Pipeline

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.

Candidate

Development Approach

Planned

Study Startup

Phase 1

Registration Directed

Trial

Menin Inhibitor

Ziftomenib

Monotherapy

Phase 1

NPM1-mutant acute myeloid leukemia (AML)

Monotherapy

Study Startup

Non-NPM1-m / Non-KMT2A-r AML

Monotherapy

Study Startup

KMT2A-rearranged ALL

Combinations with venetoclax + azacitidine (ven/aza), cytarabine + daunorubicin (7+3)

Study Startup

NPM1-mutant AML

Combinations with venetoclax + azacitidine (ven/aza), cytarabine + daunorubicin (7+3)

Study Startup

KMT2A-rearranged AML

Combinations with gilteritinib, FLAG-IDA, LDAC

Study Startup

NPM1-mutant AML

Combinations with gilteritinib, FLAG-IDA, LDAC

Study Startup

KMT2A-rearranged AML

Post-Transplant Maintenance

Study Startup

NPM1-mutant AML

Post-Transplant Maintenance

Study Startup

KMT2A-rearranged AML

Combination with FLA

Study Startup

Pediatric AML & ALL

Combination with BV-DAM

Study Startup

Pediatric ALL

Ziftomenib

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 currently being evaluated in the KOMET-001 Trial.

View publications and presentations

Farnesyl Transferase Inhibitors (FTI)

Tipifarnib

Combination with alpelisib

Phase 1

PIK3CA-dependent head and neck
squamous cell carcinoma (HNSCC)

Tipifarnib

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).

View publications and presentations

Farnesyl Transferase Inhibitors

KO-2806

Next-Generation FTI

Combinations with targeted therapies

Study Startup

Clear Cell Renal Cell Carcinoma

Combinations with targeted therapies

Study Startup

Non-Small Cell
Lung Cancer

Combinations with targeted therapies

Study Startup

Other Solid tumors

KO-2806

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 FTIs in combination with other targeted therapies to potentially overcome or prevent emergence of drug resistance to certain classes of drugs. The FDA has cleared the IND application for KO-2806 and Kura intends to evaluate KO-2806 for the treatment of advanced solid tumors (FIT-001 Trial).

View publications and presentations

FLAG-IDA: fludarabine, high-dose cytarabine (Ara-C), granulocyte-colony stimulating factor (G-CSF) and idarubicin; LDAC: Low-dose cytarabine

FLA: fludarabine and high dose cytarabine; BV-DAM: bortezomib, vorinostat, dexamethasone, PEG-asparaginase and mitoxantrone

XOSPATA® (gilteritinib); PIQRAY® (alpelisib)

ABOUT MENIN INHIBITORS

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.

ABOUT FARNESYL TRANSFERASE INHIBITORS

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 foundational role in many cellular pathways that drive the development and growth of different types of tumors. By inhibiting the enzyme’s function through various mechanisms of action, we believe we can reshape 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. FTI’s are also promising for other types of cancer and preclinical data is supportive of its combination with certain approved cancer therapies, which we believe will help address treatment resistance and potentially lead to long-term remission for patients.

Posters and Presentations

ZIFTOMENIB / MENIN INHIBITION

  • Update on a Phase 1/2 First-in-Human Study of the Menin-KMT2A (MLL) Inhibitor Ziftomenib (KO-539) in Patients with Relapsed or Refractory Acute Myeloid Leukemia

  • Novel Combination of Clinical Menin Inhibitor Ziftomenib and the Nuclear Export Inhibitor Selinexor Synergistically Inhibit MLL-r AML

  • The Menin Inhibitor Ziftomenib (KO-539) Synergizes with Agents Targeting Chromatin Regulation or Apoptosis and Sensitizes AML with MLL Rearrangement or NPM1 Mutation to Venetoclax

  • Preclinical In Vivo Activity of the Menin Inhibitor Ziftomenib (KO-539) in Pediatric KMT2A-Rearranged Acute Lymphoblastic Leukemia

  • In vivo CRISPR screens identify dual function of MEN1 in regulating tumor-microenvironment interactions

  • Clinical-Stage Menin Inhibitor KO-539 is Synergistically Active with Multiple Classes of Targeted Agents in KMT2A/MLL-r and NPM1-Mutant AML Models.

  • A Novel Small Molecule Menin-MLL Inhibitor for Potential Treatment of MLL-rearranged Leukemias and NPM1/DNMT3A-mutant AML.

  • A Novel Small Molecule Menin-MLL Inhibitor for Potential Treatment of MLL-rearranged Leukemias.

  • Discovery of Novel Menin-MLL Small Molecule Inhibitors That Display High Potency and Selectivity in Vitro and in Vivo.

TIPIFARNIB / FARNESYLTRANSFERASE INHIBITION

  • Tipifarnib Synergizes With a TKI in Clear Cell Renal Cell Carcinoma Models

  • Combination of Tipifarnib with KRASG12C Inhibitors to Prevent Adaptive Resistance

  • A Phase 1/2 trial to evaluate the safety and antitumor activity of tipifarnib and alpelisib for patients with HRAS-overexpressing and/or PIK3CA-mutated/amplified recurrent/metastatic head and neck squamous cell carcinoma (The KURRENT-HN Trial)

  • Tipifarnib prevents emergence of resistance to osimertinib in EGFR-mutant NSCLC

  • Tipifarnib potentiates the antitumor effects of PI3Kα blockade in HNSCC via convergent inhibition of mTOR activity

  • A Phase 1/2 trial to evaluate the safety and antitumor activity of tipifarnib and alpelisib for patients with HRAS-overexpressing and/or PIK3CA-mutated/amplified recurrent/metastatic head and neck squamous cell carcinoma (The KURRENT Trial)

  • Translating genotype to immunophenotype in HRAS mutated head and neck squamous cell carcinoma (HNSCC) to identify effective Tipifarnib partners for optimal patient outcomes

  • Final Results from KO-TIP-002 a Phase 2 Study of Tipifarnib in Subjects with Relapsed or Refractory Peripheral T-Cell Lymphoma (NCT02464228)

  • Final results of a phase 2 study of tipifarnib in chronic myelomonocytic leukemia (CMML) and other myelodysplastic/myeloproliferative neoplasms (MDS/MPN)

  • The AIM-HN Study: A registrational-directed study evaluating the efficacy of tipifarnib in patients with recurrent or metastatic head and neck squamous cell carcinoma with HRAS mutations

  • Preliminary Results From an Open-Label, Phase 2 Study of Tipifarnib in Chronic Myelomonocytic Leukemia (CMML) and Other Myelodysplastic/Myeloproliferative Neoplasias (MDS/MPNS)

  • Proof of Concept for Tipifarnib in Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma (AITL): Preliminary Results from an Open-Label, Phase 2 Study

  • Preliminary Activity of Tipifarnib in Tumors of the Head & Neck, Salivary Gland, and Urothelial Tract With HRAS Mutations

  • The AIM-HN and SEQ-HN Study: A Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) with HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN)

  • Tipifarnib, a Farnesyltransferase Inhibitor, for Metastatic Urothelial Carcinoma Harboring HRAS Mutations

  • Proof of Concept for Tipifarnib in Relapsed or Refractory Angioimmunoblastic T-Cell Lymphoma (AITL) and CXCL12+ Peripheral T-Cell Lymphoma (PTCL): Preliminary Results from an Open-Label, Phase 2 Study

  • Tipifarnib in Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma (AITL) and CXCL12+ Peripheral T-cell Lymphoma (PTCL): Preliminary Results from an Open-Label, Phase 2 Study

  • KIR3DL2 Mutation May Define a High Rate of Response of Aitl to Tipifarnib

  • Tipifarnib in Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma (AITL) and CXCL12+ Peripheral T-cell Lymphoma (PTCL): Preliminary Results from an Open-Label, Phase 2 Study

  • CXCL12 and CXCR3 May Identify Complete Response in Acute Myeloid Leukemia Patients Treated With Tipifarnib

  • Mechanism of Action of the Farnesyltransferase Inhibitor Tipifarnib and its Potential Clinical Applications

  • Patient Reported Abdominal Pain as a Surrogate of the Clinical Benefit of Tipifarnib in Pancreatic Cancer Patients

  • Tipifarnib in Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma (AITL) and CXCL12+ Peripheral T-cell Lymphoma (PTCL): Preliminary Results from an Open-Label, Phase 2 Study

  • Identification of Tipifarnib Sensitivity Biomarkers in T-Cell Tumor cell lines

  • Preliminary Results From a Phase 2 Proof of Concept Trial of Tipifarnib in Squamous Cell Carcinomas (SCCS) With HRAS Mutations

  • Tipifarnib is Highly Active in HRAS-mutant Lung Squamous Cell Carcinoma Tumor Models

  • Pre-clinical Activity of Tipifarnib in Cutaneous T-cell Lymphoma

  • Preliminary Results from a Phase 2 Trial of Tipifarnib in HRAS mutant Head & Neck Squamous Cell Carcinomas (HNSCC)

  • The CXCL12/CXCR4 Pathway As a Potential Target of Tipifarnib in Acute Myeloid Leukemia and Myelodysplastic Syndromes

  • The CXCL12/CXCR4 Pathway As a Potential Target of Tipifarnib: Preliminary Results from an Open-Label, Phase II Study in Relapsed or Refractory Peripheral T-Cell Lymphoma

  • Preliminary Results From an Open-Label, Phase 2 Study of Tipifarnib in Chronic Myelomonocytic Leukemia (CMML)

  • Killer Immunoglobulin-like Receptors (KIR) in Low-Risk Myelodysplastic Syndrome: Genotyping and Gene Expression Evaluation

  • Preliminary Results From an Open-Label, Phase II Study of Tipifarnib in Relapsed or Refractory Peripheral T-Cell Lymphoma.

  • Preliminary Results From an Open-Label, Phase II Study of Tipifarnib in Relapsed or Refractory Peripheral T-Cell Lymphoma.

Scientific Publications

TIPIFARNIB / FARNESYLTRANSFERASE INHIBITION