Next Gen Factor Mimetics: Why Are They Needed?

So to set the stage for our listeners who may not be as familiar with factor mimetics, could you please share with us, Sanjay, a little bit about how these agents work and who they are indicated for?

Factor VIII memetics are actually a really elegant example of how our understanding of coagulation biology has really moved or translated into a completely different way of treating hemophilia.

So normally, if you go back to the biology of coagulation, normally activated factor VIII acts as a cofactor that brings activated factor IX and factor X together.

And this happens on a phospholipid surface.

And that markedly accelerates activation of factor X.

And ultimately, that leads to thrombin generation.

Now, in hemophilia A specifically, factor VIII deficiency, that cofactor function is missing or it's deficient.

And that's the biology of the disease.

Now, the memetics, factor VIII memetics, essentially recreate that function without replacing factor VIII.

So these are bispecific antibodies with one arm binding activated factor IX and the other arm binding factor X.

By bringing these two proteins into the appropriate special relationship, they facilitate the activation of factor X and then therefore restore trauma and generation.

Now, the distinction is that they mimic the cofactor function of activated factor VIII, but they're not factor VIII.

So they don't require activation by trauma, for example.

And the most important fact here is that they're not neutralized by factor VIII inhibitors, which positions them in a novel way to be used for patients who develop these inhibitors at an alarming rate in hemophilia.

So that's how the factor VIII mimetics work, and they've found a place in our therapeutic armamentarium.

Very good.

Thank you so much for that introduction.

It's really helpful to hear the biology and how it actually is working.