Protein design startup Archon adds $20 million to show how “cages” can transform antibody drugs

Antibodies have been established as a central therapy method for a variety of diseases over decades. But antibodies like those found in nature didn't evolve to be used as drugs, says James Lazarovits, co-founder and CEO of Archon Biosciences. These proteins became drugs because scientists used them for specific purposes.

One of the limitations of currently available antibodies is the therapeutic window, i.e. the dose range in which a drug exerts its therapeutic effect without simultaneously causing dose-limiting toxicity. Lazarovits describes this window of time as the interplay between the amount of drug that gets where you want it and the amount that gets where you don't want it (causing toxic effects). Archon's technology changes the size and shape of an antibody, adjusting how a therapy gets to where it needs to go in the body, what it does when it gets there, and whether or not it stays there. The Seattle-based startup came out of stealth last week and raised $20 million in funding for research and development on a new class of antibody drugs.

The field of antibody drug research and development includes efforts in the areas of multivalency, which is the ability to bind to multiple sites on the same target, and multispecificity, which is the ability to bind to two or more different antigens. These antibodies may be good for certain applications but not so good for others, Lazarovits said. Instead of designing an antibody by changing the order of amino acids that make up a protein or adding different arms or multiple binding domains, Archon designs antibodies in a way that controls their structures. Archon calls its drugs antibody cages, or AbCs. These antibodies are manufactured in a way that follows the established format for producing antibodies and simply adds an additional step at the end of the manufacturing process. But this extra step gives the antibody properties it didn't originally have.

An AbC offers tunability not naturally found in antibodies, Lazarovits said. The structure of the AbC can not only turn a goal on or off, but also adjust its magnitude. Antibodies often require secondary signals for activation. While this is achievable and controllable in a closed system, it becomes more difficult within a patient and across patient populations. Lazarovits said the structure of the AbC can activate pathways autonomously without anything having to happen elsewhere.

“The structure we create changes the way we actually activate the biology of a cell surface,” he said. “It’s not a matter of whether the antibody binds to the target, but rather how it binds to the target.”

The Archon technology comes from the University of Washington's Institute for Protein Design, led by David Baker, the professor of biochemistry who won the Nobel Prize in Chemistry in 2024 for his work in computational protein design. Computational protein companies that have emerged from the institute include vaccine developer Icosavax, which was acquired by AstraZeneca for $800 million last year, and A-Alpha Bio, whose technology for analyzing protein-protein interactions has partners such as Bristol Myers Squibb won.

Archon co-founder George Ueda worked with Baker for more than a decade. Lazarovits said their research was originally aimed at developing proteins that had never existed in nature. They then wanted to design proteins with unique structures. From there, they wanted to find out if these structures could make a difference.

Lazarovits came on the scene about five and a half years ago, bringing with him experience in antibody delivery. Baker awarded both Ueda and Lazarovits faculty positions. Their research generated $7 million in grants to further develop the eventual AbC platform. The scientists were able to generate preclinical data to show what problems these novel antibodies could solve. This research was published in the journal Science in 2021. Lazarovits said the research also helped scientists understand what kind of capital would be needed to use this new antibody science to develop novel drugs. Archon was founded in early 2023.

Archon does not yet disclose the therapeutic indications it is researching. But Lazarovits said the programs the startup has chosen address clearly defined goals that have previously been out of reach for the pharmaceutical industry. Based on preclinical research, Archon understands the contingencies for activation and deactivation of its selected targets. What this could mean for an Archon drug is a similar effect to an already available drug, but fewer side effects, increased effectiveness or a combination of both, Lazarovits said. He added that the company is pursuing acute indications and not chronic therapies.

By focusing on known, desirable targets that are difficult to reach, the “check box” of data Archon requires is very standardized, Lazarovits said. The company knows the data it needs to collect and what it needs to show to show how its antibodies are differentiated. Because all of this is known from the start, data generation can be done quickly.

The startup's strategy was well received by investors. Archon's seed funding was led by Madrona Ventures, a Seattle-based venture capital firm that has invested in several artificial intelligence biotechnology companies, including Ozette and Nautilus Biotechnology. Other participants in the Archon financing include DUMAC Inc., Sahsen Ventures, WRF Capital, Pack Ventures, Alexandria Venture Investments and Cornucopian Capital. Lazarovits said the financing gives Archon a term of about two years.

In addition to generating data to demonstrate the science of AbCs, Archon will also use its new capital to develop a business model. Ultimately, the startup aims to partner with larger companies, Lazarovits said. In this case, he wants to have enough data to know which assets he should outsource and which he should keep in order to add value to the young company. Discussions with pharmaceutical companies and other investors are already underway, said Lazarovits.

“Because it's a technology that lends itself so well to partnerships, we're safe,” he said. “If you try to do everything, you’ll do everything pretty badly.”

Image: Archon Biosciences