Emerging Drug Developer: CombinatoRx

Year ahead will put CombinatoRx’s discovery model to the test
 
Alexis Borisy doesn’t think small.

A lead development program in osteoarthritis and rheumatoid arthritis can attract the attention of “the big boys.” In the right pharma hands, with the right data, it could be worth billions in revenue. The partnering floodgates may soon open up. And key events this year are crucial milestones.

Borisy launched the company eight years ago and at this stage, superlatives roll of his tongue easily.

“We have a fantastic discovery machine that looks at compounds in a new way,” he says with obvious zeal. “That’s the beauty of the model.”

He tells a convincing story. CombinatoRx has raised more than $200 million from investors. And it’s struck development deals with other pharma companies eager to find out if the biotech company can employ its technology to hit one of their targets.

CombinatoRx helped create the biotech business model for developing new drugs from old -- matching old generic compounds in innovative fashion to treat a different disease. By working with proven therapies, researchers can get out of the discovery gate earlier with a lot less to prove on the safety/toxicity side. Also, the race to harvest the kind of mid-stage data that can bring in a deep-pocket pharma company for Phase III and beyond isn’t necessarily as fraught with danger on the efficacy side, either.

“We are far faster, better and quicker,” says Borisy about the company’s discovery engine. Scientists at the company started examining a combination therapy for B-cell cancers in January of last year, he says. “Our first experimental evidence was April or May of last year and now it’s rapidly maturing. We’re on the cusp of moving into the clinic.”

But the time advantages are all upfront.

“Once you’re in Phase II and it’s about Phase II efficacy and safety parameters,” says Borisy, “then you’re in the same game as anybody else.”

CombinatorRx is relying on some learned guesswork, highly touted technology and longstanding clinical experience. Its high throughput screening program can run through seven-figure combinations of generics to see what affect they have on a target cell. If the scientists have a hunch on a likely pair, they’re free to test it. And then there’s a long track record in medical care that tells researchers that two drugs often work better than one in any case.

All of that thinking is in play with their lead therapy, CRx-102, which marries the steroid prednisolone with the anticoagulant dipyridamole. It just makes sense that an anticoagulant can buffer the undesirable side effects of a steroid, allowing a low-dose of the steroid to offer a better outcome. CombinatoRx has already published Phase IIa results, and more data is slated to come in soon.

“The first Phase IIb is set for second half of this year, in osteoarthritis,” says the CEO. “What we’ve said is that rheumatoid arthritis could be in second half or in 2009.”

There are no partners signed on for CRx-102 -- yet. That’s an intentional gambit, says Borisy. It just makes good economic sense to keep your powder dry here and see just how big a therapeutic this can become. With the right data, a collaboration later could be big.

“If Phase IIb studies are successful, for osteoarthritis and rheumatoid arthritis, this becomes a multi-target opportunity ready for Phase III, and there aren’t a lot of those in the industry,” he adds. “You saw what Genzyme paid to Isis (in a recent pact containing up fronts and milestones of $1.9 billion). This is a product all the big boys would be interested in.”

It hasn’t been all clear sailing for the company. Last June the company discontinued a development program for another RA drug that offered signs of efficacy but wasn’t likely to be able to compete with the therapies already in the market. And CombinatoRx’s stock price is languishing under the $5 mark as of Monday morning, well below its $7 debut in late 2005.

But that will change; one way or the other.

“We’re in a watershed moment in time for the company,” adds Borisy. With its lead therapy in mid-stage trials in diverse programs, “we’re going to introduce the next wave in the clinic. And we said last year that we’d do a partnering campaign in ‘08 and ‘09, and we’re on track.” Besides, he adds, a validation of CRx-102 validates the company’s whole approach to development. And it positions the company to “monetize a whole bunch of assets.”

“If we get good osteoarthritis data, the partnering flood gates open,” says Borisy. “If osteoarthritis works, it is likely the rheumatoid arthritis works. The converse is not true. Osteoarthritis could fail and rheumatoid arthritis could work. The osteoarthritis is the higher risk trial. Rheumatoid arthritis is the higher probability trial.”

The data will determine what partnerships can be had.

“You want whatever gives us the best economic deal out there,” says Borisy, but he’s well aware that the company isn’t ready to field a large marketing force that would be required for a drug that hits a big audience. A partnership that leaves room for a “small specialty force, though, would be lovely.”

“We want a partner that brings Phase III and Phase IV medical resources, as well as the field force. This can be a multi-billion dollar drug. In the wrong hands; $500 million.”

There are more programs on deck, including a combination drug for type 2 diabetes, a hepatitis C drug in the clinic, its work in B-cell malignancy and ophthalmic drugs.

“These are all fantastic opportunities,” enthuses Borisy. “The key thing depends on what works.”