Technology: The SparX SAILING^TM Multi-specific Antibody Discovery Platform

Multi-specific antibodies combine the binding specificities of multiple antibody domains into one molecule allowing it to bind different surface targets or epitopes on the same cell or between different cells.  This unique mechanism of action brings together two or more targets leading to unprecedented target specificity, synergistic activity or mechanistic activity that revolutionizes the way we treat diseases. 

At SparX, our goal is to unlock the full potential of multi-specific antibodies as cancer therapeutics. Charged by integrated monoclonal antibody development platforms and game-changing biologics CMC and manufacturing capacity, SparX is in a powerful position to validate, develop and manufacture multi-specific antibody-based therapeutics.

SparX’s SAILING^TM platform applies a comprehensive suite of proprietary technologies to generate multi-specific antibodies that not only retain the favorable developability associated with conventional mAbs but also possess differentiated modes of action. Explore our cutting-edge technologies below to see how they help us to accelerate our antibody discovery and shape the future of cancer treatment.

Synthetic Multidimension-programmed Antibody (SynMab^TM)

SynMab^TM (Synthetic Multidimension-programmed Antibody) combines a novel construction and optimization of multispecific antibodies. The unique structure of SynMab^TM makes it possible to retain the binding affinity and function of each parental monoclonal antibody composition. A high-throughput optimization via a disruptive display technology of a library of 10⁸ recombinant antibody variants provides highly optimized antibody candidates within 3 months. Compared to traditional bispecific antibody technologies, the SynMab^TM bispecific antibody construction and optimization platform furnishes multispecific antibodies with properties much like to a monoclonal antibody with improved solubility and stability. They are also simpler to purify, expressed in higher yield, and less prone to aggregate. 

AI-Assisted Target Mining & Validation

Target validation remains a bottleneck for drug discovery. The intrinsic complexity of the biology and pathology of a given disease and the ever-growing knowledge body make the traditional target validation process inefficient. Machine learning in combination with big data analysis can potentially overcome this challenge by ingesting massive and multidimensional datasets and identifying relationships among targets and diseases with unprecedented speed and depth. 

At SparX, we incorporate AI into our multi-specific antibody discovery platform by starting with the MoA or pathway for the primary target (such as LILRB2 or CLDN 18.2) and searching for hidden synergies with 3C rules: cooperative binding, complementary expression, and compensatory function, or novel immunological activation processes employing multi-cellular engagements. Digitalization is an important driver in innovation today.  At SparX, we construct 3-D AI algorithms consisting of model training, text queries, and data annotation, and refine the algorithms with continuous feedback. As a result, SparX AI reduces the risk of failure and accelerates our antibody discovery process. 

Integrated Monoclonal Antibody Development

We strive to bring much-needed therapies to patients sooner by significantly reducing the timeline from target validation to IND filing. We believe one critical aspect in shortening the timeline is a vertically integrated platform where we can drive monoclonal antibody development from target validation to cGMP manufacturing with a minimum transition gap to other parties. 

Our integrated monoclonal discovery program starts with an AI-assisted target validation followed by three parallel antibody discovery platforms (hybridoma, phage display, and transgenic mice models). Additional selection and optimization processes increase the affinity and diminish the immunogenicity of antibody candidates. In vitro and in vivo methods evaluate antibody candidates for their specificity, manufacturability, and safety to streamline the transition from discovery to development. Our game-changing biologics CMC and manufacturing capacity allows us to swiftly move the best candidate to cGMP and clinical CMC phases. All together, these core in-house drug discovery and development capabilities enable highly efficient timelines and speed.

LEMMAB^TM

LEMMAB^TM (Linker Enhanced Mono-chained Multi-specific Antibody) is proprietary technology platform that uses linker and CDR maturation by phage display to optimize multi-specific antibodies for desired properties. These antibodies are designed and screened for α-helix and/or disulfide insertions to improve stability and solubility. Owing to their single-chain and symmetrical nature, LEMMAB^TM antibodies are free of mismatches, less prone to aggregation, simpler to purify, and are expressed in higher yield.

In-house in vitro/in vivo pharmacology

Pharmacological evaluation is essential throughout the process of drug discovery and development. Pharmacology assays help to select and optimize the best drug candidates, predict the clinical risk profile before first-in-human studies, and explore and understand side effects that may arise during clinical development. Our pharmacology team has extensive expertise in oncology and immunology. We developed an array of in vitro assays to characterize our molecules’ impact on cancer cell signaling, proliferation, apoptosis, migration, invasion, and metabolism to better define the relationship of antibody characteristics with efficacy.  In addition, we have established a range of mouse and xenograft models to conduct efficacy evaluations in our state-of-the-art animal facility. Together, our ability to quickly assess drug candidates in-house enables us to significantly shorten discovery and development timelines.

NECOR^TM Glycan Remodeling

Glycosylation has a tremendous impact on the efficacy and safety of therapeutic antibodies. The nature of N-linked glycosylation in the Fc domain influences the effector functions of an IgG either enhancing or suppressing cytotoxicity. Current antibody manufacturing processes can lead to a highly heterogeneous population of glycans that can result in suboptimal safety and efficacy, and batch-to-batch inconsistencies

The NECOR^TM platform removes heterogeneous glycoforms of a given antibody and remodels it with homogeneous, precisely defined glycoforms in a highly efficient two reaction, one-pot system. Our approach offers significant benefits such as enhanced antibody functions, improved safety profiles, and higher batch-to-batch consistency.

Game-changing biologics CMC and manufacturing

Due to their molecular structure and complex nature, biologic manufacturing requires sophisticated and well-controlled processes.  At SparX, we established internal capacity and expertise in analytical characterization, cell line development, process optimization, formulation, and cGMP DS and DP manufacturing. By avoiding technology handoffs and conducting most of the CMC activities in-house, we compress the drug development timeline and leverage manufacturing capabilities during discovery and development processes.

We believe innovation is the key to enable manufacturing advances. We have been driving innovations throughout the entire biologic CMC and manufacturing process. For example, our cell line development process from DNA to a proprietary master cell bank, has been shortened to a 14 weeks. Together, our state of the art biologics CMC and manufacturing capabilities promises to deliver speed-to-market and consistent quality of drug products.