HERAKL1S Platform Technology
A dedicated engine for monovalent antibody discovery
HERAKL1S is ValeriusBio’s proprietary fully human monovalent antibody platform. It combines the chimeric Ig-domains CH3/CH1 (CH31) and CH3CLk (CH3k) to generate monovalent antibodies (Fc-one-kappa platform). The Fc-one-kappa platform results in monovalent molecule with antibody-like developability properties, including efficient producibility, high stability, less aggregation, and extended half-life compared with other monovalent antibody formats.
The design offers a controlled monovalent architecture with natural dimerization and Fc-based characteristics, enabling selective target engagement while retaining key advantages of a full-length antibody.
Our adaptable HERAKL1S platform technology supports both antagonistic and agonistic mechanisms and can be tailored to the desired mode of action. Fc regions can be engineered for either active or silenced FcγR engagement, enabling the deliberate inclusion or elimination of effector functions.
HERAKL1S Derived Antibody Structure
Generation of a heterodimerizing Fc with FcRn-interacting regions. A novel heterodimerizing Fc was generated by replacing the IgG1 CH3 domains with interspersed constant immunoglobulin domains based on the intrinsically heterodimerizing CH1 and Cκ domains. Elements of the IgG1 CH3 domains responsible for FcRn interaction were incorporated to retain FcRn-mediated recycling. The resulting heterodimerizing Fc was designated Fc1κ.
Richter et al, 2019 - MAbs. 2019 May/Jun;11(4):653-665
Technical Features
Fixed monovalent backbone: Uses a consistent fully human Fc‑one‑kappa scaffold based on CH31 and CH3k chimeric Ig-domains to generate monovalent antibodies with antibody‑like properties.
Controlled architecture: Natural dimerization occurs via a covalent disulfide bond between the modified CH3 domains providing a defined monovalent format that is inherently less prone to multimer formation and aggregation.
Fc-driven developability: Retains Fc-based advantages such as adaption of established mAb manufacturing processes.
Native Fc glycosylation site: Preserves the standard IgG Fc glycosylation site, supporting predictable effector-function engineering and alignment with existing CMC and analytical frameworks.
Configurable effector function: The Fc region can be tailored for active or silenced FcγR engagement, providing precise control over effector function and minimizing unintended Fc-mediated activity.
Clinical and Translational Profile
Suited for sensitive targets: Particularly powerful for targets where precise monovalent engagement and avoidance of receptor crosslinking are essential to achieve the desired pharmacology, whether antagonistic or agonistic.
PK profile: Optimized for a balance of tissue penetration and half-life, combining an intermediate molecular size (~70 kDa) with FcRn-mediated recycling. Flexibility of Fc domain enables further engineering using half-life extension and pharmacokinetic optimization.
Low immunogenicity potential: The HERAKL1S backbone uses fully human sequences and has shown low predicted immunogenicity in silico; Clinical studies with the first HERAKL1S-derived antibody support the favorable immunogenicity profile during phase I.