By Peter Winter

BioWorld International Correspondent

OTTAWA, Ontario - The challenge for the biotech industry is not always in the discovery phase of therapeutically promising small molecules, but in devising ways to elongate their half-lives in the body. Often these peptides and organic molecules are found to have half-lives in the region of minutes, thereby limiting their use as drugs.

A Montreal-based company, Conjuchem Inc., said it has discovered a therapeutic niche for its bioconjugation technology platform that can be applied for both targeting and extending the duration of the drug's effect, systemically or locally. The technology enables the design of specific drug constructs, called drug affinity complexes (DACs), which permanently attach drugs to endogenous protein carriers in vivo.

Duffy DuFresne, president & CEO of Conjuchem, said his company may be the only one to have developed in vivo bioconjugation technology that allows both drug and target proteins to maintain activity after covalent attachment.

The wide applicability of the technology has attracted the attention of several major investors from Quebec and Europe. In fact, it was venture financing from Montreal-based groups BioCapital Investment and Societe Innovatech du Grand Montreal that helped create Conjuchem in 1997, with the acquisition of the DAC technology from RedCell Inc., of South San Francisco, in a stock and asset transfer.

In 1998, the PSTQ (Fonds de solidarite des travailleurs du Quebec) and the Business Development Bank of Canada in Montreal completed a Series A financing with an investment of C$6 million (US$4.1 million).

Conjuchem earlier this month completed a follow-on C$12.7 million Series B private financing round to support its preclinical and Phase I/II studies. The single largest investment in this financing was made by Finedix BV, a new investor in the company. Finedix BV is an affiliate of Halisol, a Paris-based company involved in biopharmaceutical investment and product development. Halisol is led by Niocole Bru, who has a long association with the pharmaceutical industry, particularly in pain research.

"This was one of the reasons of their interest in Conjuchem," DuFresne said, "since we are currently working on a DAC opioid compound."

According to DuFresne, the company has several proprietary products in preclinical development, including the lead opioid compound for the treatment of chronic or sub-acute pain. A local thrombin inhibitor also is being developed to prevent clotting in peripheral bypass grafts and arterial-venous shunts. This compound is expected to begin human trials later this year. In addition, Conjuchem has a collaboration with the Institut de Recherches Servier, the R&D arm of Servier, of Paris, for the development of drugs for the prevention of cancer metastases. These drugs use the company's proprietary DAC technology to modify matrix metalloproteinase inhibitor (MMPI) compounds created by Servier. MMPI compounds have been found to inhibit tumor invasion, metastasis and angiogenesis.

Conjuchem said it developed two novel chemistry platforms for in vivo bioconjugation that provide all of the benefits of traditional drug delivery systems, while eliminating the need for drug release and the associated problems of circulating free drug inherent to those systems.

One of those technologies enables local, tissue-specific delivery in a manner that retains high levels of localized biological activity for very long periods with very limited systemic exposure. In the other platform, by specifically bioconjugating to albumin, a naturally circulating protein, the company's systemic DAC constructs acquire a half life in the body identical to that of albumin (about 20 days). In evaluations, bioconjugation of various active drug compounds to albumin has resulted in 100-fold increases in drug half-life.

DuFresne said Conjuchem is pursuing a drug delivery type of business model that emphasizes corporate collaborations for the commercialization of DAC technologies.