RE:Gregory Bell, MD, Chief Medical Officer at AttralusLet me explain something about the transferrin receptor (TfR), or any receptor, for that matter.
Receptor-mediated transcytosis, as we use the term, requires something like xB3 to be attached to a therapeutic payload. xB3 is the "hook" that attaches to the receptor with the result that the xB3-Drug combination is pulled into the BBB cell and out its other side.
It's the same with TfR. Many companies use the TfR, all of them with a similar "hook" to attach to the TfR. However, for IP reasons, the structure containing that hook is different for each company. To me, the Ossianix TXP1 that Attralus is using for its AT-04 drug is just another structure using the TfR like all the others.
The TfR can be compared to the gates of a sports venue. There are only so many gates to any venue. It doesn't make any difference where your seat is or what ticket you have, you still have to go through one of the gates. It doesn't matter how you're dressed or who you're rooting for, you still have to go through one of the gates. Even if you have a friend on the inside to help you, you still have to go through one of the gates.
There are only so many gates and there are only so many transferrin receptors. No matter what structure carries the "hook," there are still only so many Tf receptors. The structues that hold the "hook" may differ. They may even have desireable or undesireable attributes, such as what happens after crossing the BBB, but they all still have to get through those gates.
In the end, there may be greater and lesser structures, but the transferrin receptor is common to them all and that suggest that less than 2%, maybe only 1% to 1.5%, of a dose will get through the BBB via the TfR. That makes the structures of these TfR drugs less interesting to me. Why bother when the TfR "gates" are such a limiting factor.
jd