Kymera Therapeutics

A New Wave of Transformational Therapies

Our Focused Path from Target ID to Patients

Kymera is leveraging its knowledge and pre-clinical data packages to rapidly advance multiple drug candidates to the clinic – promising new therapies designed to treat serious immune inflammatory diseases and cancers with limited or no known treatment options. We focus on high impact targets, identifying clinically validated biological pathways with key nodes or proteins that drive the pathogenesis of multiple serious diseases, but have been elusive to conventional modalities. Our initial programs target IRAK4, IRAKIMiD, and STAT3, each of which center on a single critical signaling node within the IL-1R/TLR or JAK/STAT pathways. By degrading these targets, we have the potential to treat a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors.

Pathway Program Indication(s) Discovery Pre-Clinical Phase 1 Phase 2 Phase 3 Next
Milestone
Rights*

IL–1R/
TLR
IRAK4 HS, AD, RA KT-474 Ph1: 1H '21
IRAKIMiD
(IRAK4, Ikaros, Aiolos)
MYD88
MT

DLBCL
Ph1: 2H '21
JAK/
STAT
STAT3 Liquid & Solid Tumors Ph1: 2H '21

Oncology Inflammation/Immunology
*Kymera will have the option to participate equally in the development of Sanofi-partnered programs in the US during clinical development
Program/
Indication(s)
Discovery Pre-
Clinical
Phase 1 Phase 2 Phase 3 Next
Milestone
Rights*

IRAK4

HS, AD, RA
KT-474 Ph1: 1H '21
IRAKIMiD
(IRAK4, Ikaros, Aiolos)

MYD88       
MT
DLBCL
Ph1: 2H '21
STAT3

Liquid & Solid Tumors
Ph1: 2H '21

Oncology Inflammation/Immunology
*Kymera will have the option to participate equally in the development of Sanofi-partnered programs in the US during clinical development

IRAK4

The role of the IL-1R/TLR pathway has been demonstrated in several inflammatory and autoimmune diseases, including atopic dermatitis (AD), Hidradenitis suppurativa (HS), macrophage activation syndrome, general pustular psoriasis, and rheumatoid arthritis (RA). This pathway also has been shown to play a role in cardiovascular disease (atherosclerosis) and cancer (lymphomas and lung cancer). All of these diseases have been impacted by monoclonal antibodies targeting several IL-1 family cytokines: IL-1, IL-18, IL-36, and IL-33. IRAK4 is a key component of the myddosome, a multiprotein complex involved in innate immunity that mediates signaling through TLRs and IL-1Rs. The function of IRAK4 is dependent both on its kinase activity and on its scaffolding function, which are required for the assembly of the myddosome complex following TLR or IL-1R engagement and MYD88-mutant DLBCL activation. IRAK4 degradation is capable of complete removal of the protein, thereby impacting both the kinase and scaffolding functions.

KT-474 is a potent, highly selective, orally bioavailable IRAK4 degrader, for the treatment of IL-1R/TLR-driven conditions and diseases with high unmet medical need, including HS, our first indication of focus, AD, RA, and other diseases.

IRAKIMiD

Kymera is developing novel heterobifunctional degraders that target degradation of both IRAK4 and IMiD substrates Ikaros and Aiolos with a single small molecule, addressing both the IL-1R/TLR and the Type 1 IFN pathways synergistically to broaden activity against MYD88-mutant DLBCL.

STAT3

A target long considered “undruggable,” STAT3 is a transcriptional regulator that has been linked to numerous cancers and other inflammatory and autoimmune diseases. Kymera is developing selective STAT3 degraders for the treatment of hematological malignancies and solid tumors, as well as autoimmune diseases and fibrosis. Our STAT3 degraders have the potential to provide a transformative solution to address multiple STAT3 dependent pathologies.

Discovery Programs

We are taking advantage of our proprietary E3 Ligase Whole-Body Atlas on the differential expression profile of E3 ligases to pursue targets that can benefit from potentially tissue-restricted degradation. Our early pipeline includes programs in genetically defined oncology and immunology indications.

Powered for Partnership

We believe in exploring potential synergies with the biopharmaceutical industry to accelerate the path forward to becoming a fully integrated biotechnology company and delivering transformative therapies to the broadest possible patient populations. We have in place a discovery collaboration with GSK to expand the identification of novel E3 ligases. Through our strategic partnership with Vertex, we have become a disease agnostic biopharmaceutical company. This collaboration is focused on the research and development of degraders against at least 6 targets in disease areas outside of our core strategic focus of immunology-inflammation and oncology. And most recently, we announced a collaboration with Sanofi to accelerate the path to broader clinical development and commercialization of our first-in-class protein degrader therapies targeting IRAK4 in patients with immune-inflammatory diseases.