Kymera Therapeutics

Treating Disease in a New Way:
Targeted Protein Degradation

Kymera is working at the forefront of a new and exciting unique modality called targeted protein degradation (TPD) to invent new medicines for diseases with limited or no known treatment options, which is capable of targeting proteins traditionally undrugged by small molecules. TPD is a new powerful therapeutic modality which harnesses the body’s natural cellular recycling machinery – the ubiquitin proteasome system (UPS) – to break down or degrade 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. Importantly, we can chemically co-opt this innate cellular process using novel heterobifunctional molecules to direct the UPS toward specific disease-causing proteins. Specifically, TPD can target proteins without a catalytic function such as scaffolding proteins and transcription factors using small molecule-like drugs that can potentially be dosed orally and distributed systemically, unlike oligo-based therapeutics like RNAis.

Pegasus: Powered for Drug Discovery

Kymera is defining the very parameters that can transform the UPS into a small molecule-directed protein degradation therapeutic platform with applications across diseases. We have developed a proprietary drug discovery platform we call Pegasus that enables us to move beyond empirical approaches to rationally design protein degrader therapies and evolve the next generation of degrader medicines. These are potent, highly selective heterobifunctional molecules with two actives ends—one that binds to a target protein of interest and another that binds to a specific E3 ligase, tagging the unwanted protein for degradation. Through Pegasus, we are expanding our understanding of the relationship between E3 ligases and target proteins to identify the properties that make a target ligandable and degradable, and determine how multiple factors impact potency, selectivity, and pharmacokinetic and pharmacodynamic relationships. By systematically defining these properties and relationships, we can discover degraders for the right target, with the right pharmaceutical properties, for the right patients.

The key components of our Pegasus platform combine Kymera’s broad understanding of the localization and expression levels of the hundreds of E3 ligases in the human body with our proprietary E3 Ligase Binders Toolbox, as well as our chemistry, biology, and computational capabilities to develop protein degraders that address significant, unmet medical needs.

E3 Ligase Whole-Body Atlas

We have identified the expression profile of approximately 600 naturally-occurring unique E3 ligases across different tissues. This knowledge enables us 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 profile of approximately 600 naturally-occurring unique E3 ligases across different tissues. This knowledge enables us to match a target protein with the appropriate E3 ligase based on expression, distribution, intracellular localization, and biology.

E3 Ligase Binders Toolbox

Our E3 Ligase Whole-Body Atlas has allowed us to generate a toolbox of proprietary ligands designed to bind to an expanded library of E3 ligases that we believe will enable us to develop novel small molecule protein degraders with specific degradation profiles.

E3 Ligase Binders Toolbox

Our E3 Ligase Whole-Body Atlas has allowed us to generate a toolbox of proprietary ligands designed to bind to an expanded library of E3 ligases that we believe will enable us to develop novel small molecule protein degraders with specific degradation profiles.

Ternary Complex Modeling

Our structural biology information, combined with biochemical, biophysical, and computational characterization of ternary complexes is used to prospectively design highly efficient, selective, and potent degraders.

Ternary Complex Modeling

Our structural biology information, combined with biochemical, biophysical, and computational characterization of ternary complexes is used to prospectively design highly efficient, selective, and potent degraders.

Quantitative System Pharmacology Model

Our understanding of the in vitro and in vivo pharmacokinetic/ pharmacodynamic, or PK/PD, relationships of our degraders across different tissues and cell types has allowed us to build an understanding of the diverse parameters that impact protein levels, and to model these parameters in different species, including humans.

Quantitative System Pharmacology Model

Our understanding of the in vitro and in vivo pharmacokinetic/ pharmacodynamic, or PK/PD, relationships of our degraders across different tissues and cell types has allowed us to build an understanding of the diverse parameters that impact protein levels, and to model these parameters in different species, including humans.

Proprietary Chemistry

Our expertise in proprietary chemistry provides us the opportunity to design degraders with optimized pharmaceutical properties tailored not only to specific diseases but potentially also to targeted patient populations.

Proprietary Chemistry

Our expertise in proprietary chemistry provides us the opportunity to design degraders with optimized pharmaceutical properties tailored not only to specific diseases but potentially also to targeted patient populations.

Our initial programs are focused on IRAK4, IRAKIMiD and STAT3, which are each centered on a single critical signaling node within the IL-1R/TLR or JAK/STAT Pathways.

More about our pipeline and Programs

The innovative science behind Kymera's approach
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Kymera's Pegasus platform is a powerful drug discovery engine
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