Macrolides

The lead component of the company is an in-licensed pipeline of macrolides and ketolides from Optimer Pharamceuticals, with compounds at various stages of development. Additional licensing oportunities are being evaluated to have different classes of antibacterial agents under development to meet different clinical needs.

The world market for anti-infectives is greater than $28 billion and is expected to increase to greater than $30 billion in 2006, representing the third largest pharmaceutical segment. In the pharmaceutical arena there has been waning interest in anti-infectives as the margins and market potential have typically been lower than for drugs used in cardiovascular, diabetes and psychiatric diseases. However, while management of these chronic diseases necessitates a lifetime of therapy versus the short duration of therapy used for anti-infectives, these higher potential markets are riddled with product failures and the inability to predict clinical success in the absence of very large and long clinical trials. Compared to these types of drugs, the efficacy of anti-infective products is predictable from animal models, and because of the short duration of treatments, safety is also addressed in short clinical trials. Thus, the smaller markets and lesser clinical development demands make anti-infective drug development the ideal realm for biotechnology.

The first compounds to be developed are licensed from Optimer Pharmaceuticals and include macroldies/ketolides. The selected lead molecules have the same spectrum of activity as Sanofi-Aventis' telithromycin, but with additional activity against those streptococci that are resistant to telithromycin. The lead molecule has proven oral activity in mouse infection models, and is active against organisms that cannot be treated with telithromycin, clarithromycin or azithromycin, the leading macrolide/ketolide products on the market. Our licensed lead drug candidate is expected to be the best-in-class macrolide/ketolide.

In the antibiotic arena, macrolides/ketolides are viewed as a low risk/high reward area where there are few competitors. Global sales of antibiotics were over $12 billion in 2003, with macrolides contributing global sales of over $5.6 billion in 2003, $2.5 billion of that in the United States alone. In April 2004, telithromycin became the first ketolide to be approved in the US, and it is expected to quickly exceed $200 million in U.S. sales. The ketolides are expected to make significant inroads into the $5+ billion macrolide market.

As an example of the market opportunity available to a new macrolide/ketolide, it is estimated that 60% of community acquired pneumonia is caused by Streptococcus. In 1999, 20% of Streptococcus pneumoniae isolates were macrolide-resistant in the U.S. By 2004, it was estimated that 40% of S. pneumoniae strains were resistant to macrolides and penicillin in the U.S. Thus, a new macrolide/keotlide active against macrolide-resistant S. pneumoniae and Streptococcus pyogenes will be a valuable addition to the antibiotic armamentarium. Unlike the quinolones and cephalosporins, the large macrolide/ketolide market is not crowded, there being only four approved macrolides/ketolide and only a few other macrolides in development.

Next Generation Macrolide/Ketolide Program

Cempra has licensed break-through technology from Optimer that will enable it to incorporate different sugar motifs into the macrolide ring. Some of these compounds have already shown activity unprecedented for this class of drug. Cempra's goal is to follow its first compound in development with a new generation of these macrolides/ketolides for treating multi-resistant staphylococci as well as improve the overall activity against gram-negative organisms such as Hemophilus influenzae that are currently only marginally susceptible to macrolides. The improved activity will result from enhancement the binding capability of these molecules to the target bacterial rRNA.