Narhex drug proves multi-talented

Sydney anti-viral drug developer Narhex Life Sciences has one of the world's most promising drugs for HIV/AIDS. Could it also have, in the same drug, a potential treatment for Hepatitis B?

Narhex said today that in vitro experiments with its promising AIDS therapeutic in the US have revealed unexpected inhibitory activity against Hepatitis B Virus (HBV).

The announcement comes on the eve of the company's ASX debut tomorrow, after its IPO raised more than $8 million it needed to fast-track clinical trials of its Nar 35 protease inhibitor for HIV.

Evidence for the drug's anti-HBV activity comes from no less an authority than the National Institute of Allergy and Infectious Diseases (NIAID), a division of the National Institutes of Health in Bethesda, Maryland.

NIAID researchers are now keen to test NarHex's lead compound, Nar 35 and its structural cousin, Nar 43A, against two more of the world's nastier viruses: Hepatitis C Virus (HCV) and the Severe Acute Respiratory Syndrome (SARS) virus.

NarHex co-founder and CEO John Majewski said the company has signed a partnership agreement with the institute to test the two compounds, in their native form, against HCV and SARS.

"We think SARS is a long shot, and so is Hepatitis C, but then we thought that Hepatitis B was a long shot," Majewski said.

Majewski said the drugs' developer, Dr Damian Grobelny, had no expectation that Nar 35 would work against the HBV protease enzyme, because it is from a different family to the HIV aspartyl protease.

On learning that Nar 35 was moderately active against the HBV protease, Grobelny - who is on the NarHex board - immediately recommended that the NIAID researchers try it - and Nar 43A - against HCV and SARS.

Majewski said the Nar 35 prodrug inhibits a protease reaction that creates three peptides from an HIV precursor protein called P55, by cleaving it at two aspartate residues.

The HBV protease lacks these residues, because it belongs to a different protease family, so it was a complete surprise that it exhibited any activity against an unrelated virus.

This indicated that the drug had an unsuspected, alternative mode of action, which led Grobelny to suggest it be tested against HCV and SARS.

Majewski said while the company's first priority is to continue developing and commercialising Nar 35, in its pro-drug form, for the treatment of HIV/AIDS, the agreement with NIAID opens a potential pipeline of new products for NarHax.

When NarHex closed its IPO on January 5, it was oversubscribed, and Majewski said the extra cash will allow the company to complete its clinical studies on Nar 35 in China, as well as to nurture early research towards potentially new applications.

He said it would undoubtedly be necessary to modify the structure of Nar 35 to improve its activity against HBV - and other viruses - but the company could do so knowing that, in its original form, the molecule had very low toxicity in humans.

An early Phase II clinical trial in Brazilian volunteers has already shown that the drug reduces HIV loads and improves counts of CD4-positive lymphocytes, the main marker of HIV infection.

NarHex has signed an agreement with the Chinese government under which Nar 35 will be fast tracked through clinical trials. The agreement is with the giant Chinese government trading company CMC Shaanx, which will pay the costs of Phase III clinical trials, and registering the drug for clinical use in China.