Facing a crowded market for BTK inhibitors, Oncternal bows out

Facing a crowded market for BTK inhibitors, Oncternal bows out

Oncternal Therapeutics’ pursuit of the BTK inhibitor market has come to an end after the company took a critical look at the prospects of commercial success for its blood cancer treatment.

In an effort to extend its $54.3 million cash runway into 2025, Oncternal will end a phase 1/2 study called CIRM-0001 and phase 3 trial called ZILO-301, which combined zilovertamab with Johnson & Johnson and AbbVie’s Imbruvica to treat mantle cell lymphoma, according to a Monday afternoon press release. The company will still consider the treatment’s potential in areas of high unmet medical need, according to the release. But a related Securities and Exchange Commission filing noted partnerships or collaborations will be “essential” for any further late-stage clinical work.

Oncternal cited the “rapidly changing commercial landscape for Bruton’s tyrosine kinase inhibitors,” or BTK inhibitors, as the reason for ending the two studies. Imbruvica is one of the drugs in the class, as well as AstraZeneca’s Calquence, BeiGene’s Brukinsa and Eli Lilly’s Jaypirca, all of which have been granted FDA nods in various blood cancers. With that kind of lineup already available to patients, Oncternal has decided to walk away and spend its money elsewhere.

“The dramatic adoption of recently approved Bruton’s tyrosine kinase inhibitors made the continued development of zilovertamab with ibrutinib an unviable commercial opportunity,” CEO James Breitmeyer, M.D., Ph.D., said in a statement. “The decision was not based on any concerns about the safety or efficacy of zilovertamab.”

The freed-up runway will go toward ONCT-808, a CAR T-cell therapy for relapsed or refractory aggressive B-cell lymphoma. The therapy is being tested in a phase 1/2 trial for patients with the disease who have advanced after previous CD19 CAR T therapy. Oncternal hopes that a quick, eight-day manufacturing process can set ONCT-808 apart. Clinical data are expected in late 2023 with more readouts to come next year.

Also to benefit from zilovertamab’s demise is ONCT-534, a dual-action androgen receptor inhibitor that is currently in preclinical testing. The biotech hopes to produce a therapy that can overcome common resistance issues seen with current standard of care androgen receptor treatments. Oncternal expects to submit a request for human tests in mid-2023 and to then kick off a phase 1/2 study in metastatic castrate-resistant prostate cancer. A readout is expected for mid-2024 if all that goes to plan.

With the cash runway now a little longer, Oncternal will still keep an eye on expenses. The company promised that management will “continue to drive operational efficiencies and prudent cost reduction and cost containment measures.”

And that means their own salaries, too. Oncternal’s officers and other senior management have voluntarily waived their right to annual cash performance bonuses for 2023. Breitmeyer has also agreed to a temporary 20% reduction of his base salary through Dec. 31, 2024. The officers will have a shot at a retention bonus in early 2025, however, to make up for the temporary compensatory arrangements.

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