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Today we presented additional PK data from a Ph1 study of our #IBD candidate VE202 in healthy volunteers at #UEGweek. The new data focuses on the kinetics & durability of colonization of VE202 under various dosing & pre-treatment regimens https://bwnews.pr/3iS4ipq #microbiome
Determination of Pharmacokinetic - Pharmacodynamic relationships will be important to make rational choices for dose regimen of drugs consisting of live bacteria. It cannot really be done if you don't know what your drug is made of - that's an issue with fecal transplants ...
... It is impossible to fully understand the action of a drug unless the relationship between drug exposure and effect has been described. The inherent batch-to-batch variability in the composition of FMT and FMT-like procedures makes it challenging to reasonably describe...
... quantitatively the relationship between PK and PD. As a result, when FMT works we don't know why and when it doesn't, we don't know why either.
In contrast, quantifying precisely the PK of defined LBPs like VE202 is complex but feasible. 1st, we have to deal with the non-trivial technical problem of discriminating exogenously administered LBP strains from closely-related resident strains in the host’s resident community
We've achieved this by culturing the strains in our defined LBP and obtaining high quality, complete genomes from which unique genetic markers are derived and used to track strain-level engraftment from metagenomic sequencing of DNA isolated from fecal samples
Our work using this approach is starting to clarify some basic features of LBP PK that are likely to be generalizable, specifically showing that higher dose, more frequent administration, and pretreatment with short courses of certain antibiotics to create a niche for the LBP...
... to invade and engraft can significantly improve the abundance and durability of LBP strain colonization, as well as the proportion of LBP strains that colonize any given patient.
we have now verified these general PK observations across three Ph1 studies for three different defined bacterial consortia candidates, in > 140 volunteers.
Last, if talking about PK and PD in the context of live bacteria drugs sounds abstract, this is what we mean: PK is the study of how the host affects the fate of an exogenously administered drug. In the context of LBPs, I think PK should ideally include...
... studying how abundantly and durably the LBP component strains colonize the host resident microbiota, and what proportion of the product strains colonize each patient.
Pharmacodynamics is the study of how a drug affects the organism, which typically focuses on the biochemical and physiologic effects of the drug on the host. This of course still applies to LBPs, but study of the PD of an LBP additionally requires ...
... characterizing the ecological effects of the drug on the host resident microbial community. We are not just perturbing a homo sapiens, also the microbiota being carried around in the gut of the homo sapiens! We will publish data on PD later down the line / END
