Medical Device Daily Contributing Writer

Privately held Intarcia Therapeutics' (Hayward, California) subcutaneous, osmotic-pump method of delivering the glucagon-like peptide-1 receptor agonist exenatide will enter Phase III trials in the first quarter of next year, thanks to $210 million in new cash, gained through a pair of investments.

"We have all the protocols done, and 500 sites around the world ready to go," said Kurt Graves, chairman, president/CEO of Intarcia. This financing carries us through Phase III results, and it was designed to do so."

Developed as Bydureon by Amylin Pharmaceuticals (San Diego), for weekly injection – an improvement over Amylin's earlier form of the drug, called Byetta – exenatide has more than proven its worth to Type II diabetics. But as with oral and injected diabetes drugs, compliance remains a problem.

It's a problem that Intarcia hopes to get around, verifying the worth of a once-yearly approach through the Phase III trial to be conducted with Quintiles Transnational (Singapore).

Stepping into Phase III trials without a partner is "definitely not the traditional path," noted Graves, who spent 20 years in big pharma and was not eager to accept its terms. "You kind of know how the big pharma guys think and how they look at companies like us," he said.

When Graves came aboard at Intarcia in the fall of 2010, just as Phase II data with long-term exenatide were spilling out, he "was really convinced that this company had a game changer in probably the biggest disease on the planet," and he wanted to protect the asset.

Data from the Phase II program showed significant, sustained reductions in HbA1c and body weight over 48 weeks of treatment, along with a marked reduction in the gastrointestinal adverse events typically associated with self-injection.

Graves began talks not only with potential pharma partners but also with contract research organizations, "just in case we didn't get the right deal or couldn't maintain sufficient control" by going the pharma route, Graves said.

That's how the company decided on Quintiles.

'Complete, continuous, precise' delivery

In 2004, Intarcia, then located in Emeryville, California, changed its name from BioMedicines, deriving the replacement name from an Italian art form called Intarsia in which Renaissance artisans created inlaid mosaics out of various types of hardwoods. Back then, the firm focused on cancer, and immunological and infectious diseases.

Several years later, after the breast cancer drug atamestane – an oral steroidal aromatase inhibitor licensed from Berlin-based Schering AG – had blown up in Phase III trials, Intarcia came out of a regrouping period with $50 million in fresh funding and a plan to reinvent itself.

The capital came as a result of enthusiasm for an internal discovery at Intarcia: how to stabilize proteins, peptides, and antibody fragments at human body-like temperatures and above, so they could be administered differently.

"Our chemists kind of did the impossible," Graves said. "A lot of people knew that Intarcia was working on this [and they said,] 'Good luck, you're never going to do that.'"

Researchers came up with a suspension formulation that has stabilized "multiple proteins and peptides" at 40 degrees Celsius (104F), he said.

"When chemists see that, their jaws hit the floor," Graves said. "Exenatide, at those kinds of temperatures would literally start degrading in a period of hours."

Intarcia already had licensed DUROS titanium-implant technology from Alza (Moutain View, California) for all indications except chronic pain and prostate cancer, which were taken.

Using the suspended formula of exenatide with a DUROS mini-pump cuts back on the side effects of nausea and vomiting (experienced by as much as 25% of diabetics who self-inject), and lets therapy "dial in the sweet spot" in terms of dosing, Graves said, providing "complete, continuous, precise delivery" for 12 months.

"It's like a glacier moving at a defined rate, day by day, over the full life of the device for a year," he told Medical Device Daily.

Headquarters relocating, too

Inserting the matchstick-sized mini-pump is simple and quick, Graves said, and takes three to five minutes in a doctor's office. A nurse or physician's assistant can do it. "Some of our investigators literally do it under two minutes," he said.

The area is cleaned and injected with lidocaine for numbing. "You just make a 5 mm nick in the skin with the very tip of the scalpel," Graves said. "You don't need very much space at all. Then it's a Steri-Strip and a bandage. You're healed within a few days."

Installing the exenatide pump will not reduce doctor visits, he said. "[Patients] are still are going to have their glucose monitored by their physicians on an at least every 12-weeks basis. What it does though, is fundamentally give them a better level of control of their glucose, and cause them some important, clinically relevant weight loss," while guaranteeing compliance.

Once Intarcia has the Phase III results in hand, the company will decide whether to raise more cash, consider going public, or revisit a possible pharma deal, Graves said.

The latest financings consist of $160 million from a preferred stock private placement and $50 million from a private debt placement. Investors included existing backers New Enterprise Associates, New Leaf Venture Partners and Venrock, as well as first-time supporters, The Baupost Group, Farallon Capital Management, and three more institutional investors in Boston and New York.

Along with the Phase III trial, the new money also makes possible Intarcia's move of the corporate headquarters to the Boston area, while keeping early development capabilities and manufacturing at the current site.

Morgan Stanley acted as sole structuring advisor to Intarcia in the deal, as well as sole placement agent for the debt and lead placement agent for the equity. Leerink Swann acted as co-placement agent on the equity.

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