What is the Novel Antibody Discovery Platform?
Every B cell that survives an immune response has passed through somatic hypermutation and affinity maturation. What remains is a sequence that binds its target with high specificity and does not attack host tissue, an outcome that is difficult to reproduce by design. Elixiron’s single B cell cloning technology draws on this natural sequence repertoire, recovering paired heavy and light chain sequences at single-cell resolution to yield fully human antibodies.
This route removes the humanization step required for murine-derived antibodies, along with the immunogenicity risk that accompanies it. Once the sequence is recovered, we carry out sequence optimization to improve affinity, stability, and patentability, so that candidate molecules carry both clinical differentiation and intellectual property coverage. Our lead product indemakitug originates from this route.
For targets where no suitable natural immune response is available for sampling, such as metabolic checkpoints in the tumor microenvironment, the platform applies a second route: synthetic human antibody libraries combined with phage display.
Core Technology: Single B Cell Cloning
Fully human, high affinity, and low immunogenicity are established at the source. The workflow:
• Identify antigen-specific B cells: antigen probes identify and sort B cells that bind the target from samples carrying the relevant immune response.
• Recover paired sequences at single-cell resolution: heavy and light chain variable regions are amplified and sequenced from individual cells, preserving the native pairing that conventional library methods discard.
• Recombinant expression and functional testing: paired sequences are expressed as full-length antibodies and assessed for binding kinetics, neutralizing activity, and cell-level function.
• Sequence optimization: sequences are refined for affinity, stability, and manufacturability, while establishing patentability.
Our lead product indemakitug is a fully human anti-IFN-γ monoclonal antibody obtained through this technology, with binding affinity of 2.2×10-11 M and neutralization potency (IC50) of 18 pM, showing more than 10-fold higher in vitro anti-IFN-γ activity than the marketed antibody. In head-to-head preclinical studies using cell neutralization assays and systemic inflammation animal models, indemakitug outperformed the marketed antibody on both biological activity and survival benefit endpoints, supporting best-in-class potential in hemophagocytic lymphohistiocytosis (HLH), an indication for which it holds US FDA orphan drug designation. Indemakitug is currently in a Phase 2 trial in vitiligo.
Complementary Approach: Synthetic Antibody Libraries and Phage Display
Where no natural immune response is available, sequence diversity is built by design. Using AI-assisted design, Elixiron has constructed two synthetic human single chain Fv (scFv) libraries, with sequence diversity reaching 9×1010. The frameworks are drawn from human germline sequences selected for high stability and low immunogenicity, and the six CDR sequences were designed and selected based on binding, solubility, and stability analysis, concentrating diversity within a usable sequence space.
Phage display presents the library on the phage surface, allowing high-throughput affinity selection to recover phages carrying high-affinity single chain antibodies, which are then engineered into monoclonal or bifunctional antibody formats. The route requires no animal immunization and can be initiated directly against novel targets. EI-012 (anti-CD36 monoclonal antibody) and EI-011 (PD-L1/IL-10 bifunctional antibody) were both discovered through this route and licensed to Pilatus Biosciences Inc. after candidate optimization.
Products from the Platform
• Indemakitug (EI-001): fully human anti-IFN-γ monoclonal antibody | single B cell cloning | Phase 2 in vitiligo; US FDA orphan drug designation in HLH
• EI-012 (PLT012): anti-CD36 monoclonal antibody | synthetic library | licensed to Pilatus Biosciences
• EI-011: PD-L1/IL-10 bifunctional antibody | synthetic library | licensed to Pilatus Biosciences
• EI-017/EI-220: LAG-3/IL-10 bifunctional antibody and mRNA therapeutic | synthetic library | preclinical
Two products from this platform have been out-licensed, indicating that the candidates it produces meet the standard required to pass external technical due diligence.
