Oncology Development - Oncternal Therapeutics is focused on developing novel oncology therapies for cancers with significant unmet medical needs, particularly prostate cancer and hematological malignancies[17]. - The company aims to build a leading oncology company by targeting novel cancer pathways and focusing on therapeutic approaches with identifiable biomarkers[23]. - ONCT-534, a dual-action androgen receptor inhibitor, has shown preclinical activity against various forms of AR alterations in prostate cancer models[18]. - ONCT-534 is expected to advance through clinical development for patients with advanced prostate cancer, with a focus on those who are resistant to prior ARPI therapy[25]. - The ROR1 CAR T cell therapy program aims to treat hematological malignancies and solid tumors, leveraging ROR1's selective expression on tumor cells[48]. - The Phase 1/2 study of ONCT-808 commenced in 2023, targeting aggressive B cell lymphoma, with initial results showing two of three patients achieving complete metabolic response[58][59]. - ROR1 is expressed in over 90% of lymphomas and CLL, with high expression linked to aggressive disease and poorer prognosis[43]. - ROR1 is expressed in approximately 90% of prostate cancers, with its expression linked to poor OS in advanced cases[81]. Financial Concerns - The company has substantial doubt regarding its ability to continue as a going concern as of December 31, 2023, due to the need for additional financing[17]. - The company received an $18.3 million grant from CIRM, with $14.5 million in development milestones received from October 1, 2017, to March 31, 2022[95]. - The Regents License Agreement requires the company to pay development and regulatory milestones ranging from $20.1 million to $24.5 million per product, and sales milestones aggregating $75.0 million[92]. Clinical Trials and Results - Zilovertamab demonstrated 100% progression-free survival through 48 months in CLL patients with p53 mutations in a Phase 1/2 study[20]. - The Phase 1/2 study ONCT-534-101 commenced in 2023 to evaluate ONCT-534's safety, tolerability, and preliminary anti-tumor activity in patients with mCRPC, with dosing cohorts ranging from 40 mg to 600 mg per day[40]. - In January 2024, the first two cohorts treated one patient each at 40 mg and 80 mg ONCT-534 per day, with the third cohort confirmed at 160 mg per day[41]. - A serious adverse event occurred in the second dose level of ONCT-808, leading to modifications in eligibility criteria and testing of lower doses[60][61]. - The combination of zilovertamab and ibrutinib showed a landmark progression-free survival (PFS) of 95% at 24 months in relapsed/refractory chronic lymphocytic leukemia (CLL) patients[75]. - For relapsed or refractory mantle cell lymphoma (MCL), 89% of patients achieved an overall response rate (ORR) with the combination of zilovertamab and ibrutinib[78]. Patent and Licensing - The company has exclusive worldwide rights to DAARI technologies, with obligations to pay mid five-digit annual maintenance fees and low single-digit to low double-digit royalties on net sales[89]. - As of February 4, 2024, the company holds approximately 50 issued U.S. patents and 19 pending U.S. patent applications related to its proprietary technology[103]. - The DAARI program includes 14 issued U.S. patents and various international patents, with patent terms not expiring before April 2036[104]. - The company has an exclusive license for ROR1 antibodies and CAR T therapies, with know-how related to cancer treatment methods and compositions[108]. - The licensed patent portfolio includes patents related to zilovertamab, with patent terms not expiring before 2032 and 2033 for various patents[109]. - Approximately 30 licensed patent applications are pending related to methods of treating cancer using zilovertamab and small-molecule chemotherapeutics, with potential expiration dates ranging from 2037 to 2041[110]. Regulatory Environment - Regulatory processes for drug approval in the U.S. require substantial time and financial resources, including the submission of an IND and compliance with FDA regulations[120][121]. - The FDA aims to review standard applications within ten months and priority applications within six months after filing[135]. - The FDA may grant orphan designation for drugs intended to treat rare diseases affecting fewer than 200,000 individuals in the U.S.[139]. - The FDA offers expedited programs like Fast Track and Breakthrough Therapy to facilitate the development of drugs addressing serious conditions[142][143]. - The FDA requires pediatric assessments for most new drugs unless a deferral or waiver is granted[133]. - The FDA established the RMAT designation in 2017 to expedite the development and review of regenerative medicine therapies for serious conditions[146]. Market Potential - The global multiple myeloma market is projected to reach $31 billion by 2026, indicating significant growth potential[63]. - The competitive landscape includes various therapies such as chemotherapies, targeted therapies, and immunotherapies, posing challenges for market entry[83]. Company Structure and Workforce - The company had 27 full-time employees and three part-time employees as of March 1, 2024, with a focus on research and development activities[213].
Oncternal Therapeutics(ONCT) - 2023 Q4 - Annual Report