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

Study Startup

Dose-Escalation

Dose-Validation

Registration Directed

Trial

Menin Inhibitor

Ziftomenib

Monotherapy

REGISTRATION DIRECTED

NPM1-mutant acute myeloid leukemia (AML)

Monotherapy

DOSE-ESCALATION

KMT2A-rearranged ALL

Monotherapy

DOSE-ESCALATION

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

Combinations with venetoclax + azacitidine (ven/aza)

DOSE-ESCALATION

NPM1-mutant AML

Combinations with venetoclax + azacitidine (ven/aza)

DOSE-ESCALATION

KMT2A-rearranged AML

Combination with cytarabine + daunorubicin (7+3)

DOSE-ESCALATION

NPM1-mutant AML

Combination with cytarabine + daunorubicin (7+3)

DOSE-ESCALATION

KMT2A-rearranged AML

Combinations with gilteritinib, FLAG-IDA, LDAC

DOSE-ESCALATION

NPM1-mutant AML

Combinations with gilteritinib, FLAG-IDA, LDAC

DOSE-ESCALATION

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 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.

View publications and presentations

Farnesyl Transferase Inhibitors (FTI)

Tipifarnib

Combination with alpelisib

DOSE-VALIDATION

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

Monotherapy, combinations with cabozantinib and adagrasib

DOSE-ESCALATION

Solid tumors

Monotherapy, combinations with cabozantinib and adagrasib

DOSE-ESCALATION

Clear cell renal cell carcinoma (ccRCC)

Monotherapy, combinations with cabozantinib and adagrasib

DOSE-ESCALATION

KRASG12C-mutant non-small cell lung cancer (NSCLC)

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 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).

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 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.

Posters and Presentations

ZIFTOMENIB / MENIN INHIBITION

  • Clinical Pharmacology and Pharmacokinetic Profile of Ziftomenib, A Menin Inhibitor, In Adults With Relapsed/Refractory Acute Myeloid Leukemia

  • KOMET-008: A Phase 1 Study to Determine the Safety and Tolerability of Ziftomenib Combinations for the Treatment of KMT2A-rearranged or NPM1-mutant Relapsed/Refractory Acute Myeloid Leukemia

  • The Clinical Menin Inhibitor Ziftomenib and the Nuclear Export Inhibitor Selinexor Synergistically Inhibit the Growth of MLL-R AML

  • Activity, tolerability and resistance profile of the menin inhibitor ziftomenib in adults with relapsed or refractory NPM1-mutated AML

  • Phase 1 study of ziftomenib in combination with venetoclax, venetoclax/azacitidine, or standard induction (7+3) chemotherapy in patients with acute myeloid leukemia

  • Activity, Tolerability, and Resistance Profile of the Menin Inhibitor Ziftomenib in Adults with Relapsed or Refractory NPM1-Mutated AML

  • Phase 1 Study of Ziftomenib in Combination with Venetoclax, Venetoclax/Azacitidine, or Standard Induction (7+3) Chemotherapy in Patients with Acute Myeloid Leukemia

  • 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 / KO-2806 / FARNESYLTRANSFERASE INHIBITION

  • FIT-001: A phase 1 clinical trial of the farnesyl transferase inhibitor KO-2806 alone or as part of combination therapy for advanced solid tumors

  • A phase 1 clinical trial of the novel farnesyl transferase inhibitor KO-2806 (FIT-001) alone or as part of combination therapy for advanced solid tumors

  • A phase 2 study evaluating tipifarnib in mHRAS, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (AIM-HN)

  • KO-2806, a next-generation farnesyltransferase inhibitor, potentiates the antitumor activity of cabozantinib in clear cell renal cell carcinoma models

  • The next generation farnesyltransferase inhibitor, KO-2806, blocks oncogenic signaling at multiple nodes to enhance the antitumor efficacy of KRASG12C inhibitor adagrasib in KRASG12C non-small cell lung carcinoma

  • The next-generation farnesyltransferase inhibitor KO-2806 constrains compensatory signaling reactivation to deepen responses to KRASG12D 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 Manuscripts

TIPIFARNIB / KO-2806 / FARNESYLTRANSFERASE INHIBITION