An Approach To Recombinant R&D

Depiction of CSL’s long acting recombinant albumin fusion protein for hemophilia B (Image credit: CSL Behring)

Recombinant proteins are an innovative class of drugs in which DNA have been reprogrammed or recombined to treat diseases. CSL Behring has long been successful in innovating these technologies, and has done so by applying a similar recombinant approach to how it operates its R&D.

The company, founded 100 years ago by the Australian government, has grown into the country’s leading healthcare company, and leads the global industry in providing treatments for hemophilia and other rare diseases. Going public in 1994 was the trigger to rethink its therapies and operational structure.

“We’d expanded worldwide through smart acquisitions.”

“This challenged us to ask ourselves how we could use our resources differently to deliver on our promise to patients, and differentiate in the hemophilia space,” said Paul Perreault, CSL Behring’s CEO.

Those resources included the acquisition of ZLB from the Swiss Red Cross and the acquisition of Aventis Behring, which significantly advanced the company’s global footprint, and gave it R&D and manufacturing operations in Bern, Switzerland, Marburg, Germany, and Kankakee, Illinois. This also included expertise in immunoglobulins, recombinant technology platforms, and skills in protein fractionation. Its research center in Australia, closely affiliated with the University of Melbourne, already possessed deep knowledge in plasma and antibodies.

Market research indicated that dosing frequency, usually three times/week, was a major quality of life issue, both for patients with hemophilia and parents (the vast majority of hemophiliacs are young boys, and the gene is carried by their moms, which made treatment an emotional issue). The company set out to reduce dosing to once/month.

Setting the innovation goal was the easy part, however.

“We needed to combine our global strengths and unite researchers on three continents, in different time zones, and with language and cultural differences,” Perreault noted. “We had to get everyone working with each other as easily as they did with their test tubes.”

The distance between its researchers was immense, measured both in miles and mindsets. Each team felt it would drive the process, and the scientific challenges of finding new synergies and deciding tradeoffs often strained the established R&D processes at each facility.

“We brought in patients to talk to the scientists directly, and gave them a personal connection to a shared outcome,” Perreault said. The company also started sending researchers to work in one another’s labs and forging more expat transfers, rejected asynchronous digital platforms for project management in lieu of more real-time, personal communication, and aggressively pushed getting early trials off of computers and into humans, as Perreault noted, “the medical industry has cured more mice than anything else.”

The result was the development of a recombinant factor IX fusion-protein therapy, which can be dosed once every two weeks, and is currently under review for approval by the U.S. Food and Drug Administration. The innovation process it pioneered is now being applied to a host of other projects.

One of its latest innovations is CSL-112 which, unlike a statin that regulates cholesterol removal, actually cleans arterial plaque. Teams from Kankakee, Bern and Melbourne collaborated on its development, utilizing one of the hundreds of proteins found in plasma as the basis for the compound. The drug is currently in human trials, and could be transformational for patient care and the company.
CSL Behring has purified so far less than a dozen of those hundreds of proteins, suggesting a deep resource for future innovation.

“We’re focused on outcomes,” Perreault said. “We shift funds to projects with the greatest promise, and cut those that are more interesting than valuable.”