August 1, 2016
Building Bioscience

Melinta Therapeutics takes aim at deadly drug-resistant bacteria

HBJ PHOTO | John Stearns
HBJ PHOTO | John Stearns
Melinta Therapeutics senior research scientist Dr. Somenath Chowdhury works in the company's New Haven lab, which is developing several antibiotics to treat bacterial infections.
HBJ PHOTO | John Stearns
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.
HBJ PHOTO | John Stearns
Visitors to Melinta’s New Haven office can peek inside its labs (above), but only from outside the glass.
HBJ PHOTO | John Stearns
A poster inside Melinta’s office shares the purpose for its main drug.

About this time next year, Melinta Therapeutics hopes to celebrate federal 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 infections, including the nasty MRSA (methicillin-resistant Staphylococcus aureus), which has made many drugs obsolete. There are 3 million serious skin infections each year in the U.S. that warrant hospitalization, and a large percentage are due to MRSA, creating a significant potential customer base for Melinta.

The New Haven company also believes Baxdela, which is the trade name for delafloxacin in a class of drugs called quinolones, 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 looking 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 preclinical, 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 antibiotics 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 pneumonia and urinary-tract infection to intra-abdominal and blood-stream infections.

The company's work is important since many older antibiotics have become obsolete against bacteria, which are constantly finding new ways to adapt and survive, Sun said, adding that people also have taken antibiotics for granted.

"It's important to remember that less than 100 years ago there were no antibiotics 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 company's focus on ribosomes as its primary target 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 scientists 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, installment 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 pharmaceutical 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 sciences companies. Malin invested $45 million in Melinta last year, making it the second-largest 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 nonexecutive 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 bullet of an antibiotic, going after multiple different 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 antibiotics, 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 previously 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 antibiotic approvals from 2000, she said. The act provided a period of exclusivity for a drug if it met certain criteria for attacking superbugs 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 successful, 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 delafloxacin," Murphy said. "Pharmaceuticals are risky enough. When you only get one shot on goal, you have to be awful lucky to do well."

Melinta and it's predecessor, Rib-X, have been working in the field for so long that they have extraordinary insight into this new class of antibiotics that will hopefully produce a stream of products going forward, he said.

Melinta's window of opportunity is more relevant today than when it started, Murphy added.

"No one anticipated that there will be patients out there that are resistant to all antibiotics — a pretty scary proposition," he said. "So I think their timing is most appropriate. And it's not often that you can find a company that has near-term assets and longer-term assets and platforms all in one company — so that's what intrigued us with Melinta."

Melinta was the brainchild of Susan Froshauer, now president and CEO of CURE, a nonprofit that works to support and build Connecticut's bioscience sector.

Froshauer said the idea for the company incubated in her head while she was at Pfizer, where Duffy also worked, because some of her work there involved using computational tools to help design new small molecules. She also has a background in antibiotic drug discovery and did her postdoctoral fellowship at Yale University.

She convinced Yale professors, colleagues and friends, William Jorgensen (Duffy's husband), Peter Moore and Thomas Steitz, who won the Nobel Prize in chemistry in 2009 for his studies of the structure and function of the ribosome, to become scientific co-founders. While none works at the company, they all remain in touch with its science, said Duffy, whom Froshauer recruited.

The small group raised money through friends and family to help found the company, after which there have been various successful money raises.

Two more recent fundings included a $70 million equity investment in 2014, led by Vatera Healthcare Partners, and a $67 million equity financing announced last year and led by Malin, according to Melinta's website.

Melinta has the team and quality of science to succeed, Froshauer said.

"I think what is amazing … is the depth of their portfolio, that they have several waves of molecules coming down the pike and they are carefully guiding them to particular markets where they will be differentiated," she said.

Stan Choy, former CFO of Kolltan Pharmaceuticals Inc. in New Haven, which started in the same building as Melinta and where Choy got to know its principals, credits Melinta's team for its perseverance over the last 16 years and is confident in its potential.

"I always say the product is not in the market until it's selling in the market," Choy said, refusing to take anything for granted with clinical trials, the FDA, etc. "But in terms of the direction of Melinta, it looks like they're going to make it, which is a very, very good thing for them and for the state of Connecticut."

CURE hopes to see companies like Melinta, once they launch their drugs in the marketplace, stay in-state and grow, said Choy, a cancer researcher and now co-chairman and treasurer of CURE and self-described serial bioscience entrepreneur.

"It's where your roots are and hopefully it pays off because at the end of the day you want companies to launch and become bigger, greater companies to sustain and maintain jobs in the state," Choy said. "That's our objective, to get these companies up and running and funded well. Obviously the science has to be compelling, it's got to make sense, but we want these companies to stay" and create critical mass in the life sciences.

Related story: Duffy's roots stretch to Melinta's founding

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