Tipifarnib in Patients with HRAS Mutant Head and Neck Squamous Cell Carcinoma (HNSCC)
Tipifarnib is an oral, investigational drug candidate we are evaluating in patients with certain head and neck cancers that carry HRAS mutations.
HRAS is a proto-oncogene, which is a normal gene that can become an oncogene due to mutations or increased expression. Proto-oncogenes code for proteins that help to regulate cell growth and differentiation and HRAS is mutated and/or expressed in certain head and neck squamous cell carcinoma (HNSCC) tumors.
Although HRAS was discovered more than 40 years ago, no specific therapies have been developed that target tumors with the mutated form of the protein. Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase, a critical enzyme for the activity of HRAS.
The relapsed and/or refractory HNSCC patient population has an overall survival of approximately six to eight months and existing therapeutic options, including new therapies such as immune therapy, typically show a response rate in the range of 10-20 percent.
Tipifarnib has been studied in more than 5,000 oncology patients and was observed to have a manageable side effect profile. Clinical and preclinical data suggest that, in certain selected patient populations, tipifarnib has the potential to provide clinical benefit to cancer patients with limited treatment options.
Encouraging clinical activity of tipifarnib has been observed in patients with HRAS mutant HNSCC tumors. We are conducting a registration-directed clinical trial to evaluate the safety and activity of tipifarnib in patients with recurrent or metastatic HRAS mutant HNSCC.
View research on tipifarnib in HRAS mutant squamous head and neck cancer.
KO-539 in Patients with Acute Myeloid Leukemia (AML)
KO-539 is an oral investigational drug candidate that we are developing for treatment of genetically defined AML patients with high unmet need.
KO-539 blocks the interaction of two proteins called menin and MLL that, together, are critically important for survival, growth and proliferation of certain kinds of leukemia cells.
We have generated preclinical data that support the potential anti-tumor activity of KO-539 in genetically defined subsets of acute leukemia, including those with rearrangements or partial tandem duplications in the KMT2A gene as well as those with oncogenic driver mutations in genes such as NPM1.
Our preclinical data support the hypothesis that KO-539 targets epigenetic dysregulation and removes a key block to cellular differentiation to drive anti-tumor activity.
We believe KO-539 has the potential to address approximately 35% of AML, including NPM1-mutant AML and KMT2A-rearranged AML.
We are currently conducting a Phase 1/2A clinical trial, which we call KOMET-001, in patients with relapsed or refractory AML.
View research on KO-539 (menin inhibitor).
Tipifarnib and KO-539 are investigational drug candidates and have not yet been approved for use by the U.S. Food and Drug Administration (FDA) or other regulatory authorities.