Hi, I'm co-founder of Underdog and the scientist who invented the drugs we are developing. Cool that this community has taken an interest. I agree with a lot of the insightful comments here. If you're interested in diving deeper into the toxic cholesterol that we're targeting I've just published a review article all about its biology and all the aspects of aging and disease that it's involved in: https://www.sciencedirect.com/science/article/pii/S221323171...
To touch on a couple of the other points that have been raised here, no our drugs aren't enzymes. We at SENS were working on an enzymatic approach for many years. There is still potential to engineering enzymes for this, but I designed our cyclodextrins to be a faster/cheaper/easier path to the clinic. Well, not that much cheaper. It's still very expensive. And yes, we are well aware of the hearing loss issue. It's avoidable, we believe we understand what caused it, and we're engineering around it. We'll be able to test whether we are successfully avoiding hearing loss in a very sensitive system in the next 9 months.
How long will we last? 16 more months with our current funding and burn rate. By then we need to have moved into series A so if anyone has any pharma VC contacts I'm definitely looking for warm intros :)
What is your opinion of using a monoclonal antibody against 7KC instead of cyclodextrin since mAbs are very well understood from a regulatory and PK/PD point of view. In your review I only see that you discuss 7KC antibodies as a method of screening for people who could benefit from your therapeutic idea.
Great question. Two problems with making a therapeutic antibody against seven KC. One is that we are not sure how good the seven KC antibodies are yet. We are working on this. The problem there is that 7KC only differs from cholesterol by one atom. The other problem is that the 7KC that we are worried about is inside of cells, so our drug is designed to mechanically pull the seven KC out, which antibodies can't really do. Also, cyclodextrins are very well accepted by regulators, it's just that they are usually used as excipients rather than as Active Pharmaceutical Ingredients (APIs). There are two examples of cyclodextrin APIs already, however, one approved and one in late stage clinical trials.
Yes, we are looking at IV, as others have done already clinically. We aren't looking at aptamers or other clever ways of binding small toxic biomolecules. I hope that other groups are!
Is there a chance that you are developing CD that target 7KC but at the end of the day, it dissolved chol-containing plaques inherently and that's where you'll derive the benefit from?
To touch on a couple of the other points that have been raised here, no our drugs aren't enzymes. We at SENS were working on an enzymatic approach for many years. There is still potential to engineering enzymes for this, but I designed our cyclodextrins to be a faster/cheaper/easier path to the clinic. Well, not that much cheaper. It's still very expensive. And yes, we are well aware of the hearing loss issue. It's avoidable, we believe we understand what caused it, and we're engineering around it. We'll be able to test whether we are successfully avoiding hearing loss in a very sensitive system in the next 9 months.
How long will we last? 16 more months with our current funding and burn rate. By then we need to have moved into series A so if anyone has any pharma VC contacts I'm definitely looking for warm intros :)