Phase 1 Study Results of Investigational Anti-CTGF Therapy Reported at CHEST

South San Francisco, California - October 27, 2004 - FibroGen, Inc., today announced that FG-3019, the Company's lead investigational anti-fibrotic agent, was found safe and well tolerated in a Phase 1 clinical study conducted in patients with idiopathic pulmonary fibrosis (IPF). FG-3019 is a fully human monoclonal antibody designed to delay or halt the progression of fibrotic disease by blocking connective tissue growth factor (CTGF), a protein that plays a key role in fibrosis (excessive and persistent formation of scar tissue). Results of the Phase 1 study of FG-3019 were presented at CHEST, the annual meeting of the American College of Chest Physicians being held October 23-28, Seattle, Washington.

"Based on encouraging results of this study, FG-3019 shows promise as a safe therapy for IPF that could be easily administered as an infusion," said Lead Principal Investigator Ganesh Raghu, M.D., Professor of Medicine, University of Washington Medical Center, Seattle, WA, who presented the Phase 1 results at CHEST." There is growing evidence that CTGF plays a causal role in the progressive lung scarring that is characteristic of IPF, which suggests that FG-3019 may help to prevent disease progression and improve lung function by reducing or preventing the fibrotic effects of this pathological growth factor."

The Phase 1 trial was an open-label, single dose, sequential-group, dose-escalation study designed to evaluate safety, tolerability, pharmacokinetics, and immunogenicity of FG-3019 in patients with a well-established diagnosis of IPF as defined by American Thoracic Society criteria. The study enrolled 21 patients: 1 mg/kg (six patients), 3 mg/kg (nine patients), and 10 mg/kg (six patients). No dose limiting toxicities were reported. The mean plasma levels of FG-3019 varied from patient to patient but were above the minimum effective concentration determined in animal models of fibrosis for approximately 13 days and 23 days for the 3.0 mg/kg and 10.0 mg/kg dose levels, respectively. The results of this study suggest that a single 2-hour infusion of FG-3019 is safe and well tolerated.

"This is an important step in our program to develop a therapy for chronic fibrosis," said Pedro Urquilla, M.D., Vice President of Medical Affairs at FibroGen. "Based on these results, we plan to initiate a Phase 2 study of FG-3019 in patients with IPF in 2005."

About IPF

IPF is a debilitating and life-threatening lung disease characterized by a progressive scarring of the lungs that hinders oxygen uptake. The cause of IPF is unknown but is believed to be related to unregulated cycles of inflammation and fibrosis. As scarring progresses, patients with IPF experience shortness of breath and difficulty with performing routine functions, such as walking and talking. The prevalence of IPF has been estimated to be over 50,000 cases in the U.S., with an annual incidence of approximately 15,000. There are no FDA-approved treatments for IPF, and approximately two-thirds of patients die within five years after diagnosis. Patients are typically treated with anti-inflammatory agents; however, none have been clinically proven to improve survival or quality of life for patients with IPF.

About CTGF and Pulmonary Fibrosis

Several lines of clinical and preclinical evidence implicate CTGF in IPF. Transbronchial biopsy specimens from patients with IPF showed an increased expression of the CTGF gene. Further, increased expression of CTGF has been found in fibrotic lung tissue and in bronchoalveolar lavage cells from patients with IPF. Other studies show that CTGF is expressed predominantly in activated fibroblasts in the interstitium of fibrotic lung tissues and in proliferating type II alveolar epithelial cells in IPF. CTGF levels were shown to be much higher in fibrotic lung tissues than in normal tissues.

Preclinical models of acute lung fibrosis demonstrate that CTGF acts synergistically with other factors, such as transforming growth factor-beta (TGF-beta), and pathological conditions to induce extensive collagen deposition and massive scarring. Recently, CTGF has been shown to be necessary to cause pulmonary fibrosis in experimental models of lung fibrosis induced by the chemotherapeutic agent bleomycin, suggesting that CTGF is crucial to the pathogenesis of IPF.

CTGF is a key downstream mediator for the critical fibrotic activities of TGF-beta; notably, fibroblast proliferation and differentiation and extracellular matrix production, the primary mechanisms responsible for fibrosis. While mild scarring can be caused by either factor in experimental models, the combination of TGF-beta and CTGF results in massive scarring. Because TGF-beta has other roles outside of fibrosis, including immunosuppression and tumor suppression, complete blockade of TGF-beta activity would be undesirable in a clinical setting.

Similarly, endothelin-1 is a peptide shown to stimulate fibrosis and matrix production through upregulation of TGF-beta and fibronectin. Recent studies suggest that the CTGF gene can be directly activated by endothelin stimulation and that CTGF may be a downstream mediator of the fibrotic activities of endothelin-1. While TGF-beta and endothelin-1 are actively studied targets for IPF therapy, FibroGen believes that anti-CTGF therapy could offer a more selective and effective approach to the treatment of IPF and other fibrotic disorders.

Several other proteins implicated in IPF have been shown to operate through CTGF including vascular endothelial growth factor (VEGF), angiotensin II, and thrombin. VEGF, which induces production of CTGF through pathways independent of TGF-beta, is upregulated along with an increase in myofibroblasts in fibrotic lesions in experimental models of pulmonary fibrosis. Angiotensin II, which has been implicated in the apoptosis of activated alveolar epithelial cells in interstitial lung injuries, operates in part by directly upregulating CTGF via a response element on the promoter of the CTGF gene. Similarly, thrombin, which promotes myofibroblast differentiation, endothelial cell activation, matrix deposition, and fibrosis in the development of pulmonary fibrosis, has recently been shown to upregulate CTGF and cause the release of CTGF from activated platelets.

FibroGen research collaborations have also shown that CTGF is a necessary factor in the differentiation of fibroblasts into myofibroblasts, which are characteristic of fibrotic lesions and appear to be involved in extracellular matrix production and tissue contraction. Fibroblasts isolated from IPF patients are characteristically more myofibroblast-like than are those from normal subjects. CTGF has been shown to be a survival factor for myofibroblasts by preventing apoptosis.

About FG-3019

FG-3019, a fully human monoclonal antibody directed against CTGF, is FibroGen's lead investigational anti-fibrotic therapy designed to bind and neutralize CTGF. In animal models of lung, kidney, and systemic fibrosis including heart and liver, treatment with FG-3019 reduces scar tissue formation and preserves organ structure and function. FibroGen believes that FG-3019 could be effective in treating patients with IPF by reducing the scarring associated with the overexpression of CTGF and the resulting excess deposition of extracellular matrix components, such as collagen, and preventing the formation of myofibroblasts, allowing normal apoptosis of aberrant cells.

About FibroGen

FibroGen, Inc., is a biotechnology-based drug discovery company using its expertise in the fields of tissue fibrosis and hypoxia-inducible factor (HIF) biology to discover, develop, and commercialize novel therapeutics for fibrotic disorders, anemia, ischemic disease, 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 FibroGen's proprietary cosmetic dermal filler and biomaterials supply business.

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

Contact:
Laura Hansen, Director of Corporate Communications
E-Mail: lhansen@fibrogen.com
Phone: 650-866-7828