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Infinity Bio Brings New Technology to Antibody-Antigen Binding Analysis

Antibody Protein Cell-Free Blood

NEW YORK – With the recent release of its antibody profiling platform, startup Infinity Bio is taking a new tack to studying immune response.

Launched several months ago to commercialize technology developed in the lab of Benjamin Larman, associate professor of pathology at Johns Hopkins School of Medicine as well as cofounder and CSO of the company, Infinity uses collections of self-assembled DNA-barcoded proteins and peptides to analyze antibody-antigen binding patterns.

Based in Baltimore, Infinity has received $4 million in funding from investors including Maryland-based PTX Capital and Blackbird BioVentures and currently has 12 employees.

The company's approach is similar to existing antibody profiling firms like Protagen (acquired by Oncimmune for $5.5 million in 2019) and the now-defunct HealthTell, with a major difference — instead of presenting antigens of interest in planar arrays that can be read out via fluorescence or other optical signals, Infinity's assays take place in solution, with readout done by sequencing the DNA barcodes attached to the antigens of interest.

According to Larman, the technique, which is based on his lab's MIPSA (for Molecular Indexing of Proteins by Self-Assembly) technology, has several advantages over planar array-based systems, one of the most prominent being that a solution-based assay is considerably easier to produce than an array-based one.

"There are many technical challenges associated with solid arrays that you overcome by using a solution-based assay," Larman said.

The approach allows the company to produce large arrays of proteins or peptides in a way that is "highly programmable," he noted, providing speed and flexibility. It also makes it easier to combine full-length proteins and peptides in a single reaction, which lets researchers look at both how antibodies interact with the three-dimensional structure of full proteins as well as collect information on the specific peptide sequences that function as antibody epitopes.

The MIPSA technology is the basis of Infinity's platform and the core piece of IP underpinning its efforts, Larman said. The assay uses Promega's HaloTag technology, which allows proteins of interest to be expressed fused to a hydrolase, the HaloTag, that can be bound to various ligands, or HaloLigands. MIPSA uses HaloTags fused to the protein or peptide antigens of interest, which are covalently linked to DNA-barcoded HaloLigands.

"It's a self-assembly-based process, which means that it can be massively multiplexed in a single-pot reaction," Larman said. "That is what allows us to, for example, create a library of all viral epitopes — the roughly 300,000 different peptides that altogether cover all human viruses — in a single reaction."

These libraries are then incubated with samples of interest. After the antibodies in the sample bind to antigen-barcode complexes in solution, they are pulled down using magnetic beads functionalized with affinity reagents to immunoglobulins. Unbound antigen is then washed away and the DNA barcodes of the remaining antigens are amplified via PCR and sequenced, allowing researchers to determine patterns of antibody binding across the antigen library.

Infinity currently offers three antigen panels: its VirSight panel, which features 278,000 viral peptides to all viruses known to infect humans; its AllerSight panel, which includes 2,352 proteins and 29,775 peptides to known food and environmental allergens; and its HuSight panel, which currently features 16,000 human proteins and will soon include 60-amino acid peptides across those proteins as well as 880 full-length human extracellular and secreted proteins.

Infinity CEO Caroline Popper said that the company may eventually develop the technology as a distributed product but plans for now to offer it as a service, given the expertise involved in both running the assay and analyzing the data it produces. She noted that the company has built a highly automated, industrialized laboratory for running the assay. It can currently run around 2,000 samples per week, though Larman said it could expand well beyond that by adding shifts or additional production lines.

Popper said Infinity has six customer projects currently underway, including one multi-thousand sample cohort. They include a project from a pharma firm looking at questions around allergy therapeutics; another one studying the infectious disease etiology of a chronic disease; and several projects exploring environmental triggers for autoimmune disease. The company is also involved in an epidemiology project studying an African cohort to see what infectious agents the subjects are exposed to over time.

Popper said the company is not currently working on any projects in immuno-oncology but suggested its technology could be well suited to that space.

"Immune-oncology agents work in some patients and they don't in others, even though all those patients have the tissue marker that suggests they should work," she said. "You could make a case for understanding not just the tissue marker … but what is in the circulation that is going to fight against your therapeutic strategy."

Immuno-oncology was a major focus of antibody profiling firm Protagen prior to its acquisition by Oncimmune.

Ultimately, Popper said, Infinity hopes to see antibody profiling data become a standard part of clinical research and clinical trial work.

"Wherever people would like to sequence their clinical trial participants or whatever, we would argue that it would be equally important to understand the antibody profile of those participants," she said.