Kymera Therapeutics, Inc. provided business highlights and updates on its pipeline of protein degraders. KT-474/SAR444656 IRAK4 Degrader: Enrollment is ongoing in the two randomized, placebo-controlled Phase 2 trials being conducted by Sanofi, evaluating KT-474 for the treatment of hidradenitis suppurativa (HS) and atopic dermatitis (AD). Topline data is expected to be reported in the first half of 2025. KT-621 STAT6 Degrader: Kymera unveiled its first-in-class oral STAT6 degrader, KT-621, at its Immunology R&D Day in January 2024. KT-621 is a once daily, oral STAT6 degrader with the potential to deliver dupilumab-like activity in multiple diseases including atopic dermatitis, asthma, and chronic obstructive pulmonary disorder (COPD), among others. The Company expects to initiate a Phase 1 clinical trial with KT-621 in the second half of 2024 and report the Phase 1 results in the first half of 2025. In March 2024, Kymera presented a poster highlighting preclinical data for KT-621 at the American Academy of Dermatology (AAD) Annual Meeting. Preclinical findings showed that KT-621 was exquisitely selective for STAT6 over other STATs and fully blocked IL-4/IL-13 functions in key human TH2 cellular assays with picomolar potency that was superior to dupilumab. At low daily oral doses, KT-621 demonstrated near full in vivo STAT6 degradation in disease-relevant tissues that was well-tolerated. In an MC903-induced atopic dermatitis mouse model, KT-621 demonstrated robust degradation of STAT6 in spleen and marked reduction of total serum IgE comparable to the activity of dupilumab. These data demonstrate the potential of KT-621 for the treatment of atopic dermatitis and other allergic diseases. The Company plans to share new additional KT-621 preclinical data at upcoming medical meetings, including the American Thoracic Society International Conference, being held May 17-22, 2024, in San Diego, CA, and Digestive Disease Week, being held May 18-21, 2024, in Washington, DC.
In March 2024, Kymera presented a poster highlighting preclinical data for KT-294 at the AAD Annual Meeting. In preclinical testing, KT-294 demonstrated picomolar degradation potency and potent inhibition of the IL-23, IL-12 and Type I IFN pathways, showing its potential to recapitulate the biology of human TYK2 loss-of-function mutations. KT-294 did not impact any of the other Janus kinase (JAK) proteins and therefore, unlike the TYK2 small molecule inhibitor deucravacitinib, spared IL-10 signaling, a feature important in the treatment of inflammatory bowel disease. In addition, in preclinical studies, TYK2 degradation led to superior inhibition of the Type I IFN pathway compared to TAK-279, which is relevant to the treatment of interferonopathies like lupus. This biological differentiation of KT-294 compared to TYK2 small molecule inhibitors, combined with its ability to provide deep and sustained TYK2 knockdown in vivo with low daily oral doses, has the potential to deliver a best-in-class TYK2 profile. The Company plans to share additional preclinical data at upcoming medical meetings. KT-253 MDM2 Degrader: The dose escalation portion of the Phase 1a clinical trial in liquid and solid tumors is ongoing. Kymera will present KT-253 clinical data updates in a poster at the upcoming American Society of Clinical Oncology (ASCO) meeting being held May 31 ? June 4, 2024, in Chicago, Illinois. The Company expects to complete the MDM2 Phase 1a study and share the full data set later in 2024 at a medical meeting. Kymera is also developing a biomarker-based patient selection strategy for subsequent development beyond Phase 1a and will present data at a medical meeting this year. KT-333 STAT3 Degrader: In April 2024 at the American Association for Cancer Research (AACR) Annual Meeting, Kymera presented new preclinical data in a late-breaking research session showing the structural and molecular mechanisms underlying the anti-tumor activity of its novel STAT3 degrader, KT-333, and for the first time, disclosed VHL as the ideal E3 ligase for potent, selective, rapid, and consistent STAT3 degradation in cancer models. The dose escalation portion of the Phase 1a clinical trial in liquid and solid tumors is ongoing. Kymera will present KT-333 clinical data updates in a poster at the upcoming European Hematology Association (EHA) meeting being held June 13-16, 2024, in Madrid, Spain. The Company expects to complete the Phase 1a study and share the full data set later in 2024 at a medical meeting.