Emerging Drug Developer: Enobia

Last fall, Enobia’s chief executive concluded that the small biotech company needed a new direction. Its longtime lead program, an enzyme replacement therapy for X-linked hypophosphatemia, or XLH, was scrapped and the lead spot went to an ERT for hypophosphatasia, a disorder of bone mineralization.

“There was a lack of compelling argument to continue it,” says Dr. Robert Heft about Enobia’s original development program. Fortunately for the company, though, there’s been some compelling--if early stage--data to back its replacement. By the second quarter of this year, says Heft, who was appointed CEO in 2005, the new program was generating “breathtaking” preclinical data.

And the Montreal-based biotech has continued to shift gears, bringing in a new chief medical director, board members and other personnel. A few days ago, the company achieved an even more tangible validation of its new focus, witnessed by a $40.1 million (Canadian) second round that is being budgeted to get the biotech through a mid-stage study.

“I anticipate we’ll be in the clinic next summer,” says Heft, “when we will do a Phase I in patients. That Phase I will take us from mid-2008 to the beginning of 2009, when we will start a Phase II study which will take us to the start of 2010. The financing will take us through the end of Phase II.”

Enobia also has a second, small-molecule program for achondroplasia, a common form of dwarfism. “It is even earlier days for that,” notes Heft, adding that the recent investment round will finance additional preclinical work on that therapy.

The small biotech--Enobia has 26 employees, half with PhDs--may have switched programs, but they haven’t shifted from their original field of expertise, which focuses on bone disorders. Like other ERT companies, Enobia is looking to treat the disease by correcting an enzyme disorder. But in Enobia’s case, it has also adopted an approach that has been a focal point in oncology, using technology that allows researchers to directly target the trouble spot.

‘We know that the site of action of this enzyme is in the bone, and that is where you have to get the enzyme if you want to be effective in hypophosphatasia,” says Heft. By using technology that targets the enzyme molecule to the mineral phase of bone, he adds, the enzyme will have a longer half-life than in would find in serum.

That argument has won over OrbiMed Advisors, an experienced investor in the ERT field, as well as CTI Life Sciences Fund of Montreal, which co-led the round.

Like the rest of the ERT therapies either on the market or in development, Heft anticipates that the orphan drug can only be targeted at a tiny patient population. By one rough estimate, one in 100,000 people are born with the disease, which often results in death or skeletal deformities. In turn, he anticipates signing up only about 15 to 20 volunteers for Phase I and possibly only a few more than that for Phase II. Heft is also quick to acknowledge that any approved therapy is likely to be attached to a hefty price tag.

A small patient pool does provide Enobia a shot at commercializing the therapy on its own, though.

“I think there are multiple options,” says Heft, “even for a company our size. Given the nature of the disorder and the cost of bringing a therapy to market, we may raise more money and do it ourselves all the way through commercialization. Or we could be sold to another ERT company.”

A partnership on an ERT therapy, he acknowledges, would be hard to pull off. Any commercialization pact would require making “two small pieces out of one pie,” says Heft, which doesn’t hold a lot of appeal. On the other hand, positive data from clinical trials may be just the ingredient needed to make this pie very appealing to a handful of companies dominating this field.