Oncternal Therapeutics Ends Clinical Studies and Explores Strategic Options

SAN DIEGO, Sept. 12, 2024 -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT) announced a significant shift in its clinical development strategy. The company has made the decision to halt its clinical trials for ONCT-534 and ONCT-808, both of which target challenging forms of cancer, due to unsatisfactory interim results and high capital requirements. Instead, the company will focus on exploring strategic alternatives to maximize shareholder value.

ONCT-534, a dual action androgen receptor inhibitor, was under evaluation for treating metastatic castration-resistant prostate cancer (mCRPC). However, interim Phase 1 results did not show significant clinical improvements in prostate-specific antigen (PSA) levels among the 20 patients treated across eight dosing cohorts. Although the drug was generally well tolerated, two out of three patients at the highest dose of 1200 mg experienced dose-limiting toxicities. The lack of meaningful clinical advancement in these heavily pretreated patients was disappointing given the promising preclinical data supporting the trial.

Similarly, the ONCT-808 program, which is an autologous CAR T therapy targeting ROR1, was being tested for aggressive B-cell lymphoma. Although the interim Phase 1 analysis indicated anti-tumor activity across all doses, including a complete metabolic response lasting eight months, the trial faced significant challenges. Notably, there was one fatality due to shock at the highest dose tested. This decision to halt the trials was driven by the available clinical data and the financial requirements for continuing development.

As the company shifts gears, it will now focus on evaluating strategic alternatives to optimize shareholder returns. These alternatives could include asset sales, licensing agreements, mergers, reverse mergers, acquisitions, or other business combinations. During this strategic exploration phase, Oncternal will discontinue all product development activities and implement cost-saving measures, including a workforce reduction to preserve cash resources.

Dr. James Breitmeyer, Oncternal’s President and CEO, expressed his disappointment with the early results from the ONCT-534 study, citing the challenging financial environment as a key factor in the decision to pivot. Despite the setbacks, the company aims to find ways to advance its pipeline, which includes ONCT-534, ONCT-808, zilovertamab, and ONCT-216.

Oncternal Therapeutics is dedicated to developing innovative oncology therapies for cancers with significant unmet medical needs. The company focuses on exploiting biological pathways involved in cancer progression, particularly in hematological malignancies and prostate cancer.

ONCT-534, an investigational dual-action androgen receptor inhibitor, had shown preclinical efficacy against various forms of androgen receptor mutations and aberrations in prostate cancer models. It aimed to address the resistance observed in mCRPC patients to current androgen receptor pathway inhibitors.

ONCT-808 is an investigational CAR T cell therapy targeting ROR1, using a binding domain derived from zilovertamab. It demonstrated preclinical activity against various hematological and solid tumors and was designed to reduce the manufacturing time compared to existing CAR T therapies.

Zilovertamab, previously known as cirmtuzumab or UC-961, is an investigational monoclonal antibody targeting ROR1. It has shown promise in combination with other treatments for various types of lymphomas and chronic lymphocytic leukemia. The FDA has granted it Orphan Drug Designation for treating CLL and MCL.

ONCT-216 is an investigational targeted small-molecule inhibitor of the ETS family of oncoproteins, which includes EWS-FLI1 fusion proteins commonly found in Ewing sarcoma. The FDA has granted it Rare Pediatric Disease Designation, Orphan Drug Designation, and Fast Track Status for Ewing sarcoma. It has shown preclinical efficacy in inhibiting tumor growth and inducing apoptosis in cancer cells.

As Oncternal Therapeutics navigates these strategic shifts, it aims to preserve its cash resources and continue to explore viable paths to advance its oncology pipeline and provide value to its shareholders.

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