Biotech Values

[mcbio]

Re: ASMB R&D Day:

ASMB R&D Day: Scientific rationale for being able to eradicate HBV cccDNA with company’s core inhibitors is based on retrospective half-life analysis of decade-old patient samples.

Caveat emptor.

Finally got a chance to listen to the full presentation. The key part of the webcast specific to this starts around the 1 hour 35 minute mark. Just to add more detail on what was done, they obtained longitudinal samples (pairing plasma with biopsy) and used first-get nucs (lamivudine/telbivudine) against the samples because mutations quickly arise to these drugs and they could monitor the emergence and disappearance of the nuc mutations as a genetic marker of cccDNA turnover. ASMB also looked at samples that were lamivudine-resistant and added IFN treatment to make the samples sensitive to treatment again. Collectively, showed turnover in cccDNA in as little as 12-16 weeks.

All told, certainly plenty of caveats in trying to project this forward to actual activity in HBV patients. But, there's always going to be caveats in projecting pre-clinical data forward to the clinic. And, hopefully the fact that other big pharma (including JNJ and Roche) are specifically involved here in developing a CpAM adds credence to the approach.

Some other notes from the R&D Day (not exhaustive list of notes):

1. Phase 2 trial will be powered to show a .5 log decline in s-antigen at end of 6 months and hope to see that level of decline or even better.

2. Believe that 6 months of combo treatment in P2 trial inducing greater than 5% HBsAg loss would be considered significant.

3. Why using entecavir as part of the combo as opposed to tenofovir? Beyond joking that ASMB's CSO was behind the discovery of entecavir when at BMY, ASMB said tenofovir has renal issues and also must be dosed at much higher level compared to entecavir (300mg vs. .5mg), which makes entecavir much more suitable for co-formulation down the road.

4. ASMB mentioned advantages for its lead CpAM over competitors (including JNJ and Roche) as being that the drug is not metabolized to any significant extent in the liver and also noted that the lead is QD whereas believe Roche drug is BID (and had better activity in early trial vs. JNJ drug).