Re: ABUS Galnac abstract from EASL
I will have to delve more into the specifics of the IONIS trial but this abstract was unexpected to me and very pleasing. I have previously stated that I thought that our own (or others) developments would lead to a cure before this was all at P3 stage. But the abstract was also very helpful because it contains specific data that other abstracts fail to provide.
1. In a like for like identical model ABUS has provided that LNP is 10x more effective (in terms of max HepBsAg reduction) than GalNAc. This may be slightly different for different manufacturers but we have a clear indication of relative efficacy that I would argue is likely similar for others. Our iv dose is 0.4mg/kg. Therefore, they would likely work in the 3-4mg/kg range. 9mg/kg was most effective but for an 80kg man that is 720g sc! I remember a well respected RNA expert saying anything over 1mg/kg is excessive, requiring different sites, and prone to local complications. Times have changed of course and we accept 3-4 as OK.
2. Longevity is greater with sc, but requires a bigger dose to achieve that longevity. Smaller doses will not have that effect. Reference ARO-HBV injecting mice sc every 3 weeks. ABUS has been targetting a rapid induction of immune conversion to cure and hence 2 weekly injection. This I think is influenced by the working HCV model. But it seems to me to be a huge advantage to have both an iv and a sc version. Why? Because you could conceivably dose a sc baseline lower dose and top up with iv, or vice versa. Glad to be invested in a company with more than one option.
3. The data is in a pertinent model. The mean serum HepBsAg is 3.6 log. That is representative of human patients that may have been treated. Never easy to find this for other companies.
4. For all the hoopla about leaders in the field, and allowing for unknowable differences in in the field ARO-HBV with 4mg/kg achieves 2.0 log HepBsAg reduction after single injection, ABUS-sc 2.4 log after 3mg/kg. Well it looks like this might just be our first effort, so could be a little better still.
5. We don't at this stage know details about triggers and trigger numbers. The comment about multipl transcripts infers at least 2 but not necessarily 3. LNP Arb1467 has 3 and clearly gives best protection against mutations, genetic variations and resistance. Aro-HBV Despite the hoopla, and assurances of protection from resistance, appears to be only 2.
6. Nominating a candidate was the stage of GalNAc we were led to believe we were at. This abstract was submitted a while ago. This gives value to the proposition of including GalNAc in the assets of a potential new LNP-GalNAc venture.
7. Parentetically, EASL also has a separate abstract on AB506 and AB452. As most acknowledge that the cure to HBV will require combo therapy,I am again glad to be invested in a company with more than one option.