EP Vantage Interview - Rib-X gears up for action in antibiotic space

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Signs are that activity at antibiotic specialist Rib-X Pharmaceuticals is about to ratchet up a notch or two. Yesterday, the private Connecticut-based company unveiled its new chief executive, Mark Leuchtenberger, who will be taking over from Susan Froshauer, who co-founded the company in 2001.

Parachuting in an executive with a corporate background would certainly appear to signal that corporate activity is on the horizon; Mr Leuchtenberger was last seen bringing another antibiotics group, Targanta Therapeutics, to the market in 2007 and then selling to The Medicines Company a little over a year later, after the FDA rebuffed its lead product. Hopefully a happier ending will be achieved for Rib-X and speaking to EP Vantageon his first day in the job Mr Leuchtenberger confirms that his first tasks will include deciding on the best way to raise money and pushing forward attempts to find partners for the company’s two lead projects.

Finding the weakness

At Rib-X’s core is a technology platform that can build novel antibiotics, including new classes that the company hopes will help overcome the problems of drug resistance. Its know-how allows close examination of the bacterial ribosome, which plays an essential role in protein synthesis and is targeted by a number of existing antibiotics. The company can use that picture to build molecules to target specific, vulnerable regions of the ribosome.

The first novel class to emerge from the technology is being developed under a programme called RX-04. Speaking to EP Vantage a couple of weeks ago Susan Froshauer said one of the compounds, which are active against gram-negative bacteria, should be ready to enter human trials by the end of this year.

More advanced however are two next generation compounds, belonging to existing classes.

Firstly is radezolid, a novel oxazolidinone, a class with only one drug on the market, Pfizer’s Zyvox (linezolid). Work so far sugests the Rib-X candidate has a broader spectrum of coverage and is microbiologically more active against gram-positive organisms, including linezolid resistant bacteria. Given that Zyvox is generating over $1bn in sales a year, the potential in radezolid is clear. Dr Froshauer said they are focusing on safety as a differentiator, and phase II studies will continue over the next year.

A different class

The second candidate, delafloxacin, is a fluoroquinolone with a broad spectrum of activity, greater than other quinolones against gram-positive organisms and methicillin resistant Staphylococcus aureus (MRSA). The company hopes to start phase III trials early next year.

Dr Froshauer said although the drug belongs to the same family as brands such as Johnson & Johnson’s Levaquin and Bayer’s Cipro, its "exquisite" anti-MRSA activity and different behaviour means they believe it should belong in a different class, which they have called azetilones.

“It has remarkable membrane permeating properties and activity against a variety of organisms, it works better at the site of infection and in very acid environments. There is nothing out there with this broad spectrum of activity,” she said.

Both intravenous and oral formulations are under development and the target audience is very sick patients being admitted to hospital.

Maximising potential

Mr Leuchtenberger is clearly joining Rib-X at an exciting time in its own development, and as interest in the space is gathering. Last year saw two private antibody companies sell up, Calixa Therapeutics to Cubist Pharmaceuticals and Novexel to AstraZeneca.

“There’s a real scientific foundation to this company which when you combine with the late stage programmes is pretty rare. The road ahead is to maximise the potential of the company,” he says.

Considering he had only been at his desk for a few hours, Mr Leuchtenberger was understandably reticent to detail precisely how he plans to achieve this, stressing that all options are being considered.

In terms of deals, he said a number of discussions have been going on for a while, declining to say how advanced the talks had got. At the same time financing is being evaluated, and again all options are on the table, including the IPO route.

“Any company with late stage products has to consider the public market. We don’t have any plans but we’re just looking at the situation and encouraged by what we see,” he says.

Bringing it home

Whether Rib-X will go the way of Calixa and Novexel remains to be seen, and Mr Leuchtenberger hinted that this might not be the route he has been brought in to pursue.

“Commercialisation through a global partnership makes a lot of sense these days on both sides. Iit used to be that pharma preferred potentially to buy a company but now I think they have an option-based partnership viewpoint in many cases. We will take advantage of that and will look to do a partnership and also raise capital independently.”

Still, with a VC-heavy shareholder base, which includes GlaxoSmithKline’s SR One and Warburg Pincus, a chunky takeover offer would not be dismissed out of hand. Either way, Mr Leuchtenberger is clearly of the opinion that Rib-X is approaching a pivotal point in its existence.

“Its like a relay race where the race is pretty much set. I’m fortunate to be here in time for what hopefully will be the anchor leg,” he says.

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