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Competitor (DRNA) comments on their HBV program-an analyst even quotes ARWR research!from Q&A: With respect to HBV, we really aren’t trying to engage with partners at this point. We believe that RNAi is quite likely to be a very important part of a much better therapeutic regimen for HBV and that the value of this program will be substantially enhanced by showing strong human proof-of-concept data for at a minimum S antigen reduction and maybe more than that. And it is our plan to fund that work and conduct that work and really engage in partnering discussions once that data is in hand, not now. I’m wondering if you can expand a little bit on what do you think the design of the first HBV study will look like. I guess maybe specifically, do you anticipate having multiple ascending dose arms in this study? Yes, our post study design right now will be and which is – we are proposing is a single ascending dose study in normal healthy volunteers which will overlap what multiple ascending dose study in a wider range of patients with chronic hepatitis B, different e-antigen levels and NUC-experienced and NUC-naïve patients across a wide variation of chronic hepatitis B patients. So to clarify, the multiple doses for patients, single dose for healthy. Madhu Kumar: Hi, guys. Thanks for taking my questions. So thinking about the hepatitis B program, this is – we kind of deal with a lot of the companies in this space. What does clinical proof-of-concept in hepatitis B mean to you guys? Douglas Fambrough Hi, Madhu. That’s a really interesting question and I think one could define two levels of proof-of-concept that involve somewhat different levels of clinical assessment, if you will. Certainly, the simplest level is just are you seeing the reduction in the viral transcripts in their encoded proteins. And frankly with respect to RNAi, it’s sort of a gimme [ph] at this point in time. I think there’s very little doubt that there’s going to be a reduction in S antigen. So proof-of-concept is more about the power of the suppression. Are you seeing multiple log reductions? Are you seeing long duration reductions? So with respect to sort of Tier 1 proof-of-concept, it’s really about the quantitative depth and duration of the suppression of the viral antigen. And a second level of proof-of-concept would be are you seeing immune flares? Are you seeing suppression of S antigen beyond the pharmacodynamic effect of RNAi? And are you seeing evidence for sera-conversion? That’d be a very strong proof-of-concept. It’d be a proof-of-concept that maybe possible to be observed in a Phase 1 or maybe more likely to come out of a Phase 2 program. And I think it’s an open question right now whether at the end of the Phase 1 program that Ralph just described, whether that’s the right time to partner or whether doing a subsequent Phase 2 level of clinical work that establishes the strong POC and is the right time to seek a partner. And that’s something that I think we can’t answer now. We’ll see how the field evolves. We’ll see how other mechanisms of action are preceding and obviously we’ll have to be interacting with the potential partner. So right now, I wouldn’t say that we’re fixed on a single proof-of-concept definition but we do contemplate that it may be the case that we’re going for the strong form of proof-of-concept. It may be the case that we’re going for the simpler, more straightforward depths and duration of antigen suppression. So long answer to a short question and I hope informative. Madhu Kumar That’s interesting. So do you think kind of the consensus in the hep B community around RNAi has changed kind of based around the work from (Arrowhead) accidental discovery that when – they discontinued one of your competitors’ program, it continued to see declines in viral biomarkers. Do you think that’s any change in the grades of that Tier 1 level of proof towards more like the Tier 2 that’s really showing clinical proof-of-concept for RNAi and hep B? Douglas Fambrough Yes, that’s certainly an insightful concept. I think that observation has had a pretty powerful effect on the perception of RNAi in the field and has raised the very enticing possibility I referred to that you may start to see that in the Phase 1 itself. And so that of course has the implication. If you don’t see it in the Phase 1, then people begin to question whether you would ever see it at all. I can only speculate about that but I certainly think that the observation that you referred to of prior RNAi clinical work showing an effect on viral antigens longer than pharmacodynamic effect of RNAi has had an important effect on the view of RNAi in general for the treatment of HBV and has raised the profile and expectations for the potential of RNAi in the treatment of HBV. |
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Msg # | Subject | Author | Recs | Date Posted |
9744 | Re: Competitor (DRNA) comments on their HBV program-an analyst even quotes ARWR research! | jtrader87 | 1 | 8/9/2018 8:22:55 AM |