Kura Oncology(KURA) - 2021 Q4 - Annual Report

PART I Business Overview Kura Oncology is a clinical-stage biopharmaceutical company focused on developing precision medicines for cancer - Kura Oncology is a clinical-stage biopharmaceutical company developing precision medicines for cancer[16] - The pipeline includes clinical-stage ziftomenib and tipifarnib, preclinical KO-2806, and discovery-stage programs[16] - The company owns global commercial rights to all programs and plans to advance them through internal development and strategic partnerships[16] Forward-Looking Statements - The report contains forward-looking statements regarding future events, financial performance, and known/unknown risks, uncertainties, and other factors[11] - Key forward-looking statements include the impact of COVID-19, clinical trial progress, regulatory approvals, commercialization, intellectual property, financing, and personnel[11] - Readers are cautioned not to unduly rely on these statements, as actual results may differ materially, particularly due to factors discussed in the 'Risk Factors' section[12][13] Risk Factor Summary - Investment in common stock is speculative due to material factors summarized, including COVID-19 impact on clinical trials[14][15] - High dependence on lead product candidates (ziftomenib and tipifarnib) which are still in clinical development and may not receive regulatory approval[15] - Risks include lengthy and expensive clinical development, potential for serious adverse events, need for substantial additional capital, and reliance on third-party contractors[15][17] Company Overview - Kura Oncology is a clinical-stage biopharmaceutical company focused on precision medicines for cancer, with small molecule product candidates targeting cancer signaling pathways[16] - The company has two clinical-stage candidates (ziftomenib, tipifarnib), one preclinical (KO-2806), and additional discovery-stage programs, holding global commercial rights[16] The COVID-19 Pandemic - COVID-19 has disrupted business operations, including slower patient screening and enrollment in clinical trials, and challenges at clinical sites[35] - The company implemented precautionary measures like remote working and a contingency plan to minimize impact, but expects continued disruption[35][37] Precision Medicines in Cancer Treatment - Precision medicine aims to improve patient outcomes and reduce healthcare costs by matching targeted therapeutics to patients with specific cancers based on molecular diagnostics[38] - This approach offers potential for higher translatability from preclinical to clinical studies, increased response rates, and expedited clinical development[40] Our Approach to Development of Precision Medicines in Oncology - Translational research, synthesizing basic, preclinical, and clinical data, guides the company's precision medicine approach, using in vitro and in vivo experiments, including patient-derived xenograft (PDX) models[41] - The strategy involves using existing diagnostic tools (NGS, RNA expression profiling) to identify patient subsets and developing companion diagnostics for potential registration and marketing[42] - A disciplined clinical development approach evaluates product candidates in well-defined patient populations to identify early response signals and reduce development risks[43][44][45] Clinical Programs and Pipeline Kura Oncology Pipeline Status | Program | Preclinical | Phase 1 | Phase 2 | Registration Directed | | :--- | :--- | :--- | :--- | :--- | | Ziftomenib (KO-539) Menin Inhibitor | Acute Myeloid Leukemia (AML) KOMET-001 Trial | Enrollment in Phase 1b expansion cohorts ongoing | | | | Tipifarnib Farnesyl Transferase Inhibitor (FTI) | | HRAS mutant Head and Neck Squamous Cell Carcinoma (HNSCC) AIM-HN Trial (Enrollment ongoing) | PIK3CA/HRAS Dependent HNSCC KURRENT Trial (Enrollment ongoing) | | | KO-2806 Next-Generation FTI | Solid Tumors (IND enabling studies ongoing) | | | | Ziftomenib (KO-539) – A Selective Inhibitor of the Menin-KMT2A Interaction - Ziftomenib is an orally bioavailable small molecule inhibitor of the menin-KMT2A interaction, developed for genetically defined subsets of acute leukemias (AML, ALL)[46] - Preclinical data supports anti-tumor activity in KMT2A-rearranged and NPM1-mutant acute leukemias, potentially addressing ~35% of AML cases[18][49] - The KOMET-001 Phase 1/2 trial for relapsed/refractory AML reported preliminary clinical activity in 6 of 8 evaluable patients (including 2 complete remissions) and a manageable safety profile as of Nov 2020[20][51] - The KOMET-001 trial was placed on a partial clinical hold in Nov 2021 due to a Grade 5 adverse event, but the hold was lifted in Jan 2022 after agreement on a mitigation strategy for differentiation syndrome[25][56] - Preclinical data from Dec 2021 showed synergistic activity of ziftomenib in combination with the BCL2 inhibitor venetoclax in AML cells[26][57] Tipifarnib – An Oral Farnesyl Transferase Inhibitor - Tipifarnib is a potent, selective, orally bioavailable farnesyl transferase inhibitor, previously studied in over 5,000 cancer patients with a manageable side effect profile[27][58] - The company is evaluating tipifarnib in HRAS mutant HNSCC (AIM-HN registration-directed trial) and in combination with alpelisib (PI3 kinase alpha inhibitor) in the KURRENT trial (collaboration with Novartis)[28][32][74][78] - Tipifarnib received Breakthrough Therapy Designation from the FDA in Feb 2021 for recurrent or metastatic HRAS mutant HNSCC (variant allele frequency ≥ 20%) after platinum-based chemotherapy[30][73] - Clinical data from a Phase 2 study in relapsed/refractory PTCL showed an overall response rate of 56% and median overall survival of 32.8 months in advanced AITL patients[33][84] - The company is collaborating with Illumina, Inc. to develop and commercialize a companion diagnostic test for HRAS mutations in HNSCC patients for use with tipifarnib[81] Next-Generation Farnesyl Transferase Inhibitor - Kura Oncology is developing KO-2806, a next-generation farnesyl transferase inhibitor, which has advanced into IND-enabling studies[34][86] - KO-2806 is intended for innovative biology and larger disease indications in combination with other targeted therapies, with an IND submission expected by the end of 2022[34][86] License Agreements - The company holds exclusive worldwide rights for its menin-KMT2A program (including ziftomenib) from the University of Michigan, involving upfront fees, annual maintenance, and milestone/royalty payments[87] - Exclusive global rights for tipifarnib (excluding virology) were licensed from Janssen Pharmaceutica NV, with obligations for development, commercialization, regulatory/sales milestone payments (up to $75 million aggregate), and tiered royalties[89][90] Competition - The cancer treatment market is intensely competitive, with Kura Oncology facing major pharmaceutical, specialty pharmaceutical, and biotechnology companies globally[92] - Competitors for menin-KMT2A inhibitors include Syndax, Biomea, Janssen, Sumitomo Dainippon, and Daiichi Sankyo, with other products in clinical development for KMT2A-r or NPM1 leukemias[97] - For farnesyl transferase inhibitors (