DUBLIN – The management of Innate Pharma SA embarked on a comprehensive damage limitation exercise Monday in the wake of the failure of the firm’s lead molecule, lirilumab, to demonstrate efficacy as a monotherapy in a phase II trial in elderly patients with acute myeloid leukemia (AML).

“This is a clinical trial that tested one specific hypothesis,” said Innate CEO and Chairman Mondher Mahjoubi, during his first public investor call since his high-profile move from his former post as head of oncology at London-based Astrazeneca plc in December. “The results of the study are specific to this particular setting.”

The company will no longer pursue development of the drug in that setting, but he insisted that the outcome of the trial has no significance beyond that. “The fact that this study is negative does not alter our confidence in lirilumab,” he said. “We remain as confident as ever in lirilumab as such.”

Innate’s investors were less sanguine. Shares in the Marseille, France-based company (PARIS:IPH) dropped by more than 26 percent to a low of €9.65 (US$10.36) during early trading Monday. The stock recovered some ground and ended the day at €11.05, a drop of more than 15 percent on Friday’s close of €13.10.

That correction roughly tallies with Leerink’s price target revision on the stock, from €19 per share to €17 per share. “While the probability of success of the trial was only modest in our view . . . we think investor expectations were relatively low as well,” Leerink analyst Michael Schmidt wrote in an investor note.

The study, which recruited 150 AML patients, was testing lirilumab (IPH2102, BMS-986015) as maintenance therapy in patients, ages 60 to 80, who were in first clinical remission after chemotherapy. The patients were ineligible for allogeneic hematopoietic cell transplantation.

Two doses of the drug failed to demonstrate any difference from placebo in terms of the primary endpoint, leukemia-free survival, or on other efficacy endpoints. The company is not presenting any data at this point – that will follow at a future scientific meeting.

It was already clear almost two years ago that one of the drug treatment arms was a bust. A data safety and monitoring board called a halt to recruitment onto one of the arms, without disclosing which arm. Innate officials said Monday that the high-dose arm, which involved 1 mg of drug per kg body weight per month, had been stopped early for futility. The low-dose arm, which saturated the target in a pulsatile fashion, had been allowed to continue. (See BioWorld Today, March 27, 2015.)

Lirilumab is designed to stimulate natural killer (NK) cell activity by blocking interactions between three inhibitory killer-cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands. The antibody recognizes an epitope common to KIR2DL1, KIR2DL2 and KIR2DL3. New York-based Bristol-Myers Squibb Co. in-licensed the drug in 2011 in a deal worth up to $465 million. (See BioWorld Today, July 7, 2011.)

“We have discussed the data with BMS, who remain confident and are moving ahead with the overall program,” Mahjoubi said. Multiple trials are underway in solid tumor and combination settings – Innate’s leadership emphasized that there is no read across from the present monotherapy trial in AML to those other studies.

Innate last month banked a $15 million milestone from BMS following promising interim efficacy data from a phase I/II trial in head and neck cancer of a combination of lirilumab and BMS’s PD-1 inhibitor, Opdivo (nivolumab). BMS has five other trials of lirilumab underway, in both solid and hematological cancers. Innate had been in charge of the AML monotherapy study.

Although its outcome “is clearly disappointing,” noted Leerink’s Schmidt, he remains “cautiously optimistic” about lirilumab’s potential. “While visibility into BMS’s development plans in solid tumors is still low, phase I combination data in head and neck cancer presented at the Society for Immunotherapy of Cancer in Nov. 2016 looked very promising in our view and next steps by BMS in the near term – e.g. initiation of larger randomized trials – represent a key catalyst in our view,” he noted.