Hartford Business Journal

12 Hartford Business Journal • August 1, 2016 www.HartfordBusiness.com from page 1 Melinta eyes 2017 FDA approval for bacterial infections antibiotic By John Stearns jstearns@HartfordBusiness.com A bout this time next year, Melinta Therapeutics hopes to celebrate fed- eral approval of its first antibiotic for treating bacterial infections — paving the way for new remedies aimed at defeating deadly drug-resistant bacteria. With hoped-for approval of Baxdela by the Food and Drug Administration in mid-2017, Melinta could begin marketing and selling the antibiotic targeted at serious skin infec- tions, including the nasty MRSA (methicillin- resistant Staphylococcus aureus), which has made many drugs obsolete. There are 3 mil- lion serious skin infections each year in the U.S. that warrant hospitalization, and a large percentage are due to MRSA, creating a sig- nificant potential customer base for Melinta. The New Haven company also believes Baxdela, which is the trade name for dela- floxacin in a class of drugs called quino- lones, will work on other ailments, including pneumonia and urinary tract infections. "It will be an important day for Melinta," said company CEO Eugene Sun, referring to the anticipated FDA approval next year. "It's an important day for any company when they start to generate revenue, so we're look- ing forward to that." Melinta, which also has an office outside Chicago, isn't a one-drug wonder, either. The company, whose mission is to develop and market new antibiotics, is also developing Radezolid, to treat skin conditions, with an initial focus on bacterial acne. Perhaps most noteworthy, Melinta has another program, ESKAPE, that is still preclini- cal, but the company is hopeful it will move to human clinical trials next year. Each letter in ESKAPE stands for bacteria with multi-drug resistance features, "so most classes of antibiot- ics no longer work against the worst of the worst of every one of those pathogens," Sun said. Melinta is working on one antibiotic, in a completely new class of drugs, to treat all six superbugs or bacteria in ESKAPE, which cause various ailments ranging from pneu- monia and urinary-tract infection to intra- abdominal and blood-stream infections. The company's work is important since many older antibiotics have become obso- lete against bacteria, which are constantly finding new ways to adapt and survive, Sun said, adding that people also have taken anti- biotics for granted. "It's important to remember that less than 100 years ago there were no antibiot- ics and the most common causes of death or serious illness were things that are easily treatable now, so antibiotics are probably one of the greatest triumphs of science in the last 100 years," he said. "But like many good things, people just sort of assume that they've always been there." That, along with the fact that bacteria are a moving target morphing and mutating to survive, raises "the concern that we're going back to that, what people call pre-antibiotic era, which was a scary time," Sun said. "So we think we have an important mission." The early days Melinta was founded in 2000 as Rib-X Pharmaceuticals, which reflects the com- pany's focus on ribosomes as its primary tar- get for new antibiotics and "the engine room of all cells," said Erin Duffy, chief scientific officer, who joined the company in 2002 and evolved into her current role heading the New Haven research team. The company can better target ribosomes using X-ray crystallography, a technique to help show how the bacterial ribosome looks with antibiotics bound to it and where the antibiotics bind to the ribosome, a process that inhibits bacteria function. Melinta sci- entists discovered how to map the ribosome using the X-ray crystallography technique. The company was renamed Melinta in 2013 after a new round of investment, install- ment of a largely new management team and to reflect the company's shift towards a more commercial enterprise, Duffy said. Melinta now has about 50 employees, 35 of those in the scientific offices of the 300 George St. incubator building that also houses other bioscience companies in New Haven. The balance of employees, mostly business-related staff, including Sun, work in Lincolnshire, Ill. Melinta's platform of drugs excites Sean Murphy, who retired as vice president of business development for pharmaceuti- cal company Abbott Laboratories in 2010 and went on to cofound Malin Corp. PLC, a Dublin-based company with offices in New Haven and the U.K. that invests in life scienc- es companies. Malin invested $45 million in Melinta last year, making it the second-larg- est investor, behind New York-based Vatera Healthcare Partners. The company has raised several hundred million dollars since its inception. "They're clearly pioneers in coming up with agents that treat a very, very broad range of targeted bacteria," said Murphy, a nonex- ecutive director on Melinta's board who works out of the Chicago area. "And it's something … companies that are in the antibiotic business have always pursued — kind of the silver bul- let of an antibiotic, going after multiple differ- ent types of organisms with one drug. If they can accomplish it, it will change medicine." Melinta is moving aggressively in a field that many in big pharma exited, in part because of the financial return on antibiot- ics, according to Duffy. "Antibiotics are the cheapest life-saving drugs," she said, adding that people take them for 10 to 14 days and they're cured. "And so if you think about the kind of money you can make from that versus, for instance, a cardiovascular drug or a lifestyle drug, where you're taking it chronically, I think for a lot of companies the math didn't add up." That, in part, explains the long time frame from Rib-X's birth in 2000 to today, Duffy said of companies exiting the field. At the same time, changes at the FDA previ- ously made the regulatory path to antibiotic development more challenging, she said. That improved with the 2012 GAIN Act (Generate Antibiotics Incentives Now), which was a response to the sharp drop in new anti- biotic approvals from 2000, she said. The act provided a period of exclusivity for a drug if it met certain criteria for attacking super- bugs and also provided a fast track for review with the FDA. Follow-up legislation is being sought to help accelerate pathways for drugs that meet the highest unmet medical needs, she said. Regulatory challenges are among myriad challenges companies like Melinta face, Sun said. They also include economic, financial and scientific challenges, but that's the story for all companies in the industry, he said. "And the only reason that you stick with it is because those few times when you're suc- cessful, it's enormously rewarding," he said. Abbott connection Abbott was one of those companies that got out of antibiotics in the late-1990s or early 2000s, thinking antibiotics had basically peaked, Murphy said. In fact, Melinta now has the rights to delafloxacin, which Abbott was developing at the time, he said. Murphy's familiarity with delafloxacin from Abbott and the fact that Sun had also worked at Abbott, gave him and Malin more comfort in investing in Melinta. But it's more than that one drug, he said. "We would have not invested in just dela- floxacin," Murphy said. "Pharmaceuticals are Building Bioscience A N H B J S E R I E S O N C T ' S B I O S C I E N C E S E C T O R Melinta's R&D team in New Haven includes: (from left) Ashoke Bhattacharjee, director of medicinal chemistry; Zoltan Kanyo, director of structure-based drug design; Andrea Marra, director of pharmacology and microbiology; Joe Ippolito, research director; and Erin Duffy, chief scientific officer. H B J P H O T O | J O H N S T E A R N S

• Cover