Sengenics
Novel Technology for Identifying and Measuring Autoantibodies

The pharmaceutical industry is continually striving to bring safer and more effective drugs to market. The most recent reports indicate that 88 percent of drugs fail to reach the market due to either efficacy issues or toxicity. Singapore-based Sengenics is in a unique position of addressing this predicament by guiding decision-making strategies through enhancing early failing of drugs that may have high downstream failure rates due to issues with efficacy and adverse drug reactions (ADRs). The company’s KREX protein array technology is a unique technology for identifying and measuring autoantibodies at exceptionally high specificity and sensitivity. These autoantibodies are not only biomarkers for diagnostics or therapeutics but may also be used for predicting responders, non-responders and ADRs in patients taking either cancer immunotherapy or autoimmune drugs.

The fundamental advantage of Sengenics' core technology is its unrivalled success rate of close to 100 percent in producing correctly folded, functional proteins even if they are highly complex proteins. This is based on its core KREX patent family which actively selects only for correctly folded proteins. The mechanism of how the selection method works is based on using a secondary fusion protein partner called Biotin Carboxyl Carrier Protein (BCCP), which functions as a folding marker. Unlike other platforms, Sengenics’ proteins are correctly folded, functional, and full-length. Since the company does not use protein fragments or peptides, both continuous and discontinuous epitopes are preserved in the protein. KREX-based protein arrays can detect autoantibodies in serum even if it is diluted by a million-fold, proving the high sensitivity of the platform. Further, the highly flexible platform allows for assay customisation with any number of autoantigen targets, within a relatively short timeframe. "Our platform is hardware-independent, hence enabling great adaptability in terms of how and where the assay is run, and we can detect autoantibodies down to 1 picogram/ml at exceptional specificity, resulting in very high signal-to-noise ratios,” says Professor Jonathan Blackburn, CSO of the company.

Currently, Sengenics holds intellectual property (IP) on a wide variety of autoantibody-based diagnostic, therapeutic and companion diagnostic collaborations. In terms of pharma, the company’s focus is on stratifying response and ADRs to cancer immunotherapy drugs. In light of this, Sengenics has completed various studies recently on achieving very high NPV (negative predictive value) and PPV (positive predictive value) of above 0.9 for cancer immunotherapy drugs. “We see the cancer immunotherapy stratification space as paramount in terms of clinical need and we are now focusing our efforts with several pharmaceutical companies in this space,” remarks Blackburn. The other area of Sengenics’ focus is based on autoimmune drugs where there are particular issues with response. “We’ve been collaborating with an academic institution on response stratification of Abbvie’s Humira drug which we are able to achieve at PPVs of above 0.95,” mentions Blackburn.

Our platform is hardware-independent, hence enabling great adaptability in terms of how and where the assay is run, and we can detect autoantibodies down to 1 picogram/ml at exceptional specificity,resulting in very high signal-to-noise ratios

The company has a highly developed business model based on working in a flexible, collaborative mode with pharma companies. “We either license the technology outright for internal use or the entire autoantibody-based drug screening process can be outsourced to one of our three proteomics facilities,” says Blackburn. Sengenics has successfully come through extensive technical due diligence that has been carried out on its technology by 8 of the top 10 pharma who are now adopting the technology. At present, the company is developing three of its discoveries in the diagnostic and companion diagnostic space for FDA approval and plans to bring them to the market within the next two to three years.“That is really where we see the future of the company, taking discoveries that we have made jointly with our pharmaceutical and academic institution collaborators right to the patient,” concludes Blackburn.