[wdwvt1]

I love the spirit of this grant but it has big "programmer knows better then pharma" vibes. At a first glance:

1) The original strain (BCS3-L1) is a clinically derived isolate with who knows what properties. Why not just take the well characterized ATCC/DSMZ strain and knock out the lactate dehydrogenase? I am sure the FDA would look more kindly on a better characterized strain - especially since you don't need whatever wild type mutations it has to keep it in the dental microbiome (the lantibiotic does that).

2) Who pays for this? Why? Finding the appropriate payer for a pharmaceutical intervention is difficult. Getting this through FDA trial costs (let's say) $200 million dollars. At the point of sale (PCP, dentist) the competitive product will be...toothpaste and a toothbrush. Getting a patient or insurance to purchase this under current models of care is going to be extremely difficult.

[akrolsmir]

Yeah, agreed that the proposal has a whiff of "too good to be true". The applicant's track record looks fairly good, though (he's previously invested in my startup, Manifold Markets, and otherwise has an interesting history in many different domains).

I think if there's even a 1% chance that the intervention looks as good as promised, it'd be worth further study for the proposed costs.

[wdwvt1]

I am a drug developer working on identifying novel therapeutics from human skin, oral, and intestinal bacteria.

I love the idea of Manifund - but I think this may not be the best project for it. This proposal needs some review by a biologist. In its current form, I think this is a much less impactful use of money than other things on Manifund.