Nearly 80% of patients saw tumor shrinkage after being treated with Kura Oncology’s darlifarnib plus Bristol Myers Squibb’s Krazati, findings Mizuho analysts say could open up a $2 billion opportunity for the biotech.
An experimental regimen combining Kura Oncology’s darlifarnib with Bristol Myers Squibb’s Krazati shrunk tumors in patients with KRAS-mutated tumors, unlocking what Mizuho Securities anticipates to be a $2-billion market opportunity.
In the first-in-human FIT-001 trial, the investigational combo showed an objective response rate of 67% in patients with pancreatic cancer, 50% in non-small cell lung cancer and 29% in colorectal cancer, according to a Tuesday news release. Overall, 77% of the 26 patients saw tumor shrinkage after receiving darlifarnib plus Krazati, including 94% of the 16 patients who had not been treated with a KRAS inhibitor before.
Mizuho called these findings “encouraging” while emphasizing that “the data are early yet.” Still, the analysts noted that, at least on a historical basis, darlifarnib plus Krazati either matches or outperforms Krazati monotherapy in a clutch of indications, including colorectal, lung and pancreatic cancer—particularly in heavily pretreated patients.
“We currently model unadjusted ~$2Bn peak sales for darlifarnib,” the firm continued, “across multiple combinations and tumor types.” For Kura, darlifarnib presents a “significant potential opportunity” outside of its main product Komzifti, a menin inhibitor approved for relapsed or refractory acute myeloid leukemia.
Darlifarnib is a next-generation blocker of the farnesyltransferase enzyme, a mechanism of action that, according to the biotech’s website, could “unlock multiple targeted treatment paths for a range of difficult cancers.” Farnesyltransferase is involved in cellular cascades that could drive resistance to cancer therapies, Kura explained, and darlifarnib’s activity could counteract drug resistance and boost the efficacy of existing cancer therapies.
FIT-001’s study population is reflective of this mechanism: 43% of patients had already undergone at least three previous lines of systemic treatment, while 40% had been exposed to KRAS inhibition before. Darlifarnib’s efficacy in this particular study sample suggests “activity in patients that had previously failed” prior KRAS inhibitor treatments, Mizuho said.
“With compelling clinical activity across multiple tumor types and a manageable safety profile, darlifarnib is well-positioned as a preferred combination partner for KRAS inhibitors and other precision therapies,” Kura CEO Troy Wilson said in a prepared statement on Tuesday. The biotech has yet to provide a specific timeline for when it plans to push darlifarnib into more advanced development.
