Ann: Letter to Shareholders from the Board of Ave, page-30

re: Ann: Letter to Shareholders from the Boar... Worthind,

Ok, first Drona, as a chairman doesn't run the company, the board does. Also, on a day to day basis, the CEO runs the company and generally puts up the strategy options to the board. Drona is not the sole person to blame. ATC, however, has been a monumental waste of money and I would have expected him to stand aside.

Doctors can tell you what drugs they would have a use for. Generally, however, their threshold for desiring that drug is fairly low. Sort of "oh yeah, I had a patient last year that that type of drug would be useful in". The point being that while they can tell you what they would like to have, they have no idea whether the drug is worth developing in a commercial sense. Special interest groups are even worse when it comes to commercial decisions. The best ones are the pharmas probably followed by health insurers.

Of course ATC would be competing with other NRTI's, because resistance to it will develop, too. The same thing is occurring with antibiotics and older antibiotics are coming back. Not to mention the fact that it is simply another NRTI with slightly different characteristics which has not been shown to be superior to 3TC in any clinical trial so far.

With respect to salvage therapy, few if any drugs work for a long time because the patients are very sick by this stage, have resistance to numerous drugs and a life expectency that is very short. The sicker the patient, the more drugs they have been treated with, the less efficacious any new treatment will be, as a general rule.

Yes you are right, doctors do choose drugs on the basis of safety and efficacy. They also try and use as many different drugs as they can with distinct modes of action to try and hit a disease at multiple different points. That is why combination therapies are used in treating HIV and why Issentriss is vastly superior commercially to any single NRTI. It represent a new way of treating the disease, not just a minor improvement on an old class of drugs.

Finally, I have seen no data that demonstrates ATC is better than any of the other NRTI's you have mentioned. Trends yes, proof, no. Not even in the 2b study. This leads me to believe that ATC may have better clinical performance in some areas, but that it really isn't that much better than what is going around and, consequently,not worth pouring millions more into to develop.

Cheers,

Bob