With a strong investor syndicate of venture capital funds, closely held Aquinox Pharmaceuticals of Vancouver is in an enviable position ahead of the release, in June, of Phase 2a clinical trial results for its AQX-1125 lead drug candidate in patients with asthma and chronic obstructive pulmonary disease (COPD).
David Main
“Virtually every pharmaceutical company that has an inflammation program has been talking to us since we made our interim results available in January,” CEO David Main says in an interview with BioTuesdays.com. “And if the final data next month is as strong as the interim data, we’ll be in a position to do a deal.”
Mr. Main explains that Aquinox’s scientific founders discovered a unique biochemical enzyme known as SHIP1 and have shown that it regulates the critical phosphoinositide 3-kinase (PI3K) pathway in blood cells.
PI3Ks are one of the most heavily researched pathways by pharma and biotech companies in the area of cancer, immune disorders and metabolic diseases. PI3Ks are a family of related enzymes that have been linked to a diverse group of cellular functions and biological processes, such as cell growth and proliferation, adhesion, differentiation, survival and intracellular transport, which cover both cancer and inflammation.
“Every pharma company, other than us, is focused on the enzyme PI3 kinase itself and trying to find drugs to block that enzyme,” Mr. Main points out. “What we’ve built this company around is the fact that nature has a natural way of regulating the PI3K pathway, so when it’s turned on, potentially causing either cancer or inflammation, it also tries to turn on the SHIP1 enzyme that down-regulates the pathway.”
According to Mr. Main, Aquinox occupies a world leadership position in doing what nature already does to regulate this pathway. “There is no natural PI3 kinase inhibitor, but that’s what other pharmaceutical companies are trying to develop. Instead, we are developing a drug that increases the natural braking system for this pathway. So that’s where we are differentiated.”
SHIP1 activators have the potential to become the next generation anti-inflammatory drugs
He says that as a result, all of the big players in the space are interested in what Aquinox is doing, because they already have the PI3 kinase inhibition approach covered. “We’re the only company on the other side of the equation, which would give these companies another way to play in the same pathway,” he adds. “SHIP1 activators have the potential to become the next generation anti-inflammatory drugs.”
Mr. Main, who is best known for his stint in the early- to mid-2000s at the helm of Inex Pharmaceuticals, which developed the cancer drug Marqibo, founded Aquinox in 2006 as a spin-off from research conducted at the University of British Columbia, the BC Cancer Agency and the Vancouver Coastal Health Research Institute.
In June 2007, the company raised $14.5 million in a Series A venture capital financing, which was led by Ventures West Capital and included new investors, J &J Development and Baker Brothers Investments of New York. Three years later, it secured an additional $25 million in a Series B venture capital financing, again led by Ventures West Capital. A new investor, Pfizer Venture Investments, participated in that financing, along with all other existing investors.
“Going public is probably not in the cards right now,” Mr. Main figures. “To go public, we’d have to be much further along. So, one of the things that we are considering, and investors have talked to us about, is the possibility of doing a series C round of financing, with the goal of taking AQX-1125 closer to approval, which might enable us to go public at some point in the future.”
When Phase 2a data are available next month, “we’ll look at the partnering opportunities that are there, and if they’re attractive, that’s what we’ll do,” he says. “But if not, we may do another financing, because we’ve already had expressions of interest for that as well. So we feel we’re in a strong position as long as the data cooperate.”
Aquinox Pipeline
AQX-1125 is the company’s most advanced product, because it is a potent activator of SHIP1 in the treatment of blood and immune disorders. It has shown anti-inflammatory activity in animals and humans and can be dosed as a once-a-day pill, making it highly attractive to potential partners. The company also has a large and diverse library of potential backup compounds.
“Our whole theory is that when SHIP1 isn’t working properly, you develop a whole list of inflammatory diseases,” he says, adding, “If we can use our drug to increase the activity of SHIP1, we should be able to correct some of these diseases.” Moreover, the company has generated data to prove that its drug doesn’t work in the absence of the SHIP1 enzyme, thus proving that the SHIP1 enzyme is the drug’s exclusive target.
AQX-1125 Indication Logic: A once-a-day oral product offers >$5 billion opportunity
AQX-1125 has achieved positive animal data against inflammation of the airways, bladder, bowel and skin. Citing diseases such as asthma, COPD, fibrosis and interstitial cystitis, Aquinox figures a once-a-day pill has a potential market opportunity exceeding $5 billion a year.
In Phase 1 human studies, AQX-1125 was well tolerated at single doses up to 542 mg and at multiple doses for 10 days up to 542 mg, with ideal pharmacokinetics. “The drug performed near perfectly,” Mr. Main recalls.
The company began two Phase 2a proof-of-concept studies in COPD and asthma in the fourth quarter last year. The COPD study used lipopolysaccharide (LPS), which is an endotoxin found on bacteria that grow on tobacco leaves. LPS was used to induce acute inflammation in the lungs of healthy volunteers, similar to COPD in the lungs of smokers. While LPS inflammation goes away in three or four days, it never goes away in smokers.
“In our interim results from the COPD study, we were able to inhibit 70% of the inflammation caused by the LPS challenge,” Mr. Main contends. “That’s one of the highest amounts of inhibition ever reported by any other drug that has gone through the same type of study.”
The interim data were derived from the high-dose cohort, taking 450 mg a day. Results from the group taking 200 mg a day will be available in June. One of the primary endpoints is measuring the number of inflammatory cells in sputum.
In the asthma trial, the company used a skin prick test with patients known to be asthmatic to determine which allergen would cause an allergic reaction. Patients took AQX-1125 for seven days, and then were exposed to either a placebo or allergen, and then tested to see how much of the asthmatic response was reduced by having taken the drug beforehand.
To determine the drug’s efficacy, lung function or a forced respiratory volume test was used to measure how much air a person can push out through his or her lungs. When a person has an asthmatic attack, his or her airways constrict, resulting in less air pushed out through the airways. Inflammatory cells in sputum also are being measured.
“These are both very complementary studies because the type of inflammation that is caused by LPS is very different than the inflammation caused by an allergen,” Mr. Main says. “These two trials would lead us to very different markets.”