Another FVIII variant to tune into Dr. Denise Sabatino from CHOP because we are all looking to do the following in 2nd gen AAV gene therapy. Follow this thread to learn more (read my prior one on #FVIII-QQ from yesterday also) #ASH22 1/n 
Canine FVIII has increased expression due to a variant of the furin and a3 cleavage site which they put into this product (using AAV8 vector). (known as delta3-SP/BDD) #ASH22 2/n
Blue lines here show 2-4x higher factor VIII activity in canine hemophilia models and they moved onto non-human primate models (with endogenous f8 production (hence the %of F8) that developed immune response). #ASH22 3/n
Conclusion: this variant provides a potential way to decrease AAV vector dose and improving safety profile. #ASH22 4/4
in Q&A - lots of variability in the animal models, unclear why. Of course, this happens in clinical trials as well! We should do some investigation in these animal model patients as well. #ASH22
What about immunogenicity of this protein? They challenged mice with inhibitor to normal FVIII but they do NOT see immune response in those mice. Interesting! #ASH22
Did they look at the binding of VWF? They don't see a higher affinity to VWF so that's not he mechanism of this increase. #ASH22
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