Small Molecules acting to degrade proteins

Kymera Therapeutics is pioneering the field of targeted protein degradation, a transformative approach that fundamentally alters the way drugs can be developed and utilized. This innovative modality allows for the selective degradation of disease-causing proteins, thereby addressing the root causes of various diseases rather than merely alleviating symptoms. By harnessing this technology, Kymera aims to create a new generation of therapeutics that can effectively treat a wide range of conditions, expanding the possibilities for patient care and improving health outcomes.

The company is driven by a robust drug discovery engine that supports the development of first-in-class therapeutics. Their pipeline includes novel candidates designed to redefine treatment standards across multiple disease areas, particularly focusing on conditions that have been challenging to address with traditional therapies. Kymera's commitment to advancing cutting-edge science is evident in their ongoing clinical trials and research initiatives, which aim to deliver life-changing medicines to patients in need.

United States

Kymera Therapeutics, Inc., a biopharmaceutical company, focuses on discovering and developing novel small molecule therapeutics that selectively degrade disease-causing proteins by harnessing the body's own natural protein degradation system. It engages in developing IRAK4 program for the treatment of immunology-inflammation diseases, including hidradenitis suppurativa, atopic dermatitis, and rheumatoid arthritis; IRAKIMiD program to treat MYD88-mutated diffuse large B cell lymphoma; and STAT3 program for the treatment of hematologic malignancies and solid tumors, as well as autoimmune diseases. The company was founded in 2015 and is headquartered in Watertown, Massachusetts.

Cancer

Digestive System Diseases

Endocrine System Diseases

Hematologic Diseases

Immune System Diseases

Lung Diseases

Kymera Therapeutics

Asthma

First-in-class oral STAT6 degrader, KT-621, at its <a href="https://investors.kymeratx.com/news-releases/news-release-details/rd-day-highlights-kymeras-immunology-strategy-and-emerging" rel="nofollow" target="_blank">Immunology R&amp;D Day</a> in January. STAT6 is a transcription factor specific for the IL-4/IL-13 signaling pathway that drives Type 2 inflammation in allergic diseases. In Kymera’s preclinical testing, KT-621 selectively and potently degraded STAT6 and fully blocked the IL-4/IL-13 pathway with preclinical activity in human cells and animal models equal or superior to the monoclonal antibody targeting IL-4Rα, dupilumab, thereby demonstrating broad potential across a number of dermatologic, respiratory and gastrointestinal allergic diseases.

KT-621

Allergy

Inflammatory disease

Autoimmune disease

First-in-class oral TYK2 degrader, KT-294, at its <a href="https://investors.kymeratx.com/news-releases/news-release-details/rd-day-highlights-kymeras-immunology-strategy-and-emerging" rel="nofollow" target="_blank">Immunology R&amp;D Day</a> in January. TYK2 is a member of the Janus Kinase (JAK) family required for Type I interferon, IL-12 and IL-23 signaling with both genetic and clinical validation in autoimmune and inflammatory diseases. KT-294 selectively and potently degrades TYK2, phenocopying the inhibition of Type I interferon, IL-12 and IL-23 signaling seen in humans with TYK2 loss of function mutations, while sparing IL-10 signaling needed for gastrointestinal epithelial integrity and mucosal healing. This profile has the potential to circumvent the limitations of both selective and non-selective TYK2 small molecule inhibitors, providing a best-in-class opportunity in several indications including inflammatory bowel disease, lupus and psoriasis.

KT-294

Atopic dermatitis

KT-579 is a first-in-class, oral small molecule degrader that selectively targets IRF5, a transcription factor known as a master regulator of innate and adaptive immune responses. IRF5 controls the expression of key pro-inflammatory cytokines (e.g., TNFα, IL-6, IL-12, IL-23), Type I interferons, and B cell-driven autoantibody production. Unlike traditional inhibitors, KT-579 induces degradation of IRF5 via the ubiquitin-proteasome system, offering a novel immunomodulatory approach with high selectivity and potency across disease-relevant immune cells such as B cells, monocytes, macrophages, and dendritic cells.

In preclinical studies, KT-579 demonstrated >90% IRF5 degradation in vivo, effectively suppressing TLR-driven inflammatory signaling while sparing normal immune function. It showed superior efficacy compared to standard-of-care biologics and small molecules in lupus and rheumatoid arthritis models, significantly reducing disease biomarkers like proteinuria, autoantibodies, and joint inflammation.

KT-579

KT-485/SAR447971 is a first-in-class, selective, potent, oral IRAK4 degrader in development for the treatment of immuno-inflammatory diseases with significant patient need. IRAK4 is a master regulator of innate immunity and key protein of the myddosome complex that mediates signaling through IL-1 and toll-like receptors. IRAK4 is a scaffolding kinase that acts at the interface of the innate and adaptive immune responses with a variety of functions depending on its kinase activity and scaffolding function. Eliminating IRAK4 completely through degradation impacts both the kinase and scaffolding functions, therefore having the potential to achieve a broad, well-tolerated, anti-inflammatory effect providing a novel therapeutic approach for a variety of immune-inflammatory diseases.

KT-485 (IRAK4 degrader)

Solid tumor/s

KT-413

KT-333

Hidradenitis suppurativa

Rheumatoid arthritis

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

KT-474

Acute myeloid leukemia

Lymphoma

Targets MDM2, the crucial regulator of the most common tumor suppressor, p53. p53 remains intact (wild type) in close to 50% of cancers, meaning that it retains its ability to modulate cancer cell growth. While small molecule inhibitors have been developed to stabilize and upregulate p53 expression, they have been found to induce a feedback loop that increases MDM2 protein levels, which can repress p53 and limit their efficacy.

Kymera Therapeutics

Company Details