Lessons from Biotech: Tweaking the Imperfections

An increasing number of small biotech companies are being hatched to focus on a single disease or condition. The strategy goes against the diversified portfolio approach most Big Pharma companies have embraced, and instead puts all the eggs in one basket.

Dart Therapeutics—one such company—has taken on Duchenne Muscular Dystrophy (DMD), a disease found in 1 out every 3,600 boys where muscle tissue progressively deteriorates over time, and for which a combination of therapies is likely necessary. Founded in 2010 by two patient foundations and a seasoned management team, Dart’s strategy focuses on tweaking the imperfections of promising therapies and changing the risk equation in clinical trials to gain efficiency in time and investment. And true to its formation, patient groups are integral in the decision-making process.

The company’s CEO and co-founder, Eugene Williams, is no stranger to the triage activities at big pharma companies, where many molecules are assessed as matters of priority for efficacy, or dismissed at the slightest hint of unpleasant side effects, problems with delivery, metabolic issues, et cetera. Williams, formerly an SVP at Genzyme, explained, “In disease spaces like DMD where available therapies are few and far between and a magic bullet is unlikely, we are willing to cultivate diamonds in the rough, to address their imperfections, many of which are fixable.” Dart’s DMD candidate halofuginone, for example, initially had oral tolerability issues, causing nausea and vomiting in patients. The company developed an enteric-coated (delayed-release) version, HT-100, which is currently in study and so far has had no tolerability issues, says Williams.

Dart has tweaked the risk equation, says Williams, to improve efficiency in clinical trials and to maximize invested resources. Dart set up master service agreements across contract research organizations, which allow start times to occur an average of four months faster and with an average savings of $1 million, according to Williams. He advocates investment in easy-to-use, non-invasive biomarkers that help detect treatment effects that allow for smaller enrollment size than in trials based on less methodologically stable endpoints. Dart’s use of electrical impedance myography (EIM) is one such biomarker that measures the health of muscle tissue over time, instead of the six-minute walk, a standard endpoint in DMD that often fails to adequately address variability in the disease.

Much of Dart’s management team understands the need for efficiency, based on their experiences at larger pharma companies. As Williams recounted, “We spent years together trying to make trials more efficient during the 1980s when the CRO industry hadn’t quite taken off. Now, so much is outsourced to CROs that companies themselves don’t do that much investing in that efficiency.” While this model today serves as a rational approach for larger companies who can rely on CROs with broad cumulative experience, “in a disease state like DMD no one has that experience. So we’re looking to create it by doing a lot of things ourselves, and in that, learning to do it better the next time,” Williams said.

In DMD, as with any other disease space, the patients are always important. But in the case of Dart, the patient foundations they work with most closely, Charlie’s Fund and Nash Avery Foundation, are on the board of directors, and are an integral part of how the company functions. In addition to attracting investment in the development of promising therapies, both help to evaluate the pipeline of potential therapies in DMD to determine which seem most promising. Benjy Seckler, co-founder of Charlie’s Fund, initially identified halofuginone as a potential treatment. Dart acquired the drug candidate after a review of its properties, and is developing it under the name HT-100.

With R&D budgets slashed in recent years and months, and with productivity slowed considerably, small biotechs like Dart show the industry not only that change is necessary, but it can be beneficial for those who are willing to get involved, and that includes patients. In engineering workarounds to bypass drug imperfections, and by working to eliminate clinical trial inefficiency, addressing unmet need may only be a matter of tweaking ideas, not scrapping them completely.