Kymera Therapeutics reports positive data in cancer drug trials
US clinical-stage biopharmaceutical company Kymera Therapeutics has shared new data regarding its oncology programmes KT-333 and KT-413, highlighting their robust dose-dependent target knockdown in ongoing phase 1a trials. Both programmes also demonstrated no dose-limiting toxicities (DLTs).
KT-333 has been designed to be a potent degrader of STAT3, a transcriptional regulator that has been found in numerous cancers, as well as inflammatory and autoimmune diseases. KT-413 is a novel heterobifunctional degrader that targets both IRAK4 and the immune mediated inflammatory disease (IMiD) substrates Ikaros and Aiolos, designed to target both the IL-1R/TLR and Type 1 IFN pathways with a single molecule. It has been developed for the treatment of MYD88-mutant B-cell malignancies.
KT-333’s phase 1 clinical trial is evaluating its safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD) and clinical activity over 28-day cycles in patients with relapsed and/or refractory lymphomas, leukaemias and solid tumours. Data reported from the first three dose levels (DL1-3) showed KT-333 demonstrated strong mean maximum reduction in peripheral blood mononuclear cells (PMBCs), and that degradation profiles at DL-3 were near levels of knockdown that lead to anti-tumour activity in preclinical models.
KT-413’s phase 1 clinical trial is evaluating its safety, tolerability, PK/PD and clinical activity through IV-administered infusions once every three weeks to adult patients with relapsed and or/refractory B-cell non-Hodgkin’s lymphomas. Five patients were treated across DL1-3, where KT-413 achieved high dose-dependent degradation in PMBC after one dose.
Nello Mainolfi, founder, president and CEO of Kymera Therapeutics, stated: “Our focus this year for our ongoing KT-333 and KT-413 clinical trials will be to analyse the degradation profiles and safety of these first-in-class mechanisms and evaluate their biological and clinical impact in the appropriate patient populations. We continue to see encouraging data from the trials’ dose escalation phases as they show fidelity of PK/PD translation from preclinical models to patients, demonstrating target degradation without any DLTs observed, and approaching levels we believe are needed to achieve anti-tumour activity. We are proud and excited to be the first company to have shown clinical translation of our degraders’ profiles across three programmes and across multiple diseases and indications. We look forward to sharing additional data evaluating anti-tumour activity in the target patient populations for these programmes later this year.”
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