BUSINESS
FORMING A BLOOD TIE LAST MONTH, the health care giant Baxter
agreed to buy AesRx, a virtual biotech firm developing a drug for sickle cell disease. If successful, the drug, Aes-103, could be the first dedicated treatment for the more than 85,000 people in the U.S. with sickle cell. But despite a sizable market and significant need, the drug might just as easily have disappeared into obscurity. Developing drugs for sickle cell has proven daunting, and investors were not interested in Aes-103. The compound was kept alive in large part because of a National Institutes of Health program called Therapeutics for Rare & Neglected Diseases (TRND). It was started in 2009 to forge partnerships with companies or institutions in need of help with drug development projects that are high risk but potentially offer high therapeutic reward. Sickle cell is the result of a mutation in hemoglobin, the component of red blood cells tasked with carrying oxygen from SOLVING SICKLE the lungs to the rest of the body. After rebrowning sugar. VCU CELL AesRx is leasing its oxygen, the errant hemoglobin patented the comtrying to prevent polymerizes, causing the red blood cell to pound and licensed it red blood cells warp and stiffen. The sickle-shaped cell can in 2005 to Xechem Infrom becoming clog blood vessels, depriving organs and warped, as in this ternational, which semicrograph. tissues of oxygen-rich blood. cured a small-business Currently, the only treatment for sickle grant from NIH to supcell disease is hydroxyurea, an anticancer port toxicity studies. compound that doesn’t work for everyone But Xechem went bankrupt in late and is replete with side effects. 2008 and sold 5-HMF to the newly formed For years, researchers tried to develop AesRx. The new owner’s chief executive, molecules that prevent sickling by increasStephen R. Seiler, immediately began looking the mutated hemoglobin’s ing for capital to advance the H affinity for oxygen. Most of the drug, now called Aes-103. “I’ve O efforts centered on aromatic alO OH been in the industry for 20 years, dehydes, an avenue that proved and when I acquired control of effective—one compound got 103, I went around to the usual Aes-103 all the way to Phase II clinical suspects,” Seiler recalls. studies—but was stymied by toxicity. But the timing was terrible: It was just a A team led by Virginia Commonwealth few months after the collapse of Lehman University medicinal chemist Donald J. Brothers, and venture capitalists (VCs) Abraham decided to look at aromatic alweren’t interested in risky projects. Moredehydes found in food. He reasoned that over, drugs for orphan diseases, now a hot anything we eat should be safe as a drug, commodity, weren’t popular at the time. explains VCU chemist Martin Safo, who The biggest hurdle, however, was the was a postdoc in Abraham’s lab at the time. perception that the path to approval was The researchers landed on 5-hydroxytoo onerous. VCs were turned off by the methylfurfural (5-HMF), which is found in prospect of running a clinical trial similar coffee and dried fruit and is a by-product of to the one that got hydroxyurea approved CEN.ACS.ORG
23
AUGUST 4, 2014
JAN ICE HANEY CARR/CDC
An NIH program helped keep alive AesRx’s treatment for SICKLE CELL DISEASE
as a sickle cell treatment. A Phase III study of that drug began in 1992, and it took until 1998 for it to be approved because recruiting patients proved difficult. The worry was that Aes-103 would run into the same patient recruitment challenge. “Over the next 12 months, we really got no positive feedback from VCs,” Seiler says. THEN, IN THE SPRING of 2010, Seiler met
John C. McKew, acting director of TRND’s preclinical division. AesRx struck a deal with TRND later that year, and the partners quickly set out a series of objectives and “go/no-go” decision points, Seiler says. The idea was to get the project, which still needed preclinical tests, into a Phase II study, a stage at which investors’ interest might be piqued. Indeed, the results from a Phase I/II trial of Aes-103 and the start of a Phase II study lured Baxter. The collaboration with TRND removed uncertainty around the program, Seiler says. Not only did data on the compound grow, but NIH also helped smooth its clinical path by organizing a meeting with the Food & Drug Administration related to clinical trial design, a key consideration for potential investors. Moreover, the collaboration with TRND helped AesRx secure other financing to stay afloat. In 2011, the firm won a $750,000 loan—recently repaid with interest—from Massachusetts Life Sciences Center. NIH learned a lot by working with AesRx, one of its first TRND collaborators, such as how to set up government contracts to advance a drug development project, according to TRND’s McKew. And the agency had to work out how it would handle any intellectual property generated through a TRND collaboration. Aes-103 is one of four molecules in the TRND program to have moved into clinical studies and the first to be acquired. Some of the corporate partners have been successful in securing funding from VCs or patient groups based on the progress made through TRND. TRND’s capacity is limited: The program can take on only about three new projects a year. But the projects that are adopted move swiftly through development, partners note. The TRND scientists were “transparent in decision making and collaborative, and their turnaround time was really quick,” Seiler says. “This is not your father’s NIH.”—LISA JARVIS
