Oncternal Therapeutics is halting its clinical trials and reducing its workforce by approximately 37% after disappointing clinical trial results and a prior patient death. The decision follows the termination of trials for ONCT-534, an androgen receptor inhibitor, and ONCT-808, a ROR1-targeting CAR-T therapy, leading to a significant drop in the company's stock value.
Clinical Trial Discontinuations
The company is discontinuing the clinical trials for ONCT-534, which was being evaluated for metastatic castration-resistant prostate cancer, and ONCT-808, a CAR-T candidate targeting ROR1 for aggressive B-cell lymphoma. This decision was influenced by interim Phase I trial results for ONCT-534 (NCT05917470) that did not demonstrate clinically meaningful improvements in disease, including prostate-specific antigen (PSA) levels, across 20 enrolled patients in various dosing cohorts. Furthermore, in December 2023, a patient death occurred in a Phase I/II dose escalation study (NCT05588440) of ONCT-808, with the patient exhibiting signs consistent with cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome after receiving a higher dose level.
Financial Impact and Restructuring
The announcement led to a 60% decrease in Oncternal's stock price, dropping from $4.17 per share to $1.70. In response, the company is implementing cost-saving measures, including a workforce reduction of 37%, expected to be completed by Q3 2024, incurring charges of approximately $1 million. According to Oncternal's CEO James Breitmeyer, the early results from the ONCT-534 Phase I/II studies were disappointing, despite extensive preclinical data supporting the trial's design to address unmet medical needs in advanced prostate cancer.
Previous Setbacks
This restructuring follows a previous decision in April 2023 to terminate two trials investigating zilovertamab, a tyrosine kinase inhibitor (TKI), to conserve cash. One of these trials was a Phase III study evaluating zilovertamab in combination with Johnson & Johnson and AbbVie’s Imbruvica (ibrutinib) for mantle cell lymphoma. These repeated setbacks have placed significant financial strain on the company, leading to the current strategic shift.
