Pipeline

Kymera’s pipeline is focused on addressing disease targets where there is significant patient need and where we believe protein degradation is the only or best way to improve the standard of care.

Therapeutic Areas
Immunology-inflamation
Oncology
Program
IND-Enabling
Phase 1
Phase 2
Phase 3
Rights
Immunology
IRAK4
KT-474/SAR444656 (AD)
KT-474/SAR444656 (HS)
Current Indications: AD and HS
TARGET & PATHWAY
IRAK4 (KT-474/SAR444656)

KT-474 is a first-in-class IRAK4 degrader in development for the treatment of immune-inflammatory diseases with significant patient need, such as hidradenitis suppurativa (HS), atopic dermatitis (AD), and potentially others. IRAK4 is a key protein of the myddosome complex that mediates signaling through IL-1 and toll-like receptors, which play a crucial role in initiating the immune response against invading pathogens. 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-474 (SAR444656) is partnered with Sanofi, who is leading the Phase 2 clinical development program. Kymera has the option to participate in future development and commercialization, and 50/50 profit split, in the United States. Double digit tiered royalties in ROW.

Diseases where the TLR/IL-1 pathway has been implicated in pathogenesis and are potential opportunities: Psoriasis, Generalized Pustular Psoriasis, IBD, Asthma, COPD, SSc ILD, RA, PSA, SLE, OA, PSS, MS, AMD.

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STAT6
KT-621
Potential Indications: AD, Asthma, COPD, CRSwNP, EoE, PN, others
Target & Pathway
STAT6 (KT-621)

STAT6 is an essential transcription factor in the IL-4/IL-13 signaling pathways and the central driver of TH2 inflammation in allergic diseases. Multiple gain of function mutations of STAT6 were identified to cause severe allergic diseases in humans. Dupilumab, an injectable monoclonal antibody that blocks IL-4/IL-13 signaling, is an approved therapy for multiple allergic diseases. STAT6 targeting is therefore supported by both human genetics and clinical pathway validation. STAT6 functions through protein-protein and protein-DNA interactions and it has been challenging to selectively and potently inhibit STAT6 with small molecule inhibitors. However, it is well suited for a targeted protein degradation approach, where a binding event is sufficient to drive degradation. In preclinical studies, KT-621, Kymera’s first-in-class oral STAT6 degrader, demonstrated full inhibition of the IL-4/IL-13 pathway in all relevant human cell contexts with picomolar potency that was superior to dupilumab, and equivalent or superior efficacy to dupilumab in multiple preclinical efficacy studies. In addition, at low oral doses, KT-621 demonstrated near full in vivo STAT6 degradation and was well-tolerated in multiple preclinical toxicity studies.

Potential Indications

Atopic Dermatitis
Asthma
Chronic Obstructive Pulmonary Disease
Chronic Rhinosinusitis with Nasal Polyps
Eosinophilic Esophagitis
Prurigo Nodularis
Others

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TYK2
KT-294
Potential Indications: IBD, PsO, PsA, Lupus, others
Target & Pathway
TYK2 (KT-294)

TYK2 is a member of the JAK family of kinases that binds the IL-12, IL-23 and interferon (IFN) receptors to recruit and phosphorylate STAT transcription factors. A loss of function variant is protective in autoimmune diseases and an allosteric inhibitor of TYK2, as well as biological agents targeting IL-12, IL-23 and Type I IFN, have been approved for the treatment of multiple autoimmune diseases, making TYK2 a highly validated target. TYK2 has a well-established scaffolding function that plays a key role in cytokine receptor surface expression and activation. In preclinical studies, KT-294, Kymera’s first-in-class oral TYK2 degrader, demonstrated picomolar to nanomolar potencies across all relevant human cell contexts evaluated, representing what Kymera believes is the only approach to TYK2 targeting that has the potential to recapitulate the human loss-of-function biology of near full pathway inhibition of Type I IFN, IL-12 and IL-23, while also sparing IL-10. Degradation of TYK2 has the potential to overcome the challenges of small molecule inhibitors, which have limitations due to lack of selectivity, limited target engagement, and/or lack of potent activity against Type I IFN.

Potential Indications

Inflammatory Bowel Disease
Psoriasis
Psoriatic Arthritis
Lupus
Others

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Oncology
STAT3
KT-333
Potential Indications: CTCL, LGL-L, PTCL, Solid Tumors / Assessment of STAT3 I/I opportunity is ongoing.
Target & Pathway
STAT3 (KT-333)

KT-333 is a potent, highly selective degrader of STAT3 in development for the treatment of multiple STAT3-dependent pathologies, including hematological malignancies and solid tumors. STAT3 is an undrugged transcription factor activated through a variety of different cytokine and growth factor receptors via Janus kinases (JAKs), as well as through oncogenic fusion proteins and mutations in STAT3 itself. In certain malignant cells, STAT3 activation is set into overdrive, leading to a dampened immune response, tumor progression, and metastasis. STAT3’s role as a cancer driver and tumor microenvironment modulator has been validated in a multitude of studies, making it a strong candidate to target in the treatment of cancer. The Phase 1 clinical trial of KT-333 is designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of KT-333 dosed weekly in adult patients with relapsed and/or refractory lymphomas, leukemias, and solid tumors. Clinical data from the KT-333 Phase 1 trial has shown evidence of STAT3 targeted protein degradation in humans with associated STAT3 pathway inhibition, along with early signs of antitumor activity, highlighting the potential of heterobifunctional degraders for targeting this previously undruggable transcription factor.

Potential Indications

Large Granular Lymphoma Leukemia
Peripheral T-cell Lymphomas
Primary Cutaneous T-cell Lymphomas
Solid Tumors

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MDM2
KT-253
Potential Indications: ALL, AML, Solid tumors
Target & Pathway
MDM2 (KT-253)

KT-253 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 (SMIs) have been developed to stabilize and upregulate p53 expression, they have been unable to show meaningful clinical benefits of P53 stabilization, with acceptable safety margins, likely due to their inability to overcome a feedback loop that increases MDM2 protein levels when P53 is upregulated. In preclinical studies, KT-253 has shown the ability to overcome the MDM2 feedback loop and rapidly induce cancer cell death with brief exposures, providing the opportunity for an improved efficacy and safety profile. The Phase 1 study of KT-253 will evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics, and clinical activity of KT-253 in patients with relapsed or refractory high grade myeloid malignancies, including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), lymphomas, and solid tumors. KT-253 has achieved clinical proof-of-mechanism in the Phase 1 trial and shown signs of anti-tumor activity in liquid and solid tumor types.

Potential Indications

Acute Lymphocytic Leukemia
Acute Myeloid Leukemia
Lymphoma
Solid Tumors

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Partnerships for Amplified Impact

When appropriate, we partner with leading global pharmaceutical companies to maximize the reach of our degrader programs and develop transformative therapies for the broadest possible patient populations.

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Our current partnership with Sanofi is designed 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.

Learn More About Sanofi
Opportunities for Partnerships
We are open to collaborations with commercial and academic partners to expand the impact of our platform and pipeline. To learn more about partnership opportunities, reach out to our team.