Kymera to Present New Phase 1 Data on STAT3 Degrader KT-333 at EHA Meeting

Kymera Therapeutics, Inc. (NASDAQ: KYMR), a biopharmaceutical company at the forefront of developing new small molecule medicines through targeted protein degradation (TPD), announced promising Phase 1 data for KT-333. KT-333 is a pioneering STAT3 degrader, and these findings are set to be showcased at the European Hematology Association (EHA) Annual Meeting from June 13-16, 2024, in Madrid, Spain. The data, with a cut-off date of February 6, 2024, illustrate KT-333’s efficacy and safety in specific patient groups.

The abstract reveals that KT-333 is a potent and selective degrader of STAT3, showing significant clinical responses. The presentation will include more comprehensive data, encompassing pharmacokinetics (PK), pharmacodynamics (PD), safety, and outcomes from additional patients beyond the abstract’s cut-off date.

“We are optimistic about the Phase 1 data so far. We've observed notable clinical responses in certain patient groups, such as classic Hodgkin’s lymphoma (cHL) and cutaneous T-cell lymphoma (CTCL), at doses that are well-tolerated. We've also achieved significant target knockdown and pathway activation,” stated Jared Gollob, MD, Chief Medical Officer at Kymera Therapeutics. “We anticipate completing the Phase 1 study and sharing further updates across a variety of indications later this year.”

The KT-333 clinical abstract reports data from 39 patients across six dose levels, with an average of 8.7 doses administered. Patients included those with cHL, B-cell non-Hodgkin’s lymphoma, CTCL, peripheral T-cell lymphoma (PTCL), large granular lymphocytic leukemia (LGL-L), T-cell prolymphocytic leukemia (T-PLL), and various solid tumors.

Key findings from the study include:

- Two complete responses among cHL patients at the fourth dose level, three partial responses in CTCL patients at the second, fourth, and fifth dose levels, and stable disease in four solid tumor patients at the third and fourth dose levels.
- Maximum degradation of up to 97.5% in peripheral blood mononuclear cells at dose levels 1-5 in Cycle 1, with evidence of STAT3 pathway inhibition and downregulation of inflammatory biomarkers.
- Notable reduction of STAT3, pSTAT3, and SOCS3 expression in a CTCL tumor biopsy at the fourth dose level.
- Induction of an IFN-γ stimulated gene signature, predictive of sensitivity to anti-PD1, in both peripheral blood and tumor samples. This suggests a favorable immunomodulatory response in the tumor microenvironment following KT-333 treatment.
- Dose-dependent increases in KT-333 plasma exposure, reaching levels predicted to be effective.
- KT-333 was generally well-tolerated, with the most common adverse events being stomatitis, nausea, increased ALT levels, constipation, and fatigue. Two dose-limiting toxicities (DLTs) were observed at dose level 5, including Grade 3 stomatitis and arthralgia in two separate patients with LGL-L. No DLTs were observed in lymphoma or solid tumor patients at the time of the cut-off. Grade 3 stomatitis was the only serious adverse event related to KT-333.

The ongoing Phase 1a trial aims to evaluate the safety, tolerability, PK, PD, and clinical activity of KT-333 administered weekly to adult patients with relapsed and/or refractory lymphomas, leukemias, and solid tumors. Kymera expects to complete this study and present additional clinical data in 2024 at an upcoming medical meeting.

KT-333 represents a significant advancement in targeting undruggable transcription factors, exhibiting early signs of antitumor activity and the potential of heterobifunctional degraders in oncology. Kymera Therapeutics continues to pioneer the development of TPD-based therapies, aiming to create novel, highly effective treatments for diseases previously deemed intractable with conventional therapeutics.