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Exclusive Life Science Feature ment involving lawsuits over its private-investor stock pricing. There was no romance in the cleanup, according to Rabin. "It was just blocking and tackling," he says. "You just have to go to the office every day and deal with it." Rabin also inherited a financial hangover when he came to ACT in 2010 — the result of a weird funding history, which we'll get into in Part Two. Good thing he is an economist, having spent most of his career raising funds for life sciences companies. If putting the right top executives in place is a best practice, recruiting and keeping talent at all levels of the company is an absolutely critical one. Melinta has won several "Best Places to Work" awards that cite its loyalty to the people who helped build it, as well as its readiness to listen to even the newest recruit. Lesson: You can't just relax and say your company is a cool place to work because it is entrepreneurial. You have to work at creating an environment that rewards people for going the extra mile in their jobs. People will be inspired by the common cause of developing a unique product, but inspiration is vulnerable; it will fade quickly if not accompanied by positive treatment in the workplace. FROM EXPERIMENT TO DEVELOPMENT A common failing of micro-innovator companies is to languish in the experimental stage without ever breaking out and moving toward a work, they found no one was buying. "They were prepared to give this program away," he says. "I took the job because I believed we found the right application for this technology, and I wanted to put it on a fast track." In December, 2010, Garabedian announced cancellation of a scheduled dosing study, saying it was the wrong study design, and the delay of a Phase 2b study. He spent his first month with his manufacturing heads and started producing more drug, while at the same time, directing the head of preclinical to start the long-term animal toxicology work. He spoke with key opinion leaders in DMD and used their advice to help design an optimal study. With a still limited supply of the drug, the study had a small sample size, eight patients treated and twelve patients in total when it began in 2011. Additional evidence also encouraged Sarepta's focus on DMD. Knowledge about the dystrophin gene had increased; academic researchers had done "micro-walks" along the genome to find the gene and were figuring out how to silence a part of the gene, called exon 51, and thereby correct translation of the gene to the protein in patients with certain genetic mutations. Sarepta seized on the unique mechanism of using phosphorodiamidate morpholino oligomer (PMO) antisense technology to target precursors to messenger RNA, with the aim of skipping over an exon in the gene to restore dystrophin production. It also made the fateful All of our featured micro-innovators have gone through multiple management turnovers. clear product goal. Sarepta is a particularly good example. Garabedian recalls how the company spent years investigating numerous disease areas — such as West Nile virus, polycystic kidney disease, HCV, and coronary artery disease — before settling on DMD. "When I came on board, the company hadn't yet done the type of early development, translational work that you need to optimize a drug and ensure you have an active dose and regimen in the clinic. Also, the company wasn't attracting the right level of talent. Like many companies that exist on limited cash, the work is all science experiments, almost academic, and as private-enterprise businesses, they fail to achieve any success. We quickly homed in on the area with the most value." One of Sarepta's experiments in the U.K. hit its target, yielding evidence that, with systemic delivery, an antisense drug could enter the cell and produce a desired protein, in this case, the dystrophin protein in Duchenne muscular dystrophy. Even though the study elicited a rather low dose response, Garabedian says, "It showed a hint of a promise." He says the previous management could not envision the complicated path it would take to develop the drug further and sought to sell off the worldwide rights. But without further development 28 LifeScienceLeader.com December 2013 decision to make dystrophin levels the primary biomarker and basis for regulatory approval. Now, news stories on Sarepta's approval strategy, the regulatory response, and the fortunes of its DMD competitors appear almost daily. It has become a stock to watch as all of those variables play out. (In September, Sarepta announced favorable data from the Phase 2b eteplirsen study at 96 weeks, showing a "continued stabilization of walking ability" in treated patients on a standard six-minute walk test. The company had previously reported the study met its primary endpoint of increased novel dystrophin. But in November, the FDA directed Sarepta not to file for accelerated approval for eteplirsen and asked for a new placebo-controlled trial, inevitably delaying a long-term follow up on the 2b study and causing the company's stock to free-fall. No doubt the news-sensitive dynamics will continue indefinitely.) As with Sarepta, Melinta might have chosen to build a business or partnership with its ribosome crystallography platform that targets the large (50S) ribosomal subunit of bacteria, leaving the drug development work to someone else. But the scientific DNA of the company obviously propelled it into using the platform to discover and develop