San Diego, Calif. - November 17, 2006 - FibroGen, Inc. today announced preclinical data showing that FG-4539, a novel small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) in development for the treatment of tissue damage, improved renal function and achieved cytoprotective effects in preclinical models of acute kidney injury (AKI). The data (Abstract TH-PO1025; Abstract) were presented at Renal Week 2006, the annual meeting of the American Society of Nephrology (ASN).

FG-4539 was tested for its renoprotective effects in several models of renal injury, including ischemia-reperfusion injury and radiocontrast-induced nephropathy. Prophylactic or therapeutic dosing with FG-4539 improved renal function as evidenced by lower BUN and serum creatinine levels, improved GFR, and prevented acute tubular necrosis as confirmed by histological analysis.

"The renal studies provide additional evidence that FG-4539 exhibits a unique cyto- and tissue protective profile that we believe will have therapeutic benefit in a range of conditions and diseases," said David Y. Liu, Vice President of Research at FibroGen. "The data are consistent with those obtained in models of ischemic stroke in which FG-4539 was reported to be neuroprotective (1) through its ability to activate a multi-factorial response to ischemic and reperfusion injuries, including local production of erythropoietin and other protective factors." (Also see company press release dated February 17, 2006.)

FG-4539 demonstrated the ability to mobilize a coordinated set of cytoprotective mechanisms, including expression of soluble anti-apoptotic factors such as erythropoietin and VEGF. FG-4539 pretreatment also resulted in selective upregulation of relevant genes, including the glycolytic enzyme phosphofructokinase-L. Expression of glycolytic enzymes may play an important role in preservation of tissue by promoting ATP generation through increased glycolysis in the setting of insufficient oxygen. The harmful effects of inflammation, considered a key factor in tissue injury in organs subjected to ischemia, were mitigated by pretreatment with FG-4539, resulting in attenuation and more rapid decline in expression of inflammatory mediators IL-6, MCP-1 and COX2. Finally, by altering the expression of genes including JUNB, S100A6, CTGF, SMA and collagen genes, FG-4539 pretreatment resulted in attenuation, more rapid resolution, or delayed induction of these markers of kidney damage and fibrosis.

"The data continue to support the development of FG-4539 in a variety of settings in which activation of the HIF-mediated cytoprotective profile may offer meaningful clinical benefit," said Thomas B. Neff, Chief Executive Officer at FibroGen. "We plan to initiate clinical testing of FG-4539 in renal injuries beginning with delayed graft function. Further studies to assess neuroprotective effects of FG-4539 after stroke and cardioprotective effects after myocardial infarction are also planned."

FibroGen HIF-PH Inhibitor Therapeutic Platform

FibroGen is focused on the discovery and development of small molecule inhibitors of HIF-PH for therapeutic benefit in multiple clinical settings. Using distinct HIF-PH inhibitors with unique pharmacodynamic profiles, FibroGen seeks to selectively harness and direct specific HIF-mediated biological pathways as required in different tissues to address tissue damage and organ-specific pathophysiologies. FibroGen's first two HIF-PH inhibitors in clinical development are FG-2216 and FG-4592, designed to selectively stimulate HIF-mediated erythropoiesis for the treatment of anemia.

FG-4539 was discovered and optimized as an cytoprotective molecule using an extensive array of in vitro and in vivo assays. FibroGen chemists have designed numerous compounds with desirable pharmacodynamic profiles for use in various therapeutic/cytoprotection programs. In preclinical myocardial infarction studies employing coronary artery ligation, for example, treatment with a HIF-PH inhibitor preserved heart function and improved survival rate (2). These results were confirmed in studies using additional HIF-PH inhibitors.

About FibroGen

FibroGen, Inc. is a biotechnology-based drug discovery company using its expertise in the fields of tissue fibrosis, connective tissue growth factor (CTGF), and hypoxia-inducible factor (HIF) biology to discover, develop, and commercialize novel therapeutics for fibrotic disorders, diabetic complications, anemia, conditions associated with tissue damage or injury, cancer, and other areas of unmet medical need. FibroGen also develops and produces recombinant human collagens and gelatins using unique production technology that provides the basis for FibroGens proprietary cosmetic dermal filler and biomaterials supply business.

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

References

1. Langsetmo I, Jacob C, Ho W, Stephenson R, Sirenko O, Sidhu P, Flippin L, Seeley T, Klaus S, Lin A, Liu D. Inhibition of HIF-Prolyl Hydroxylases with FG-4539 is Neuroprotective in a Mouse Model of Permanent Focal Ischemia. International Stroke Conference 2006 , Kissimmee, Florida Presentation #427. (Abstract).

2. Nwogu JI, Geenen D, Bean M, Brenner MC, Huang X, Buttrick PM. Inhibition of collagen synthesis with prolyl 4-hydroxylase inhibitor improves left ventricular function and alters the pattern of left ventricular dilatation after myocardial infarction. Circulation. 2001 Oct 30;104(18):2216-21.

Contact:
Laura Hansen 650-866-7828 or lhansen@fibrogen.com