Company Overview
FibroGen was founded to discover, develop, and commercialize novel therapeutics that stop fibrosis, or pathological scarring, addressing unmet needs in fibrotic disorders affecting the major organs, diabetes, surgical procedures, and fibroproliferative tumor progression and metastasis. Since lab operations commenced in 1995, FibroGen has focused on internally generated research and development programs in fibrosis and in related areas where our work is unique, proprietary, and has high potential to address major markets.
Anti-Connective Tissue Growth Factor (CTGF)
Connective tissue growth factor (CTGF) is one of the Company's key fibrogenic molecular targets. FibroGen's basic research on CTGF, other fibrogenic growth factors, such as transforming growth factor-β (TGF-β), and the molecular mechanisms underlying the fibrotic process have provided the foundation upon which we are developing a portfolio of powerful, selective product candidates for the treatment of life-threatening diseases affecting the kidneys, lungs, eyes, skin, heart, and liver.
Chronic kidney disease, particularly in people with diabetic kidney disease (DKD), has been a key therapeutic focus area for FibroGen. Over the past half decade the Company's researchers and academic collaborators have shown that CTGF is the critical mediator in the fibrotic damage resulting from multiple pathological processes that collectively cause end-stage renal disease including proteinuria, epithelial-to-mesenchymal transition (EMT) and fibrosis. Recent preclinical work also demonstrates the potential for using anti-CTGF therapy to treat diabetic vascular disease.
FibroGen's expertise in extracellular matrix biology as it relates to fibrosis has led the Company's research teams and our academic collaborators into the breakthrough area of tumor-stromal interactions. These interactions involve chemical signaling pathways between a tumor and its dynamic extracellular matrix environment, which affect the various stages of tumor progression including EMT, angiogenesis, cell adhesion and migration. This research has led to the identification of common mechanisms underlying tumor-stromal communication, which show promise as targets for therapeutic intervention with anti-CTGF therapy in metastatic cancers including pancreatic cancer.
Today, FibroGen has a clinical program with a fully human therapeutic antibody against CTGF, FG-3019. FibroGen is also working to find appropriate small molecule antagonists to CTGF as second-generation therapy.
Prolyl hydroxylase inhibition and hypoxia-inducible factor (HIF) stabilization
FibroGen is the world leader in drug discovery based on prolyl hydroxylase inhibition. FibroGen's early efforts were focused on inhibition of collagen prolyl hydroxylases for designing new anti-scarring treatments. Interestingly, studies in cardiovascular disease models suggested that early therapeutic benefits from prolyl hydroxylase inhibition occurred too soon to be attributable to an inhibitory effect on collagen synthesis and a reduction in scarring observed later.
The mystery was solved when the scientific community first reported in 2001 the key role of prolyl hydroxylases in regulating the stability and activity of a transcription factor known as hypoxia-inducible factor (HIF). HIF is a key regulatory protein that coordinates the body's protective physiological responses to the dangerous effects of hypoxia (oxygen deprivation) by turning on sets of genes whose protein products are involved in cytoprotection, erythropoiesis, metabolism, and vascular biology. These processes protect against tissue damage and cell death in the short-term and help to restore normal oxygen levels in the tissues in the long-term.
Upon the discovery of HIF-specific prolyl hydroxylases (HIF-PH), FibroGen was uniquely positioned to develop small molecule inhibitors that selectively inhibit members of the HIF-PH family (e.g., HIF-PHD 1, HIF-PHD 2, and/or HIF-PHD 3). In preclinical studies, FibroGen has shown that HIF-PH inhibitors act to stabilize HIF and elicit selective effects within the HIF system. FibroGen has established a large discovery effort on using unique HIF-PH inhibitors to harness and direct the protective effects of HIF-mediated physiology for treating a broad range of diseases and medical conditions.
Today, FibroGen has HIF-stabilizing therapeutics under development for treating anemia, whereby endogenous erythropoietin (EPO) is upregulated in response to hypoxic signaling, and in iron processing deficiency and inflammatory disease anemias, whereby the broader erythropoietic biology under the control of HIF is utilized to address anemias for which currently available recombinant EPO therapy has not proven effective. The two lead candidates in development for anemia of chronic kidney disease are FG-4592 and FG-2216.
As part of a separate clinical program, FibroGen is developing novel cytoprotective HIF-PH inhibitors for the treatment of conditions associated with tissue damage or injury based on preclinical evidence that demonstrates efficacy of HIF stabilization therapy in acute ischemic settings including myocardial infarction, acute renal failure and stroke. In addition, FibroGen is exploring potential for HIF-PHIs in chronic cytoprotection, particularly in chronic neurodegenerative disease. FibroGen is also exploring new clinical applications using new HIF-PH inhibitors that produce different treatment profiles, in areas such as sickle cell disease, neuroprotection, mobilization of endothelial progenitor cells with the potential to repopulate infarcted tissues, revascularization for peripheral vascular disease, treatment of sepsis (e.g., associated with severe inflammation), metabolic shifts to burn fats, and pulmonary dysplasia.
Recombinant human collagens and gelatins
Based on expertise in collagen and the role of prolyl hydroxylase enzymes in the formation of collagen, FibroGen has developed the first known recombinant methodology for making fully synthetic collagens that are essentially identical to those found in nature. By making and testing different types of collagen that exist in nature, FibroGen scientists have demonstrated that recombinant type III collagen persists longer in tissue than any form of human or animal type I collagen. This unique characteristic of type III collagen serves as the basis for FibroGen's dermal filler product candidate for cosmetic applications.
Focused efforts over several years have also led to the development of a highly efficient production system employed by FibroGen to supply recombinant human collagens and gelatins (collagen fragments) as biomaterials for use in a variety of pharmaceutical and medical device applications. FibroGen produces recombinant human type III collagen (never before available in commercial quantities), recombinant human type I collagen, and distinct recombinant gelatin molecules optimized for specific applications. FibroGen's biomaterials address the needs of a wide range of customers in the pharmaceutical and medical device industries for safer, highly pure, and fully characterized alternatives to animal-sourced collagen and gelatin.
Clinical development
Today, FibroGen has several internally developed product candidates in clinical development:
- FG-3019 is a fully human antibody that blocks the action of CTGF. FG-3019 is in phase 2 development for the treatment of diabetic kidney disease. Additionally, FibroGen has successfully completed a single-dose phase 1 safety study in patients with idiopathic pulmonary fibrosis and a phase 1 study is ongoing in pancreatic cancer.
- FG-4592 is an orally administered erythropoietic small molecule drug in development for the treatment of anemia. FG-4592 is in phase 2 development for treatment of anemia of chronic kidney disease.
- FG-2216 is another orally administered, erythropoietic small molecule drug in development for the treatment of anemia which is also in phase 2 development for treatment of anemia of chronic kidney disease.
- FG-5030 is recombinant human collagen (type III) formulated as an injectable dermal filler for use in cosmetic applications. FibroGen plans to apply for regulatory clearance to enable future clinical testing with FG-5030.
FibroGen's mission, approach, and responsibility
FibroGen's mission is to create meaningful new therapies that address unmet patient need in severe disease areas. Our approach is to develop new products where there is limited or no competition. We are a research-driven company with leadership positions in tissue fibrosis, diabetic complications, fibroproliferative cancers and metastasis, the many areas of protective HIF-mediated physiology, and production of recombinant human collagens and gelatins. We collaborate extensively with academic partners worldwide.
FibroGen intends to make products that we can commercialize. We strive to accomplish this through pragmatic and sensible business arrangements, including various forms of partnering that confer a strategic advantage to FibroGen, and by retaining key product opportunities that enable our vertical entry into North American markets when the risk-adjusted financial value of the opportunity is not achievable through other means.
We employ aggressive cost management programs to limit burn rate and take advantage of a wide variety of financing mechanisms. To date, FibroGen has been able to raise sufficient capital to maintain a margin of safety against the Company's core burn rate and provide FibroGen with adequate capitalization to fund operations and successfully grow from a discovery-stage to a development-stage company.
These are exciting times for FibroGen as our research is translated into clinical reality. We invite you to explore other areas of our web site to learn more.
