Pascal Soriot, CEO of Astrazeneca plc, and his senior management team came out fighting against Pfizer Inc.'s takeover bid Tuesday, setting out an ambitious long-term growth plan for the company based on current growth drivers and a rapidly maturing pipeline which, they claim, will lead to $45 billion in revenue by 2023.

The top-line growth is expected to kick in after 2017. The company predicts that 2017 revenues will be in line with those of 2013, which dropped 6 percent to $25.7 billion. It hopes that further revenue falls, due to the loss of exclusivity on Crestor, Seroquel and Nexium, will be offset in the near term by growth from its diabetes business, from its respiratory franchise, from sales of its platelet inhibitor Brilinta (ticagrelor), from sales in Japan, and from emerging market sales.

But by 2020, it expects add another 10 new products to its portfolio. Handily, one of those gained approval Tuesday. Although Epanova (omega-3-carboxylic acids), which the FDA approved as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridaemia, is unlikely to set investors on fire, its approval is a welcome return to form for Astrazeneca's clinical development organization. It has endured several setbacks of late.

The company is attaching optimistic revenue targets to its key growth drivers – it expects its diabetes business to turn over $8 billion nine years from now, and Brilinta to achieve $3.5 billion in sales by then. The latter attained sales of just $283 million in 2013, but the company aims to steadily ramp up that figure by broadening the label from its present indication, the prevention of stroke and heart attack in patients with acute coronary syndrome, into other cardiovascular indications.

It currently has 11 new molecular entities (NMEs) in either phase III trials or in registration, and expects another four or five NMEs to start phase III studies this year. The frontrunners include AZD9291, a third-generation kinase inhibitor targeting EGFR in development for non-small-cell lung cancer; MEDI4736, an antibody targeting programmed cell death ligand 1 (PDL-1) in development for treating solid tumors; tralokinumab, an anti-interleukin-13 antibody for asthma; roxadustat for treating anemia in patients with advanced kidney disease; AZD3293, a BACE inhibitor, in Alzheimer's disease; and mavrilimumab, which targets the alpha subunit of the granulocyte-macrophage colony-stimulating factor receptor, in rheumatoid arthritis.

Achieving all of its goals will require a sharp focus on the pipeline. "The important thing to keep in mind is the pipeline we have has changed dramatically over the last 15 to 18 months," Soriot told analysts. "Any distraction can certainly have a big negative impact."

Other pipeline assets the company highlighted include PARP inhibitor olarparib, which has a PDUFA date of Oct. 3; PT003, a combination therapy for chronic obstructive pulmonary disorder (COPD), which will report phase III data early next year; and PT0101, a triple therapy for COPD and asthma, which will being phase III studies in 2015.

Immuno-oncology is a key area for Astrazeneca, Soriot said, and the company has a breadth of drug mechanisms in its portfolio and its pipeline that will enable it to combine drugs targeting immune checkpoints in multiple regimens. PD-1, PDL-1 and CTLA-4 are "the first 10 yards in a marathon race," he said, and cited a "breadth of key mechanisms."

The Street didn't really buy the story, however. "We see this very optimistic assessment of the long-term revenue potential of Astrazeneca as a clear negotiating tactic to push up the price Pfizer will need to pay and significantly change the ratio of cash to shares in the offer. We doubt that shareholders will take these estimates as being realistic given the scale of the upgrade to expectations and the coincidental timing of the Pfizer approach," Jefferies analyst Jeffrey Holford wrote in a research note.

Sawas Neophytu, analyst at Panmure Gordon & Co., wrote in a research note that the new forecasts represent a near-doubling of "trough-year" consensus forecasts of $23.8 billion. Assuming some additional cost gains, Panmure Gordon derives a value of £105 (US$178.33) per share based on the company's predictions.

"Clearly the management has some convincing to do as most analysts remain skeptical on the achievability of these targets, but at least it sets out the rationale why management turned down Pfizer's advances last week," he stated.

Shares in Astrazeneca (LONDON:AZN) dipped 2.7 percent Tuesday to close at £46.775.

WHAT ABOUT SWEDEN?

International commentary on the potential takeover has so far focused more or less exclusively on the UK, and Pfizer CEO and chairman Ian Read has offered UK Prime Minister David Cameron several assurances about the enlarged company's continued commitment to the UK, including the location there of at least 20 percent of its R&D. (See BioWorld Today, May 5, 2014.)

No such overtures have been made to the Swedish authorities, however, and in its public communication so far Pfizer has been markedly silent about its intentions towards Astrazeneca's operations in Sweden, where, despite recent downsizing, it still employs 5,900 people at its R&D site in Mölndal, near Gothenburg, and at Södertälje, south of Stockholm.

"The R&D site was chosen last year as one of three global R&D sites," Jacob Lund, spokesman for Astrazeneca in Sweden, told BioWorld Today. "We have currently 2,200 employees. Of those, 1,190 are in R&D positions." Mölndal is Astrazeneca's lead R&D site for small-molecule research in two of its three core therapy areas, namely cardiovascular and metabolic disease, and respiratory disease, inflammation and autoimmunity. "In Södertälje we have another 3,700 employees," Lund said.

That site is focused now mainly on manufacturing, following Astrazeneca's decision to shut down neuroscience R&D there, a move that caused considerable shock in Sweden. Government officials are now concerned that a Pfizer takeover of Astrazeneca could lead to further job losses.

"From a Swedish perspective, we are very keen that the jobs remain here and not move to the UK or elsewhere. We want them to remain here and we want them to grow," Oscar Sundevall, press secretary to Sweden's enterprise minister Annie Lööf, told BioWorld Today.

The country has far less leverage than the UK, however, given Astrazeneca's domicile in London, and New York-based Pfizer's plans to move its headquarters to the UK in the event of a successful takeover. In response to questions on its intentions toward Sweden, Pfizer declined to offer any specifics.

"It is premature to speculate at this stage on the exact research mix and location of specific R&D operations. However we recognize that, like Pfizer, Astrazeneca also has world class science and scientists," the company stated. "It's worth noting again that at this time we are bound by the UK Takeover Code regarding statements we can make about our interaction with Astrazeneca.

"There is no consummated transaction at this point," the statement continued. "If and when there is a consummated transaction we will then be able to speak to specific aspects and details as appropriate."