BioWorld International Correspondent

PARIS - Entomed SA, which is developing compounds based on natural peptides and small molecules derived from insects, appointed Jean Combalbert CEO to replace Mario Thomas, who resigned last summer for personal reasons.

Combalbert was previously head of the pharmaceutical business unit of another small French biotechnology company, Proteus SA, of N mes, and will have the task of taking Entomed's first drug candidates into clinical development.

During the interim, the company has been run by Chairman Simon Cartmell, who will continue to manage for a period, before reverting to a nonexecutive role. Cartmell told BioWorld International that the departure of Thomas had prompted a strategy review that left the company with a broader focus and a stronger commitment to drug development.

Strasbourg-based Entomed, which was founded in January 1999, focused initially on developing natural peptides derived from insects as antifungal and antibacterial drugs. However, Cartmell said, "we found those peptides expensive to produce and decided that wasn't where the future lay." The company has now gone beyond insects' biological diversity per se to focus on the chemical diversity engendered by their biological activity. Entomed has thus extended its biological search to tap the large number of new molecules present in insects, which have a variety of pharmacological properties.

The company's lead compound, ETD-151, nevertheless came from its antifungal and antibacterial drug program. It is in late-stage preclinical development for the treatment of hospital-acquired invasive fungal infections, and Cartmell said Phase I trials would begin in the third or fourth quarter.

He added that the product had such a low level of toxicity that the company had found it hard to determine the maximum tolerated dose. As a result, Entomed was having to have a lot more of the substance manufactured than initially planned. Moreover, Cartmell said, because of the likely cost of clinical development, Entomed was already looking for a licensee to co-develop the product and was talking to half a dozen biopharmaceutical companies on both sides of the Atlantic. He expects to sign an agreement in the second half of this year.

Cartmell said Entomed was not planning to develop a second antifungal and that its future lead compounds would be generated by two other research programs. Its second series of lead compounds is based on another family of peptides, native defensins extracted from various insect species. Its lead compound in this program, ETD-1263, "is highly potent against Gram-positive bacteria," said Cartmell, stressing that it had proved highly effective in destroying superbugs that have become resistant to existing antimicrobial agents. This compound is at the lead-optimization stage and will enter preclinical development in the second half of this year. Other compounds based on organic small molecules and new peptides also could be developed for treating various forms of microbial infection.

In addition, the company has embarked on a cancer program that involves identifying small molecules with novel anticancer and anti-cell proliferation mechanisms. It has so far identified three families of small molecules that demonstrate activity against a range of cancer cells, and it is in the process of selecting lead compounds for optimization. Cartmell said they had been found to be active against not only the most common cancers - breast, lung and colon - but also against less common ones, such as bladder, prostate and brain. In selecting and optimizing a lead compound, he said the company would have to decide between one targeted at a particular cancer and one with broader application.

Entomed's financial situation remains comfortable insofar as it has two years' funding left from the €20 million it raised in its second funding round at the end of 2000. But Cartmell said the company was planning another funding round toward the end of this year or early in 2004.