German biopharma Scil Proteins signed a collaboration with the Martin Luther University Halle-Wittenberg that ultimately aims to develop Affilin®-based therapeutics for the treatment of gastrointestinal tumors. The project, run by scientists at the University Hospital, will initially focus on the discovery and characterization of disease-related targets. Scil will then use its Affilin scaffold platform to identify relevant drug candidates and advance them into clinical development.
Scil’s Affilin molecules are based on the human serum protein ubiquitin, engineered with the introduction of new amino acids at defined positions on the protein surface. The firm says that as up to 19 different amino acids are possible at 8–14 positions, the platform provides the opportunity to generate extremely diverse libraries with a complexity of up to 1019 molecules. Screening and selection technologies are used to isolate Affilin® molecules specific for disease-related targets, and primary hits are further optimized and characterized through biological and biochemical assays.
Affilin molecules can in addition be generated bispecific molecules with antibody-like neutralization and blocking activities, or as designed as tetramers or octamers through a multimerization technology that Scil claims enables the production of Affilin therapeutic with adjustable serum half-lives spanning minutes to days. Conjugation technology further allows the design of effector-Affilin-based fusion products with an even greater sphere of functionalities.
The firm says Affilin molecules combine the advantages of conventional antibodies with those of small molecules, resulting in drug candidates with high target affinity and specificity, small size, high stability, cost-effective manufacturing, and amenability to genetic and chemical manipulation.
Moreover, as a natural product, ubiquitin is nonimmunogenic, and the protein is conserved in animal species, allowing straightforward development of final leads. The ubiqitin scaffold is in addition highly stable in gastrointestinal fluid, which supports development of orally administered products, and lacks disulfide bonds and posttranslational modifications, which facilitates microbial production and compliance with CMC requirements, Scil adds.
The firm is exploiting the technology both for the development of an in-house pipeline to the Phase I/II stage, and through product partnerships and collaborations. Current pipeline projects are focused on cancer and inflammatory diseases. Lead preclinical-stage candidates SPVF 2901-10 and SPVF 2801-30 are in development for use in cancer imaging and solid tumor therapy, respectively.
Scil’s Protein Production operation separately provides full up- and downstream process development for the manufacture of recombinant proteins in microbial expression systems. The business offers non-GMP process development and premanufaturing production of pilot batches from research-grade to IND-quality, and GMP capacity for the manufacture of APIs for clinical development and commercial supply.