Oncternal Therapeutics, Inc. (NASDAQ:ONCT) is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for patients with cancers that have critical unmet medical needs. The company's pipeline includes two first-in-class clinical programs targeting promising, yet untapped biological pathways implicated in cancer generation or progression.
Business Overview
Oncternal's lead product candidate, ONCT-534, is an investigational dual-action androgen receptor inhibitor (DAARI) with a novel mechanism of action that includes inhibition of androgen receptor (AR) function and degradation of the AR protein. ONCT-534 has demonstrated preclinical activity against both unmutated AR and multiple forms of AR alteration, including those with AR amplification, mutations in the AR ligand binding domain (LBD), and splice variants with loss of the AR LBD. ONCT-534 is being evaluated in a Phase 1/2 study (ONCT-534-101) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have relapsed or are refractory to approved androgen receptor pathway inhibitors (ARPIs).The company's second clinical program, ONCT-808, is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1). ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process for ONCT-808 that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced, compared with currently approved CAR T products. ONCT-808 is being evaluated in a Phase 1/2 study (ONCT-808-101) for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including those who have failed previous CD19 CAR T treatment.
In addition to its two clinical-stage programs, Oncternal is also developing zilovertamab, an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab has been evaluated in a Phase 1/2 study (CIRM-0001) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and marginal zone lymphoma (MZL), which resulted in 100% progression-free survival (PFS) at 42 months in CLL patients expressing a p53 mutation/del(17p), a population underserved by current treatment options. Zilovertamab is also being evaluated in an investigator-initiated Phase 1b study in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905).
Financials
For the full year ended December 31, 2023, Oncternal reported annual revenue of $785,000 and a net loss of $39,479,000. The company's annual operating cash flow and free cash flow were both -$32,164,000. As of March 31, 2024, Oncternal had $27.0 million in cash, cash equivalents, and short-term investments, and no debt.During the first quarter of 2024, Oncternal reported grant revenue of $569,000. Total operating expenses for the quarter were $9.3 million, including $1.4 million in non-cash stock-based compensation. Research and development expenses were $6.0 million, while general and administrative expenses were $3.3 million. The company's net loss for the quarter was $8.4 million, or $2.83 per share.
Oncternal's cash position provides funding into the first quarter of 2025, though the company has concluded that the balance of cash, cash equivalents, and short-term investments may not be sufficient to fund its planned expenditures and meet its obligations for the twelve months following the financial statement issuance date without raising additional funding or making changes to its operating plans or programs to reduce expenses. As a result, there is substantial doubt about the company's ability to continue as a going concern for twelve months following the issuance date of the financial statements.
ONCT-534 Clinical Program
Oncternal's lead product candidate, ONCT-534, is an investigational dual-action androgen receptor inhibitor (DAARI) that has demonstrated preclinical activity against both unmutated androgen receptor (AR) and multiple forms of AR alteration, including those with AR amplification, mutations in the AR ligand binding domain (LBD), and splice variants with loss of the AR LBD. ONCT-534 is being evaluated in the Phase 1/2 ONCT-534-101 study for the treatment of patients with mCRPC who have relapsed or are refractory to approved ARPIs.The Phase 1 portion of the ONCT-534-101 study utilizes an adaptive Bayesian Optimal Interval (BOIN) design with five ONCT-534 dosing cohorts ranging from 40 mg to 600 mg per day. The company has recently completed enrollment and initiated dosing in the sixth dose cohort, with patients receiving ONCT-534 at a dose of 1200 mg taken orally once each day. The decision to proceed to this higher dose level was made by the study's Safety Review Committee after reviewing data from the fifth dose level of 600 mg ONCT-534 daily.
Oncternal expects to provide an initial update on ONCT-534 safety and efficacy based on prostate-specific antigen (PSA) levels from the ONCT-534-101 study in the third quarter of 2024, which will include data from the 1200 mg dose cohort.
ONCT-808 Clinical Program
Oncternal's ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1). ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1.The ONCT-808-101 study is evaluating ONCT-808 in patients with relapsed or refractory aggressive B-cell lymphoma, including those who have failed previous CD19 CAR T treatment. Oncternal recently announced that the study is again open and enrolling patients, with modifications to the protocol, including changes to the eligibility criteria, increased monitoring for infection, and evaluating lower doses.
In December 2023, Oncternal reported encouraging initial response data from the ONCT-808-101 study, with 2 of the 3 patients treated at the 1x10^6 CAR T cells per kilogram dose achieving complete metabolic response and the third patient achieving a partial response. The company expects to report updated clinical results, including data from patients treated with the new dosing schedule, in mid-2024.
Zilovertamab Clinical Program
Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab has been evaluated in a Phase 1/2 study (CIRM-0001) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and marginal zone lymphoma (MZL). The study resulted in 100% progression-free survival (PFS) at 42 months in CLL patients expressing a p53 mutation/del(17p), a population underserved by current treatment options.Zilovertamab is also being evaluated in an investigator-initiated Phase 1b study in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905).
Liquidity
For the full year ended December 31, 2023, Oncternal reported annual revenue of $785,000 and a net loss of $39,479,000. The company's annual operating cash flow and free cash flow were both -$32,164,000. As of March 31, 2024, Oncternal had $27.0 million in cash, cash equivalents, and short-term investments, and no debt.During the first quarter of 2024, Oncternal reported grant revenue of $569,000. Total operating expenses for the quarter were $9.3 million, including $1.4 million in non-cash stock-based compensation. Research and development expenses were $6.0 million, while general and administrative expenses were $3.3 million. The company's net loss for the quarter was $8.4 million, or $2.83 per share.
Oncternal's cash position provides funding into the first quarter of 2025, though the company has concluded that the balance of cash, cash equivalents, and short-term investments may not be sufficient to fund its planned expenditures and meet its obligations for the twelve months following the financial statement issuance date without raising additional funding or making changes to its operating plans or programs to reduce expenses. As a result, there is substantial doubt about the company's ability to continue as a going concern for twelve months following the issuance date of the financial statements.