Vaccine/Biologic Stabilization
FibroGen has developed FG-5009, a low molecular weight (8.5 kd) recombinant gelatin molecule optimized for use in vaccine and biologic formulations. Working with leaders in the vaccine market, FibroGen has tested the ability of FG-5009 to stabilize several live attenuated viral vaccines. In vitro stabilization studies have demonstrated that recombinant gelatin is equivalent to the animal-derived gelatin stabilizer in commercially available vaccines. FibroGen is currently working with customers on formulation development and testing FG-5009 as a stabilizer for other biopharmaceuticals and as an alternative to human serum albumin.

Human safety data. The safety of FG-5009 was examined in human volunteers at doses similar to, and significantly greater than, the dosage of animal-derived gelatin found in marketed vaccines. Healthy volunteers received a total of three doses of either 1 mg, 15 mg, or 60 mg of recombinant gelatin administered intramuscularly at two-week intervals. The subjects were followed for 56 days after administration of the last dose. No adverse events related to the study material were observed in any of the three dose groups. Serum was analyzed by ELISA for antibody production against recombinant gelatin or potential yeast host cell contaminants. No significant changes in antibody titers against recombinant gelatin or yeast-derived protein were seen over the course of the study. Finally, no significant changes related to study material were observed for the standard serum chemistry parameters measured over the course of the study.

Purity. FG-5009 has been subjected to a battery of analytical tests to demonstrate its suitability as a key component of pharmaceutical preparations. These tests were used to characterize product purity, heterogeneity, endotoxin levels, bioburden, and the levels of various contaminants, including those associated with the yeast expression system. The results of the studies demonstrate that FG-5009 is suitable for use in pharmaceutical preparations.

Immunogenicity. FG-5009 has been the subject of studies designed to establish an immunogenicity profile. In one study carried out with an academic collaborator in Japan, FibroGen tested the immunogenicity of FG-5009 using serum from children with confirmed gelatin allergies. Specifically, the reactivity of FibroGen's product with anti-gelatin IgE antibodies from serum samples was tested in an in vitro binding assay. These antibodies recognized bovine and human collagens but not FG-5009, establishing the low allergenic potential of FibroGen's product. Furthermore, as described above, in our human safety study no significant antibody response to gelatin was noted in any of the subjects.

For more information or a data package on FG-5009, please contact our
Business Development group at FibroGen: info@fibrogen.com or 1-650-866-7291.

Resuscitation Fluids
Plasma expanders are commonly and routinely used in emergency trauma and post-surgical settings to restore and maintain a patient's blood circulation. Because plasma expanders are injected, there is significant concern related to the transmission of animal- and human-derived materials that are contaminated with infectious viruses and with agents that cause Creutzfeldt-Jakob disease (CJD), the human variant of bovine spongiform encephalopathy (BSE). The need for safer plasma expanders presents an opportunity for synthetic products in this market. In validated experimental models, FibroGen has shown that certain of its specifically designed recombinant human gelatin fragments are effective resuscitation fluids in small- and large-animal models of shock and compare favorably with on-market plasma expander materials.

Capsule Formulation
The largest medical use of gelatin is for the manufacturing of soft gel and hard shell capsules, a $5 billion industry that currently uses 40,000 metric tons per year of animal-derived gelatin.

Demand from regulatory authorities and consumers for capsules free of animal-derived components has driven manufacturers to actively engage in the identification and development of safer, more consistent, animal component-free replacements for animal-derived gelatins currently used in manufacturing pharmaceutical products. This has been a serious challenge for the industry because, despite the inherent safety risks and undesirable heterogeneous nature of animal-derived gelatin, certain attributes, such as viscosity and gel strength, make gelatin an ideal material for producing capsules that are solid at room temperature and melt at desired physiologically relevant temperatures and pH.

FibroGen believes that the development of a cost-effective, scalable plant-based technology for the production of recombinant gelatin will address this large market need by providing a fully characterized, predictable, and animal-component free alternative source of gelatin. To this end, FibroGen is developing plant systems for the co-production of recombinant proteins for medical and pharmaceutical uses and traditional agricultural products not for human consumption (e.g., ethanol as a gasoline additive and corn oil for lubricants in motor vehicles). The sale of current agricultural products from a recombinant gelatin production crop could drive the marginal cost of recombinant gelatin production near to zero, allowing for direct competition with animal-based gelatins.

FibroGen is engaged in four commercial feasibility programs and two university research programs to explore plant-based gelatin production using either direct expression of gelatin fragments or expression of collagen from which gelatin could be derived. In addition to these external programs focused on the production side, FibroGen is initiating feasibility studies with major capsule manufacturers to evaluate the suitability of recombinant gelatin for use in their manufacturing systems. To execute these studies, FibroGen has produced several prototype recombinant gelatins using its yeast fermentation technology similar to the products expected from plant-based production.