Nia Bowers
For most people, a Fourth of July barbeque is a perfect union of smoked meat, ample libations and relaxed vibes. But for three doctors it kindled an idea – a new approach to ADHD treatment – whose years-long journey to market makes slow cooking look downright speedy.
A passion for helping ADHD patients was shared by Drs. Shane Schaffer, Matthew Brams and Raul Silva, medical veterans with overlapping backgrounds in pharmaceutical development, clinical research and psychiatry. For several years the three had connected through Schaffer’s career at pharmaceutical companies including Pfizer, Novartis and Sanofi, where he consulted with psychiatrists involved in ADHD clinical research.
The professional barbecue in Kansas City finally brought the trio together in person: Schaffer, a pharmaceutical industry veteran; Brams, the medical director of Bayou City Research in Houston with extensive experience conducting ADHD and CNS clinical research; and Silva, a researcher, author and practicing child and adolescent psychiatrist with experience at New York University School of Medicine, Rockland Children’s Psychiatric Center and Bellevue Hospital Center.
Over plates of ribs and coleslaw the three discussed how, despite decades of ADHD therapy, there still wasn’t a medication that lasted the entire active day, had rapid onset, avoided the need for boosters and reduced potential abuse. Their shared frustration with patient struggles and limited options inspired them to establish Cingulate, a new biopharmaceutical venture that would eventually develop an innovative Precision Timed Release drug delivery platform.
Like good barbeque, however, there’s a rub: That process has taken 14 years, fraught with a series of challenges: from near-bankruptcies to Covid-19 to FDA speed bumps. All told, it has been a lesson in passion and persistence.
Driven by their vision for an ADHD therapy that didn’t exist, the company was formally founded in 2012, with Schaffer as Chairman and CEO, Brams as Chief Medical Officer and Silva as Chief Science Officer. The partners chose the name Cingulate, a subtle reference to the cortex in the brain involved with executive function, including attention, emotion and behavior regulation, elements at the core of ADHD.
They began by convening a panel of experts in Kansas City, which would become the company’s headquarters. “We invited psychiatrists, neurologists, pediatricians, psychologists and others, and asked, ‘Do you agree there’s a problem? And what needs to be done to improve outcomes for patients and help providers better serve their needs?’” recalls Schaffer.
Participants agreed that existing ADHD medications can lose effectiveness after six to eight hours, leading to what is often described as “the afternoon crash.” These medications may require booster pills that adults, and especially children, might take too late or forget entirely. Participants also believed there was limited industry incentive to significantly redesign existing ADHD treatment approaches.
To design a single, multi-modal pill that provided a consistent “glide pattern” throughout the entire active day, the founders sought to achieve three key goals:
First: To utilize a delivery mechanism that would erode in a precise way, they identified then licensed erosion barrier layer technology from BDD Pharma in Scotland.
Second: To release the medication (dexmethylphenidate, an already approved ADHD stimulant) to optimize the “all-day” patient experience, the experts advised 35% as an immediate morning release, 45% three hours later, and 20% four hours after that.
Third: To manufacture this unique product, and at scale, the company went through years of development, customizing its own proprietary machinery and partnering with U.S.-based Bend Bioscience.
Also shepherding the journey of its product, known internally as CTx-1301, were clinical studies evaluating its efficacy, safety and performance under various conditions. Submitting it under the FDA’s 505(b)(2) pathway, which allows reliance on prior safety data for existing drugs, Cingulate was required to provide data supporting both its formulation and manufacturing process for what CEO Shane Schaffer describes as “a new drug delivery platform.”
This past June, the FDA issued a Complete Response Letter for CTx-1301, citing chemistry, manufacturing and controls (CMC) concerns, and specifically requesting additional information on the drug’s proposed manufacturing.
“We are encouraged that the FDA’s response was limited to specific information requests related to CMC and did not identify issues related to the clinical safety or efficacy of CTx-1301,” says Schaffer. “We believe the agency’s requests can be addressed swiftly and we are moving efficiently toward resubmission.”
Any aficionado of smoked meat understands that patience is essential to the “low and slow” process. And as they work to address the needs of ADHD patients, three doctors brought together at a Kansas City barbecue still share a burning desire to make their idea a reality.