Avilar Therapeutics

A drug company that took out the trash

Here is a fact about drug discovery that is more inconvenient than it sounds: for roughly twenty years, the most exciting new way to make medicine - targeted protein degradation, the art of tagging a bad protein for the cell's own disposal machinery - worked in exactly one place. Inside the cell. That is a large and important place. It is also, notably, not the whole body. A great many of the proteins that make people sick do their damage while floating around in the blood, or sitting on the outside surface of cells, where the cell's internal garbage disposal cannot reach them.

Avilar Therapeutics, a biopharmaceutical company that launched in 2021 out of Waltham, Massachusetts, looked at that blind spot and decided it was the interesting part. The company's whole premise is that the extracellular world - proteins in circulation, proteins on membranes - is a vast, mostly undrugged territory, and that if you could teach the body to degrade those proteins the way it already degrades intracellular ones, you would have something close to a new category of medicine.

The mechanism they landed on is elegant in the way that good biology usually is, which is to say it mostly steals from nature rather than inventing from scratch. Your liver has a receptor called ASGPR - the asialoglycoprotein receptor - whose day job is to grab certain molecules out of the bloodstream and pull them inside to be broken down. It is, functionally, a garbage chute for the blood. Avilar's insight was that if you could hand that chute a list of things to throw away, you could clear disease-causing proteins on purpose.

The molecules that do this are called ATACs, for ASGPR Targeting Chimeras, and "chimera" is the operative word. Each ATAC is a bifunctional molecule: one end is a proprietary, high-affinity small-molecule ligand that latches onto the liver's ASGPR, and the other end is a binder that grabs whatever disease-causing protein you are trying to get rid of. Snap the two ends together and you have made a molecular tow truck. It finds the bad protein in circulation, hooks it to the liver receptor, and the whole complex gets pulled inside and routed to the endolysosome for destruction. Then the ATAC lets go and does it again.

The tow-truck mechanism, in four steps

What makes this a platform rather than a single drug is the modularity. The liver-targeting end stays largely the same; the binder end swaps out depending on which protein you want to remove. That means the same architecture can, in principle, be pointed at a wide range of targets across the extracellular proteome - which is a fancy way of saying Avilar is not building one medicine, it is building a machine for making medicines. The company has also described a companion approach, the mTAC platform, which uses ligands to a different receptor (M6PR, the mannose-6-phosphate receptor) to reach still more targets.

What they're actually pointing it at

A platform is a promise; the pipeline is where you find out whether the promise means anything. Avilar has aimed its first programs at two problems where removing a protein from circulation is not a theory but a clinically validated strategy.

*The ~85% IgG figure refers to a non-human primate study and is a preclinical result, not a human clinical outcome.

Sixty million to start, seventy-five to keep going

Avilar was incubated by RA Capital Management, a Boston investment firm known for building companies around a scientific thesis rather than waiting for one to walk in the door. It launched publicly in November 2021 with a $60 million seed financing - a notably large seed, the kind of number that signals the backers think the platform, not just a single asset, is the point.

In February 2023 the company expanded that financing to $75 million total, and the new names on the cap table are worth reading closely: Sanofi Ventures and Astellas Venture Management - the corporate venture arms of two large pharmaceutical companies - joined alongside Medical Excellence Capital. When strategic pharma money shows up this early, it is usually a tell that the industry is watching the modality.

Then, in November 2023, the U.S. Patent and Trademark Office issued Patent 11,819,551, providing broad protection for Avilar's first wave of ATAC extracellular degraders. Early, broad platform IP matters for a company like this, because the whole value proposition is that the approach generalizes - and you want to own the approach, not just one molecule.

Where Avilar sits on the map

Avilar is not entirely alone in looking outside the cell - Lycia Therapeutics is pursuing a related idea with its LYTAC degraders - and the broader targeted-degradation world is crowded with well-funded intracellular players like Arvinas, Kymera, Nurix and C4 Therapeutics. What distinguishes Avilar's bet is the address. The PROTAC crowd is fighting over targets inside the cell; Avilar has claimed the extracellular and membrane space, plus a specific, ASGPR-based route to the liver that it has spent years turning into proprietary chemistry.

For the people who might eventually benefit - patients with autoimmune diseases driven by autoantibodies, or pregnancies threatened by preeclampsia - the practical promise is straightforward. If a disease is caused by too much of a particular protein circulating where older drugs can't reach it, Avilar's platform is designed to go get it. That is still a promise being tested. But it is a specific, mechanistic, testable one, which in early-stage biotech counts for a lot.