The New Scientists | March 12, 2012 Issue - Vol. 90 Issue 11 | Chemical & Engineering News
Volume 90 Issue 11 | pp. 36-38
Issue Date: March 12, 2012

The New Scientists

Researchers at patient-centered nonprofits are rolling up their sleeves to speed the development of new drugs
Department: Business
Keywords: nonprofits, drug development, myelin repair, ALS
ALS TDI scientists hunt for promising new drugs.
Credit: Jeff Dunn/ALS TDI
ALS TDI researcher working in their Cambridge, Mass., labs
ALS TDI scientists hunt for promising new drugs.
Credit: Jeff Dunn/ALS TDI

In January, the cystic fibrosis community rejoiced at the approval of Kalydeco, the first drug to fix the underlying genetic defect that drives the disease in some people. In hailing Kalydeco’s launch, Food & Drug Administration Commissioner Margaret A. Hamburg noted that the drug was made possible through a unique partnership between its developer, Vertex Pharmaceuticals, and the Cystic Fibrosis Foundation, which bankrolled much of the R&D.

Kalydeco is the first major success to emerge out of a venture philanthropy model that has grown in popularity at patient-centered nonprofits. Rather than simply writing checks for basic academic research, many nonprofits are trying to accelerate the development of new medicines by directly funding biotech firms.

Now, a handful of nonprofits are going a step further in their efforts to speed the launch of new medicines: They are opening their own laboratories, run by scientists plucked from the drug industry. The in-house teams test promising molecules in hope of generating enough data to entice industry to work in areas that might otherwise be deemed risky or lacking in commercial appeal.

The pioneer in the internal research approach is the ALS Therapy Development Institute (ALS TDI), established in 1999 to find a treatment for amyotrophic lateral sclerosis, a neurodegenerative disorder known as Lou Gehrig’s disease. Its founders believe the lab represents the long-term commitment needed to push a drug through approval. “Developing a drug is a process fraught with attrition rates, and if you don’t have a dedicated team, it would be difficult to stay in for the long haul,” says Steven Perrin, who is ALS TDI’s chief executive and chief scientific officer.

ALS TDI started with tiny labs and a handful of scientists. Today, the nonprofit has 52 employees, including 32 full-time scientists, all of whom previously worked in the drug industry, and is considered a leader in its field. This month, the organization moves into new 26,000-sq-ft labs in Cambridge, Mass.

Perrin credits the institute’s success in part to its status as a nonprofit. For example, ALS TDI can access new technology at a fraction of the cost a for-profit firm must pay. And because the institute isn’t considered a competitor to industry, its scientists can ask companies for proprietary compounds with interesting mechanisms of action to test in its ALS models. Big pharma or biotech companies also approach the nonprofit to test promising drug candidates, a service that brings in more than $1 million in revenue each year, Perrin notes.

ALS TDI’s efforts have yielded two drug candidates poised to enter Phase II clinical trials this year and a pipeline of other molecules. The institute has also validated two preclinical mouse models used for drug screening.

Other nonprofits want to repeat the success of ALS TDI. For example, Flatley Discovery Lab is a Boston-based nonprofit laboratory established in 2008 to develop small molecules to treat cystic fibrosis. Before embarking on the venture, Flatley executives reached out to ALS TDI founders and scientists to pick their brains about what makes the institute work.

Also turning to ALS TDI for advice was the Myelin Repair Foundation, a nonprofit devoted to finding treatments for multiple sclerosis. In January, it launched the MRF Translational Medicine Center. Located just a few miles from MRF’s Saratoga, Calif., headquarters, the laboratory is home to a small team of scientists drawn from companies such as Eli Lilly & Co., Amgen, and Merck & Co.

MRF’s decision to set up its own labs grew out of its Accelerated Research Collaboration (ARC), a consortium of academic scientists tasked with discovering and validating drug targets, assays, and molecules relevant in myelin repair, says Jay Tung, MRF’s vice president of drug discovery. Since its launch in 2004, ARC has generated tools and technologies that enable promising molecules to be evaluated. “Now, our mission is to motivate pharma organizations to take these on,” Tung says.

But in today’s challenging climate for big pharma R&D, MRF and its ARC partners recognized that they needed to do more to convince drug firms to bet on their discoveries. After exploring several ways to lower the risk of pursuing discoveries made in an academic setting—for example, simply paying contract research organizations to conduct further studies—MRF decided to hire its own team of scientists.

Having internal research efforts “liberates us” on several fronts, Tung says. The nonprofit can still work with academic partners and gain insight from its scientific advisory board, but it now has people with industry experience to build data packages for drug targets and candidate compounds. Meanwhile, MRF also serves as neutral territory to test compounds being developed by drug companies for other indications that might be of value in myelin repair.

In addition, having in-house scientists allows MRF to test compounds that are already on the market for different indications or that no longer have patent protection. The aim is to develop enough data and intellectual property to make a compelling case for a pharma firm to take them on. “We’re not motivated by patent exclusivity,” Tung says. But MRF does recognize that big pharma needs to make a profit and thus needs patent protection before it makes an investment.

ALS TDI scientists are also working on repurposing existing drugs for new indications, an effort that has already produced a promising ALS drug lead. On the basis of animal data that suggested Novartis’ multiple sclerosis drug fingolimod might also treat ALS, the nonprofit synthesized the compound and then tested its structural and functional activity in vitro and in vivo.

Last month, ALS TDI announced plans to launch a Phase II study of fingolimod in ALS patients. “We went from hypothesis to, hopefully, a Phase II clinical trial in 18 months,” Perrin says.

Despite success stories like that, the do-it-yourself approach isn’t for everyone. After passing through the ALS TDI labs, executives from many foundations and nonprofits realize that in-house research is more work than they are prepared to handle. “They see our microscopes and walk through our automation lab or our genomics suite,” all installed at a cost of $80 million, and are taken aback, Perrin says. “What we have here didn’t happen overnight.”

Some patient organizations believe their money is better spent complementing existing efforts within industrial and academic labs.

“We’re aware of a lot of the nonprofits that are going down this road,” says Mark Frasier, director of research programs at the Michael J. Fox Foundation, which is pursuing a cure for Parkinson’s disease. But he says he’s confident in the level of Parkinson’s disease drug discovery taking place within industry. Frasier does acknowledge that the activity is in part because of the attractive commercial opportunity an effective Parkinson’s treatment represents; not all diseases can incite the same level of enthusiasm.

But the patient-driven groups that have adopted the in-house approach are enthusiastic about the role they can play to fill the gap between the discovery lab and the clinic. With industry becoming increasingly risk-averse, the timing is right for new models of how to do research, MRF’s Tung says. “This is a kind of renaissance where nonprofits are stepping up to the plate.”

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