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.
The company operates in targeted protein degradation, or TPD, a next-generation small molecule therapeutic modality that engages the body’s natural cellular recycling system to selectively eliminate disease-causing proteins. The company intends to leverage its dr...
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.
The company operates in targeted protein degradation, or TPD, a next-generation small molecule therapeutic modality that engages the body’s natural cellular recycling system to selectively eliminate disease-causing proteins. The company intends to leverage its drug development expertise to become a fully integrated biopharmaceutical company with an industry-leading pipeline of novel medicines.
The company's focus is primarily directed at high-value targets in immunology. The company's publicly disclosed immunology programs target STAT6, TYK2, and IRAK4, each of which addresses targets within validated pathways, providing the opportunity to treat a broad range of diseases. It is developing KT-621 as part of the company's STAT6 program, which is being evaluated in a Phase 1 clinical trial in healthy volunteers. The company's lead molecule in the TYK2 program is KT-295, which it anticipates will enter the clinic in the second quarter of 2025. The company is collaborating with Sanofi S.A., or Sanofi, on the development of drug candidates targeting IRAK4, including KT-474/SAR444656, outside of oncology and immuno-oncology fields. Sanofi has initiated two Phase 2b clinical trials of KT-474 in patients with hidradenitis suppurativa (HS), and in patients with atopic dermatitis (AD). The company's pipeline focuses on addressing high-impact targets that have been elusive to conventional modalities, and that drive the pathogenesis of multiple serious diseases with significant unmet medical needs. In addition to the company's immunology focus, it also has research initiatives in other therapeutic areas.
Pipeline
STAT6 Program
The company is developing oral medicines that target STAT6, an essential transcription factor specific to the IL-4/IL-13 signaling pathway and the central driver of Type 2 inflammation in allergic and atopic diseases. STAT6 is a genetically validated target, and the IL-4/13 pathway has been clinically validated by approved biologics, including dupilumab, an injectable monoclonal antibody designed to treat T Helper 2 (TH2) diseases.
Atopic Dermatitis
Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease that occurs most frequently in children but also affects adults. In the major global markets, the diagnosed prevalence of AD is estimated at 42 million patients, with approximately 60% falling into the moderate-to-severe category. AD follows a chronic relapsing course over months to years, with dry skin and severe pruritus as the primary symptoms, sometimes accompanied by skin thickening from chronic scratching and fissuring. AD is treated symptomatically with topical therapies, including emollients, corticosteroids, and phosphodiesterase inhibitors. The leading FDA-approved systemic treatment is the IL-4Ra targeting antibody dupilumab, which is considered a safe and effective treatment for AD. Nonetheless, penetration of existing therapies, including dupilumab, remains low, leaving a significant percentage of patients who are underserved.
Asthma
Asthma is a chronic lung disease affecting people of all ages. It is caused by inflammation and muscle tightening around the airways, which makes it harder to breathe. Symptoms can include coughing, wheezing, shortness of breath and chest tightness. These symptoms can be mild or severe and can come and go over time. In major global markets, it is estimated that approximately 55 million people worldwide are diagnosed with asthma, with approximately 50% falling into the moderate or severe category. Asthma is a leading chronic disease in children, affecting about 5 million children under the age of 18. Treatments include inhaled corticosteroids, bronchodilator medications and biologics, such as dupilumab, for moderate to severe disease.
Chronic Obstructive Pulmonary Disease (COPD)
COPD is a progressive, chronic lung disease that makes it difficult to breathe. COPD damages the lungs and narrows the airways, making it difficult to move air in and out of the lungs. Smoking and air pollution are the most common causes of COPD, but it also affects nonsmokers. COPD develops gradually over many years, and symptoms are often initially mistaken for a smoker's cough or asthma. Diagnosis often occurs in patients over 60 years old, when symptoms worsen. Symptoms include coughing, shortness of breath, especially during mild activity, fatigue and frequent respiratory infections, significantly impacting quality of life. COPD is the third leading cause of death worldwide. It is estimated that approximately 34 million people worldwide are diagnosed with COPD, with up to 50% having uncontrolled disease. Treatments for COPD include inhaled steroids to reduce inflammation in the airways as well as bronchodilator inhalers to relax airways and improve airflow. Dupilumab is the only known biologic approved for the treatment of COPD.
KT-621 Preclinical Development
The company’s lead molecule in its STAT6 program is KT-621, an investigational, potentially first-in-class oral STAT6 degrader being developed for the treatment of immuno-inflammatory diseases. The company has conducted comprehensive preclinical studies in multiple models to assess KT-621’s selectivity, potency, degradation levels, efficacy and tolerability.
Preclinical Selectivity
The company evaluated KT-621’s selectivity by measuring degradation of different proteins at concentrations as high as 100 times the DC90 of KT-621, which is the degradation concentration at which 90% of the target protein is degraded. In preclinical testing, STAT6 was the only protein that KT-621 degraded out of the approximately 10,000 proteins that were detected by mass spectrometry.
Preclinical Potency
The company evaluated KT-621 potency using TH2 functional assays to assess its impact on IL-4/IL-13 signaling. The company measured IL-4 and IL-13 induced Thymus and activation-regulated chemokine (TARC), release assays in human Peripheral Blood Mononuclear Cells (PBMCs), IL-4/IL-13 induced CD23 expression assays in human CD19 B cells and IL-13 induced periostin release assays in human bronchial and esophageal smooth muscle cells. In these models, KT-621 fully blocked the IL-4/IL-13 pathway in human TH2 functional assays, with IC50’s lower than dupilumab.
Preclinical Degradation Levels
In in vivo studies, KT-621 robustly degraded STAT6 across multiple preclinical species, including mouse, rat, dog and non-human primates (NHPs). In dogs, the company tested doses ranging from 0.2 to 12.8 milligrams per kilogram (mpk), with doses between approximately 1 and 3 mpk leading to maximal STAT6 degradation near depletion, as shown in Figure 4. Additionally, KT-621, dosed at 10 mpk for 14 days, degraded STAT6 across key disease-relevant tissues, including blood, spleen, skin and lung in NHPs.
Preclinical Efficacy
To understand its efficacy potential, the company assessed KT-621 in a one-month lung inflammation model induced by intranasal house dust mite administration. KT-621 was dosed in IL4/IL4Ralpha humanized mice once daily orally for 31 days at the same three dose levels, 2, 8 and 32 mpk, leading to 72%, 85% and 91% degradation in the spleen.
Preclinical Tolerability
The company observed no adverse events in any of its preclinical safety studies of KT-621, including at doses that led to concentrations 30 to 40-fold above the predicted efficacious human exposures.
KT-621 Clinical Development
In the fourth quarter of 2024, the company initiated a Phase 1 clinical trial to test and assess single- and multiple-ascending doses of KT-621 in healthy adult volunteers. The Phase 1 trial is designed to evaluate KT-621’s safety, tolerability, PK and PD effects in an estimated 120 subjects. The company expects to disclose the Phase 1 trial results of the single- and multiple- ascending study in the second quarter of 2025. In addition, the company plans to initiate a Phase 1b trial in AD patients in the second quarter of 2025, and Phase 2b trials in AD and asthma patients in late 2025 and early 2026.
TYK2 Program
The company is developing highly potent and selective degraders of TYK2, required for Type I interferon, or IFN, IL-12 and IL-23 signaling with both genetic and clinical validation in autoimmune and inflammatory diseases.
KT-295 Preclinical Development
The company’s lead molecule in its TYK2 program is KT-295, an investigational, first-in-class oral TYK2 degrader being developed for the treatment of autoimmune and inflammatory diseases. The company has conducted comprehensive preclinical studies in multiple models to assess KT-295’s selectivity, potency, degradation levels and tolerability.
Preclinical Selectivity
The company evaluated KT-295 selectivity by measuring degradation of different proteins at concentrations as high as 100 times the DC90 of KT-295. Based on the company’s proteomics data, KT-295 is a highly selective picomolar TYK2 degrader.
Preclinical Potency
KT-295 achieved picomolar degradation in human PBMC and keratinocytes and low nanomolar (nM) inhibition of the company’s functional assays across a range of cell types. In preclinical in vitro cell assays, KT-295 potently inhibited STAT phosphorylation and downstream cytokine release in IL-23, IL-12 and type I IFN pathways. KT-295 demonstrated that the company spares the IL-10 and IL-22 pathways completely.
Preclinical Degradation Levels
KT-295 achieved dose dependent degradation of TYK2 in vivo with low oral doses. Specifically, in non-human primates, upon repeat daily low oral doses, KT-295 can degrade TYK2 in a dose responsive manner and reach full degradation of TYK2, providing a path to full target engagement.
KT-295 Clinical Development
The company intends to advance KT-295 into Phase 1 clinical testing in the second quarter of 2025.
IRAK4 Program
The company is collaborating with Sanofi on the development of drug candidates targeting IRAK4 outside of oncology and immuno-oncology fields. KT-474/SAR444656 is a highly active and selective oral IRAK4 degrader for the treatment of IL-1R/TLR-driven immuno-inflammatory conditions and diseases with high unmet medical need. Sanofi has advanced KT-474 into Phase 2 clinical trials in patients with HS and AD, both which were initiated in the fourth quarter of 2023.
Hidradenitis Suppurativa
Hidradenitis suppurativa (HS) is a chronic, destructive, painful and debilitating inflammatory skin disease affecting up to 1% of both the U.S. and global population. Patients with HS have numerous painful, draining nodules and abscesses, usually within skin folds, which are characterized by inflammation and bacterial colonization. HS is treated symptomatically with corticosteroids, antibiotics and surgery.
Atopic Dermatitis
Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease that occurs most frequently in children but also affects adults. In the major global markets, the diagnosed prevalence of AD is estimated at 42 million patients, with approximately 60% falling into the moderate-to-severe category. AD follows a chronic relapsing course over months to years, with dry skin and severe pruritus as the primary symptoms, sometimes accompanied by skin thickening from chronic scratching and fissuring. AD is treated symptomatically with topical therapies, including emollients, corticosteroids, and phosphodiesterase inhibitors. The leading FDA-approved systemic treatment is the IL-4Ra targeting antibody dupilumab, which is considered a safe and effective treatment for AD.
KT-474 Preclinical Development
The company has demonstrated KT-474’s high activity, selectivity and therapeutic potential in both in vitro and in vivo studies. Preclinical data show that orally administered KT-474 safely and selectively suppressed IRAK4 expression in rodents and non-rodents, inhibited inflammation, including neutrophil infiltration, in murine models mechanistically relevant to the pathogenesis of HS and AD and potentially other diseases, and demonstrated a therapeutic advantage of IRAK4 degradation over IRAK4 kinase inhibition.
KT-474 Clinical Development
The KT-474 Phase 1 program three-part trial was designed to evaluate single and multiple ascending doses of KT-474 to assess safety, tolerability and pharmacokinetics in healthy adult volunteers and then in HS and AD patients.
The Phase 1 trial included a patient cohort (Part C) which was an open label study in a total of 21 HS and AD patients. In the KT-474 Phase 1 trial, the proportion of HiSCR50 responders was 50% in those with moderate-to-severe disease.
In the fourth quarter of 2023, Sanofi initiated two Phase 2 clinical trials. The Phase 2 randomized, double-blind, placebo-controlled, dose ranging trials are evaluating the safety and efficacy of KT-474 as a potential treatment of HS and AD. In July 2024, Sanofi communicated to Kymera its decision to expand the ongoing Phase 2 trials in HS and AD following an interim review of safety and efficacy data by an independent data monitoring committee. The expansion of the ongoing HS and AD KT-474 Phase 2 studies to larger dose-ranging Phase 2b studies is intended to accelerate overall development timelines and enable a subsequent transition into registrational Phase 3 trials. The HS and AD Phase 2b trials are expected to be completed in the first half of 2026 and mid-2026, respectively. Additionally, the company and Sanofi are evaluating opportunities to expand in indications beyond HS and AD.
Collaboration Agreement with Sanofi
On July 7, 2020, the company entered into a collaboration agreement, or the Original Sanofi Agreement, with Genzyme Corporation, a subsidiary of Sanofi, to co-develop drug candidates directed to two biological targets. The Original Sanofi Agreement became effective during the third quarter of 2020.
On November 15, 2022, the company entered into an Amended and Restated Collaboration and License Agreement with Sanofi, or the Amended Sanofi Agreement, which amended the Original Sanofi Agreement to revise certain research terms and responsibilities set forth under the Original Sanofi Agreement. The Amended Sanofi Agreement also specifies details around the timing and number of Phase 2 trials required under the terms of the collaboration. The Amended Sanofi Agreement became effective on December 5, 2022. The Original Sanofi Agreement, as amended by the Amended Sanofi Agreement, is referred to herein as the Sanofi Agreement.
Under the Sanofi Agreement, the company granted to Sanofi a worldwide exclusive license to develop, manufacture and commercialize certain lead compounds generated during the collaboration directed against IRAK4 and one additional undisclosed target in an undisclosed field of use. Such license is exercisable on a collaboration target-by-collaboration target basis only after a specified milestone. For compounds directed against IRAK4, the field of use includes diagnosis, treatment, cure, mitigation or prevention of any diseases, disorders or conditions, excluding oncology and immune oncology.
Pursuant to the Sanofi Agreement, with respect to both targets the company is responsible for discovery and preclinical research and conducting a phase 1 clinical trial for at least one degrader directed against IRAK4 plus up to three back up degraders. With respect to both targets, Sanofi is responsible for development, manufacturing, and commercialization of product candidates after a specified development milestone occurs with respect to each collaboration candidate.
Intellectual Property
Patent Portfolio
The company’s intellectual property includes a portfolio of wholly owned patent families covering its platform E3 ligase ligand technology and its novel bifunctional degrader product candidates, including claims to compositions of matter, pharmaceutical compositions, methods of use, methods of treatment, and other related compounds and methods. The company’s intellectual property portfolio is in its early development stages, and, as of December 31, 2024, included 31 granted U.S. patents, about 92 U.S. patent applications, about 31 international patent applications, 12 granted foreign patents, and about 543 foreign patent applications. The company’s patent portfolio is generally organized into two categories: platform E3 ligase ligand patent families and protein degrader patent families, including various target-specific degrader patent families.
Platform E3 Ligase Ligand Patent Families
As of December 31, 2024, the company’s platform E3 ligase ligand patent families included five granted U.S. patents, four U.S. patent applications, and three patent applications in Europe. Any U.S. or foreign patents resulting from these applications, if granted and all appropriate maintenance fees paid, are expected to expire between 2038 and 2045, absent any patent term adjustments or extensions.
Protein Degrader Patent Families
As of December 31, 2024, the company’s protein degrader patent families included three granted U.S. patents, and about 26 patent applications in U.S., PCT, and foreign jurisdictions, such as Australia, Canada, Europe, Israel, Japan, Mexico, New Zealand, and the Russian Federation. Any U.S. or foreign patents resulting from these applications, if granted and all appropriate maintenance fees paid, are expected to expire between 2038 and 2043, absent any patent term adjustments or extensions.
Target-Specific Degrader Patent Families
As of December 31, 2024, the company’s IRAK-specific patent families included 17 granted U.S. patents, seven granted foreign patents, and about 367 patent applications filed in U.S., PCT, and foreign jurisdictions, such as Australia, Argentina, Brazil, Canada, China, Europe, Eurasia, Gulf Cooperation Council, Israel, India, Japan, Mexico, New Zealand, Singapore, South Africa, and Taiwan. Any U.S. or foreign patents resulting from its IRAK-specific patent families, if granted and all appropriate maintenance fees paid, are expected to expire between 2038 and 2044, absent any patent term adjustments or extensions.
With respect to the KT-474 product candidate, as of December 31, 2024, the company owned eight granted U.S. patents, nine pending U.S. patent applications, four pending international patent applications, three granted foreign patents and about 183 patent applications filed in foreign jurisdictions, such as Australia, Brazil, Canada, China, Europe, Israel, India, Japan, South Korea, Mexico, New Zealand, Singapore, South Africa, and Taiwan, each with claims directed to compositions of matter covering KT-474 and/or methods of making or using KT-474. Any U.S. or foreign patents resulting from these patent families, if granted and all appropriate maintenance fees paid, are expected to expire between 2039 and 2044, absent any patent term adjustments or extensions.
STAT-Specific Patent Families
As of December 31, 2024, the company’s STAT-specific patent families included three granted U.S. patents and about 106 patent applications filed in U.S., PCT, and foreign jurisdictions, such as Australia, Canada, China, Eurasia, Europe, India, Israel, Japan, South Korea, Mexico, and Taiwan. Two of the international patent applications directed to methods of treatment are co-owned with academic collaborators, and the remaining STAT-specific patent families are wholly owned. Any U.S. or foreign patents resulting from the company’s STAT-specific patent families, if granted and all appropriate maintenance fees paid, are expected to expire between 2040 and 2044, absent any patent term adjustments or extensions.
Other Target-Specific Patent Families
As of December 31, 2024, the company owned three granted U.S. patents and about 132 patent applications filed in U.S., PCT, and foreign jurisdictions, such as Australia, Argentina, Brazil, Canada, China, Europe, Gulf Cooperation Council, Israel, India, Japan, Mexico, New Zealand, Singapore, South Africa, and Taiwan which focus on degrader compounds designed to specifically target other proteins. Any U.S. or foreign patents resulting from these patent families, if granted and all appropriate maintenance fees paid, are expected to expire between 2040 and 2044, absent any patent term adjustments or extensions.
Trademarks
As of December 31, 2024, the company’s trademark portfolio included registrations and allowed applications of the KYMERA mark and the KYMERA THERAPEUTICS mark in the United States, Europe, and Canada, all covering Class 5 pharmaceutical and medical preparations and therapeutics and Class 42 pharmaceutical research and development and drug development and discovery services, and registrations, allowed applications, and pending applications in Europe, the United States, and Canada respectively for its K & Design logo mark covering the same goods and services.
The company also holds registrations of E3 HUMAN ATLAS and E3 LIGASE WHOLE BODY ATLAS in the European Union and the United Kingdom covering Class 42 pharmaceutical research and development and drug development and discovery services.
Government Regulation
In the U.S., the U.S. Food and Drug Administration (FDA) regulates drug products under the Federal Food, Drug, and Cosmetic Act, or FD&C Act, as amended, its implementing regulations and other laws.
Research and Development
The company’s research and development expenses were $240.2 million for the year ended December 31, 2024.
History
Kymera Therapeutics, Inc. was founded in 2015. The company was incorporated under the laws of Delaware in 2015.
