Diabetics know all too well that needle sticks are a routine part of managing their disease. Insulin injections have been part of the diabetes standard of care for decades. And in recent years, a new class of injectable drugs have emerged to help patients regulate their blood sugar levels.
Chapel Hill, NC, drug developer BioKier is beginning human tests of a drug that, if successful, could replace these injection therapies with a pill that coaxes the body to regulate blood sugar levels on its own, says George Szewczyk, BioKier founder and CEO. If it works, BioKier’s approach could offer some advantages over blockbuster diabetes drugs currently available from big pharmaceutical companies.
“We believe we have a better safety profile,” Szewczyk says. “We also believe that there is a very good chance that our drug will be more efficacious than other drugs.”
The inspiration for BioKier’s lofty goal comes from an unlikely origin: gastric bypass surgery.
Patients who have undergone a gastric bypass lose weight in part because shrinking the stomach’s size reduces the amount of food needed to make a person feel full, so patients eat less. But researchers observed another beneficial effect, says Roger Nolan, BioKier co-founder, president, and chief operating officer. The blood sugar of many diabetics returned to normal levels shortly after the surgery. In some cases, diabetes simply went away.
Research linked this effect to a gut hormone that regulates blood sugar. Secretion of this hormone, called a glucagon-like peptide-1, or GLP-1, is triggered by nutrients from food, Nolan explains. Because it leaves patients with a tiny stomach, gastric bypass surgery results in those nutrients being digested further along the digestive tract, at the beginning of the colon, which prompts the body to release GLP-1. BioKier’s experimental drug, for now called BKR-013, aims to mimic this effect with a pill that carries a payload of the nutrient glutamine into the colon. Nolan calls it “gastric bypass in a pill.”
The global market for diabetes treatments is in the tens of billions of dollars. BioKier is far from the first pharma company to take a GLP-1-based approach to treating the disease. Novo Nordisk’s (NYSE: NVO) Victoza (liraglutide), for instance, is an analog drug, meaning that it is similar to GLP-1. The once-daily injectable generates more than $2.1 billion in annual sales. Byetta (exenatide), a twice-daily injectable GLP-1 analog originally developed by San Diego biotech Amylin Pharmaceuticals and now marketed by AstraZeneca (NYSE: AZN), generated $206 million in 2013 sales. A once-weekly version of that drug, Bydureon, produced $151 million in sales last year for AstraZeneca. And Eli Lilly (NYSE: LLY) is awaiting the Food and Drug Administration’s decision on dulaglutide, which is expected to take market share from liraglutide.
While GLP-1-like drugs help diabetics reduce their glucose levels, these drugs have also been linked in animal tests, clinical trials, and post-marketing studies with possible higher risks of pancreatitis and cancer. Szewczyk says that GLP-1 produced in the body has a short half-life, meaning it will disappear soon after a meal. Consequently, he says, stimulating production of the hormone with BioKier’s drug shouldn’t pose the health risks associated with treatments like liraglutide and exenatide that introduce longer-lived analogs of GLP-1 into the body.
At least one other company has explored an approach similar to BioKier’s. Lumena Pharmaceuticals, a San Diego company that was acquired for $260 million earlier this year by Shire Pharmaceuticals (NASDAQ SHPG), tried using bile acids, rather than glutamine to trigger GLP-1 production. But prior to the Shire acquisition, Lumena, which was launched in North Carolina in 2011 with early investment from Durham venture capital firm Pappas Ventures, had shifted its research focus away from diabetes; Lumena instead turned toward rare liver diseases.
BioKier’s technology stems from more than Szewczyk’s research—it also comes from his own experience with diabetes. In 20 years at GlaxoSmithKline (NYSE: GSK) and its predecessor companies, Szewczyk researched treatments for diabetes and obesity. But he says it wasn’t until he left GSK in 2008 that he developed the disease himself.
Szewczyk had read studies on the research of non-digestible sugars as a diabetes treatment, research that had been conducted in rats. He decided to test whether one of these sugars, lactitol, would help control his diabetes. The experiment was a success, and with continued treatment he shows no diabetes symptoms. “My diabetes fully reversed and is fully in control,” Szewczyk now says.
At about the time of Szewczyk’s initial test, he came upon research from Fiona Gribble at the Cambridge Institute for Medical Research. He was intrigued by Gribble’s research on glutamine as a trigger for GLP-1 production. Lactitol and other similar sugars can cause side effects including diarrhea, abdominal pain, and gas, though. So Szewczyk settled on using glutamine for BKR-013 and looked to license the technology to someone who could develop it, then test it. He found no takers.
Szewczyk and Nolan, meanwhile, were introduced by a mutual friend. Nolan, who has preclinical and clinical-trial experience from contract research organizations, joined with Szewczyk to form BioKier. And Gribble, whose research inspired Szewczyk to explore glutamine’s role in GLP-1 production, has since become a BioKier collaborator and now sits on the company’s scientific advisory board.
With successful animal tests under its belt, BioKier is now trying to show its approach can work in humans. The Mayo Clinic in Rochester, MN, is currently enrolling type 2 diabetes patients in a Phase 1 study evaluating a suppository form of BKR-013. In the meantime, the company is working on making a once-daily pill form of the drug, using a coating technology that it has licensed exclusively from the University College London School of Pharmacy. That coating, along with the pill’s formulation, Szewczyk explains, will allow the tablet to travel undigested until it reaches the colon, where it will release the glutamine.
BioKier, which had received seed funding from angel investors as well as a research loan from the NC Biotechnology Center, last year raised $1.7 million from Broadview Ventures and the American Heart Association. The money is expected to take the startup through the Phase 1 study and pill formulation, after which it would need between $6 million and $10 million for Phase 2 trials. Tests could also be done comparing BKR-013 against other GLP-1 drugs. But Szewczyk says the scale of these tests are beyond the capacity of a tiny company like BioKier, whose only full-time employees are himself and Nolan.
Indeed, the startup is already talking to potential pharma partners (Szewczyk declines to say which ones), pitching BKR-013 as potentially faster and less expensive to take through the regulatory process compared to a completely new compound. Glutamine is already used in other FDA-approved drugs, and so has already been vetted for safety and toxicity. Szewczyk says the company should therefore only need to demonstrate BKR-013’s efficacy in diabetes. If the FDA signs off on BioKier taking this so-called 505(b)(2) regulatory pathway, the company or a pharma partner might not need to test BKR-013 in lengthy and expensive Phase 3 clinical trials. Szewczyk says the company is talking with the FDA to see if the agency will accept that approach and if so, what specific data it would require.
There’s a disadvantage of using an already vetted active ingredient, though—since glutamine is not a new molecule it doesn’t come with 20 years of patent protection. Szewczyk concedes that this could dissuade some pharmas from bringing BKR-013 into their drug portfolios. But he notes that BioKier does hold two patents protecting BKR-013’s method of delivering a drug formulated to release in the colon and the use of glutamine and another compound, butyrate, in treating type 2 diabetes and other metabolic diseases. Additional patents are pending.
Szewczyk says venture capitalists tell him they won’t invest in BioKier unless the company can show BKR-013 can be made in a pill form. Potential pharma partners, on the other hand, are primarily concerned with seeing clinical trial results in humans. So BioKier is pressing forward on both fronts. Szewczyk says the pill form of the drug should be ready by the end of the year. By then, the company could also have Phase 1 clinical trial results.
“We hope that the data we get will be sufficient to get enough interest to secure financing for the Phase 2 study, but we’ll see,” Szewczyk says.