pegasus drug development platform enables us to discover and develop novel, heterobifunctional molecules that optimize the key elements of the UPS to degrade disease-causing proteins and ultimately address significant, unmet medical needs.

The key components of our Pegasus platform include the following:

E3 Ligase Whole-Body Atlas

We have identified the expression profiles of the approximately 600 unique E3 ligases to match a target protein with the appropriate E3 ligase based on expression, distribution, intracellular localization, and biology.

E3 Ligase Whole-Body Atlas

We have identified the expression profiles of the approximately 600 unique E3 ligases to match a target protein with the appropriate E3 ligase based on expression, distribution, intracellular localization, and biology.

E3 Ligase Binders Toolbox

Our knowledge from our E3 Ligase Whole-Body Atlas has allowed us to generate a toolbox of proprietary ligands designed to bind to novel E3 ligases that we believe will enable new small molecule protein degraders with specific degradation profiles for different target disease states.

E3 Ligase Binders Toolbox

Our knowledge from our E3 Ligase Whole-Body Atlas has allowed us to generate a toolbox of proprietary ligands designed to bind to novel E3 ligases that we believe will enable new small molecule protein degraders with specific degradation profiles for different target disease states.

Ternary Complex Modeling

Ternary complexes are formed when a degrader molecule binds to both an E3 ligase and the protein of interest. We characterize this interaction with both structural biology and biophysical techniques and utilize a sophisticated, structure-based ternary complex modeling approach to optimize the development of highly efficient, selective, and potent degrader therapeutics.

Ternary Complex Modeling

Ternary complexes are formed when a degrader molecule binds to both an E3 ligase and the protein of interest. We characterize this interaction with both structural biology and biophysical techniques and utilize a sophisticated, structure-based ternary complex modeling approach to optimize the development of highly efficient, selective, and potent degrader therapeutics.

Quantitative System Pharmacology Model

Our understanding of PK/PD both in vitro and in vivo, and across different contexts, has allowed us to build models that refine the diverse sets of parameters that impact protein levels and to model higher species and human degradation profiles.

Quantitative System Pharmacology Model

Our understanding of PK/PD both in vitro and in vivo, and across different contexts, has allowed us to build models that refine the diverse sets of parameters that impact protein levels and to model higher species and human degradation profiles.

Proprietary Chemistry

Our expertise in proprietary chemistry enables us to design and optimize both E3 and target protein binders and convert them into degraders with optimal pharmaceutical properties tailored to specific patient populations and diseases.

Proprietary Chemistry

Our expertise in proprietary chemistry enables us to design and optimize both E3 and target protein binders and convert them into degraders with optimal pharmaceutical properties tailored to specific patient populations and diseases.

Expanding the Druggable Universe

While conventional small molecule inhibitor drugs and antibody therapeutics have had a tremendous impact on the treatment of diseases, it is estimated these traditional approaches have only been able to effectively drug ~20% of the full human genome to date. We believe TPD represents an opportunity to expand the drugged proteome/genome and provide new efficacious medicines to patients in need.