We have developed a robust clinical and preclinical pipeline through a combination of internal discovery efforts and focused asset acquisition. The following chart summarizes our product pipeline, including our lead product candidate, ENTO, as well as our discovery programs and our next anticipated milestones.
Next Anticipated Milestones
Hematologic lineage transcription factors
Small cell / neuroendocrine
Selective SYK Inhibitors
Our lead product candidate, ENTO, is a selective inhibitor targeting SYK, a critical node in a dysregulated TRN within AML defined by persistent high expression of the transcription factors HOXA9 and MEIS1 (HOX/MEIS). While directly targeting HOX/MEIS has been historically challenging, we believe that inhibiting SYK represents a tractable strategy to collapse the HOX/MEIS TRN by inhibiting phosphorylation of downstream target genes and by disrupting a positive feedback loop that maintains high levels of MEIS1. Through analysis of AML patient sample datasets, we selected the NPM1c mutation as a robust genomic biomarker of HOX/MEIS elevation in AML. The NPM1c mutation is present in approximately 30% of adult AML patients. Data from a Phase 1b/2 trial of ENTO in 53 newly diagnosed AML patients support the role of SYK as a critical node in HOX/MEIS high AML, with compelling complete response (CR) rates in NPM1c mutated patients and patients with elevated HOX/MEIS expression. Based on these data, we plan to initiate a registrational trial of ENTO in 2021 in newly diagnosed AML patients with NPM1c mutations.
SYK is a critical dependency in HOXA9/MEIS1-high AML
Our second product candidate, KB-0742, was derived from SMM-based discovery. KB-0742 is a selective, orally bioavailable inhibitor of CDK9, a global regulator of transcription and a critical node in the oncogenic TRN resulting from MYC overexpression. MYC is a well-known transcription factor and cancer driver that is dysregulated in a significant proportion of human cancers, often via genomic copy number gain, or amplification. We intend to develop KB-0742 initially for the treatment of MYC-amplified solid tumors in a tumor type-agnostic approach, with an IND submission planned for the fourth quarter of 2020.