FibroGen Reports Pharmacologic Stabilization of Hypoxia-Inducible Factor (HIF) Prevents Brain Tissue Damage and Preserves Motor Function in a Preclinical Model of Transient Ischemic Stroke.

SOUTH SAN FRANCISCO, Calif. -- FibroGen, Inc. today announced that pharmacologic stabilization of hypoxia-inducible factor (HIF) using the company's proprietary small molecule inhibitors of HIF-prolyl hydroxylase (HIF-PH) prevented brain tissue damage and preserved motor function in a preclinical model of transient ischemic stroke. The data were presented in the late-breaking abstract session held yesterday evening at the International Stroke Conference (ISC) 2007 (Poster # LB P15).

The neuroprotective potential of pharmacologic HIF stabilization was previously demonstrated in a model of permanent ischemic stroke in which a HIF-PH inhibitor, FG-4539, provided significant tissue protection in the brain when administered up to 5 hours after permanent occlusion of the middle cerebral artery. The same compound was also shown to induce cytoprotective genes in the central nervous system (see company press release dated February 17, 2006).

The data presented at ISC described results from two new studies using FG-4539 in a model of transient ischemic stroke: a short-term study (48 hours) to assess tissue damage and a long-term study (28 days) to assess functional recovery.

Short-term infarct study

In the short-term study, the middle cerebral artery of test rodents was occluded for 60 minutes to induce ischemic injury in the brain. FG-4539 was orally administered once at the time of reperfusion (when blood flow to the brain was restored) or twice, at the time of reperfusion and 24 hours later. Both dosing regimens of FG-4539 resulted in significant reductions in total ischemic damage, core infarct size, and amount of edema (swelling) as assessed 48 hours post transient occlusion.

Long-term recovery study

In a long-term study, the middle cerebral artery of test rodents was occluded for 90 minutes, and animals were allowed to recover for 28 days. FG-4539 was orally administered at the time of reperfusion, 24 hours later, and then every other day for the duration of the study. Sensorimotor assessments made during the recovery period indicated that animals treated intermittently with FG-4539 exhibited accelerated recovery in grip strength and tactile adhesion tests when compared to controls.

"These are early but promising preclinical results suggesting that pharmacological stabilization of HIF has the potential to protect neuronal tissue from acute injury and promote recovery of motor function over the long term in the setting of stroke," said David Y. Liu, Ph.D., Vice President of Research at FibroGen. "We believe the beneficial effects of HIF-PH inhibitors designed to confer neuroprotection may result from their ability to activate multiple HIF-mediated mechanisms that the body naturally employs in defense against tissue damage or injury, such as erythropoietin. Future studies will explore different dosing regimens to optimize the therapeutic benefit of HIF-PH inhibitors."

About Stroke

Approximately 15 million people worldwide suffer a stroke each year resulting in death or cognitive deficits. Ischemic stroke accounts for approximately 87% of all stroke cases and is caused by a clot obstructing the flow of blood to the brain. Hemorrhagic stroke accounts for the remainder of stroke cases and is caused by a blood vessel rupturing and bleeding into the surrounding brain tissue. In either case, the brain is deprived of oxygen and nutrients. As a result, numerous pathological pathways are triggered leading to the propagation of neuronal cell death from the initial site of neuronal damage. In ischemic stroke, additional damage can occur from tissue reperfusion when blood flow is restored after the clot dissolves, either on its own or with the aid of a thrombolytic agent.

FibroGen HIF-PH Inhibitor Therapeutic Platform

FibroGen is engaged in 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 HIF-mediated biological pathways in different tissues to address organ-specific tissue damage and pathophysiologies. FibroGen's first two HIF-PH inhibitors in clinical development, FG-2216 and FG-4592, are designed to selectively stimulate HIF-mediated erythropoiesis for the treatment of anemia. As part of a separate therapeutic program, FG-4539 was discovered and optimized as a cytoprotective molecule using an extensive array of in vitro and in vivo assays. FibroGen scientists have designed numerous compounds with desirable pharmacodynamic profiles for use in treating a variety of conditions associated with tissue damage or injury. In the kidney, for example, administration of FG-4539 and other FibroGen HIF-PH inhibitors protects kidney function in animal models of ischemia reperfusion injury and radiocontrast nephrotoxicity. In preclinical myocardial infarction studies employing coronary artery ligation, treatment with FG-4539 reduces infarct size and preserves heart function as was observed in previous studies using different 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 FibroGen's proprietary cosmetic dermal filler and biomaterials supply business.

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