Investors and Media

HIF activation shows promise as new therapeutic approach to treating acute renal failure and sickle cell disease

South San Francisco, CA - March 25, 2004

FibroGen, Inc., today announced research supporting the use of the Company's proprietary Hypoxia-Inducible Factor (HIF) activation technology for the potential treatment of serious diseases, such as acute renal failure and sickle cell disease. FibroGen scientists will present results of preclinical HIF research at the Keystone Symposium on Biology of Hypoxia, March 25th - 30th in Steamboat Springs, Colorado.

HIF is a transcription factor that exists in all cells and plays a key role in activating the expression of genes that control the body's critical defense mechanisms against low levels of oxygen, or hypoxia. Hypoxia is a central component in many serious diseases including kidney disease, anemia, heart disease, and stroke.

""FibroGen's research shows that targeting HIF for drug discovery and development is a promising new approach to the treatment of several diseases marked by hypoxia,"" said David Liu, Ph.D., Vice President of Research at FibroGen. ""We are presenting studies that demonstrate pharmacological activation of HIF in a selective manner could prove beneficial in treating acute renal failure and sickle cell disease, two areas of serious unmet medical need.""

Research suggests that activation of HIF leads to mobilization of critical elements of biology that protect cells and tissues from the harmful effects of oxygen deprivation. For example, in the short-term, HIF induces cytoprotective factors, such as heme oxygenase and adrenomedullin, and promotes changes in glucose metabolism that help conserve energy levels within cells when the oxygen supply is interrupted. Longer-term effects of HIF activation include changes in vascular biology that promote the formation of blood vessels and an increase in the production of new oxygen-carrying red blood cells (erythropoiesis).

FibroGen has developed small molecules that activate HIF through the inhibition of HIF-prolyl hydroxylases (HIF-PHs), enzymes that target HIF for degradation. Using different HIF-PH inhibitors, FibroGen has found that desired components of the protective HIF biology can be regulated in a separate and reproducible fashion, yielding unique pharmacodynamic profiles that could provide therapeutic benefit in several diseases and medical conditions. The Company is exploring application of its HIF platform across multiple therapeutic target areas including acute renal failure, sickle cell disease, anemia, obesity, diabetes, and neuroprotection.

HIF Activation in Acute Renal Failure

Acute renal failure (ARF) is a sudden decline in kidney function that often occurs in critically ill patients. Reports have indicated that 5 - 25% of hospitalized patients will develop ARF, and, depending on severity of renal decline and co-morbid conditions, mortality can reach 80%. The optimal target for therapeutic intervention in ARF has not been identified thus far, and so pharmacological management of ARF remains elusive. FibroGen will present laboratory findings demonstrating that HIF activation is an important new approach to preventing or treating renal damage through the stimulation of a multifactorial response comprised of several important protective proteins. Using a model of ischemic reperfusion injury to simulate acute renal failure, FibroGen has demonstrated that administration of HIF-PH inhibitors leads to improvement in, or preservation of, kidney function. The observed renoprotective effects of HIF activation may be linked to the induction of cytoprotective factors, including: heme oxygenase, which plays a role in the metabolism of excess heme that would otherwise cause oxidative injury; Glut-1, a critical glucose transporter that enables continued energy generation in hypoxic environments; and adrenomedullin, a potent vasodilating peptide that regulates cardiac and renal function.

HIF Activation in Sickle Cell Disease

Sickle cell disease (SCD), an inherited blood disorder affecting millions of people worldwide, is caused by a mutation in adult hemoglobin. Hemoglobin is an iron-rich molecule that carries oxygen within red blood cells. In SCD, the mutated hemoglobin forms rigid, rod-like polymers that cause mature red blood cells to take on an abnormal crescent (sickle) shape. Sickled red blood cells obstruct blood flow and are fragile and prone to bursting, leading to anemia and painful ischemic crises. It has been recognized for decades that a means to mitigate the pathophysiology of SCD is to substitute the mutant adult hemoglobin with fetal hemoglobin, which is normally not present during adulthood. Hydroxyurea, the current standard of care for SCD, is believed to work by this mechanism; however, the use of hydroxyurea is hindered by dose-limiting toxicity and the fact that many SCD patients respond poorly or not at all.

FibroGen's preclinical research indicates that HIF activation could provide multiple avenues of therapeutic benefit in SCD by inducing protective biological mechanisms that address improperly formed hemoglobin and acute ischemic events and acute pain. Using HIF-PH inhibitors, FibroGen has demonstrated that HIF activation leads to an increase in fetal hemoglobin that is additive to the hemoglobin-inducing effects of hydroxyurea. Production of anti-ischemic proteins that ameliorate vasoconstriction and oxidative stress, such as adrenomedullin and heme oxygenase, respectively, and thus the severity of painful ischemic crises, are under evaluation in experimental models and will be evaluated in early clinical studies.

About FibroGen

FibroGen, Inc., is a privately held biotechnology company focused on the discovery, development, and commercialization of therapeutics, recombinant human collagens, and recombinant gelatins to address unmet needs in the medical, pharmaceutical, and consumer markets. FibroGen's therapeutic target areas include fibrosis, anemia, and ischemia.

For more information about FibroGen, Inc., please visit www.fibrogen.com.

Contact:
Laura Hansen (investors/media), 650-866-7223

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