was just reading about one of the companies mentioned, Evelo, this morning. their IPO prospectus mentions a few other potential benefits of using "bugs as drugs

was just reading about one of the companies mentioned, Evelo, this morning. their IPO prospectus mentions a few other potential benefits of using "bugs as drugs", rather than traditional biologics or small molecules, including 1) can alter multiple biological pathways, as opposed to one target per drug w small or large molecules, 2) cheaper to optimize the product (don't have to do extensive medicinal chem or antibody optimization, just need to pick the right naturally occurring bug) and 3) potential for microbes to be safer (ppl have been eating these for a long time). a nice side effect of a safer treatment is that you can use them in less sick patients, thus increasing your market size i can see 1) being true. 2) potentially is true, though i don't have the expertise to evaluate this. however, some companeis are genetically engineering microbes to increase effectiveness, which would add to the time requried to "optimize" the microbe. for 3), ive heard differing opinions. "the tox is in the dose", so even if ppl have ingested a microbe without harm, if you increase the amount of microbe who knows what will happen. nonetheless, their approach is interesting. the idea is that circulating immune cells (dendritic cells and macrophages) "sample" the gut microbiome by sticking tendrils through the intestinal wall. they collect antigens from the gut and then migrate to regional lymph nodes (basins with a bunch of immune cells) and interact with t cells and other immune cells, changing how they function. they have a platform where they screen a bunch of different microbe strains in culture with dendritic cells (and maybe other cells) and then measure what cytokines and other chemicals the dendritic cells secrete / express. they select microbes that have the ideal "immunophenotype" to use as therapies. they then validate these in animal models of disease, and have some really impressive preliminary results (summary of data in the IPO prospectus) of course, as the article states, the big question is whether this will work in people. there's conflicting evidence as to what particular strain is most implicated in a particular cancer. and we also don't really know if just hitting one strain is enough to do anything. part of what makes evelo interesting is that they think theyve found a specific immunological mechanism for their microbes role in disease, which makes it easier to measure whether its working in early studies (ie you can measure circulating cytokine and immune cell populations as a proxy for whether the cancer is getting better). however, theres no way to know without doing the human studies. this phenomenon applies to all types of drugs however, and is the reason why drug r&d is so expensive: you never know if something works until you test in humans, and thats really expensive