Rare Diseases, Common Challenges
Regina Kelder

Rare Diseases, Common Challenges

A cancer survivor launches a biotech, and a foundation creates a blueprint for venture philanthropy. Live coverage from Charles River’s 2nd World Congress

When David Hysong founded the biotech, Shepherd Therapeutics in his late 20s, he admittedly was in virgin territory. He had no experience running a company and no background in science. But what he did have was a rare form of head and neck cancer called adeno cystic carcinoma that was largely untreatable with chemotherapy drugs, much like the thousands of other patients with rare cancers.

So he started Shepherd with the idea that it can one day be a “one-stop shop for rare cancer patients and for companies looking to expand their assets.”

Charles River’s 2nd Annual World Congress: Lessons Learned from Rare Disease and Personalized Medicine Approaches honored Hysong yesterday for his work in advancing the cause of rare cancers, which by some estimates represent 30% of all human cancers yet are woefully under-represented in clinical trials.

The mission of Shepherd Therapeutics is to seek out the best therapeutics and delivery mechanisms for rare cancers. The company uses software and proprietary algorithms to analyze research on rare cancers. Their analysis is paired with patient profiles, demographics, and any other data they can accumulate to develop treatment plans for patients with rare cancers.

Extending beyond the original scope of Shepherd Therapeutics are Hysong’s two nonprofits, a public foundation and a private charity, which will be used to fund research and treatment plans for rare cancers. All three institutions have come about through Hysong’s tireless networking and his excellent team, including his co-founder Gene Williams, formerly of biotech giant Genzyme.

“What do you do when you are left to die, when you are 27 and they tell you ‘Good Luck, you might have five years, you might have 10’ ” said Hysong.  “So eight months after being diagnosed I founded a company. It would be like waking up and saying now I’m going to develop a bicycle that can fly to Mars. I had no idea what I was doing.”

The two-day World Congress meeting in Cambridge, MA, drew researchers, nonprofits, contract research organizations, academic scientists and patients and patient advocates to explore the best ways to develop new treatments for rare diseases and disorders, of which there are many.  The US National Institutes of Health (NIH) lists at least 7,000 rare diseases, and estimate that 25 million Americans have a rare disease.

For the vast majority of rare diseases, there is little to offer patients beyond a diagnosis, and those with ultra-rare diseases can’t even guarantee that. But there are lately definite glimmers of hope, and winds of change. There have been some major breakthroughs in rare disease drug development and a growth of new technologies and tools that are helping researchers mine the limited patient populations afflicted with a rare disease. Disease foundations are now a driving force in rare disease drug discovery, pharmaceutical companies are forging partnerships with academic laboratories to develop new drugs, and the regulatory agencies are opening up avenues to that allow rare disease drugs to move to market faster.

Venture Philanthropy

Clearly, one of the biggest success stories in rare diseases is cystic fibrosis, an incurable lung condition where it used to be that children rarely lived past the age of 5. Today, the average life expectancy is 46 and growing, thanks to the availability of drugs that target the underlying cause of the disease.

The irony is that this progress many not have occurred were it not for a nonprofit foundation that was formed in 1955 by a group of parents determined to save the lives of their children. The nonprofit created accredited care centers, and launched a patient care registry. Research supported by the foundation led to the discovery of the defective cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989—well before the human genome was mapped—followed quickly by the first approved drugs for cystic fibrosis in 1993 addressing complications of the disease.

With the help of more than 140 care centers, the foundation seemingly had a blueprint for cystic fibrosis, said Preston W. Campbell, III, MD, who delivered a keynote address on Monday. “We were able to create cell lines and animal lines and unravel the structure of CFTR,” he said. “We also learned from genotypes and phenotypes that if you were fortunate to have a variant that conferred just a little of the activity then your CF disease was much milder.”

Yet despite this “embarrassment of riches in the science”, no one was focusing on CFTR as a target, said Campbell. So with the urging of the board, the Cystic Fibrosis Foundation developed a venture philanthropy model—which they call the Therapeutics Potential Program. Campbell said they provided financial resources to lower the bar for companies to come in, and provided the companies with a rich resource of scientific tools. They also embedded a scientific advisory committee to help them design and develop endpoints for their studies. With Aurora Biosciences (now part of Vertex Pharmaceuticals), the Foundation co-developed two groundbreaking drugs that target some of the mutations in the CFTR gene; the drugs caused an immediate sensation.

“This has exploded the CF space,” says Campbell. “Patients are living longer and leading healthier lives. Successful collaborations breed successful collaborations.”

If you are interested in learning more about David Hysong’s work, check out this recent podcast. And if you would like to learn more about the families impacted by cystic fibrosis, check out this recent blog post.