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New Haven BIZ January-February 2019

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n e w h a v e n b i z . c o m J a n u a r y / F e b r u a r y 2 0 1 9 | n e w h a v e n B I Z 23 a co-founder who helmed the company from 2000 to 2010, when it was known as Rib-X Pharmaceuticals. ose who closely follow the industry weren't surprised. e antibiotics market is especially tough to crack, experts say, and it can be a long, bumpy road before a new infectious disease drug ever turns a profit, as they struggle to compete with cheaper generic drugs. Major U.S. pharma players have all but abandoned the space, choosing instead to focus on drugs to treat cancer or chronic diseases, where there's a much higher return on investment, experts say. Last July, Swiss drugmaker Novartis was the latest to make news when it closed its California-based anti-infective research program, shedding 140 jobs. "You can't buy a lot of corporate jets and steam yachts for corporate officers on the antibiotic market, and therefore they don't like it," Peter Moore, professor emeritus of chemistry at Yale and anoth- er Melinta co-founder, said of the phar- maceutical industry. "Here's an unmet need where the economic incentives are all completely in the wrong direction." Yale beginnings Melinta's New Haven roots stretch back to the turn of the millennium, in the lab of Yale's Nobel Prize-winning molecular biophysicist omas Steitz. In 2000, Moore and Steitz had just finished mapping the atomic structure of the ribosome — the cell's protein-making factory. (Steitz, who won the Nobel Prize in 2009 for his work on the ribosome, died of pancreatic cancer in October.) Around the same time, public health officials were sounding an alarm about the spread of drug-resistant bacteria — especially methi- cillin-resistant Staphylococcus aureus, better known as MRSA — and the need for new types of antibiotics to defeat the deadly bugs. "Turns out that the ribosome, which makes protein for all cells, is the target for half the an- tibiotics that have ever been discovered," says Moore, explaining the drugs kill bacteria by destroying their ability to manufacture protein. rough X-ray crystallography, Steitz and Moore were able to determine how an antibi- otic binds to bacterial ribosomes — unlock- ing knowledge that could be used to create new antibiotics to combat the drug-resistant pathogens. "We knew exactly where [the antibiotics] went and how they interact and all the nitty gritty M e l i n t a T h e r a p e u t i c s "It's a sad day for antibiotics" - Susan Froshauer a co-founder who helmed the company (then know as Rib-X Pharmaceuticals) from 2000 to 2010 details that you would like to have if you were in the pharmaceutical business," Moore says. Meanwhile Froshauer, who had been working in antibiotics discovery at Pfizer, was confiding in her good friend Steitz about her desire to leave big pharma and launch a startup. In 2000, just as his work on the ribosome was about to be published, Steitz took Froshau- er up on her idea, eager to apply his ground- breaking research to improving medicine. "He said, 'Come on — time to start the company,'" Froshauer recalls. e pair convinced Moore and Yale com- putational chemist William Jorgensen to join them as scientific co-founders, and together they raised nearly $2 million from family and friends to launch the new company. ey assembled a top-notch research team, drawing heavily from ex-Pfizer scientists. e resulting enterprise, Rib-X Phar- maceuticals, would go on to become a pioneer in Connecticut's nascent biosci- ence industry, among the first biotech startups spun out of Yale in the 1990s and early 2000s. Along with Alexion, Achillion, Cura- Gen and other early New Haven biotechs collectively known as the Seven Sisters, Rib-X is credited with helping to put the Elm City on the map as an emerging hub of life science innovation. In 2013, the company was renamed Melinta erapeutics following a new round of follow-on investment and the hiring of new management. In late 2017, it merged with North Carolina antibi- otics-maker Cempra Inc. and started trading on the NASDAQ exchange. e following January, Melinta ac- quired the infectious-diseases division of New Jersey-based e Medicines Co. for $270 million, along with the latter's three commercial drugs — Vabomere, Orbactiv and Minocin. Although the founders are no longer directly involved in the company, much of Rib-X's original R&D team stayed together, bonded by their belief in Steitz's mission, Froshauer says. "ere's a lot of passion and sense of mission as well as a deep appreciation of the quality of the science and the opportunity to utilize that science," she explains. "at's the special sauce that existed in Rib-X and Melinta, and I don't know how oen that happens today." 'Getting worse every year' at mission is even more urgent today than when the company started, health officials say. According to the Centers for Disease Con- trol, around 23,000 people die annually in the U.S. from drug-resistant infections, and health organizations warn that so-called superbugs could kill as many as 10 million people a year worldwide by 2050. Matthew McCarthy, an infectious disease specialist at New York Presbyterian Hospi- tal Weill Cornell Medical Center and author of the book Superbugs: e Race to Stop an Epidemic, says bacteria that were treatable with pills just a few years ago are now requiring IV antibiotics and hospitalization. "It's getting worse every year," says McCarthy, who worked in Steitz's lab while he was a Yale un- dergrad in 2000, but is not connected to Melinta. Continued on next page

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