Privately held Collegium Pharmaceutical Inc. closed a $22.5 million Series B round to advance its development program for COL-003, a tamper-resistant, extended-release oxycodone product that uses its DETERx technology.

The financing was led by Longitude Capital and Skyline Ventures, with Series A investors Frazier Healthcare Ventures and Boston Millennia Partners also participating in the round.

Collegium's Series A in 2008 raised $20 million, bringing its total haul to date to about $57.5 million. (See BioWorld Today, July 18, 2008.)

Michael Heffernan, president and CEO of Providence, R.I.-based Collegium, said the company plans to file a new drug application for COL-003 next year. The new financing is expected to support Collegium through FDA approval of the compound.

"We have initiated our Phase III trial for COL-003 and are working to complete the remaining development activities required for regulatory submission," Heffernan said.

The Series B came together after Collegium met with FDA officials in August 2011 to define the regulatory path for COL-003.

"On the back of that information we had a pretty good understanding of what was required, and that led to our financing," Heffernan told BioWorld Today.

Based on FDA guidance, the Phase III trial will enroll about 500 patients in the U.S. in a 12-week study in chronic low back pain using a randomized withdrawal design. The trial will compare DETERx to placebo across both opioid-experienced and opioid-naïve patients, with change in pain scores as its endpoint.

"We have to do a single, well-controlled Phase III trial in a well-recognized chronic pain model," Heffernan said.

Collegium will submit additional pharmacokinetic studies to support the 505(b)(2) filing and any label differentiation it may seek, he added.

The company expects to release top-line data from the study in mid-2013, followed by the NDA filing.

Management of chronic pain is an enormous challenge for clinicians, who often undertreat, in part, due to concerns about abuse. Collegium is among a small cadre of biotechs seeking to build a better mousetrap by developing opioid formulations that incorporate barriers to common forms of tampering.

But Collegium's technology differs markedly from competitors in the tamper-resistant space. One approach – combining antagonists and agonists – is the strategy underpinning Embeda (morphine sulfate extended-release with sequestered naltrexone hydrochloride), a tamper-resistant extended-release morphine product developed by Alpharma Inc. and approved by the FDA in 2009. King Pharmaceuticals Inc., of Bristol, Tenn., now a wholly owned subsidiary of Pfizer Inc., acquired Alpharma in 2008 and currently markets the drug. (See BioWorld Today, Nov. 25, 2008.)

A second strategy involves the use of prodrugs, which must be released in the stomach to take effect.

In contrast, Collegium's DETERx platform consists of a multiparticulate matrix formulation designed to protect against common tampering methods such as chewing, crushing, snorting and extraction for intravenous injection. Each of the small beads, which range from 200 to 300 microns in size, contains both the active ingredient and excipient when loaded into the capsule, rendering them impervious to abuse.

"If you were to try to crush, grind or break these beads, or to dissolve them in common solvents, you will not change the release profile," Heffernan explained.

The benefits of the technology are twofold. On the one hand, users cannot break down the time-release system and gain access to high levels of the drug – eliminating it as a target for abuse.

In addition, the multiparticulate design enables the capsule to be opened and the contents administered on food or through a gastronomy tube to patients who have difficulty swallowing, without affecting the extended-release properties of the active ingredient. Thus, the DETERx technology can be used not only with drugs that are commonly abused, such as opioids and amphetamines, but also with compounds that have narrow therapeutic windows that would benefit from protection against breakage or crushing.

"This is the only technology we're aware of where a patient can open a capsule and sprinkle it or titrate the dose and still retain the extended-released properties," Heffernan said.

Successful commercialization could give Collegium enormous leverage in mainstream pain markets, particularly if it wins the much-sought FDA endorsement of a tamper-resistant claim. Although Purdue Pharma LP gained FDA approval in 2010 to sell a reformulated version of its potent controlled-release oxycodone drug, OxyContin, the agency characterized the reformulation only as an "incremental advantage" of the original drug. (See BioWorld Insight, Oct. 12, 2009, and BioWorld Today, Apr. 7, 2010.)

Other tamper-resistant reformulations have not fared as well. Pain Therapeutics Inc., of Austin, Texas, has received two complete response letters on Remoxy, another controlled-release oxycodone formulation. Remoxy was developed using technology from Durect Corp., of Cupertino, Calif., to discourage tampering and is partnered with Pfizer, of New York, which acquired the rights through its February 2011 buyout of King. (See BioWorld Today, June 27, 2011, and Oct. 13, 2010.)

And Acurox, a product from King and Palatine, Ill.-based Acura Pharmaceuticals Inc. that combines oxycodone and niacin, got a negative panel vote in 2010 and subsequently was resubmitted for a different formulation of Acurox (oxycodone HCl), with the firms requesting priority review. (See BioWorld Today, Dec. 12, 2008, and April 26, 2010.)

Neither product has gained FDA approval.

Collegium's technology differentiation is precisely what drew Longitude Capital to the Series B, according to David Hirsch, a managing director in the firm's Greenwich, Conn., office who has joined Collegium's board.

"We think the features of the Collegium product are very distinctive, with a profile that is extremely tamper-resistant but also patient-friendly," Hirsch told BioWorld Today.

Fortuitously, Collegium is moving its tamper-resistant formulation to market in the wake created by other products, so the FDA has developed a comfort zone in reviewing that class of technology.

"Tamper resistance can mean a lot of things," Hirsch pointed out. "Now that the FDA has evaluated a couple of products, they've effectively set milestones and goalposts. The company has some pretty clear guidance from the agency about what's important and what tests they need to do."

In the interim, the problem of abuse has grown exponentially, adding a sense of urgency to the FDA's reviews of such products, he added.

Although Collegium's primary goal is to bring COL-003 to market, a second opioid compound, COL-172, also has received fast-track designation from the FDA. Collegium has additional early stage compounds in pain and other non-opioid indications.

Collegium could take COL-172 to market on its own, Heffernan said, but once Phase III data are in hand, the company will more likely seek a partner "because there's a large revenue opportunity" associated with the product.