Kymera Therapeutics highlights immunology strategy at R&D Day

Kymera Therapeutics will share an overview of its strategy to build the industry leading immunology pipeline of oral degrader medicines that target validated pathways and demonstrate efficacy comparable to biologic therapies. As part of its strategy, Kymera is unveiling two new programs that each have the potential to address multiple immune-mediated diseases, each with considerable market potential. The new programs target STAT6, the obligate and specific transcription factor of the IL-4/13 pathway, and TYK2, the key scaffolding kinase of the IL-23/IFN pathways. These represent two essential signaling nodes in genetically and clinically validated pathways driving inflammation in autoimmune diseases that are undrugged or inadequately drugged with other technologies. Kymera will share its immunology strategy, including market insights, program updates, new preclinical data and development timelines, at its virtual R&D Day this morning. The R&D Day presentation will focus on three first-in-class oral degrader immunology programs, including Kymera’s new, wholly-owned STAT6 and TYK2 degraders and its IRAK4 degrader: KT-621: STAT6 is an essential transcription factor specific to the IL-4/IL-13 signaling pathway and the central driver of Type 2 inflammation in allergic diseases. STAT6 is a genetically validated target and the pathway has been clinically validated by approved IL-4/IL-13-targeting biologics, including dupilumab. 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. KT-621, a once daily oral small molecule degrader with a preclinical biologics-like efficacy profile, has the potential to have broad activity across multiple diseases, including atopic dermatitis, asthma, chronic obstructive pulmonary disorder, eosinophilic esophagitis and chronic rhinosinusitis with nasal polyps, among others. The Company expects to initiate a Phase 1 clinical trial in the second half of 2024 and report the Phase 1 results in 2025. KT-294: TYK2 is a member of the Janus Kinase family required for Type I interferon, IL-12 and IL-23 signaling with both genetic and clinical validation in autoimmune and inflammatory diseases. 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. KT-294, a once daily oral small molecule degrader with a potential biologics-like efficacy profile, has the opportunity to address conditions such as inflammatory bowel disease, psoriasis, psoriatic arthritis and lupus, among others. Kymera intends to initiate a Phase 1 clinical trial in the first half of 2025 and report the Phase 1 results in 2025. KT-474/SAR444656: KT-474 is a first-in-class IRAK4 degrader in Phase 2 clinical trials for the treatment of hidradenitis suppurativa and atopic dermatitis. IRAK4 is a key scaffolding protein of the myddosome complex that mediates signaling through IL-1 receptors and toll-like receptors, which play a crucial role in inflammation across multiple autoimmune diseases. In a Phase 1 trial published last November in Nature Medicine, KT-474 demonstrated robust degradation of IRAK4 in the blood and skin of healthy volunteers and patients with HS and AD, which was associated with a systemic anti-inflammatory effect and preliminary evidence of clinical activity. Enrollment in both Phase 2 trials is ongoing and anticipated to be completed in the fourth quarter of 2024, with topline data expected in the first half of 2025. Kymera is collaborating with Sanofi on the development of KT-474.