AstraZeneca's (AZN.L) long-time CEO Pascal Soriot has rarely put a foot wrong. The company's shares have more that quadrupled in price during his 14-year tenure, soaring above the wider FTSE 100 index and main British rival GSK (GSK.L).
AstraZeneca's huge diversity and number of drugs on the market and success in clinical trials in different therapeutic areas set it apart from peers, giving Soriot the golden touch in the eyes of investors.
Now, though, investors have some cause for concern after news this month of the unexpected failure of nerve drug Wainua in a late-stage heart disease trial, which hammered the shares and turned attention on the firm's drug R&D pipeline.
AstraZeneca's shares are down 10% this year and trail GSK and the wider London stock index over two years, with attention now on two other late-stage trials that could shape confidence in AstraZeneca's research engine and long-term growth outlook.
When it releases second-quarter earnings on Monday, analysts and investors say they will be focusing less on the numbers and more on what executives say about the outlook for breast cancer study SERENA-4 and lung cancer trial AVANZAR - seen now as key.
Three sequential trial failures this year would start to raise questions about whether AstraZeneca's R&D success story is starting to falter, analysts say.
HSBC analyst Rajesh Kumar has already downgraded his rating from buy to hold after AstraZeneca reported the Wainua trial failure on July 9.
"Fundamentally, do I like AstraZeneca's R&D strategy, engine, company? Yes I do," Kumar said. "Do I feel confident that investing in the stock right now is a good idea? No, I don't."
IS SHARE PRICE FALL A MARKET OVERREACTION?
Concerns mounted after the failure of Wainua, an approved treatment for rare neurological disorder ATTR-CM, in a Phase III trial that was testing the medicine in a form of heart disease. The setback erased some $20 billion of the firm's market value.
SERENA-4 and AVANZAR are among AstraZeneca's most closely watched late-stage oncology trials due to report this year. Successful results would boost confidence in the firm's ability to replace blockbuster medicines losing patent protection in the next decade, analysts said. Failures could sharpen scrutiny.
"If both fail, Astra will have missed three out of three important readouts this year," said Union Investment portfolio manager Markus Manns, adding investors would start questioning the clinical trial design, pipeline selection and long-term sales ambitions, while pressure for acquisitions could increase.
Kumar said the outcome of the AVANZAR trial was particularly important because it would validate the firm's proprietary biomarker for selecting patients, with implications for several future oncology trials.
CEO SORIOT STILL HAS HIS 'MIDAS TOUCH'
Not everyone, however, believes that the Wainua setback is a sign of wider problems.
Jefferies analyst Michael Leuchten said the firm had some 200 assets in the late stage pipeline that could be future growth drivers, such as respiratory drug tozorakimab, and the falling share price was a "significant overreaction".
TD Cowen analyst Michael Nedelcovych also cautioned against drawing broad conclusions from the single trial failure.
AstraZeneca set a target in 2024 to raise annual revenue to $80 billion by 2030, saying it expected to achieve this through the launch of around 20 new medicines and continued growth across its cancer, biopharma and rare disease portfolios. The company reported annual revenue of about $59 billion last year.
A Citeline report in January showed AstraZeneca leading in new drug development programmes and with the most Phase III or late-stage trial assets among the 10 top drugmakers globally.
Leuchten added the trial failure looked like a one-off and that Soriot, 67, still had his "Midas touch".
"Sometimes you just don't get the answer you were looking for. That's part of the R&D game," he said. "I think they can stomach that kick in the shin, even if it hurts."
