Kura Narrows Pipeline After Strategic Review Prompted by COVID-19

Xconomy San Diego — 

Kura Oncology is discontinuing development of one of its three clinical-stage cancer drug candidates amid pandemic-related impacts to its clinical trial plans.

The decision to end work on the drug, KO-947, comes after San Diego-based Kura (NASDAQ: KURA) was successful in lifting a partial clinical hold placed on a Phase 1 trial of the drug earlier this year by the FDA following a serious side effect experienced by one patient in the study.

The company had recently landed on a recommended Phase 2 dose of KO-947, and was preparing to test it in patients with head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma with a specific genetic signature. But Kura announced Monday it would drop that program and focus its attention on its two remaining small-molecule drug candidates, both of which target cancers with particular genetic mutations.

“This sharpened focus will enhance our efforts around each of these important programs and help to ensure that we are in a strong cash position as we navigate the challenges of the COVID-19 pandemic and continue to advance toward potential value inflection points,” Troy Wilson, CEO of the San Diego-based biotech, said in a statement.

Kura’s lead drug candidate, tipifarnib, is being developed as a treatment for head and neck squamous cell carcinoma (HNSCC) with HRAS mutations. The protein is a member of the RAS family; when mutated, the genes are believed to drive many cancers. The company licensed the rights to tipifarnib for oncology indications from Johnson & Johnson (NYSE: JNJ) unit Janssen Pharmaceutica in 2015.

According to the company, there are more than 60,000 cases of HNSCC diagnosed in the US yearly. But only about one-third of patients given diagnoses of advanced HNSCC survive five years. Worldwide the disease is the sixth most common cancer.

Tipifarnib is under evaluation in a pivotal trial—but while the company previously anticipated enrollment in the study would be complete by the end of March, it withdrew that guidance Monday, citing the impact of COVID-19 on the process, plus its recent decision to amend the study to allow a broader swath of patients to enroll. The choice to broaden the enrollment criteria to HNSCC patients whose cancers overexpress HRAS, as well as those with HRAS mutations, was based on the Phase 2 dataset and feedback from treating physicians, the company said.

The data indicate that excess HRAS in cancer may drive resistance to other therapies, and have “distinct biology” that is targeted by tipifarnib, Kura says. However, the trial’s main goal won’t change.

Expansion into other indications, however, is being put on hold. Kura, which has long talked up expansion opportunities for tipifarnib, said it has halted planned studies evaluating the drug in patients with T-cell lymphomas and in pancreatic cancer.

As part of its new strategy the company is also focusing its resources on KO-539, a potential treatment for patients with acute myeloid leukemia whose disease is relapsed or refractory. The drug, intended for patients whose cancer has NPM1 mutations or a reshuffling of the mixed lineage leukemia (MLL) gene, referred to as MLL-rearranged AML, is under evaluation in a Phase 1/2a trial.

Last month Syndax Pharmaceuticals (NASDAQ: SNDX), which is advancing a competitor drug, presented data at the annual American Association for Cancer Research meeting indicating that some patients with MLL-rearranged AML responded to its treatment.

“[That data] injected a lot of interest and a lot of enthusiasm throughout, from all corners, in this molecular target,” Wilson said on the conference call.

SVB Leerink analyst Jonathan Chang said Kura’s strategy changes prompted the firm to reduce its price target for the company’s stock from $24 to $23, but reiterated its “outperform” rating. Kura shares closed at $14.61 on Tuesday.

“We continue to view [Kura] as well-positioned long term to execute on their tipifarnib and KO-539 development strategy,” Chang wrote in a research note issued Tuesday.

As of the end of March Kura’s war chest of cash, cash equivalents, and short-term investments totaled about $216.9 million, money its management team said would carry it through 2022. However, on Tuesday the company said it planned to pursue a public offering to bulk up its holdings.