Good morning thermal-cupreous colleagues. The sun is just coming up here. I agree with andrewm's comments, and do hope that people with doubts about Benitec bring them up here. Let's flesh out the objections and dispel them. The difference between antisense methods and ddRNAi is like the difference between throwing a bullet and shooting it.
I think it might be worth bringing up an objection I had to the company before I bought BNIKF shares last summer. It is this. To call HCV a hepatitis virus is a misnomer. It is an inefficient infector of hepatocytes, occupying perhaps 10 per cent of them (unlike HBV, where 100 per cent of hepatocytes are involved). HCV replicates in lymphoid cells (it is highly lymphotropic), macrophages, the central nervous system, buccal mucosa, genital mucosa. A friend of mine showed it replicates in kidney. Its liver effects get noticed more because in the liver it activates a fibrogenesis response: Ito/stellate cells basically become fibroblasts that begin laying down collagen strands in portal-to-portal arcs.
Because of this body-wide distribution of virus, I was convinced that TT-034, based on an AAV8 that trafficks just to liver, was doomed to fail because it would not purge HCV from its sanctuaries (if it has any). I burned midnight oil and went through maybe 250 studies of HCV replication in various cells populations before I bought shares.
We know that whenever HCV infects a cell type, it infects only 5-10 per cent of those cells, not all of them. If we knew why this is, we would have a deeper and more elemental clue for how to drive it out. Something deters it from pan-infection. We do not know what that is.
What we do know, however, is that in addition to infecting hepatocytes, it infects all liver cells. When we speak of liver cells, we are speaking of all cells within liver. This includes cholangiocytes, endothelial cells, Kupffer cells, resident macrophages. it inefficiently gets into all of them. We also know that in HCV patients, even after sustained virologic response (whereupon virus never ever comes back, even with leukopenia inducing chemotherapy, unless the patient is exposed to virus again), all of these cell types actually do continue to display both + and - strands of the HCV RNA.
What we have in liver, particularly in portal triads, where HCV is most active (it doesn't both hepatocytes out in the lobule very much) is an exceptional environment where many cells types commingle. My views that HCV passes among those, hopscotching. I think it preferentially partitions in liver, and that its presence in all other compartments and cell lines is in equilibrium with liver. Deplete the liver viremia, and you thereby do an even greater depletion of extrahepatic compartments. Moreover, it is known that with ddRNAi systems encoding shRNA, that after "dicer" does its work and affords active RNA strands, that those strands can be found within exosomes, bits of cell-membrane encapsulated material that bud off from transduced hepatocytes. And these exosomes probably will confer virus neutralization on cholangiocytes, endothelium and white cells resident in liver.
People ask Should I buy? Should I get in now? I will not equivocate. Yes you should. No one knows whether the TT-034 trial will show an effect. But all the best preclinical science, based on work in cell cultures and non-human primates, suggests that it will. This train is pulling out of the station. IN about a month, data from the TT-034 will begin trickling in. Benitec is at this very unusual stage of having JUST become a clinical stage company, and still not quite having clinical data of its own. If that data is positive, expect shares to explode.
Benitec is far ahead of Arrowhead as regards getting its RNAi method for virus hepatitis into humans. And yet look at the difference in market cap between the two! The same American outfit that just participated in capital raising for Benitec, RA Capital, did the same thing less than a year ago for Arrowhead. Its market cap has grown nearly 1000 per cent since then.
All biotech investing is speculative. But can you afford to miss this chance?
BLT Price at posting:
$2.24 Sentiment: Buy Disclosure: Held
