Neos Therapeutics Inc.’s upsized series C financing – from $15.5 million to $18 million – along with a $20 million loan facility with Hercules Technology Growth Capital Inc. means the firm will “not only have enough money to hit the key regulatory milestones over the next 12-15 months, but to give us financial flexibility into 2016,” said Victor Miller, vice president of finance.
The Grand Prairie, Texas-based firm uses what it calls Dynamic Time Release Suspension and Rapidly Disintegrating Ionic Masking technologies to deliver controlled-release versions of already approved small-molecule pharmaceuticals in liquid or oral disintegrating tablet (ODT) forms.
CEO Vipin Garg told BioWorld Today that the company plans to file three new drug applications (NDAs) between the third or fourth quarter of this year and the middle of next year, all for drugs to treat attention deficit hyperactivity disorder (ADHD). One is for an ODT form of Adderall XR (mixed salts of a single-entity amphetamine, Shire plc), another is for the liquid form of Adderall, and the third is an ODT version of Metadate (methylphenidate, Celltech Group plc). “In the ADHD space, there are different patient populations that react better to one drug than the other, even though they are both stimulants,” Garg noted, hence the double-barrel approach.
Mark Tengler, chief technology officer, said the dual, liquid-ODT attack with existing therapies “has market and patient advantage for those who have difficulty swallowing or suffer from pill fatigue,” as well as pediatric users (abundant in ADHD) and older patients.
“We take the drug and bind it to an ion resin,” Tengler said. “These are very small particles in the size of 100 microns, so small you can’t crush them with your teeth or in any other manner as you ingest the product. Then we put a membrane around it for either delayed release, or controlled release or to impart the profile that we’re looking for.”
The company has made “millions of these microparticles, and [they bear] no single point of failure,” Tengler said. “In the past, people would crush oxycodone and dose-dump it, but here you cannot do that.” Neos’ pain program is still at the feasibility stage.
“Since all membranes leak over time, aqueous liquid suspensions have been very difficult to formulate as extended release,” Tengler said. An exception is Tussionex (a mixture of hydrocodone polistirex and chlorpheniramine polistirex), the cough and cold therapy owned by UCB SA, of Brussels, Belgium. UCB also developed a generic version, as did partners Par Pharmaceutical Companies Inc., of Woodcliff Lake, N.J., and Monmouth Junction, N.J.-based Tris Pharma Inc.
Neos came up with one, too, and it’s approved. The drug “has been quite successful over the years, but you couldn’t use that technology today to gain an FDA approval, because [Tussionex makers] take lots that are too slow and blend them with lots that are too fast to get their target profile,” Tengler said.
UCB’s method “was to bind a drug to a resin and coat it, and then use that in a liquid suspension,” he said. “[The effort] has been problematic, and every large pharma out there over the years has tried to use ion resin technology to formulate drug products,” before Neos broke through with a more sophisticated strategy. “Not only can we match ion resin for ion resin, but a very difficult profile such as Adderall XR, we’re able to manipulate the technology because ours is more robust and more applicable to other molecules and other profiles.”
Based on findings by Tengler and his team, Neos dissociates the sulfate amphetamine in Adderall to end up with the amphetamine base, which is then bound to a polistirex ion resin to create a partially soluble salt. Thus, the amphetamine gets digested in the stomach or intestinal tract, and the polistirex passes through the body.
A once-per-day, Adderall-equivalent therapy in the $10 billion ADHD market would be important because the drug is scheduled as a class 2 substance subject to abuses. Neos’ version could be taken by kids before school. The ODT is as easy as the liquid. “Less than 30 seconds after you put it in your mouth, it fully disintegrates and you’re able to swallow it without the aid of water,” Tengler said. Finance VP Miller noted that “up to 63 percent of patients have trouble taking the existing oral dosage forms, so there’s a very, clear strong need.”
The NDA for the ODT Adderall XR drug was submitted in December 2012, and garnered a complete response letter from the FDA. “We will be re-filing that with some modifications to the chemistry, manufacturing and controls section,” said Garg, calling the agency’s concerns “things that can be easily fixed.” Two more NDAs – for the liquid Adderall and ODT Metadate – will be submitted in the meantime, he said.
With about 65 employees, Neos has its own 100,000-sq. ft. facility compliant with current good manufacturing practices. The trio of ADHD drugs “provides a nice basket,” Garg said. “It is attractive to partners. We’ve had discussions, so people are interested in marketing [the compounds], but we believe we can develop them on our own for sure, and then evaluate our options, whether to partner it or build a sales force on our own. We’ll cross that bridge when we come to it.”
Source – Bio World April 2014
By Sharon Kingman, Staff Writer