While these studies are only in the pre-clinical stage, they are very encouraging. Both BB-102 and BB-103, when used in conjunction with existing drugs, reduced serum HBV DNA to the lowest quantifiable levels. Furthermore, HBsAg (a viral protein associated with immunosurpression) and HBeAg (a protein which circulates in the blood and is an indicator of infection) levels were reduced substantially more than by the existing drug alone. These are all extremely positive outcomes.
The results were obtained from experiments in which mice had part of their liver removed and replaced with grafted human liver cells. These chimeric livered mice are able to be infected with HBV, a disease not normally associated with mice. This is the first piece of evidence that the FDA will require in order to progress a move to trials in humans.
The next stage in the clinical trial approval process is not so clear. The FDA usually requires at least two different animal trials before granting authority to proceed to human trials. It also requires biodistribution and toxicology studies to be carried out. So far, Benitec has not indicated what the next animal model will be but it is likely that they will use a specie of macaques that contract HBV.
The simian model will also provide evidence of biodistribution and toxicity for BB-103. This will be essential for this drug candidate but it may not be necessary for BB-102. This is because BB-102 uses the same AAV8 vector used by TT-034, the treatment for HCV, which has already proven to be safe in human trials. It is possible that the FDA will accept the safety evidence accumulated in the TT-034 clinical trial and waive the need to provide further biodistribution data. As the drug targets conserved regions of the HBV genome and is expressed from a cassette similar in design to TT-034, the FDA may also waive the need for further toxicology studies but I suspect that this will not be the case. Benitec may get away with the need for further biodistibution studies but I think the FDA will insist on seeing additional toxicology studies.
BB-103 is a new design and so there is little chance that this could take a shortcut to human trials.
So, with excellent mouse model results, a possible faster track to human trials for BB-102 and the prospect of a newer and more efficacious BB-103, will these data be sufficient to catch the eye of a potential partner? How long will a potential partner wait before making a move to invest in the program? With HBV being such a hot topic, I like to think that a least one big pharma has an eye on this program.
Disclosure: I am/we are long BNTC.
Additional disclosure: This article is not intended to be investment advice. Readers should do their own research.