Preclinical Data Supporting Anti-CTGF Therapy in Diabetic Kidney Disease Reported at the Annual Meeting of the American Society of Nephrology

St. Louis - (Business Wire) - Nov. 1, 2004 - FibroGen, Inc., today announced that FG-3019, the Company's lead investigational anti-fibrotic agent, significantly improved glomerular filtration rate (a measure of kidney function) and reduced proteinuria (abnormal presence of protein in the urine) in a preclinical model of overt diabetic nephropathy (DN). The data support the therapeutic potential of FG-3019 in treating DN by inhibiting fibrosis, or excessive and persistent scarring, which ultimately causes kidney failure.

FG-3019 is a fully human monoclonal antibody designed to inhibit the fibrotic activity of connective tissue growth factor (CTGF). These results were part of multiple abstracts evaluating the effect of FG-3019 and the pathological role of CTGF throughout the progression of DN presented by FibroGen and collaborators at Renal Week 2004, the annual meeting of the American Society of Nephrology (ASN), being held in St. Louis, Missouri, October 27th - November 1st.

In a model of type 1 diabetes induced by streptozotocin, diabetic rats were subjected to a comparatively short renal ischemia of thirty minutes, which caused a progressive injury characterized by tubular atrophy, dilation of the remaining tubuli, pronounced infiltration of inflammatory cells and tubulointerstitial fibrosis. The results demonstrated that treatment with FG-3019 improved kidney function and histopathology and reduced proteinuria, effects attributed, in part, to reduced fibrosis (1).

"The demonstrated ability of FG-3019 to improve kidney function in this preclinical model that resembles late-stage DN in humans reinforces the therapeutic concept that blocking fibrosis is key to improving clinical outcomes in overt kidney disease," said David Y. Liu, Ph.D., Vice President of Research at FibroGen.

A second study evaluated the effects of FG-3019 on key clinical manifestations of early-stage DN in db/db obese type 2 diabetic mice, characterized by kidney hypertrophy, hyperfiltration and proteinuria, but with little interstitial fibrosis characteristic of more advanced disease. FG-3019 treatment led to significant improvements in important clinical parameters of early stage DN including reduced kidney hypertrophy, normalized kidney hyperfiltration, reduced excess urine production, reduced albuminuria, and reduced glomerular basement membrane thickening (2).

"The demonstrated ability of FG-3019 to reduce proteinuria in a model of early-stage DN further suggests that blocking CTGF activity may be effective in treating all stages of the disease," added Dr. Liu.

FibroGen and collaborators also presented data from a clinical study of twenty type 2 diabetic patients with hypertension and nephropathy designed to evaluate the effect of dual therapy using two classes of hypertension medications, angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), on levels of urinary CTGF. (Other studies have demonstrated that levels of CTGF in the urine and plasma increase with progression of DN.) Although patients who received ARB therapy (in addition to existing treatment with ACEi) exhibited a significant 18% reduction in urinary CTGF levels compared to the starting levels when only ACEi were given, dual therapy was not effective in reducing urinary CTGF to normal levels (3).

"These data are the first evidence that intensive dual therapy with ACEi and ARB will not reduce CTGF to normal levels," said Thomas B. Neff, Chief Executive Officer of FibroGen. "FibroGen believes that anti-CTGF therapy used in addition to ACEi and ARB therapy is the most effective approach to stopping fibrosis that progressively destroys kidney function and is a promising approach to treatment of the earlier pre-overt stages of DN."

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 deep organ systemic fibrosis (including heart and liver), treatment with FG-3019 reduces scar tissue formation and preserves organ structure and function. FG-3019 is in clinical development for the treatment of idiopathic pulmonary fibrosis and diabetic nephropathy.

References

1. Wang Q, Guo G, Liu D, Zhang W, Usinger W, Li D, Brenner M, Yeowell D, Lin A (2004) Amelioration of Diabetic Nephropathy (DN) Induced by Renal Ischemia-Reperfusion (IR) in Rats with Diabetes Mellitus (DM) by Treatment with FG-3019, a Monoclonal Antibody Against Connective Tissue Growth Factor (CTGF) (abstract SU-PO925) J Am Soc Nephrol 15: 737A

2. Flyvbjerg A, Khatir D, Jensen LJN, Lomongsod E, Liu DY, Rasch R, Usinger WR (2004) Long-term Renal Effects of a Neutralizing Connective Tissue Growth Factor (CTGF)-Antibody in Obese Type 2 Diabetic Mice (abstract F-PO900) J Am Soc Nephrol 15: 261A

3. van Nieuwenhoven FA, Rossing K, Andersen N, Oliver N, Goldschmeding R, Parving HH (2004) Beneficial Effect of Dual Blockade of the Renin-Angiotensin System (RAS) on Urinary Connective Tissue Growth Factor (CTGF) in Type 2 Diabetic Patients with Nephropathy (abstract SU-PO180) J Am Soc Nephrol 15: 571A

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.

Contacts
FibroGen, Inc.
Laura Hansen, 650-866-7828
lhansen@fibrogen.com