The new round of Phase II studies funded by Aquinox Pharmaceuticals Inc.'s $18 million Series C financing should let the company bolster data gained already in chronic obstructive pulmonary disease (COPD), gain data in bladder pain syndrome/interstitial cystitis (BPS/IC) and then make decisions on whether to partner at the pivotal-trial stage.

AQX-1125, the firm's lead candidate from the SH2-containing inositol-5'-phosphatase (SHIP1) program, has undergone a pair of Phase II studies testing its efficacy in preventing airway inflammation in patients with asthma exposed to known allergens in the first study and in volunteers exposed to an environmental inflammatory stimulus.

In the first half of 2013, the company will start a Phase II study with the compound to reduce the severity and duration of lung attacks in COPD.

Another will try the drug in patients with BPS/IC, as a way of relieving pain and inflammation. The financing gives Aquinox enough cash to finish toxicity studies, too, and scale up manufacturing.

The company's Series B financing took place in the summer of 2010, when Aquinox raised $25 million for the pipeline star, a nonsteroid approach for those with lung disorders who are unsuited for steroids and do better on such therapies as Merck & Co. Inc.'s Singulair (montelukast sodium), which lost patent protection last August. (See BioWorld Today, June 18, 2010.)

Aquinox hopes AQX-1125 will improve on Singulair's efficacy while proving safer than inhibitors of the phosphoinositide-3-kinase (PI3K) pathway. The firm's scientific founders discovered the SHIP1 enzyme that AQX-1125 targets, and have shown that SHIP1 also affects the critical PI3K pathway in blood cells but does not cross-react with other PI3K inhibitors, which are undergoing tests in oncology by other developers.

"Virtually everyone else in the PI3K space has focused on cancer," said David Main, president and CEO of Vancouver, British Columbia-based Aquinox, and most are developing PI3K inhibitors. Among them is Foster City, Calif.-based Gilead Sciences Inc., which has idelalisib (GS-1101) in Phase III trials for chronic lymphocytic leukemia. (See BioWorld Today, May 3, 2012.)

"When you turn on SHIP1 , it down-regulates the PI3K pathway," Main said. "So, while other companies are developing drugs that block the gas pedal, we're developing drugs that turn on the brakes."

The inflammatory space was not chosen over cancer because it looked less arduous, Main said.

"I don't think anything in this business is easy," he pointed out. "There were many companies ahead of us, so that made [oncology] less attractive. We felt that going after the natural conditions that occur when SHIP1 isn't regulating the pathway properly gave us a better sense that we might have success in the clinic, and so far that's holding up."

What's more, PI3K inhibitors are "not entirely selective drugs," Main said. "They may hit PI3K, but they hit other enzymes. When you're trying to attack cancer, that's probably a good thing." Drugs for inflammatory conditions, though, require more safety.

Partnering decisions, he told BioWorld Today, "really depend on what the environment looks like at the conclusion of these trials, and whether we win both trials or just one. If the data were there, and the environment was such that the money was available, [BPS/IC] is an indication that we could envision taking through to approval ourselves."

In respiratory indications, partnering makes more sense, but "you never know, one partner may be very interested in both indications," Main said.

BPS/IC is "a new nomenclature that the urology community has placed upon [the condition]," Main said. In cystitis, women develop chronic inflammation of the bladder, which has "pretty significant ramifications for their quality of life," he said, since it impairs their ability to hold jobs, interferes with their sex lives and disrupts their sleep patterns.

"It's the pain that goes with it that defines the overall syndrome," he said.

Although the SHIP1 pathway is "well studied by many other companies" and has shown promise in cancer, Aquinox probably will not enter that space, Main said. "Right now we have a lot on the table for a small company," he said, noting that the lead compound is one of the more advanced oral, small-molecule therapies in inflammation. "There isn't a rationale to divert our energies from what we've done well so far," he said.

Aquinox is evaluating analogues that may lend themselves to different routes of administration, and is pushing the follow-on products into studies that could enable investigational new drug applications.

The company also disclosed the appointment of Stephen Shrewsbury as senior vice president of clinical development and chief medical officer (CMO). He was most recently CMO at AVI Biopharma, now Sarepta Therapeutics Inc.

Johnson & Johnson Development Corp. led the financing. New investor Augment Investments Ltd. participated, along with existing investors Pfizer Venture Investments, Ventures West Capital and Baker Brothers Investments.