Prof. Myers, among the world’s leading synthetic chemists, has developed the first and only practical total synthesis of a major class of antibiotics, termed macrolides. This class, which includes azithromycin, clarithromycin and erythromycin, is among the most widely used and successful classes of antibiotics, but its efficacy has been limited by the development of bacterial resistance, and introduction of new macrolides has been severely constrained by limitations in chemical synthesis. Prof. Myers’ technology solves this problem and enables the total synthesis of virtually any macrolide, so thousands of novel macrolide compounds can now be made and tested that were previously inaccessible.
Macrolides are among the most widely used, most effective and safest antibiotics to reach clinical practice; in fact, azithromycin has been among the world’s most widely used antibiotics for the past several years. But, while current macrolides are highly effective against some major bacteria, they are ineffective against others, especially gram-negative bacteria, the cause of most serious infections in the US.
The first three generations of macrolides have very limited activity against gram-negatives, and the sole drug in the current fourth generation, solithromycin, has only slightly greater activity. Within other antibiotic classes, a limited number of compounds are in development to treat resistant gram-negative infections, and even fewer are available both intravenously and orally, as would be expected with macrolides.
TechnologyThe transformative new technology developed by Prof. Myers for the first time enables a practical, intrinsically scalable and readily diversifiable, total synthesis of macrolide structures from basic building blocks. The synthesis has been proven in the laboratory, and is already producing significant numbers of novel, fifth generation macrolide compounds for testing. In fact, more than 200 completely novel macrolides have already been synthesized with excellent yields, indicating that the synthetic route is commercially viable. In vitro testing of these new compounds indicates that several compounds from multiple different “scaffolds” have activity approaching clinical effectiveness against highly resistant gram-negative bacteria. In addition, a number of compounds are highly active against gram-positive bacteria including resistant clinical strains, potentially even more active than currently available macrolides.
Lawrence G. Miller, M.D.
Dr. Miller is a highly experienced company founder and manager, working closely with 9 companies over the past 25 years, including HPR, Avicenna Systems, Serenex, PharMetrics. He was a co-founder of Tetraphase Pharmaceuticals with Prof. Myers. He was educated at Harvard and completed clinical training at the Massachusetts General Hospital.
Prof. Andrew G. Myers
Prof. Myer, Houghton Professor of Chemistry and Harvard University, is among the world’s leading synthetic chemists. He was a co-founder of Tetraphase Pharmaceuticals with Dr. Miller. He was educated at MIT and Harvard, and previously was a faculty member at Caltech.
Lawrence G. Miller
Gurnet Point Capital
Advent Life Sciences