LONDON ¿ Protherics plc said the two partners for the human and veterinary versions of its gonadatrophin-releasing hormone (GnRH) immunotherapeutic are both reviewing the commercial potential of the compound, and it believes the projects are likely to be dropped.

CEO Andrew Heath told BioWorld International, ¿This is the nature of drug discovery. We haven¿t internally put a lot of weight on GnRH, and we¿ve not advised analysts to weigh it heavily, either.¿

ML Laboratories plc, which is developing the human version of the vaccine called Prolog as a treatment for prostate cancer, announced the review after preliminary analysis of Phase II trials indicated that higher doses of the vaccine would be required. Prolog is designed to stimulate the production of antibodies to block GnRH, thus reducing testosterone levels.

In the veterinary application of chemical castration, partner Janssen Pharmaceutica BV demonstrated proof of concept in cats, but said it also wants to review the commercial potential.

¿We have discussions ongoing with ML, but there is not a huge amount of value for us,¿ Heath said. Although the vaccine generated antibodies, there was no effect on testosterone levels. ¿It¿s not clear why,¿ Heath said.

In the veterinary area Janssen has demonstrated efficacy. ¿We know it works in cats, but it is the commercial aspects of getting to the market that Janssen is reviewing.¿ There are other potential applications in animal husbandry including fertility, behavior control and improvement in meat quality.

Protherics, based in Macclesfield, Cheshire, has dropped a further product, TriTAb for the treatment of overdoses of tricyclic antidepressants (TCA), because the investment required in manufacturing means the product would not be profitable. ¿This was effective in Phase II of reversing the symptoms but you need huge quantities of antibodies. We would need so many sheep to generate them it would not profitable.¿ The market for such an antidote is falling with the introduction of safer non-TCA antidepressant drugs. However, Heath said there has been some interest in the compound and a sale is possible, though it would be for a small amount of money.

Heath said he is positive about the prospects of soon finding a partner to take a further product, CytoTAb, an anti-TNF antibody, into Phase III. The company has been looking for a partner since September 1999 when CytoTAb completed Phase IIb in sepsis. The trial, in 81 patients, showed a statistically significant reduction in the amount of time patients spent on ventilators and in intensive care. ¿The history [of failed anti-TNF products] has dogged us, but we are very, very positive,¿ said Heath.

Earlier this month Protherics sold its computer-aided drug design business to Tularik Inc. for #6.6 million in shares, giving it sufficient funding to reach the break-even point. It also is expecting to receive its second FDA approval later this year, for DigiFAB, a treatment for digoxin overdoses.