[Dr. KSS writes about medicine and biotech stocks for the Irregulars. He has agreed to our trade restrictions, chooses his own topics, and his words and opinions are his own. You can see all his past articles and more recent comments here.]
Picture the gurbling fumaroles of Yellowstone: from the late 1990’s and on into the oughties, drug giant Pfizer ($PFE) was biomedicine’s great hotbed of lipid research. Most of the great fundamental discoveries about nature and biology come from academia, from NIH-funded labs asking open-ended questions that lead to licensable mechanisms and chemical entities. But when the work has high likelihood of leading to a major drug, the best research in biology still is in the hands of biotech and drugmakers.
This era at Pfizer was spearheaded by the great Roger Newton, Ph.D., now chief scientific officer of functional if not actual Pfizer spin-out Esperion ($ESPR). Although atorvastatin was discovered at rival Genentech (a unit of Roche $RHHBY), Newton led development efforts for atorvastatin at Pfizer. Between the quality of his work and champion marketing efforts, atorvastatin (Lipitor) became, up until around 2012, the biggest selling lipid drug of all time and the best selling drug in US history.
But Newton was deep into the biochemistry and molecular biology of cholesterol processing, manufacture and trafficking, especially as regards liver. Cholesterol is vital for life: it’s the main constituent of brain, where it provides the lining, similar to wire insulation, for the extensions of nerve cells; this lining is called the myelin sheath. Cholesterol assists with wound healing, Moreover, its structural template, its carbon-based rings, are a basis for many hormones, biological messengers and even key players in neurotransmission (here I refer to the neurosteroids, based upon which Sage Therapeutics ($SAGE) and Marinus ($MRNS) are promulgating exciting new psychoactive drugs).
Newton recognized that in the body, cholesterol is made via two independent and parallel pathways. The first pathway has as its fulcrum an enzyme called HMG CoA reductase (HMG is hydroxymethylglutaryl). The Japanese had been the first to recognize that many fungi protect themselves from the adverse sociology of other fungi competing for limited nutrient supplies by making molecules that poison HMG CoA reductase. HMG CoA reductase produces mevalonate, a cornerstone molecule for making ergosterols in fungi and cholesterol in mammals. Fungi are just as dependent upon mevalonate as we are, and when one strangles their ability ...