Partners HealthCare spinoff, Annovation BioPharma's next-generation intravenous anesthetic, ABP700, garnered promising clinical results and is expected to be acquired by The Medicines Company in early 2015.
The Massachusetts General Hospital has been celebrated worldwide for nearly 200 years of anesthetic innovation – the iconic image of the Ether Dome surgery is hallowed throughout the medical world. With all that history there is still much to look forward to, judging by the recent success of Partners HealthCare spinoff Annovation BioPharma. The company's next-generation intravenous anesthetic, ABP700, garnered promising clinical results is expected to be acquired by The Medicines Company in early 2015. The idea behind ABP700 began with anesthesiologist and clinical scientist Douglas Raines, MD, who leads a MGH research laboratory looking at the molecular mechanisms of anesthesia. “General anesthesia is an indispensable part of surgical care. Unfortunately the drugs that we have to achieve this state are fraught with problems,” Raines says. Propofol—introduced in the early 1980s revolutionized surgery, paving the way for fast track care, outpatient surgery, and procedural sedation. As the deaths of several major celebrities attest, the drug has a dark side. Poorly titratable sedation, respiratory complications, and hypotension pose significant risks to patient safety. Drawing from his deep understanding of drug structure-activity relationships, Raines set out to modify the structure of an existing anesthetic, etomidate, to create a safer alternative to propofol. Raines and a team of medicinal chemists at BWH and MGH synthesized a family of compounds safer than propofol and also overcame etomidate's troubling tendency to suppress cortisol production and interfere with the normal inflammatory response. “He would show us movies of rats put to sleep with his lead compound, MOC-etomidate, and then a rat that had been anesthetized with propofol,” recalls Carl Berke, PhD, who represents the Partners Innovation Fund on the Annovation Board of Directors. “You would see first the propofol-injected rats waking up very slowly and acting very groggy. With his new drug, the rats would pop awake and immediately start running around and urinating and all the things that rats like to do. The difference was dramatic,” Berke says. “The department of anesthesia, critical care and pain medicine has benefited greatly from past innovation in drug delivery. We are therefore, devoted to improving anesthetics with molecules like ABP700,” said Jeanine Wiener-Kronish, MD, Anesthetist-in-Chief, Department of Anesthesia, Critical Care and Pain Medicine, MGH. “We also are developing methods to detect the effect of anesthetics on the brain. Our mission is to use discovery and innovation to improve patient care and patient outcomes.” Raines and his team continued to optimize their lead compound to fine tune the drug's properties, guided by animal testing to create the current clinical candidate: ABP700. “If ABP700 acts in humans the way it does in animals – and the early clinical data suggest that it does – then it could be better than currently available anesthetics,” Raines says. “It would allow anesthesiologists to put patients to sleep more safely and then wake them up more quickly once surgery is done, without suppressing cortisol production. ABP700 is sort of a pharmacological switch that allows consciousness to be turned off and on rapidly.” In 2009, Raines teamed with an entrepreneur, investors, and Partners Innovation Fund to launch Annovation BioPharma, a startup company aimed at bringing to market safer and more effective intravenous anesthetic agents. By 2012, Annovation had raised nearly $9 million in product development funding from Atlas Venture, Partners Innovation Fund, Mass Medical Angels, and The Medicines Company. Human studies conducted in the Netherlands earlier this year confirmed preliminary findings in animals and demonstrated strong clinical evidence that ABP700 will overcome the limitations of existing IV anesthetics. Patients responded to the drug with rapid induction and rapid recovery, even after extended periods of anesthesia. The Medicines Company recently announced a plan to acquire Annovation and advance the product through pivotal trials and regulatory submission for FDA approval in 2017. “Rapid onset and emergence of anesthesia should enable faster recovery with less risk and fewer adverse effects,” notes Berke. “Precision control of anesthesia has been a long-sought holy grail since that historic day in the MGH Ether Dome.”