Oncternal Therapeutics Cuts Two Programs Amidst Changing BTK Landscape

cancer patient

Pictured: Cancer patient in bed looking out window / iStock, Ridofranz

Oncternal Therapeutics will walk away from the Bruton’s tyrosine kinase (BTK) inhibitor market after arguing that it has become commercially unviable to continue pursuing its candidate in combination with the approved BTK inhibitor ibrutinib.

As part of its plan to reprioritize its $54.3 million cash runway, the San Diego-based biopharma announced Monday it will shut down two studies evaluating its experimental monoclonal antibody zilovertamab in combination with ibrutinib. These include a global Phase III trial aimed at treating relapsed or refractory mantle cell lymphoma (MCL) and a Phase I/II trial of patients with MCL, chronic lymphocytic leukemia (CLL) or marginal zone lymphoma.

The company has not lost all hope for zilovertamab, however. It plans to keep exploring the drug's potential value in high unmet medical need areas, as it has already seen robust response rates and prolonged progression-free survival in MCL and CLL patients. As such, Oncternal will now look at other tumor types, such as lung cancer and prostate cancer. Partnerships and collaborations are expected to be essential to carry out future late-stage trials of zilovertamab.

Renewed Focus 

In the meantime, the money saved on canceling the existing studies is intended to fund the advancement of two other oncology pipeline assets, the CAR T therapy ONCT-808 and an androgen receptor inhibitor called ONCT-534. 

Oncternal officers and other senior management members have also voluntarily agreed to waive their rights to receive annual cash performance bonuses for 2023, according to an SEC filing.

The decision was “based largely on the rapidly changing commercial landscape” for BTK inhibitors, Oncternal President and CEO James Breitmeyer said during a Monday webcast.

In particular, several competing BTK inhibitors have already been brought to market. Most recently, Jaypirca received FDA approval in January 2023 as the first reversible BTK inhibitor for adults with relapsed or refractory MCL. In addition, many more drugs of this class are in development, with about 30 manufacturers total in the BTK inhibitor space.

Breitmeyer also agreed to a 20% reduction to his base salary through December 31, 2024.

ONCT-808, a ROR1 targeting autologous CAR T cell therapy, is being tested in a Phase I/II trial for patients with relapsed or refractory aggressive B-cell lymphoma, including those who have failed prior CD19 CAR T therapy. Oncternal plans to present initial clinical data on ONCT-808 in late 2023 with additional readouts expected in 2024.

Oncternal presented preclinical data on ONCT-534 at a virtual conference in October 2021 and expects to submit an IND in mid-2023 for the drug’s use in treating patients with prostate cancer resistant to standard of care androgen receptor inhibitors. The company said initial clinical data should be available in mid-2024.

Ana Mulero is a freelance science writer based in Puerto Rico. She can be reached at anacmulero@outlook.com and @anitamulero.

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