[May 31, 2014]

FibroGen Announces Results of Phase 2 Study of FG-3019 Indicating Positive Activity Against Pancreatic Cancer

FibroGen, Inc. (FibroGen) today announced results from a Phase 2 open-label study of FG-3019, an investigational anti-fibrotic antibody, in combination with gemcitabine and erlotinib for the treatment of patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC). In the study, FG-3019 demonstrated a dose-dependent improvement in one-year and overall survival rates, and appeared to be safe and well tolerated. The full data will be presented today at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting in a poster session from 8:00 AM to 11:45 AM CDT (News - Alert), Location S Hall A2, Abstract Number 4138.

The Phase 2 study is an open-label, single-arm, dose-escalation study to evaluate safety, tolerability, pharmacokinetics and ability of FG-3019 to improve outcomes in patients with pancreatic cancer treated with chemotherapy. Seventy-five patients were enrolled in the trial, 66 (88%) with stage 4 metastatic disease. The study evaluated FG-3019 doses of 3 mg/kg, 10 mg/kg, 15 mg/kg, 25 mg/kg, 35 mg/kg and 45 mg/kg administered every two weeks, and FG-3019 doses of 17.5 mg/kg and 22.5 mg/kg administered weekly after a double loading dose. On Day 15, treatment began with gemcitabine 1000 mg/m2 twice weekly for three of every four weeks and erlotinib 100 mg daily. Treatment continued until progression of the cancer or the patient withdrew for other reasons. Patients were then followed until death. Tumor status was evaluated by CT imaging every eight weeks to assess changes in tumor mass.

The study demonstrated a dose-related increase in survival. At the lowest doses, no patients survived for one year, while at the highest doses approximately 30% of patients survived one year. The results showed a significant relationship between patient survival and trough plasma levels of FG-3019 (Cmin) measured immediately before the second dose of drug at Day 15. Cmin greater than or equal to 150 µg/mL was associated with significantly improved progression free survival (p=0.01) and overall survival (p=0.03) versus Cmin less than 150 µg/mL. For patients with Cmin greater than 150 µg/mL, median survival was 9.4 months compared to median survival of 4.8 months for patients with Cmin less than 150 µg/mL. Similarly, 37% of patients with Cmin greater than 150 ug/mL survived for one year or longer compared to 11% for patients with Cmin less than 150 µg/mL. The best results were obtained in the subset of patients with low baseline plasma CTGF and high plasma FG-3019 (n=20) where the median survival was 11.2 months and 45% of subjects survived for one year or longer. These data suggest that sufficient blockade of CTGF to improve survival in patients with advanced pancreatic cancer requires FG-3019 threshold blood levels of approximately 150 µg/mL. Survival was better than th results of the pivotal trial of gemcitabine plus erlotinib (median OS = 6.24 months; Moore J Clin Oncol 2007; 25:1960-1966) and was comparable to results of the pivotal trial of gemcitabine plus nab-paclitaxel (median OS = 8.5 months; von Hoff N Engl J Med. 2013; 369:1691-703).

Most adverse events in the study were mild to moderate, and were consistent with those observed for erlotinib plus gemcitabine treatment without FG-3019. No evolving dose-dependent pattern was identified, and higher doses of FG-3019 were not associated with higher numbers or greater severity of SAEs. FG-3019 treatment was associated with improved survival with no apparent increase to the toxicity of the chemotherapy regimen, suggesting that FG-3019 could provide an effective adjunct to other chemotherapeutic regimens.

FibroGen plans to open a randomized Phase 2 trial of FG-3019 combined with gemcitabine plus nab-paclitaxel chemotherapy versus the chemotherapy regimen alone in patients with marginally inoperable pancreatic cancer that has not been previously treated. The overall goal of the trial is to determine whether FG-3019 in combination with other treatments can convert inoperable pancreatic cancer to operable cancer. Tumor removal is generally the only chance for cure of pancreatic cancer, but only 20% of patients are eligible for surgery.

Preclinical Studies of FG-3019 for Pancreatic Cancer

FG-3019 has demonstrated a reduction of tumor mass and metastasis in several mouse models of pancreatic cancer including the genetically engineered KPC mouse model. KPC mice spontaneously develop pancreatic cancer that closely approximates many features of the human disease, including similar genetic mutations, expression of CTGF, extensive stroma, metastases and ascites, or abdominal fluid, formation. KPC mouse tumors, like human pancreatic cancer tumors, are highly resistant to anti-cancer therapies. FG-3019 plus gemcitabine more than doubled the survival time of mice treated with chemotherapy alone. FG-3019 inhibited expression of XIAP, one of a family of proteins whose function is to inhibit apoptosis. Elevated expression of XIAP promotes cell survival and is one mechanism by which tumor cells can become resistant to chemotherapeutic agents. FG-3019 decreased XIAP levels significantly whereas gemcitabine did not, and the combination of FG-3019 and gemcitabine was even more effective. In both the KPC mouse study and in this clinical trial, FG-3019 treatment had a substantial effect on survival with no apparent increase to the toxicity of the chemotherapeutic regimen.

About Pancreatic Cancer

Pancreatic ductal adenocarcinoma, or pancreatic cancer, is the fourth leading cause of cancer deaths in the United States. According to the National Cancer Institute, in 2014 in the United States, there are projected to be approximately 46,000 new cases of pancreatic cancer and approximately 39,000 deaths from the disease. Pancreatic cancer is aggressive and typically not diagnosed until it is largely incurable. Most patients are diagnosed after the age of 45, and 94% (American Cancer Society) of patients die within five years from diagnosis.

About FG-3019

FG-3019 is an investigational therapeutic antibody developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. FibroGen is currently conducting clinical studies of FG-3019 in idiopathic pulmonary fibrosis, pancreatic cancer, and liver fibrosis. FG-3019 has been well tolerated, with no apparent safety signals, in more than nine clinical studies and more than 340 treated patients to date.

In desmoplastic, or fibrotic, cancers such as pancreatic cancer, CTGF in the extensive fibrous stroma associated with the tumor promotes abnormal proliferation of stromal cells and tumor cells, induces extracellular-matrix, or ECM, deposition that provides a substrate for tumor cell adherence, promotes angiogenesis, and promotes metastasis by enhancing cell motility, invasion and survival. Studies in a transgenic mouse model of pancreatic cancer indicate that treatment with FG-3019 in combination with chemotherapy can enhance the efficacy of chemotherapy and significantly improve survival.

About FibroGen, Inc.

FibroGen is a privately-held biotechnology company focused on the discovery, development, and commercialization of therapeutic agents for treatment of fibrosis, anemia, cancer, and other serious unmet medical needs. FibroGen's FG-3019 fully human monoclonal antibody is in clinical development for treatment of idiopathic pulmonary fibrosis and other proliferative diseases, including pancreatic cancer and liver fibrosis. Roxadustat (FG-4592), FibroGen's small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase, is currently in clinical development for the treatment of anemia. FibroGen is also currently pursuing the use of proprietary recombinant human type III collagens in synthetic corneas for treatment of corneal blindness. For more information please visit: www.fibrogen.com.

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