Biota hot on the trail of cold cure

Melbourne drug design company Biota Holdings is preparing to sign up a partner to develop its new lead compound to quell the so-called 'common' cold.

In his address to last week's annual general meeting, Biota CEO Peter Molloy told shareholders that the new compound, BTA798, is at least twice as potent as the company's original lead molecule, BTA188, and free of the unwelcome effects that BTA188 exhibited in pre-clinical toxicology tests.

BTA798 is a new permutation of the same molecular theme. Molloy said. Toxicology tests showed it had an excellent safety profile, and was ready for pre-clinical development and partnering.

Molloy said BTA798 was also "markedly more active" than a rival compound, pleconaril, developed by US biotech Viropharma.

Pleconaril has run into problems during clinical trials leading to FDA approval, and has not yet been marketed.

Like GlaxoSmithKline's influenza inhibitor Relenza, also a Biota development, BTA788 is custom-designed to inhibit infectious rhinoviruses, the most common agent of the group of similar respiratory infections commonly known as the common cold.

Biota's science director, Dr Simon Tucker, said the prototype antiviral was designed to bind to a pocket-like motif hidden within a canyon-like cleft in the capsid protein of common-cold rhinoviruses. Although rhinoviruses strains vary considerably, and constantly mutate, defeating efforts to develop a common-cold vaccine, the target motif is shared by most rhinovirus strains, as well as by closely related human enteroviruses.

The capsid protein is essential for rhinoviruses to infect the cells lining the human respiratory tract -- it binds to ICAM-1, one of the intracellular adhesion molecules that allows cells to cling together and form specialised tissues.

The capsid protein is also the passkey that allows newly assembled virions to exit infected cells, maintaining the cycle of infection.

Where Biota's flu drug stifled infection by blocking the exit of new influenza virions through the membranes of infected cells, the new rhinovirus drug has dual activity, inhibiting both the entry and exit of rhinoviruses.

Tucker said rhinoviruses typically accounted for more than 50 per cent of the circulating viruses that cause the common cold -- various strains of adenovirus, respiratory syncytial virus (RSV), coronavirus, and some enteroviruses collectively account for the remainder of common cold infections.

Biota's BTA798, if it reaches commercialisation, would only prevent or abate common colds caused by rhinoviruses and certain enteroviruses -- potentially including strains that cause a dangerous brain infection, aseptic viral meningitis.

Molloy told the Biota AGM that despite the enormous potential market for an effective drug against the most common agent of the common cold -- in the US alone, 500 million people catch rhinovirus common colds each year -- the company will focus on high-risk groups like asthmatics, cystic fibrosis patients, and patients with chronic obstructive pulmonary disease (COPD) or underlying respiratory diseases like chronic bronchitis.

He said initial estimates suggested this market could be worth US$300-400 million in the US alone.