Replies to post #71110 on Biotech Values

[genisi]

The preclinical tox issue (intense immune stimulation) have been found with ANA975, a toll-like receptor-7 (TLR-7) agonist. ANA598 is an oral nonnucleoside HCV polymerase inhibitor that binds to a unique site on the HCV NS5b enzyme and has a clean safety profile so far.

[DewDiligence]

Re: ANDS

Hasn't this class of antivirals been dogged by side effect problems after longer term dosing?

HCV-796, a non-nucleoside polymerase inhibitor from VPHM, was killed due to toxicity; however, the HCV non-nukes as a group have had fewer safety issues than the nukes.

The magnitude of toxicity for direct-acting HCV antivirals varies according to: i) the affinity for hepatoctyes relative to other tissues; and ii) in the case of protease inhibitors, the specificity for the HCV protease relative to human proteases. On these metrics, each drug candidate has to be evaluated on its own merits, although all protease inhibitors share the latter concern.

Finally, bear in mind that different HCV non-nukes may employ different binding sites on the polymerase, which further differentiates one drug in this “class” from another.