Replies to post #6890 on Biotech Values

[bladerunner1717]

Winchem, thanks for that post. I didn't realize that Squalamine had been tried intravitreally in primates.

Bladerunner

[DewDiligence]

>>Squalamine may not be effective as intravitreal injection.<<

When treating a small organ such as the eye, it’s unusual to have a drug show more efficacy administered systemically rather than locally. Perhaps this odd finding was caused by the idiosyncrasies of the laser-induced neovascularization used in animal models, which is not always a good guide for the “natural” neovascularization that causes AMD.

Also, I wonder if clever medicinal chemistry couldn’t have circumvented whatever the problem was with local administration.

[isolution]

Squalamine may not be effective as intravitreal injection

Thanks Winchem for reminding this excellent study. If that is true, they could have a problem for their only choice would be systemic delivery in phase III and you know that long-term side-effect appear in PhIII.
Also, I think FDA will never allow systemic delivery to treat eye diseases (except for diabetic retinopathy that also concerns the rest of the body).
Still we don't known the Squalamine MOA. In the article, they explain that Squalamine may improve retinal oxygenation and then suppress hypoxia mediated signaling for VEGF. In summary, it looks like an anti-VEGF drug but it is not.
If that is the true MOA, then it will have to be delivered systematically to work.