Sanofi's Elias Zerhouni has announced his retirement as head of research and development after nine years at the Paris-based drug giant, where he pioneered the concept of "a pipeline in a drug" and secured over $15 billion worth of acquisitions in the first few weeks of 2018, to bulk up the number of late-stage medicines heading for approval.

Zerhouni, who was persuaded into the industry from a career largely spent in academia at Johns Hopkins University and Hospital and the U.S. National Institutes of Health, introduced the novel "pipeline in a drug" concept to Sanofi, resulting in a smaller number of molecules in development but an increased range of disease areas that the same molecule could be applied to.

The concept was best illustrated by Dupixent, a targeted biologic medicine first approved by U.S. regulators for the most common form of eczema, which is awaiting approval for use in the treatment of severe asthma, with possible uses for nasal polyps, allergic diseases and chronic obstructive pulmonary disease at a later stage.

"I don't think you can sustain a vibrant portfolio nowadays if you don't go after disease pathways, disease mechanisms, rather than clinical descriptions of diseases — and if you do that, if you understand the pathway, if you act on the pathway ... you're much more likely to succeed," Zerhouni said in an interview with S&P Global Market Intelligence before announcing his retirement.

"That's what I kept saying that people don't understand the Sanofi portfolio because I've reduced the number of molecules we work on, but each molecule is multi-potent: that's what I mean [by] a pipeline in a drug," he said.

Zerhouni's departure — and the announcement that John Reed previously of Roche Holding AG is to take over the position July 1 — comes at a time of significant change among the top researchers in European pharmaceutical companies: GlaxoSmithKline PLC appointed Hal Barron, who had once been chief medical officer at Roche, as head of R&D in January, while Novartis AG's Vas Narasimhan said John Tsai of Amgen will take over the role vacated when he became the CEO, on Feb. 1.

He leaves a company staffed by former academics who retain strong links to so-called bench science, or basic research, taking place in universities across the world. Rand Sutherland, who heads up research into rare diseases from Boston, was previously professor of medicine at the University of Colorado specializing in rare pulmonary disorders, and Rita Balice Gordon, global head of central nervous system research, joined after a four-year stint running Pfizer Inc.'s neuro-inflammation group following a career at the University of Pennsylvania.

"I'm very happy to have the opportunity to work at Sanofi with people who have one foot firmly planted in great science and a second foot very firmly planted in translating what we learn on the lab bench into the bedside, into the patient," Balice Gordon told S&P Global Market Intelligence in an interview.

Balice Gordon is working on venglustat, a phase 2 treatment expected to yield clinical trial results in 2019 for a specific type of Parkinson's disease that is related to a genetic disorder called Gauchers' disease. Insights from work undertaken on the genetic forms of Parkinson's disease — the GB8 mutation or some of the rarer mutations — are being leveraged into therapeutic concepts that Balice Gordon believes will be "transformative" for people that have sporadic Parkinson's disease, she said.

Complex network of molecules

"Biology is not a one-on-one relationship between a target and a disease," Zerhouni said. "It's a multi-targeting environment with multiple players in a complex network of molecules," said Zerhouni.

Still, the complexity of the research being undertaken means that Sanofi has not been immune to setbacks on Zerhouni's watch. Iniparib, a targeted experimental lung cancer drug commonly known as a PARP inhibitor — and gained from the acquisition of San-Francisco-based BiPar in 2011 — was shelved after failing to meet its primary endpoint. Sanofi also severed an oncology partnership with Merrimack Pharmaceuticals Inc. in 2014 after its MM-121 compound suffered a string of trial failures. More recently, sales of the cholesterol medicine Praluent have yet to match expectations due to continuing restrictions from payers in the U.S. and despite the recent Odyssey trial of nearly 19,000 patients that showed mortality benefit compared with a rival drug — as well as a pledge to cut the price.

Zerhouni was sanguine about the need to acquire technologies or expertise in therapeutic areas where Sanofi considers itself lacking. Both of its most recent acquisitions, of Belgian biotech Ablynx NV, where it gained a nanobody technology platform and 45 more experimental compounds in development, and the $11.6 billion deal to secure Bioverativ Inc., have broadened its capacity to undertake research and access new technologies. The Bioverativ deal was the largest transaction carried out by the Paris-based group since it bought Genzyme in 2011.

"The toolbox is as important as the understanding of the biology," Zerhouni told S&P. "And I think this is where the collaboration plays out: either someone has a toolbox that we don't have, like when we collaborated with [Regeneron Pharmaceuticals Inc.] in 2009 because they had the best toolbox for that, or today, we have our own toolbox which we want to grow and we acquired Ablynx in that regard."

As of the end of February, the French pharmaceuticals business had a pipeline of 70 projects, 25 of which are in the last stage of development usually required for regulatory approval, or are awaiting approval. The acquisition of Bioverativ added a franchise in rare hematological diseases to its existing hemophilia presence, with the rest of the research focused on cardiovascular diseases, vaccines, immunology, oncology and central nervous system disorders — in addition to diabetes, which has been under significant pressure from competition and pricing pressures in the U.S. market.

Still, Zerhouni was not blind to the limitations of R&D within large, complex pharmaceutical organizations.

"I don't believe that any R&D organization can do everything, and understand everything and be good at everything: that's a pipe dream," he said. "If you are not open in terms of understanding where the emerging science is, exploring it with partners and academia and biotech, you're really not going to be a big player because you'll never see the next turn," he said.

"You cannot just be a buyer of innovation, you have to be an innovator."