The Freedom to Dream

By Marie Shields, Editor

Boehringer Ingelheim's Andreas Barner believes in allowing his researchers the space to follow their inspiration. The result has been three promising new compounds in diabetes and oncology in the last two years for the German company.

Andreas Barner is clearly tired. It's been a long day at Boehringer Ingelheim's R&D facility in Biberach, Germany. The company has just announced its entry into the type 2 diabetes arena, and Barner and a panel of scientists have been busy explaining the new compounds to a room packed with journalists from all over the world.

I am his last interview of the day, and have been forewarned that he has a train to catch, which makes me apprehensive about the kind of welcome I might get as I walk into the light-filled meeting room. Yet Barner, immaculate in a dark suit and crisp white shirt, is unfailing charming and polite. He offers me water from the bottles arrayed on a silver tray on the table and makes small talk about the brand of digital recorder I am using.

This calm exterior belies a hectic professional schedule. Barner is a member and past Chairman of the German Association of Research-based Pharmaceutical Companies, has served as Deputy Chair Person of the National Genome Research Network Steering Committee, and has been a member of the Advisory Board to the University of Mainz, as well as the Board of Trustees of the German Chemical Industry Fund.

Armed with a doctoral degree in medicine and a PhD in mathematics, Barner began his professional career at Ciba-Geigy, before joining Boehringer in 1992 and working his way up to his current position as Vice Chairman of the Board of Managing Directors and Head of the Corporate Board Division for Pharma Research, Development and Medicine.

New frontiers

It is in this position that he has led the unveiling of Boehringer's new pipeline of antidiabetic compounds. In his quiet yet authoritative voice, Barner explains the company's decision to enter the diabetes arena: "When we enter a new area, we always look first to see if there is a true medical need, or a problem that needs to be solved. Secondly, we ask ourselves: do we believe that we can find a research approach to meet this need? The problem must be medically relevant. It's then up to the researchers to decide if there is a possibility that we can deal with this problem. Is there a target; do we have a mechanism we can use to change the course of the disease?

"In the case of diabetes, it was very obvious that there was a medical problem; it was very obvious that we had approaches that were possible, and the new compounds show that this has worked out well."

Treatments for type 2 diabetes clearly represent a growing market in the pharmaceutical industry. The World Health Organzation estimates that 180 million adults around the world are currently living with diabetes, with this number is expected to rise to more than 360 million by 2030.

Type 2 diabetes accounts for 90 percent of all diabetes cases. According to the International Diabetes Federation, the highest rate of diabetes prevalence per capita is in North America at 9.2 percent of the population, but Europe follows closely behind at 8. 4 percent.

Here at the BI's Biberach location, the company's research teams have been focusing on the discovery and development of novel oral antidiabetic treatments targeting two new principles, the inhibition of DPP-4 (dipeptidylpeptidase inhibitors) and the inhibition of SGLT-2 (sodium-dependent glucosetransporter-2 inhibitors).

While there have been a number of advances in the treatment of type 2 diabetes in recent years, traditional therapies have failed to meet the demands of the huge number of people currently living with the condition. When Boehringer's compounds, currently in phase II and III clinical trials, eventually reach the marketplace, they could prove to be a goldmine for the company.

A medical necessity?

As with treatments for many chronic conditions, you can't help but wonder where the true interest lies - in making money or in helping sufferers? In the case of type 2 diabetes, it can be argued that more money should be put into preventing the onset of the condition as well as treating it. Even the information pack handed out at Boehringer's press conference points out that up to 80 percent of type 2 diabetes could be prevented by encouraging people to adopt a healthy diet and increase their physical activity.

I suggest to Barner that it would be better to encourage people to live healthier lives rather than waiting until they develop the disease and then treating them with a drug, but he is having none of it. He leans forward in his chair and clasps his hands against the pristine white tablecloth. "I would be fully supportive of making sure that prevention is a cornerstone of any healthcare system," he says. "Prevention means educating people, especially children, to eat healthy food and to eat less of it, and to be more physically active so they do not become obese and diabetes does not have the chance to develop. That's the first step.

"However, there will be people for whom this does not work. And then there are those who already have the disease as an existing condition. We have to make sure there are optimal treatments available for them. This is where I see the role of the diabetes medications we are developing."

In development

Boehringer's frontrunner compound for diabetes is BI 1356, currently in phase III clinical development. BI 1356 (Ondero) is a DPP-4 inhibitor - a new class of oral hypoglacaemics that inhibit DPP-4 and enhance the body's ability to control blood glucose by increasing active levels of incretin hormones. They control elevated blood glucose by triggering pancreatic insulin secretion, suppressing pancreatic glucagon (a hormone involved in carbohydrate metabolism) secretion and notifying the liver to decrease production of glucose.

According to Barner, phase IIb trials confirmed the unique properties that may positively differentiate BI 1356 from others in the same class. He says BI 1356's safety profile was very favorable, and that a large phase III clinical programme currently under way aims to further confirm its efficacy and tolerability for long-term use.

The company also has two other antidiabetic compounds, BI 44847 and BI 10773, in phase II trials. They are both SGLT-2 inhibitors that express their therapeutic effect mainly be eliminating excess blood glucose via the urine. Due to their unique mechanism of action, SGLT-2 inhibitors have a different safety profile to that of other agents traditionally used to combat type 2 diabetes.

Diabetes is not the only area in which Boehringer Ingelheim is forging ahead: the company is also broadening its oncology pipeline. Out of the four leading compounds developed as a result of BI's entry into oncolocy in November 2006, the agent BIBW 2992 (Tovok) has recently entered phase III clinical trials. BIBW 2992 targets non-small cell lung cancer (NSCLC), the most common form of lung cancer.

The phase II trial, called the LUX-Lung 1 study, will determine the efficacy of BIBW 2992 in lung cancer patients in whom the most commonly used treatments of the same class (gefitinib or erlotinib) have failed. Barner says that phase II data showed that advanced NSCLC patients treated with BIBW 2992 experienced a high rate of disease control (87 percent) and a promsing overall response rate (50 percent).

Another oncology compound, BIBF 1120 (Vargatef), will enter phase III development in the near future. BIBF 1120 is a novel triple angiokinase inhibitor that simultaneously inhibits three growth factors and receptors that play an important role in angiogenesis: VEGFR, PDGFR and FGFR.

BI is also active in developing treatments for premenopausal women suffering from hypoactive sexual desire disorder. Its compound Fibanserin is currently being investigated in the ongoing Bouquet phase III trial programme, which involves 5000 women. Results are expected next year.

I have to add that there were some bemused looks among the journalists when this last disorder was mentioned at the press conference, although it is classified as a disorder in DSM-IV and some estimates put its incidence at about 45 percent of premenopausal women. Whether this is the type of condition best treated through medication is open to debate.

Family business

The press conference in Biberach was the second of its kind for Boehringer since 2006, which in itself is interesting, since BI is still majority owned by the Boehringer family and so is not required to disclose the progress of its pipeline or research. Why then go to all this trouble?

"We think that a certain amount of transparency is necessary," Barner explains. "We do have some luxury there, in that we do not report on compounds earlier than phase II, because we prefer not to raise hopes and then a year later have to say that unfortunately it didn't work out. We might still have to do that, because if a compound fails in later trials, then it fails. But we prefer to go public with compounds only once we have a solid base for doing so. This saves time for everybody, and it's luxury we can afford.

"We feel obliged to transparency - we publish all trials and we inform the public about all activities in research and development after phase II."

The luxury of choosing when and what to disclose is not the only advantage conferred on a non-publicly quoted pharmaceutical company. The industry is having a bit of a rough ride at the moment, with the crisis in the financial markets adding to the existing woes of looming patent expiries and a lack of new blockbusters.

Being family-owned means not having to worry about the ups and downs of the stock market, as Barner points out: "It allows us to be more stable. We are less affected by the stock market, very obviously, and continue to follow our long-term vision, and we do that very successfully."

The proof of this is that in 2007 BI invested €1.73 billion in research and development, and added 400 new employees, to bring its global headcount in R&D to 6400 people.  This stands in sharp contrast to many of its rivals. In October, Merck & Co. announced that it will cut 7200 jobs, more than 12 percent of its workforce, as it faces generic competition to its top-selling drugs and falling sales of its cholesterol medicine and its cervical cancer vaccine, Gardasil.

Schering-Plough will cut 10 percent of its workforce, or about 5000 jobs, to reduce spending by €1.15 billion. Pfizer, the world's biggest drugmaker, has cut more than 14,000 employees since 2007 and may have to further reduce its workforce.

In Europe, the UK's GlaxoSmithKline has said that it will cut 850 jobs from its R&D operation, Switzerland's Novartis will fire 550 people, and France's Sanofi-Aventis will eliminate 927 positions.

Rising to the top

Aside from relative job security, another plus for Boehringer's staff is that in each of the past four years, the company has been named among the top four scientific employers by Science magazine. This year it was number four, last year number one. I ask Barner whether this has an impact on the calibre of staff the company can attract, but he shakes his head. "It's good to know. It's a good group of companies to be in the company of. As always, it's a challenge to maintain these ratings, and we do hope that we can continue to do so.

"But I'm not sure whether it has had a major impact on attracting employees. I would be concerned if we were in 100^th place, but you do have to take it with a grain of salt. It's a positive signal, but we should not overestimate it, nor, on the other hand, should we be overly concerned about it."

Perhaps more important to BI's staff retention rates is the way it treats its employees once they have been hired. One important tenet of this, mentioned by Barner during the press briefing, is to give researchers 'the freedom and space to be curious'. When I ask him exactly what this means, he smiles.

"It means that we ask the research teams to come up with ideas about what they want to do and then they go about it in an interdisciplinary fashion - though of course there is always the question of what is medically relevant. We listen to the researchers, we don't have it filtered or decided upon based on arbitrary criteria - we encourage the teams to take a creative approach."

And the future is also looking bright. As Barner puts it, "We have a good pipeline. We believe we have the right strategic approaches to look at the right diseases, and we want to continue in this way. We like what we see - we have our oncology compound, we have the new diabetes compounds, we have new products in the full pipeline; that's a good situation to be in. We want to keep it like that, which is always a challenge in our industry."

With that, the interview is over. Barner shakes my hand, collects his briefcase and overcoat, and is off to catch his train. I walk back through the modern wood and glass building to the atrium, where earlier we were served an unusual lunch of hors d'oeurves on a pharmaceutical theme - strange-colored drinks in test tubes, skewered prawns on what looked like sample slides, a mushroom concoction in a glass vial - accented by beakers billowing dry ice. It was all delicious, and yet Barner was whisked away before it began, and I suddenly wonder whether he even had time to eat.

I gaze down through the huge windows separating the atrium from the employees' restaurant on the ground floor, where a few remaining staff members are lingering over the last of their lunches or placing their trays on the futuristic conveyor belt system. From what I've heard and seen today, Boehringer seems like a forward-thinking employer, using its status as a family-owned company to further its research goals and allowing its employees the freedom to follow their inspiration. I'm almost sorry to leave.

Type 1 and type 2 diabetes

Type 1 diabetes is a disorder in which the body does not produce insulin (a hormone that aids in moving sugar from the blood to the cells). This type of diabetes can be due to a virus or autoimmune disorder in which the body does not recognize an organ as its own and attacks it. In this case the body attacks an organ known as the pancreas where insulin is made.

People with type 1 diabetes are required to take insulin injections to move sugar from the bloodstream. This type of diabetes is usually diagnosed before age 40

Type 2 diabetes occurs when insulin that the body produces is less efficient at moving sugar out of the bloodstream. Some sugar is moved out of the blood, just not as effectively compared to a person with normal insulin efficiency, resulting in high blood sugar.

This type of diabetes is associated with physical inactivity and obesity.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 135 affiliates in 47 countries and 39,800 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing therapeutic products for human and veterinary medicine.

In 2007, Boehringer Ingelheim posted net sales of €10.9 billion while spending one fifth of net sales in its largest business segment, prescription medicines, on research and development.