Trio Medicines Ltd (Trio) was started in 2007 by HMR and the late Sir James (Jim) Black, the Nobel Laureate who invented of two classes of medicines, β-adrenoceptor antagonists (β-ADRA; “β-blockers”), for treatment of cardiovascular diseases, and histamine H2-receptor antagonists (H2RA), for treatment of gastric acid-related diseases. We’re still finding new uses for β-ADRA many years after their introduction into clinical practice, whereas H2RA have largely been superseded by the proton pump inhibitors (PPI).
Both H2RA and PPI inhibit gastric acid production, but by different mechanisms. However, anything that inhibits acid production results in a secondary increase in serum gastrin (hypergastrinaemia), which leads to tolerance to H2RA and loss of clinical efficacy but not to PPI, because the proton pump is the final step in acid production . Subsequently, the James Black Foundation (JBF) synthesised many gastrin/CCK2 receptor antagonists (GRA), but none matched the selectivity, potency and bioavailability of netazepide (formerly YF476), a GRA invented by staff of Ferring Pharmaceuticals, Chilworth, UK. Other pharmaceutical companies that worked on GRA encountered similar difficulties, and they abandoned their efforts when the PPI were introduced into clinical practice. But, we now know that gastrin does much more than just control acid production.
Malcolm Boyce, Medical Director, HMR, was the principal investigator of all the early clinical pharmacology studies of netazepide, which were sponsored initially by Ferring and then by JBF during the short period that JBF licensed netazepide from Ferring. When JBF subsequently closed, Sir James was free to join Malcolm in founding Trio in order to license netazepide from Ferring and to continue its development. Sadly, Sir James died in 2010, but Trio has continued to develop netazepide, which is on schedule to start phase 3 studies in 2020. Trio now has a second GRA, ceclazepide, which is at an earlier stage of development.