OmniAb, Inc
Discovering High-Quality Therapeutic Antibodies; Unparalleled Antibody Discovery

Antibodies are one of the fastest-growing classes of drugs and are currently used across multiple therapeutic areas, including oncology, inflammation, and neurodegeneration. Antibodies have many favorable drug-like properties: high specificity, limited off-target toxicity, superior immune stimulation, and generally long serum half-life, which in many cases can be tuned for particular indications. As a result, antibody therapeutics have a higher clinical success rate than small molecules, according to Clinical Development Success Rates and Contributing Factors 2011-2020, a study of over 9,000 clinical development programs published by PharmaIntelligence. These factors have led to substantial investments in therapeutic antibodies across the entire clinical continuum.

However, clinical efficacy and safety can only be achieved after research and development teams discover a specific, developable antibody candidate. Traditionally, therapeutic antibodies have been sourced from the immunization of animals followed by in vitro engineering of the antibody sequence to make it more human-like (a process known as ‘humanization’) to lower the risk of unwanted immunogenicity and toxicity in patients. However, humanization is time-consuming and may reduce the potency of some antibodies and introduce unwanted developability issues. To bypass the need for humanization, the industry is trending towards using fully human sources for antibody discovery, such as naïve antibody repertoires from healthy donors or the use of transgenic animals that are engineered to produce fully human antibodies. Immunizing transgenic animals is an attractive solution to this problem because it harnesses natural biological mechanisms to produce more diversity, in vivo affinity maturation and clonal selection for antibody optimization.

OmniAb® has the most diverse host systems for fully human and bi-specific in vivo antibody discovery in the marketplace. The OmniAb platform consists of transgenic mice, rats, chickens, and cow based technologies, each with their own application in discovery. “Our broad antibody discovery platform allows us to uncover diverse antibody candidates against some of the industry’s most challenging targets,” comments Matt Foehr, CEO of OmniAb, Inc. “Using these proprietary and validated transgenic animals, our team can generate high-quality human antibodies, that are naturally optimized through in vivo affinity maturation,” says Foehr.

OmniAb’s first animal platform, OmniRat®, allows for the generation of human antibodies in a rodent host. This results in stable, selective, high-affinity antibodies suitable for further development with minimal additional optimization by in vitro engineering. OmniAb enhanced their rodent model platforms with the addition of a second species, OmniMouse®, which also produces human antibodies. The company then expanded its portfolio with OmniFlic®, a transgenic rat host that is capable of generating antibodies specially tailored for bispecific antibody discovery. Given their dual-targeting capabilities, industry interest in bispecific antibodies continues to grow as a novel therapeutic modality. However, they face discovery and development challenges due to the “pairing” problem encountered when heterodimeric heavy chains require two different light chains, resulting in many possible heavy + light combinations, only one of which is the desired product. OmniFlic rats are engineered to express a fixed light chain, bypassing this issue entirely.

The addition of OmniChicken® increased the diversity of OmniAb’s antibody discovery capabilities. Chickens are more evolutionarily divergent from humans than are rodents or other mammals, enabling OmniAb to generate antibodies against highly conserved mammalian proteins that are difficult to target with mice or rats. The large evolutionary distance (300 million years) between birds and mammals allows a chicken to recognize more areas (epitopes) on a target antigen as foreign and develop an immune response to them, even if the epitopes are conserved among mammals and therefore not immunogenic in rodents.

In response to most antigens, chickens will target additional epitopes compared to rodents resulting in a more diverse antibody repertoire, potentially allowing access to rare or uniquely differentiated antibodies. OmniChicken animals have been used as a foundation for generating two other technologies, OmniClic® and OmnidAb™. Like OmniFlic, OmniClic animals express a common (or fixed) light chain for bispecific antibody discovery projects, while OmnidAb chickens express a heavy-chain only transgene (also known as a single-domain antibody or nanobody(R ®)) inspired by camelid VHH domains.

“VHHs are small, stable, and highly manufacturable compared to monoclonal antibodies, making them an attractive framework for antibody discovery,” says Foehr. “The addition of OmnidAb combines the advantages of our OmniChicken technology with the novel structure of camelid heavy-chain only antibodies for discovery of human single-domain antibodies, which can facilitate the development of bispecific or multi specific therapeutics and other modalities as well.”

Another powerful offering from OmniAb is the OmniTaur™ model that generates antibodies based on the structural features of cow antibodies. Cows can generate antibodies with long, protruding CDR-H3 domains that make them particularly suitable for targeting recessed or cryptic epitopes on target molecules. Taken together, OmniAb’s portfolio of in vivo discovery tools provides multi faceted solutions for discovering therapeutic antibodies against the hard-to-drug targets.

Equipped with an Integrated Toolbox

OmniAb's in vivo discovery platform is further enhanced by powerful in vitro and in silico technology including antigen preparation and antibody characterization. A critical aspect of any therapeutic antibody discovery campaign is immunization with a biologically relevant form of the target antigen in order to shape the immune repertoire appropriately. For many soluble protein and single-pass membrane protein targets, procuring relevant antigen is straightforward, but for more complex targets, including multi-chain and multi-pass membrane proteins, antigen preparation can be considerably more demanding. OmniAb has optimized antigen modalities including reconstitution of purified protein in native conformation using nanodiscs, as well as efficient nucleic acid immunization using custom mRNA-LNP formulations. Screening and characterization of candidate antibodies are accomplished with OmniAb’s high-throughput automated xPloration® platform, which can rapidly screen and recover individual B cells representing desired profiles and efficiently sequence a large number of antibody hits by leveraging NGS workflows. Expressed recombinant antibodies are typically characterized through epitope binning, affinity kinetics measurements, developability profiling, and a variety of target-specific assays. High-throughput electrophysiology, x-ray fluorescence and other plate-based formats allow high-capacity functional analysis to rapidly select the most promising antibody candidates. This technology is particularly well suited for ion channels and other challenging membrane spanning proteins.

The company’s in silico platform, OmniDeep™, facilitates the rapid identification of candidates with the proper affinity, specificity, and developability profiles for more effective and efficient drug development. The OmniDeep platform is not just a single tool but a suite of models and databases, including structural modeling, molecular dynamics simulations, large multi-species antibody databases, AI, machine learning, deep learning models, and more.

The insights generated from this collection of computational tools for therapeutic discovery and optimization are woven throughout OmniAb’s various technologies and capabilities.

At the in vivo level, the OmniDeep platform taps into “Biological Intelligence™,” leveraging species-optimized transgenes and structure-focused antigen design. The aim is to create on-demand repertoires of antibodies rich in leads, which are directed toward partners’ targets of interest. At the in vitro level, its multiplexed, high-throughput, single cell phenotypic screening technologies are designed to rapidly interrogate millions of B cells and directly identify functional antibodies. The in silico technologies featured in the OmniDeep platform enhance phenotypic screens through efficient big data processing, providing the ability to go deeper into our immune repertoires, where additional promising antibody candidates may exist.

“OmniDeep's ability to enhance repertoire analysis and high-throughput screening technologies accelerates the identification of functional antibodies,” Foehr states. “In an industry defined by complexities and challenges, our capabilities simplify the path to groundbreaking therapeutic candidates.”

A Deliberate Business Model, Focused on Biology’s Most Difficult Targets

OmniDeep’s recent launch underscores OmniAb’s continued commitment to invest in new technologies and further expand the existing technology stack. The result has been the strategic integration of OmniAb’s in vivo, in vitro, and in silico offerings.

“Our technology investments have been methodical and deliberate to leverage cutting-edge solutions for our partners and solve the biggest challenges in antibody drug discovery,” reflects Foehr. “We've adopted a flexible approach to make the most of our proprietary platforms. Some partners prefer integrated end-to-end discovery capabilities, while others prefer to use our technologies in their own labs, alongside their own technologies or capabilities. This strategy has made OmniAb scalable since we don’t have to build capacity for partners that prefer to use some of their technologies in the process.”

In addition to this operational model, the company has decided to build specialized capabilities around targeting ion channels and transporters, positioning them for more future successes. Ion channels and transporters have traditionally been challenging targets for antibodies due to the structure of these proteins. Combining OmniAb’s comprehensive antibody discovery platform with deep experience in ion channel and transporter drug discovery and Icagen Ion Channel Technology® makes for a rare blend in the industry.

Ultimately, OmniAb’s model has paid off: OmniAb has high profile partnerships with many biopharmaceutical companies that have led to drug approvals in the US, Europe, and Asia and an increasing number of antibodies in clinical trials from its technology. “We believe we’ve built an unparalleled antibody discovery platform that has helped therapeutic antibody developers traverse the barriers that have been holding them back for years,” Foehr finishes. “As the industry continues to evolve, new challenges will come; however, with our unwavering commitment to innovation, we are confident that we’ll not only overcome these new challenges but pioneer groundbreaking solutions that will drive antibodies into new and exciting therapeutic spaces.”