We are advancing a diverse pipeline of precision medicines for the treatment of blood cancers and solid tumors.
Our programs comprise of small molecule drug candidates that target cancer signaling pathways, where each program builds on our expertise in precision medicines and seeks to drive better outcomes for patients and broaden the eligible patient population through rational combinations.
Ziftomenib is an investigational drug candidate and oral inhibitor of menin-KMT2A (MLL) for the treatment of Acute Myeloid Leukemia (AML), with the potential to combine with other targeted therapies. Ziftomenib is currently being evaluated as a monotherapy in the KOMET-001 trial and as a combination therapy with certain standards of care across multiple lines of therapy in the KOMET-007 and KOMET-008 trials. The R/R NPM1-m AML portion of the Phase 2 KOMET-001 trial has completed enrollment and is not currently recruiting.
Tipifarnib is an oral, investigational drug candidate and highly selective inhibitor of farnesyltransferase. Farnesyl transferase inhibitors (FTI) – such as tipifarnib – have multiple potential therapeutic applications, including direct inhibition of oncogenic proteins; overcoming drug resistance; and preventing emergence of resistance. Tipifarnib is currently being evaluated in patients with PIK3CA-dependent HNSCC (enrollment ongoing in KURRENT-HN trial).
Next-Generation FTI
KO-2806 is a potent next-generation FTI designed to improve upon potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates and address large oncology indications of high unmet need through rational combinations. Preclinical data is supportive of KO-2806 in combination with tyrosine kinase inhibitors (TKIs) and KRAS inhibitors, to drive enhanced antitumor activity and address mechanisms of innate and adapted resistance to targeted therapies. KO-2806 is currently being evaluated as a monotherapy and in combination with cabozantinib in ccRCC and with adagrasib in KRASG12C-mutated NSCLC (FIT-001).
FLAG-IDA: fludarabine, high-dose cytarabine (Ara-C), granulocyte-colony stimulating factor (G-CSF) and idarubicin; LDAC: Low-dose cytarabine
XOSPATA® (gilteritinib); PIQRAY® (alpelisib)
Most cancer drugs work by killing diseased cells faster than they kill healthy tissue. But what if you didn’t have to kill the cancer cell? What if you could convince it to become a healthy cell? That’s the mechanism underlying an emerging class of targeted therapies called menin inhibitors.
Our menin inhibitor, ziftomenib, prevents the interaction of two proteins, menin and KMT2A/MLL, that, when fused together, are responsible for survival and proliferation of certain kinds of leukemia cells. When this process is blocked, cancerous juvenile cells can mature into healthy white blood cells.
We believe ziftomenib has potential to address approximately 35% of acute myeloid leukemia cases, including NPM1-mutant AML and KMT2A-rearranged AML. Importantly, we believe it can be combined with other cancer therapies to minimize or prevent treatment resistance and foster enduring patient outcomes.
Imagine if a single key could unlock multiple targeted treatment paths for a range of difficult cancers. A class of precision medicines known as farnesyl transferase inhibitors may hold that power.
Farnesyltransferase is an enzyme that plays a key regulatory role in cellular pathways that drive resistance to a range of targeted therapies in different types of tumors. By inhibiting the enzyme’s function, we believe we can reshape combination treatment options for many cancers.
Our investigational drug tipifarnib is a farnesyl transferase inhibitor, or FTI, that has demonstrated encouraging clinical activity in a genetically defined subset of head and neck squamous cell carcinoma (HNSCC) — specifically in tumors that express a mutation in the HRAS proto-oncogene. KO-2806 is a potent next-generation inhibitor of farnesyl transferase designed to improve upon potency, pharmacokinetic and physicochemical properties of earlier FTI drug candidates. Preclinical data is supportive of clinical combinations of FTIs and their potential to drive enhanced antitumor activity and address mechanisms of innate and adaptive resistance to targeted therapies, such as KRAS inhibitors and tyrosine kinase inhibitors.