Monoclonal antibodies (mAbs) are highly specific, have long-lasting efficacy, and offer a favorable safety profile. They enable precise targeting while minimizing off-target effects and are widely used in the treatment of various diseases, including cancers. The GeniusMab™ mouse platform features complete in-situ replacement of both the human antibody heavy and light chain variable regions. This enables the development of fully human mAbs with high diversity, high affinity, and low immunogenicity.

Challenges in Therapeutic Antibody Development

The development of therapeutic monoclonal antibodies faces significant challenges. A primary concern is immunogenicity, where non-human sequences can trigger unwanted immune responses, compromising both safety and efficacy of the therapy. Furthermore, high-value targets like GPCRs are notoriously difficult to address because their native conformations are hard to preserve outside a living system, limiting antibody diversity. Finally, the discovery and optimization process is often lengthy and inefficient, struggling to consistently yield antibodies with the desired high affinity, specificity, and developability profiles.

GeniusMab™: Fully Human Monoclonal Antibody Platform

The GeniusMab™ platform directly addresses these challenges through its innovative mouse model, in which the complete human variable regions for both heavy and light antibody chains have been inserted in situ. This groundbreaking approach enables the native immune system to generate a highly diverse repertoire of truly fully human monoclonal antibodies. By leveraging in vivo affinity maturation, the platform consistently yields antibodies with high affinity and specificity against even the most complex targets, while the fully human sequence dramatically reduces the risk of immunogenicity, streamlining the path to clinical success.

Fig.1 With complete in-situ replacement of human antibody heavy and light chain variable regions, the GeniusMab™ mouse possesses a fully human antibody repertoire.

Platform Core: GeniusMab™ Mice

At the core of the platform is the GeniusMab™ mouse, engineered to eliminate the need for cumbersome humanization steps. By generating natively human antibodies from the start, it directly shortens the antibody development timeline by 3-4 months. This allows you to advance from target identification to high-quality, development-ready leads with unprecedented speed.

Fig.2 The GeniusMab™ mouse generates fully human monoclonal antibodies directly, bypassing the need for in vitro humanization and saving an estimated 3-4 months in development time.

Advantages of GeniusMab™ Platform

The GeniusMab™ platform overcomes fundamental limitations of previous technologies and represents a paradigm shift in therapeutic antibody development. This platform genetically engineered mice to resemble the natural human immune system, a unique design that offers a number of key advantages:

A Truly Diverse, Fully Human Antibody Repertoire

Unlike platforms that use a limited set of human V-genes or require in vitro engineering, the GeniusMab™ mouse possesses the entire human variable gene library. This supports robust B-cell development and V(D)J recombination, generating an exceptionally diverse pre-immune repertoire. This extensive diversity is crucial for successfully targeting complex antigens and other difficult-to-drug targets.

Potent Immune Responses Comparable to Wild-Type Mice

A key differentiator of the GeniusMab™ platform is its ability to mount strong and effective immune responses upon immunization. The engineered immune system functions with an efficiency on par with wild-type mice, leading to robust affinity maturation. This results in the consistent generation of high-affinity antibodies with subnanomolar binding capabilities, directly from the native in vivo environment.

Capability to Target Complex Antigens

A key differentiator is the platform's ability to generate antibodies against challenging target classes, such as GPCRs, ion channels, and tumor microenvironment antigens. By leveraging a native in vivo immune system that presents targets in their natural conformation, the GeniusMab™ platform unlocks targets that are often intractable with conventional in vitro methods.

Drastically Reduced Immunogenicity Risk

Since the antibodies are derived from fully human sequences from the outset, the GeniusMab™ platform eliminates the need for cumbersome and often imperfect humanization steps. This not only saves 3-4 months of development time but also significantly de-risks future clinical development by minimizing the potential for anti-drug antibody (ADA) responses, thereby enhancing patient safety and therapeutic efficacy.

Streamlined and De-risked Path to Clinical Candidates

The platform integrates the critical steps of antigen recognition, B-cell selection, and affinity maturation into a single, efficient in vivo process. This streamlined workflow delivers optimized, high-quality lead candidates with superior developability profiles, accelerating your program from target identification to IND-enabling studies.

Applications of the GeniusMab™ Platform

The GeniusMab™ platform is a versatile and powerful engine for discovering fully human therapeutic monoclonal antibodies across a broad spectrum of disease areas. Its ability to generate diverse, high-affinity, and de-risked leads directly from a native immune system makes it ideally suited for both conventional and challenging drug discovery programs.

Case Study

Fig.3 GeniusMab™ mice exhibit robust immune responses comparable to those of wild-type (WT) mice.

Pipeline

Protheragen offers an integrated, end-to-end solution for therapeutic antibody development, spanning from initial antibody discovery and screening through comprehensive preclinical validation. Leveraging the powerful GeniusMab™ fully human monoclonal antibody platform, we are uniquely positioned to generate high-quality, de-risked therapeutic candidates efficiently. We invite you to partner with us to accelerate your programs and unlock the full potential of fully human antibodies.