About FibroGen

FibroGen, Inc. (FibroGen) engages in developing and commercializing a diversified pipeline of novel therapeutics that work at the frontiers of cancer biology and anemia. Through its new partnership with Fortis Therapeutics (Fortis), the company is also developing FG-3246 in metastatic castrate resistant prostate cancer (mCRPC) and potentially other cancers, and it also looks forward to advancing its late-stage pre-clinical programs: its anti-Gal9 antibody FG-3165 and its anti-CCR8 antibody FG-3175. Pamrevlumab For the Treatment of Pancreatic Cancer Pamrevlumab is the company's first-in-class antibody developed to inhibit the activity of CTGF, a protein that has been shown to promote growth, survival, and spread of pancreatic tumors. As of December 31, 2023, the company had retained exclusive worldwide rights for pamrevlumab. In clinical studies involving more than 1,000 pamrevlumab-treated patients (approximately half of whom were dosed for more than six months), pamrevlumab has been well-tolerated across the range of doses studied, and there have been no dose-limiting toxicities seen thus far. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to pamrevlumab for the treatment of patients with locally advanced pancreatic cancer (LAPC). The FDA has granted orphan drug designation to pamrevlumab for the treatment of pancreatic cancer. In 2024, the company expects to report topline results from its two ongoing pivotal studies of pamrevlumab, in LAPC and in metastatic pancreatic cancer. Phase 3 Clinical Trial in Locally Advanced Unresectable Pancreatic Cancer LAPIS is the company's double-blind placebo-controlled Phase 3 clinical trial of pamrevlumab as a therapy for LAPC. The company completed enrollment of 284 patients, who were randomized at a 1:1 ratio to receive either pamrevlumab or placebo, in each case in combination with chemotherapy (either FOLFIRINOX or gemcitabine plus nab-paclitaxel). The company expecst topline data for the primary endpoint of overall survival in mid-year 2024. Phase 2/3 Clinical Trial in Metastatic Pancreatic Cancer In June 2021, the Pancreatic Cancer Action Network's (PanCAN) Precision Promise adaptive trial platform included pamrevlumab in combination with standard-of-care chemotherapy treatments for pancreatic cancer (gemcitabine and Abraxane), for patients with metastatic pancreatic cancer. Drug candidates in the Precision Promise study will progress from Stage 1 to Stage 2 of this seamless Phase 2/3 study, unless stopped sooner for safety or futility. The objective of Precision Promise is to expedite the study and approval of promising therapies for pancreatic cancer by bringing multiple stakeholders together, including academic, industry, and regulatory entities. In the third quarter of 2022, pamrevlumab graduated from Stage 1 to Stage 2, achieving a protocol pre-specified greater than or equal to 35% predictive probability of success for the primary endpoint of overall survival at the completion of the trial. Pamrevlumab was the first experimental treatment arm to graduate to Stage 2 of the trial. The pamrevlumab combination therapy was offered to patients as either a first- or second-line treatment option. In the first quarter of 2024, the pamrevlumab portion of the trial was completed, and the company expects topline results in the second quarter of 2024. Precision Promise is a registration study, and the statistical design has been discussed by PanCAN with the FDA. Completed Clinical Trials for Pancreatic Cancer In addition to the aforementioned ongoing clinical trials, the company has completed two other trials of pamrevlumab in pancreatic cancer. Completed Phase 1/2 Clinical Trial in Locally Advanced Unresectable Pancreatic Cancer The company completed an open-label, randomized (2:1) Phase 1/2 trial (FGC004C-3019-069) of pamrevlumab combined with gemcitabine plus nab-paclitaxel chemotherapy vs. the chemotherapy regimen alone in patients with inoperable LAPC that had not been previously treated. We enrolled 37 patients in this study and completed the six-month treatment period and surgical assessment at the end of 2017. The overall goal of the trial was to determine whether pamrevlumab in combination with chemotherapy can convert inoperable pancreatic cancer to operable, or resectable, cancer. Tumor removal is the best chance for cure of pancreatic cancer, but only approximately 15% to 20% of patients are eligible for surgery. The company reported updated results from this study at the American Society of Clinical Oncology Annual Meeting in June 2018. A higher proportion (70.8%) of pamrevlumab-treated patients whose tumors were previously considered unresectable became eligible for surgical exploration than patients who received chemotherapy alone (15.4%), based on pre-specified eligibility criteria at the end of six months of treatment. Furthermore, a higher proportion of pamrevlumab-treated patients (33.3%) achieved surgical resection than those who received chemotherapy alone (7.7%). Completed Phase 1/2 Clinical Trial in Pancreatic Cancer The company completed an open-label Phase 1/2 (FGCL-MC3019-028) dose finding trial of pamrevlumab combined with gemcitabine plus erlotinib in patients with previously untreated locally advanced (Stage 3) or metastatic (Stage 4) pancreatic cancer. These study results were published in the Journal of Cancer Clinical Trials (Picozzi et al., J Cancer Clin Trials 2017, 2:123). Idiopathic Pulmonary Fibrosis and Duchenne Muscular Dystrophy In June 2023, the company announced topline results from ZEPHYRUS-1, its first Phase 3 trial of pamrevlumab in 356 IPF patients. The study did not meet the primary endpoint of change from baseline in forced vital capacity (FVC) at week 48. Preliminary safety data showed that pamrevlumab was generally safe and well tolerated, with the majority of treatment-emergent adverse events being mild or moderate. Given the results from ZEPHYRUS-1, the company discontinued ZEPHYRUS-2, its second Phase 3 trial of pamrevlumab in approximately 340 IPF patients. In 2023, the company also announced topline results from LELANTOS-1 and LELANTOS-2, its double-blind, placebo-controlled Phase 3 trials evaluating pamrevlumab in non-ambulatory and ambulatory DMD, respectively. Roxadustat for the Treatment of Anemia Chronic Kidney Disease In collaboration with its partners Astellas Pharma Inc. (Astellas) and AstraZeneca, the company has completed 16 Phase 3 studies worldwide in over 11,000 patients to support its marketing approvals of roxadustat to treat anemia in chronic kidney disease in China, Europe, Japan, and numerous other countries. China - Roxadustat Commercial Program Since the launch of roxadustat in 2019, the anemia of CKD market has expanded significantly. In 2023, roxadustat sales in China continued to see significant volume growth in the treatment of anemia caused by CKD in non-dialysis and dialysis patients. As of December 2023, roxadustat was the top CKD anemia brand in China with approximately 42% value share within the segment of erythropoiesis-stimulating agents (ESAs) and HIF-PH inhibitors (roxadustat is the only HIF-PH inhibitor on the market in China). Roxadustat has seen broad adoption across the three segments of hemodialysis, peritoneal dialysis, and non-dialysis. The company has established significant clinical experience and market leadership in treating CKD anemia in China. Europe - Roxadustat Commercial Program In Europe, the company's partner Astellas continues the commercialization of EVRENZO (roxadustat). EVRENZO is approved for the treatment of anemia associated with CKD in both non-dialysis and dialysis patients. Japan - Roxadustat Commercial Program In Japan, the company's partner Astellas continues the commercialization of EVRENZO (roxadustat), targeting healthcare providers that care for approximately 330,000 dialysis patients across Japan. EVRENZO is approved for the treatment of anemia associated with CKD in both non-dialysis and dialysis patients. EVRENZO is one of five HIF-PH inhibitors currently on the market in Japan. Chemotherapy-Induced Anemia Phase 3 Clinical Trial in Chemotherapy-Induced Anemia In May 2023, the company announced positive topline data from its Phase 3 clinical study of roxadustat for the treatment of anemia in patients receiving concurrent chemotherapy treatment for non-myeloid malignancies in China. Roxadustat demonstrated non-inferiority compared to recombinant erythropoietin alfa (SEPO) on the primary endpoint of change in hemoglobin (Hb) level from baseline to the average level during Weeks 9-13. In the preliminary safety analysis, the adverse event profile of roxadustat was generally consistent with previous findings and supportive of a positive benefit risk in this patient population. A total of 159 patients with non-myeloid malignancy (solid tumor) with a baseline hemoglobin level at or below 10 g/dL were enrolled into this Phase 3, randomized, open-label, active-controlled study investigating the efficacy and safety of roxadustat for the treatment of CIA. Patients were randomly assigned roxadustat or erythropoietin alfa three times per week (TIW), during a treatment period of 12 weeks, with an additional 4-week follow-up period. The company presented results from this study in an oral presentation at the European Society for Medical Oncology Congress 2023. The company's supplemental New Drug Application for roxadustat in CIA was accepted by the China Health Authority in August 2023, and it expects an approval decision mid-2024. Prostate Cancer FG-3246 for the Treatment of Metastatic Castration-Resistant Prostate Cancer In May 2023, the company obtained an exclusive license to develop FG-3246 (previously FOR46) in metastatic castration-resistant prostate cancer (mCRPC) and other cancer indications. FG-3246 is a first-in-class antibody-drug conjugate (ADC) targeting a novel epitope on CD46 that is expressed at high levels in certain tumor types with limited expression in most normal tissues. The cytotoxic payload of FG-3246 is monomethyl auristatin E, an anti-mitotic agent that has been utilized in four commercially approved antibody-drug conjugate drugs. FG-3246 showed monotherapy efficacy in a Phase 1 clinical study in patients with mCRPC. Interim efficacy results presented at ASCO 2022 showed a PSA50 response rate of 45% and an objective response rate of 19%. Preclinical Pipeline The company's preclinical pipeline consists of two antibodies for immuno-oncology that are in investigational New Drug Application-enabling studies. FG-3165: Anti-Gal9 Antibody FG-3165 is a galectin-9 (Gal9) targeted antibody under development for the treatment of solid tumors characterized by high Gal9 levels of expression. Gal9 has been reported to bind to multiple immune checkpoints on lymphocytes that suppress T and natural killer cell activation, and it is a driver of cancer progression in acute myeloid leukemia. In preclinical studies FG-3165 and its variants inhibit Gal9 mediated T cell death, and also promotes anti-tumor immune responses in combination with other immune checkpoint targeted drugs. The company plans to submit an investigational new drug application (IND) in the first quarter of 2024. FG-3175: Anti-CCR8 Antibody FG-3175 is a c-c motif chemokine receptor 8 (CCR8) targeted antibody under development for the treatment of solid tumors that are highly infiltrated by CCR8-positive T regulatory cells. T regulatory cells contribute to an immune suppressed tumor microenvironment, and multiple preclinical studies have demonstrated immune activation and tumor regression following depletion of this cell type from the tumor microenvironment. FG-3175 is a variant of the company's previous lead anti-CCR8 antibody, FG-3163, and was deemed to be a superior clinical candidate following extended characterization of both antibodies. FG-3175 has enhanced antibody dependent cellular cytotoxicity activity and induces potent killing of CCR8 expressing cells by natural killer cells in in vitro assay systems. The company plans to submit an investigational new drug application (IND) in 2025. Collaborations Collaboration Partnerships for Roxadustat The company's revenue to date has been generated primarily from its collaboration agreements with Astellas and AstraZeneca for the development and commercialization of roxadustat. In addition, the company started roxadustat commercial sales in China in 2019. For the fiscal year ended December 31, 2023, 25% of the company's revenue was related to its collaboration agreements, and 68% of its revenue was from roxadustat commercial sales in China. For the fiscal year ended December 31, 2022, 40% of the company's revenue was related to its collaboration agreements, and 59% of its revenue was from roxadustat commercial sales in China. Astellas The company has two agreements with Astellas for the development and commercialization of roxadustat, one for Japan, and one for Europe, the Commonwealth of Independent States, the Middle East and South Africa. Under these agreements, it provided Astellas the right to develop and commercialize roxadustat for anemia in these territories. AstraZeneca Under the AstraZeneca China Agreement, which is conducted through FibroGen China Anemia Holdings, Ltd., FibroGen Beijing, and FibroGen International (Hong Kong) Limited (collectively, FibroGen China), the commercial collaboration was structured as a 50/50 profit share, which was amended by the AstraZeneca China Amendment in the third quarter of 2020. In 2020, the company entered into a Master Supply Agreement under the AstraZeneca U.S./RoW Agreement to define general forecast, order, supply, and payment terms for AstraZeneca to purchase roxadustat bulk drug product from FibroGen in support of commercial supplies. In July 2020, FibroGen China and AstraZeneca entered into an amendment, effective July 1, 2020, to the AstraZeneca China Agreement, relating to the development and commercialization of roxadustat in China (the AstraZeneca China Amendment). Under the AstraZeneca China Amendment, in September 2020, FibroGen Beijing and AstraZeneca completed the establishment of a jointly owned entity, Beijing Falikang Pharmaceutical Co. Ltd. (Falikang), which performs roxadustat distribution, as well as conduct sales and marketing through AstraZeneca. FibroGen Beijing manufactures and supplies commercial product to Falikang based on a gross transaction price, adjusted for the estimated profit share. Revenue is recognized upon the transfer of control of commercial products to Falikang in an amount that reflects the allocation of transaction price of the China manufacturing and supply obligation to the performance obligation satisfied during the reporting period. Exclusive License from HiFiBiO In 2021, the company entered into an exclusive license and option agreement with HiFiBiO (HK) Ltd. (doing business as HiFiBiO Therapeutics) (HiFiBiO), pursuant to which it exclusively licensed from HiFiBiO all product candidates in HiFiBiO's Galectin-9 program and subsequently exclusively licensed all product candidates in HiFiBiO's CCR8 program. Exclusive License and Option to Acquire Fortis Therapeutics On May 5, 2023, the company entered into an exclusive option agreement to acquire Fortis with its novel Phase 1 antibody-drug conjugate, FG-3246 that targets a novel epitope on CD46 preferentially expressed on certain cancer cells. FG-3246 is in development for the treatment of metastatic castration-resistant prostate cancer with potential applicability in other solid tumors and hematologic malignancies. Pursuant to an evaluation agreement entered into with Fortis concurrent with the option agreement, FibroGen has exclusively licensed FG-3246 and will control and fund future research and development, including a Phase 2 clinical study sponsored by FibroGen, and manufacturing of FG-3246 during the option period. As part of the clinical development strategy, it will continue the work to develop a PET-based biomarker utilizing a radiolabeled version of the targeting antibody for patient selection. Exclusive License with Eluminex In July 2021, the company exclusively licensed to Eluminex Biosciences (Suzhou) Limited (Eluminex) global rights to its investigational biosynthetic cornea derived from recombinant human collagen type III. FibroGen will be eligible to receive mid-single-digit to low double-digit royalties based upon worldwide net sales of cornea products, and low single-digit to mid-single-digit royalties based on worldwide net sales of other recombinant human collagen type III products that are not cornea products. Manufacture and Supply Roxadustat Roxadustat is a small-molecule drug manufactured from generally available commercial starting materials and chemical technologies and multi-purpose equipment available from many third-party contract manufacturers. The company has entered into commercial supply arrangements with Shanghai SynTheAll Pharmaceutical Co., Ltd. (WuXi STA) and Catalent Pharma Solutions, LLC (Catalent) as its primary manufacturers of roxadustat drug substance (also known as active pharmaceutical ingredient or API) and roxadustat drug product, respectively. WuXi STA is located in China and currently supplies its API globally except for China, for which it manufactures an intermediate to be further manufactured by FibroGen Beijing. WuXi STA has passed inspections by several regulatory agencies, including the FDA and NMPA, and is Current Good Manufacturing Practice (cGMP) compliant. Catalent is located in the U.S. and supplies its drug product tablets globally except for Japan, where they are manufactured by Astellas, and China, where they are manufactured by FibroGen Beijing. Catalent has passed several regulatory inspections, including by the FDA, and manufactures commercial products for other clients. Pamrevlumab The company has entered into a clinical and commercial supply agreement for the manufacture of pamrevlumab with Samsung Biologics Co., Ltd., which passed several regulatory inspections, including by the FDA, and manufactures commercial products for other clients. The company is transitioning its manufacturing of pamrevlumab from Boehringer Ingelheim to Samsung Biologics Co., Ltd. Intellectual Property The patent positions for the company's most advanced programs are summarized below. Roxadustat Patent Portfolio While the composition-of-matter patents covering roxadustat expire in 2024 (except in the U.S., where they expire in 2025), the roxadustat patent portfolio includes additional patents providing protection for roxadustat, including protection for the commercial crystalline form, pharmaceutical compositions, and key intermediates in roxadustat synthesis. Subject to the additional details outlined below for particular territories, and exclusive of any patent term extension, U.S. and foreign patents relating to crystalline forms of roxadustat and key intermediates in roxadustat synthesis are due to expire in 2033, and U.S. and foreign patents relating to photostable formulations of roxadustat are due to expire in 2034. Supplemental Protection Certificates (SPCs) are pending or have been granted in European Union member states, where roxadustat has been granted marketing approval, on its European Patent No. 3470397 (the 397 Patent), which claims formulations comprising the commercial crystalline form of roxadustat, thereby extending patent protection to 2036. Patent term extensions (PTEs) have also been granted for several roxadustat-related patents in Japan, where roxadustat has been granted marketing approval, including on composition-of-matter and crystal form patents extending patent protection to 2029 and 2035, respectively. In China, no photostable formulation patent has yet been granted (applications are pending). The company's roxadustat China patent portfolio additionally includes a granted patent and pending patent applications directed to roxadustat particle size distribution (PSD) in commercial formulations and use of roxadustat to treat select CIA patient populations. These patents and patent applications, upon grant, could extend the exclusivity of the roxadustat franchise with respect to the claimed subject matter to 2043. Several patents in the company's roxadustat patent portfolio have been challenged in Europe and China. In particular, patent challenges have been filed against its crystal form patents in Europe and China, and against the company's photostable formulations patent in Europe. While European Patent No. 2872488 (the 488 Patent), which claims the commercial crystalline form of roxadustat, was originally revoked in opposition, the decision is under appeal. While both the `397 Patent and the company's European Patent No. 3003284 (the 284 Patent), which claims photostable formulations of roxadustat, were upheld in opposition, the opponents have appealed the decision in the `284 Patent and it anticipates the opponents will appeal the decision in the `397 Patent. In China, three roxadustat crystal form patents were revoked in first-round proceedings and two revocations were upheld on first appeal; however, all decisions remain on appeal. Final resolution of these proceedings in Europe and China will take time. Pamrevlumab Patent Portfolio The company's pamrevlumab patent portfolio includes U.S. and foreign patents providing composition-of-matter protection for pamrevlumab. Exclusive of any patent term extension, the last of the U.S. patents relating to pamrevlumab composition-of-matter is due to expire in 2025 and corresponding foreign patents are due to expire, exclusive of any patent term extension, in 2024. Therefore, in most jurisdictions, exclusivity for pamrevlumab will rely primarily on regulatory exclusivities, including a 12-year reference product exclusivity period from approval in the U.S. and a 10-year marketing protection period from approval in Europe. The company also holds additional granted the U.S. and foreign patents and pending patent applications directed to the use of pamrevlumab to treat pancreatic cancer. Upon marketing approval of pamrevlumab in most jurisdictions, the company can request patent term extension on a non-expired patent in that jurisdiction that is relevant to the approved label. FG-3246 Patent Portfolio The company's FG-3246 patent portfolio includes U.S. and foreign patents and pending patent applications providing, upon grant, composition-of-mater protection for FG-3246 that are due to expire in 2035 exclusive of any patent term extension. Trade Secrets and Know-How In addition to patents, the company relies upon proprietary trade secrets and know-how and continuing technological innovation to develop and maintain its competitive position. In-Licenses Bristol-Myers Squibb Company (Medarex, Inc.) Effective July 9, 1998, and as amended on June 30, 2001 and January 28, 2002, the company entered into a research and commercialization agreement with Medarex, Inc. and its wholly-owned subsidiary GenPharm International, Inc. (collectively, part of Bristol-Myers Squibb Company (Medarex)) to develop fully human monoclonal antibodies for potential anti-fibrotic therapies. Under the agreement, Medarex was responsible for using its proprietary immunizable transgenic mice (HuMAb-Mouse technology) during a specified research period (the Research Period), to produce fully human antibodies against its proprietary antigen targets, including CTGF, for the company's exclusive use. Fortis Therapeutics / University of California, San Francisco (UCSF) Effective May 5, 2023, the company entered into an Evaluation Agreement with Fortis Therapeutics, Inc., under which FibroGen was granted an exclusive license to certain Fortis intellectual property (IP) and additional IP in-licensed by Fortis from UCSF for the purpose of performing evaluation activities associated with use of FG-3246/FOR46 particularly for treatment of metastatic castration-resistant prostate cancer (mCRPC). The IP includes know-how, patents, and patent applications related to FG-3246 composition-of-matter and variants thereof, anti-CD46 antibodies and immunoconjugates made therefrom, and formulations, dosing regimens, and uses thereof. Composition-of-matter patents for FG-3246 are due to expire in 2035, and formulation and dosing regimen patents are due to expire in 2041, in each case exclusive of any patent term extension or adjustment that may be available. HiFiBiO Therapeutics Effective June 16, 2021, the company entered into an Exclusive License and Option Agreement with HiFiBiO (HK) Ltd. (doing business as HiFiBiO Therapeutics), under which FibroGen was granted an exclusive, worldwide license to HiFiBiO know-how and patent rights to all galectin-9 (Gal-9)-directed products for all uses, and a sublicense from HiFiBiO to in-licensed anti-Gal-9 antibodies from Societe d'Acceleration du Transfert de Technologie (SATT-NORD). The patent rights include U.S. and foreign patents and patent applications directed to specific anti-Gal-9 antibodies, fragments, and uses, and are due to expire in 2041 exclusive of any patent term extension or adjustment that may be available. The licensed patents relate to FG-3165 and related products. The company was also granted an option under the agreement to license a second program from HiFiBiO which it exercised on December 10, 2021, with respect to HiFiBiO know-how and patent rights to all CCR8-directed products for all uses. The patent rights include U.S. and foreign patents and patent applications directed to specific anti-CCR8 antibodies, fragments, and uses, and are due to expire in 2042 exclusive of any patent term extension or adjustment that may be available. The licensed patents relate to FG-3175 and related products. Research and Development The company's research and development expenses were $282.9 million for the year ended December 31, 2023. Government Regulation As a developer, manufacturer and supplier of drugs, the company is subject to regulation and oversight by the NMPA and its provincial and local branches. History FibroGen, Inc. was incorporated in 1993 in Delaware.