Biologics Discovery and Development

KLUS Pharma has a proprietary discovery and development platform for therapeutic antibodies, which provides full coverage on all key development steps in the pre-clinical stage, including discovery, engineering, validation and manufacturing. 

  • Our discovery capacity enables development of antibodies against different types of targets, such as GPCR, integral membrane proteins, and surface proteins. The mouse immunization platform generates diverse and precise antigen designs using hybridoma with high throughput screening technology. Animal immunization and yeast display enalbe us to develop bispecific antibodies with shared light chains. In addition, we also developed the phage display platform (KAL library) powered by a naïve scFv library constructed with racially diverse human PBMC. With a size larger than 1x 10¹⁰, the library can produce fragments with excellent affinity (sub-nM levels). 

  • The identified antibodies will go through function development and optimization to receive further improvement in affinity maturation, humanization, Fc engineering, and bispecific engineering. 

  • The in-house validation team will examine the antibody candidates for in vivo efficacy, PK/PD properties, and the safety profile. 

  • Our manufacturing capacities ensure reliable supplies of antibody products from pre-clinical to commercial stages, including cell line development, 20 L pilot run with upstream process optimization, GMP quality system based on single-use processes, two 2,000 L mammalian bioreactors, and cold-chain solutions for storage and transportation.  

 
Antibody-Drug Conjugates (ADC)

KLUS Pharma has demonstrated outstanding efficacy and safety with our third-generation ADC platform. In addition to high affinity and internalization activity, multiple drug candidates show wider therapeutic windows than benchmarks.

 

The design and development of ADCs is based on our proprietary conjugation technology. To address the common issues of activity losses and high toxicity, we use novel conjugation chemistry to link the antibody to the payload. The highly stable, irreversible conjugation reduces the risk of toxic systemic exposure to the payload by reducing unwanted hydrolysis reactions. As a result, lower toxicity and higher efficacy were achieved. This conjugation reaction was fully developed to demonstrate production of batches with payloads up to 100 grams. 

 

Since the conjugation technology is compatible with most antibodies and payloads, KLUS Pharma has built a library of linkers and warheads that can be used to rapidly develop ADCs with the following advantages: 

  • Third generation: Homogenous and tunable DAR from 2-8. 

  • Linker: Highly stable and hydrophilic, site-specific, cleavable and uncleavable.  

  • Warhead: High potency, versatile MOA’s such as tubulin binders, DNA alkylating agents and novel topoisomerase I inhibitors. 

 
Bispecific Platform 

At KLUS Pharma, we believe that the optimal design of a therapeutic can ultimately lead to the best therapeutic result. Since no bispecific design has been singled out as the best, our development platform for bispecific antibodies supports a variety of bispecific formats, including shared light chain, scFv-IgG, scFv-Fab IgG, and others. Each bispecific antibody will be tested with different formats in order to maximize its efficacy. This strategy has proved useful for selecting the optimal bispecific design for several MOAs: 

  • Combinations with immuno-oncology

  • Effector cell recruitment 

  • Blockage of two ligands or two different pathways 

  • Tissue-specific delivery or function improvement 

 

In addition, excellent in vivo stability was observed with our bispecific antibodies in comparison to monoclonal antibodies. Efficient production as high as 4.5 g/L was also demonstrated. 

 

©2020 by KLUS Pharma Inc.