First in class
BFP-B3T-001 seeks to be the first molecule that crosses into the brain and targets the PD-1 receptor.
Current Status
We currently have a molecule that is capable of crossing into the brain in murine models.
Rapid adjustment
Crossing the Blood-Brain Barrier is a huge challenge that requires careful engineering. We are exploring several different approaches to BFP-B3T-001’s successful payload delivery. Our Antibody Drug Conjugate design will cross into the brain to enhance T cell efficacy by blocking the PD1 protein cascade inhibitor.
The challenging part . . .
Crossing into the brain
For us to have an antibody block PD1 in the brain and allow for T cells to do their job, those antibodies must first cross the blood-brain barrier (BBB).
The BBB exists to protect the brain from harmful molecules. Antibodies are proteins, much larger than small-molecule drugs, and they’re often water-attracting, while the BBB favors small fat-attracting substances. Without help, most antibodies can’t cross this barrier efficiently, which limits their use in treating brain-related conditions like tumors.
However, the BBB has specific receptors that naturally transport essential molecules, like glucose or insulin, into the brain. We aim to hijack these type of transport systems to deliver antibodies. researchers can trick the barrier into shuttling them across via a process called receptor-mediated transcytosis. Essentially, the antibody hitches a ride on the receptor, gets pulled through the endothelial cells, and is released into the brain.
Other receptors, like the insulin receptor or low-density lipoprotein receptor-related protein (LRP1), can also be targeted similarly. The challenge lies in engineering antibodies to bind these receptors just right—strong enough to get transported, but not so strong that they get stuck. This approach is promising but still being refined for practical use in diseases like brain cancer or Alzheimer’s. In simple terms, the BBB is a tough gatekeeper, but certain receptors act like keys we can use to sneak antibodies past it.
On the surface of immune cells called T-cells, there is a protein called PD-1 (Programmed Death-1). PD-1 normally acts like a brake on T-cells, preventing them from attacking healthy cells in the body. Cancer cells can exploit this by producing a protein called PD-L1, which binds to PD-1 and “turns off” the T-cells, allowing the cancer to evade the immune system.
PD-1 blocker antibodies work by binding to PD-1 and blocking the interaction between PD-1 and PDL-1. By doing so, they release the brakes on the T-cells, enabling them to recognize and attack cancer cells. This boosts the immune system’s built-in ability to fight the cancer. This is the receptor we have been working to target.