We are solving one of the world's most intractable health problems
Infections due to multidrug-resistant (MDR) Gram-negative bacterial organisms have emerged as an area of enormous unmet clinical need. Three illnesses — Hospital- and Ventilator-acquired bacterial pneumonia (HABP/VABP), complicated intra-abdominal infections, (cIAIs) and complicated urinary tract infections (cUTIs)–account for approximately 100 million days of treatment annually in the US and western Europe; these conditions have a mortality rate exceeding 10%. Bacterial resistance has severely limited the effectiveness of existing antibiotics against these pathogens.
Our macrolides are first-in-class for serious Gram-negative infections
Macrolide class antibiotics (including the original naturally-occurring erythromycin and its derivatives clarithromycin and azithromycin) are among the most successful and widely used classes of antibiotics, and the class holds the key advantages of a well-understood safety profile, excellent tissue penetration and oral availability. But there has been limited innovation in the class, in large part due to difficulties in synthesis. Macrolide class antibiotics have typically been developed for Gram-positive pathogens in community acquired bacterial pneumonia, but have not been prescribed for serious Gram-negative infections due to their unfavorable physico-chemical properties and the inability to modulate those properties via semi-synthesis.
Our platform, published in Nature in 2016, allows for the synthesis of macrolides not limited by the structure of the natural product erythromycin, but instead from basic chemical building blocks (see illustration above). This enables us to rationally design Gram-negative activity into our compounds and to anticipate and overcome resistance mechanisms. Our macrolide compounds are specifically designed to combat Gram-negative organisms; this first-in-class approach is sorely needed given the existing patterns of resistance to β-lactam, tetracycline and fluoroquinolone class antibiotics that are commonly used to treat Gram-negative infections.
- Seiple IB et al. A platform for the discovery of new macrolide antibiotics. Nature. 2016 May 19;533(7603):338-45. Pubmed.
- Lahiri SD and Alm RA. Improved Antimicrobial Activity of Fully Synthetic Macrolides against Macrolide Resistant Gram-positive Isolates. Poster presented at: ASM Microbe; June 19, 2016; Boston, MA. Link.
Partner with us
We are eager to collaborate with academic institutions and other companies who are interested in macrolide development, and anti-bacterials broadly.