Collagen, a major component of the extracellular matrix, is a fibrous protein that provides tensile strength to tissues giving them structural integrity. Collagen and its derivative, gelatin, have been widely used in medical, pharmaceutical and consumer products for more than 100 years. The supply of these materials, created from animal remains, is both abundant and inexpensive. However, most formulations are not highly purified and have the potential to cause an inflammatory reaction in some product users. In addition, concerns have been raised over the last several years about the potential for contamination of bovine products with the agent that causes mad cow disease and its human variant, Creutzfeldt-Jakob Disease.

FibroGen develops synthetic versions of human collagens using proprietary recombinant methodology in a yeast expression system. FibroGen's recombinant human collagens offer superior, highly purified, fully characterized, biocompatible alternatives to animal-derived collagen for use in numerous pharmaceutical and medical applications.

FibroGen currently produces recombinant human collagens, types I and III. Type III is the subject of a Master File application. Both materials are available for development.

Advantages of recombinant human collagens:

• Right collagen for the application of interest. Current medical applications of collagen utilize material that is extracted from its source material (animal bone, hide, tendon) as a mixture of collagen type I with some collagen type III. A preparation consisting of exclusively type I collagen or type III collagen is not available from non-recombinant sources on a commercial scale. Nonetheless, specific individual types of collagen have properties that make them desirable in certain applications. FibroGen is able to produce pure specific types of recombinant collagen (e.g., types I or III) as opposed to the mixture of various types found in bovine collagens. Pure forms of recombinant collagen have performance characteristics that in some applications will be superior to those from animal mixtures.

• Lot-to-lot consistency. Animal collagens are subject to extensive modifications that continue over the life of the molecule in the extracellular space. These differences influence both the extractability of collagens from tissue and the biophysical characteristics of these collagens. As a result, collagens isolated from tissues exhibit significant lot-to-lot variability and, as bulk materials, are often analytically intractable. FibroGen has developed simple, scalable purification processes that provide highly purified and reproducible lots of protein in any desired quantity, and employs a series of rigorous analytical tests to ensure consistent high quality.

• Biocompatibility. Products that contain animal-derived collagen can induce potentially harmful inflammatory or immune responses in humans and pose risk of contamination with viruses or prions, potentially life-threatening pathogens. FibroGen's technology eliminates the risk of viral or prion contamination. Using human DNA sequences, FibroGen's recombinant collagens are essentially identical to the native collagen protein thereby reducing the risk of inflammation, immune response, and disease as compared to animal-sourced collagen.