AstraZeneca plc (AZN) could once again be vulnerable to takeover speculation, after disappointing trial results for a pipeline lung cancer drug that was a key component of the company's successful defense against Pfizer Inc's (PFE) hostile £69.4 billion ($91.2 billion) bid of 2014.

The result of the Mystic trial, released a full 11 minutes after a set of better-than-expected second quarter earnings from the U.K.'s second-largest pharma group, and five minutes after the separate announcement of a multi-billion dollar strategic alliance with Merck & Co.  (MRK) , did little to soothe investors already troubled by rumors that chief executive Pascal Soriot is preparing to step down.

AstraZeneca was changing hands at 4,292.5 pence, down 16.05% on Wednesday's close in London on Thursday, July 27. AstraZeneca's U.S.-listed shares were down 15% to $28.88 apiece by Thursday's close.

The bombshell news was that in the much-hyped Mystic trial, AstraZeneca's stage-IV lung cancer drug Imfinzi failed to meet its hoped for target for progression free survival compared with standard chemotherapy, either in combination with tremelimumab or on its own.

It did say that it will continue to test for further primary endpoints for overall survival for Imfinzi, or durvalumab, both in monotherapy and in combination. But the results of the study of the human monoclonal antibody, which is intended to counter a tumor's immune-evading tactics and trigger an immune response, will not be available before the first half of 2018.

AstraZeneca also released the result of another phase III lung-cancer drug trial, the Flaura trial for its central nervous system metastasis inhibitor Tagrisso, which it said had demonstrated "statistically-significant and clinically-meaningful" progression-free survival benefits. But the drug has already been approved in many countries for certain mutations, so the trial is for additional benefits.

Analysts were cautious about possible takeover talk, however. Roger Franklin and Graham Doyle of Liberum Capital Ltd. said that while the price would likely fall on the news, the share could still find support on bid-speculation

The deal with Merck will see the companies collaborate on the development of two AstraZeneca cancer drugs, Lynparza and selumetinib, sharing the development and commercialization costs as well as the profits. As part of the agreement, Merck will pay AstraZeneca up to $8.5 billion in total consideration, including $1.6 billion upfront, $750 million for certain license options and up to $6.15 billion contingent on successful achievement of future regulatory and sales milestones.

AstraZeneca anticipates it will record $1 billion from the deal as "externalization revenue" in 2017.

A Jefferies International LLC team led team led by Jeffrey Holford, Ian Hilliker and David Gu made a similar point, calling AstraZeneca a consolidation target.

They added: "The dividend may now look less safe and we expect some investors will start to question its long-term sustainability, despite prior reassurances from management."

"In the wake of these announcements, we fully expect investor concerns surrounding the sustainability of the dividend to be the main question on today's conference call given the massive contribution of externalization revenue to the overall P&L and the company's extraordinary cost structure," added Leerink Partners Seamus Fernandez in a note Thursday.

However, the Liberum note pointed out that AstraZeneca still has an immuno-oncology franchise for Imfinzi for stage-III lung cancer where its recent phase-III Pacific trial program did show positive progression-free survival endpoints.

And Jefferies too saw further potential in AstraZeneca's pipeline. "The company still has a number of other interesting pipelines and recently launched assets and durvalumab (Imfinzi) have already had success in other settings (Stage III unresectable NSCLC and bladder) and could still show benefits in other indications including head & neck, SCLC, breast and pancreatic cancer," the note said.

--Michael Brown contributed to this report

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