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Form 8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): February 11, 2015

 

 

FibroGen, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-36740   77-0357827

(State or other jurisdiction

of incorporation)

  

(Commission

File Number)

  

(IRS Employer

Identification No.)

FibroGen, Inc.

409 Illinois Street

San Francisco, CA 94158

(Address of principal executive offices, including zip code)

(415) 978-1200

(Registrant’s telephone number, including area code)

Not Applicable

(Former name or former address, if changed since last report.)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

 

 

 

Item 7.01 Regulation FD Disclosure

Beginning February 11, 2015, FibroGen, Inc. (the Company) intends to conduct meetings with existing and prospective investors and analysts in which its corporate slide presentation will be presented. A copy of the presentation materials, including a slide setting forth certain cautionary statements intended to qualify the forward-looking statements therein, is attached as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.

The information in this Item 7.01 is being furnished, not filed, pursuant to Regulation FD. Accordingly, the information in Item 7.01 of this report will not be incorporated by reference into any registration statement filed by the Company under the Securities Act of 1933, as amended, unless specifically identified therein as being incorporated therein by reference. The furnishing of the information in this report is not intended to, and does not, constitute a determination or admission by the Company that the information in this report is material or complete, or that investors should consider this information before making an investment decision with respect to any security of the Company.

 

Item 9.01 Financial Statements and Exhibits.

 

(d) Exhibits

 

Exhibit

No.

   

Description

99.1    FibroGen, Inc. Presentation Materials dated February 2015

 

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

    FIBROGEN, INC.
Dated: February 11, 2015    
    By:  

/s/ Michael Lowenstein

      Michael Lowenstein
      VP, Legal Affairs

 

INDEX TO EXHIBITS

 

Exhibit

No.

   

Description

99.1    FibroGen, Inc. Presentation Materials dated February 2015
EX-99.1
Discussion Materials
February 2015
Exhibit 99.1

Forward-Looking Statements
2
2
This presentation, the accompanying modules, and in each case the oral commentary contain “forward-looking”
statements that involve substantial risks and uncertainties. All statements other than statements of historical
facts contained in this presentation, the accompanying modules, and in each case the oral commentary,
including statements regarding our future financial condition, business strategy and plans and objectives of
management for future operations, are forward looking statements. In some cases, you can identify forward-
looking statements by terminology such as “believe,” “will,” “may,” “estimate,” “continue,” “anticipate,”
“contemplate,” “intend,” “target,” “project,” “should,” “plan,” “expect,” “predict,” “could,” “potentially” or the
negative of these terms or other similar expressions. Forward looking statements appear in a number of places
throughout this presentation, the accompanying modules, and in each case the accompanying oral commentary
and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations
concerning, among other things, our ongoing and planned preclinical development and clinical trials, the timing
of and our ability to initiate or enroll clinical trials, and our ability to make regulatory filings and obtain and
maintain regulatory approvals for roxadustat, FG-3019 and our other product candidates, our intellectual
property position, the potential safety, efficacy, reimbursement, convenience clinical and pharmaco-economic 
benefits of our product candidates, commercial opportunities, including potential market sizes and segments,
the potential markets for any of our product candidates, our ability to develop commercial functions, our ability
to operate in China, expectations regarding clinical trial data, including all of the foregoing as it pertains to our
collaboration partners AstraZeneca, AB and Astellas Pharma Inc., our results of operations, cash needs,
spending of the proceeds from this offering, financial condition, liquidity, prospects, growth and strategies, the
industry in which we operate and the trends that may affect the industry or us.
Forward-looking statements involve known and unknown risks, uncertainties, assumptions and other factors
that may cause our actual results, performance or achievements to be materially different from any future
results, performance or achievements expressed or implied by the forward-looking statements. Forward-looking
statements represent our management’s beliefs and assumptions only as of the date of this presentation, the
accompanying modules, and in each case the oral commentary. Except as required by law, we assume no
obligation to update these forward-looking statements publicly, or to update the reasons why actual results
could differ materially from those anticipated in the forward-looking statements, even if new information
becomes available in the future.

Investment Highlights
IPF: idiopathic pulmonary fibrosis
DMD: Duchenne Muscular Dystrophy
•
Three broad technology platforms generating multiple product candidates
•
Roxadustat
–
a
novel
oral
treatment
for
anemia
in
Phase 3
•
Targeting the multi-billion dollar global anemia market
•
IP protection expected through 2033 and potentially beyond
•
>1400
subjects
evaluated
in
P1
+
P2;
P3
to
enroll
~
7500
to
8500
subjects
globally
•
Global collaborations: Astellas and AstraZeneca
•
$2.5 billion in potential payments ($683 million received through 9/30/14)
•
Plus royalties, transfer prices, and clinical development support
•
Regulatory filings anticipated 2016 (China), 2018 (US)
•
Funded through expected global commercialization
•
FG-3019 –
a novel anti-CTGF Ab for treating fibrotic disease
•
FG-5200
–
collagen
type
III
replacement
cornea
&
scaffold
for
corneal
blindness
•
$343
M
-
$348
M
cash,
cash
equivalents,
investments,
receivables
as
of
12/31/14
(unaudited)
•
Phase 2 proof of concept established in IPF and pancreatic cancer
•
DMD clinical trial design reviewed by expert body of TREAT-NMD and pre-IND
activities underway
3
3
TREAT-NMD is an EU-based network aiming to advance treatments and care for patients with neuromuscular disease; TACT, the TREAT-NMD Advisory Committee for
Therapeutics, is an expert multidisciplinary body that provides the neuromuscular community with guidance on advancing new therapies for neuromuscular diseases

Management Team
¹
Predecessor entities.
4
4
THOMAS NEFF
Chief Executive Officer
PAT COTRONEO
Chief Financial Officer
FRANK VALONE, MD
Chief Medical Officer
K. PEONY YU, MD
VP, Clinical Development
CHRIS CHUNG
Exec Director & China Project Leader
LEANNE PRICE, JD
VP, Intellectual Property & Corp Strategy
R. WAYNE FROST, PHARM D
VP, Regulatory Affairs
ELIAS KOUCHAKJI, MD
VP, Drug Safety
MICHAEL LOWENSTEIN, JD
VP, Legal Affairs
ANATOLE BESARAB, MD
Exec Director, Clinical Research
LYNDA SZCZECH, MD
Exec Director, Clinical Development
SETH PORTER, PHD
Exec Director & FG-3019 Project Leader
GREG MANN
Exec Director, IR

Our Platforms and Product Portfolio
¹
5-year POC study in 10 patients completed; filed as device in China.
Wholly-Owned
Partnered
5
5
HIF
PLATFORM
PRECLINICAL
PHASE 1
PHASE 2
PHASE 3
Roxadustat
(HIF-PH
Inhibitor for anemia)
•
United States / Europe
•
China
•
Japan
FG-6874
(HIF-PH
Inhibitor; Stem Cell Mobilization)
FG-8205
(Selective HIF-
PH Inhibitor for heart failure
after myocardial infarction)
FIBROTIC DISEASE PLATFORM
PRECLINICAL
PHASE 1
PHASE 2
PHASE 3
FG-3019
(Anti-CTGF
Antibody)
•
Pancreatic Cancer
•
IPF
•
Liver Fibrosis
•
Duchenne
Muscular Dystrophy
rhCOLLAGEN
III
SCAFFOLD
PILOT
PIVOTAL
FG-5200
(Corneal Blindness)
1

Roxadustat

Anemia 101
THE
CONDITION
Reduced Oxygen-Carrying
Capacity of Blood
Capacity of Blood
ANEMIA IN CKD
Dialysis & Pre-Dialysis
INCREASED
MORTALITY
RED BLOOD CELL CREATION
(ERYTHROPOIESIS)
-
Reduces Availability of
Iron for RBC Production
7
7

8
8
LOW
OXYGEN
(e.g. High Altitude)
or
HIF
ROXADUSTAT
HIF
HIF-PH
Enzymes
HIF-PH Enzymes
NORMAL
OXYGEN
Degradation
HIF
Roxadustat Stabilizes  HIF
Gene Transcription
Degrades Rapidly
EPO Within or Near 
Physiological Range
Red Blood Cell
Production
Hepcidin Levels
Iron Transport to the
Bone Marrow and
Hemoglobin (Hb)
Synthesis
Iron Absorption
Roxadustat Activates a Natural Pathway to Increase
Red Blood Cell Production
HIF
1
HIF-PH -
hypoxia-inducible factor prolyl hydroxylase
1

1
C
max
data for roxadustat estimated for a subset of 243 patients who achieved Hb response and were dosed at expected therapeutic doses.
2
Milledge & Cotes (1985) J Appl Physiol 59:360.
3 
Goldberg et al. (1993), Clin Biochem 26:183, Maeda et al. (1992)
Int J Hematol 55:111.
4
Kato et al. (1994) Ren Fail 16:645.
5 
Based on Flaherty et al. (1990) Clin Pharmacol Ther 47:557.
EPO C
max
(mIU/mL)
Altitude
Blood Loss
Pulm
Edema
4
0.99
1.20
1.60
20
44
93
0.16
3.86
Dose Distribution by Percentile
mg/kg/dose
Min
25%
50%
75%
Max
Dose Distribution by Percentile
(DOPPS Q4, 2011)
U/kg/dose TIW
25%
50%
75%
95%
197
Roxadustat Achieves Target Hb with Physiologic
EPO C
max
Levels
ROXADUSTAT
(Target Hb 11 to 13 g/dL)
PHYSIOLOGICAL
ADAPTATION
(U.S. ESA Label:
Hb 10 to 11 g/dL)
ESA
5
9
9
0
1,000
2,000
3,000
4,000
5,000
6,000
2
3
1

10
10
•
Roxadustat Increased Hb
•
Aranesp
®
Increased Hb but Reduced
Mean Cell Volume (Depletes Iron)
•
IV Iron Ineffective
•
Roxadustat Increased Hb
•
Aranesp
®
or IV Iron Ineffective for
Anemia of Inflammation
ESAs Ineffective or Require High Doses in
Presence of Inflammation in Preclinical Model
Abs Hb g/dL
19.6
Aranesp
(ESA)
15.4
IV Iron
19.3
Roxadustat
16.3
Vehicle
-1
0
1
2
3
4
5
10.4
Vehicle
13.0
Roxadustat
9.8
Aranesp
(ESA)
9.5
IV Iron
-1
0
1
2
3
4
5
Abs Hb g/dL
Normal Animals
Anemia of Inflammation
Model of inflammation using rats challenged with PG-PS, ACD; Klaus, S, et al, Induction of
Erythropoiesis and Iron Utilization by FG-4592, Poster Presentation, ASN 2005.

11
11
Roxadustat Reduces Hepcidin
Decreased Hepcidin Improves Iron Availability and Reduces ESA Resistance
CKD-DD Patients Previously Treated with
EPO and Randomized (Study 040a)
(Conversion, ESA Hyporesponders)
CKD-DD Newly Initiated Dialysis
(Study 053)
Mean
(±SE)
Hepcidin
(ng/mL)
n=52
Baseline
Week 7
Baseline
Week 7
¹
p-value: change in hepcidin level at Week 7
from baseline in roxadustat vs EPO
n=9
n=9
Mean
(±SE)
Hepcidin
(ng/mL)
0
50
100
150
200
250
300
350
400
p=0.038
1
Roxadustat
2 mg/kg
EPO
Control
0
20
40
60
80
100
Baseline
Week 5
p
<0.0001
n=52
Roxadustat

Hb Correction by Roxadustat
is Independent of Inflammatory State (Study 053)
*EE Population
Besarab, et al., ASN 2014 poster presentation, “Impact of Iron
Regimen on Iron Indices and Hepcidin During Roxadustat (FG-
4592) Anemia Correction in Incident Dialysis Patients”.
0
1
2
4
5
6
7
8
0.1
1
10
100
HD no iron (n=23)
HD IV iron (n=10)
PD oral iron (n=10)
All* (n=55), R
2
=0.0049,  p=0.61
3
CRP-Level (mg/L)
ULN
12
12
HD oral iron (n=12)

13
13
Roxadustat Dose Required for Hb Maintenance is
Independent of Inflammatory State (Study 053)
*EE Population
Besarab, et al., ASN 2014 poster presentation, “Impact of Iron
Regimen on Iron Indices and Hepcidin During Roxadustat (FG-
4592) Anemia Correction in Incident Dialysis Patients”.
0
2
4
6
8
10
12
14
16
18
0.1
1
10
100
CRP
-Level (mg/L)
HD no iron (n=23)
HD oral iron (n=12)
PD oral iron (n=10)
HD IV iron (n=10)
ULN
All*
(n=55): R
2
=0.0024, p=0.72

14
Larger Hepcidin Reduction in
Patients with Higher BL CRP (Study 053)
*EE-Population
hepcidin: change from baseline in hepcidin levels by EOT after
12 Weeks
Besarab, et al., ASN 2014 poster presentation, “Impact of Iron Regimen on Iron Indices and
Hepcidin During Roxadustat (FG-4592) Anemia Correction in Incident Dialysis Patients”.
-400
-300
-200
-100
0
100
200
0.1
1
10
100
Baseline CRP (mg/L)
no iron (n=22)
oral iron (n=22)
IV iron (n=9)
R
2
=0.0358, p=0.40
R
2
=0.3614, p=0.003
R
2
=0.0548, p=0.54

15
Phase 2 Program Conducted Across Different CKD
Populations
* Many patients were ESA hyporesponsive. Higher doses of ESA are
generally needed to treat such patients.
STUDY
PATIENTS
WEEKS
DOSE
LEVELS
TIER
WEIGHTS
CONTROL
KEY
RESULTS
Placebo-Controlled Pre-Dialysis
017
Dose
Range
Finding, NDD
116
4
4
No
Placebo
•
Reduction
in Hepcidin
•
Dose-dependent
Increase in Hb
047
Pre-dialysis
91
8
2
3
Placebo
•
Encouraging Safety Data
•
Validation of
Tier Weight-based Dosing
ESA-Controlled Dialysis Conversion
048
Dialysis
(Converted)
96
6
3
3
ESA
•
Encouraging Safety Data
•
Successful
Conversion from ESA IV & SQ
040a
Dialysis
60
6
3
No
ESA
•
Successful Conversion, Includes ESA
Hyporesponsive
Patients
•
Dose Dependent Decrease in Hepcidin
Phase 2b Key
Proof of Concept Studies
041
Pre-dialysis
(Six Correction and
Maintenance
Dose
Cohorts)
145
16
and
24
6
3
•
Both tier weight and fixed starting doses can
initiate Hb correction
•
Maintained Hb with TIW, BIW, QW
•
Decrease in Blood Pressure Observed
(Subgroup)
•
Reduced Total Cholesterol Levels
040b
Dialysis*
(Conversion)
101
19
5
3
ESA
•
Maintenance
•
Reduced Total Cholesterol Levels
053
Dialysis
(Newly Initiated)
60
12
1
3
•
•
Oral Iron
IV Iron
Oral Iron HD
oral Iron PD

16
16
Study 017: Placebo-Controlled Proof of Concept
Study in Pre-Dialysis
•
Anemic Pre-dialysis Patients
not Receiving ESA
•
Randomized to Placebo or
Roxadustat, BIW or TIW
–
4-week Dose Ranging Study
Evaluating 4 Weight-based
Doses
–
Responder =  Hb rise
1 g/dL
Mean (±
SE)
hb
max
(g/dL)
MEDIAN TIME TO RESPONSE
24.5
Days
14
14
Days
Days
21
Days
14
14
Days
Days
DESIGN
100
%
91
%
80
%
100
%
40
%
58
%
30
%
60
%
•
Statistically significant, dose-
dependent Hb increase for all
4 doses and for all
assessments from Day 8
(p=0.025) to end of treatment
(Day 22 p=0.0001; Day 26-29
p<0.0001)
•
100% Response Rate at
Highest Dose
•
Hepcidin reduction in 1.5
mg/kg cohort (p=0.048) and in
2.0 mg/kg cohort (p=0.001)
OBSERVATIONS
0.0
0.5
1.0
1.5
2.0
2.5
3.0
DESIGN
Hb Responders
Placebo
(N=23)
BIW 
(N=10)
TIW 
(N=12)
BIW 
(N=5)
TIW 
(N=5)
BIW 
(N=10)
TIW 
(N=11)
BIW 
(N=9)
TIW 
(N=11)
%
1.0 mg/kg
0.7 mg/kg
1.5 mg/kg
2.0 mg/kg
13
%

17
Study 047: Placebo-Controlled Study in
Pre-dialysis
OBSERVATIONS
High Dose: 1.77 mg/kg (n=31)
Low Dose: 1.37 mg/kg (n=30)*
Placebo (n=30)
Mean (±SE) Hb Change from BL (g/dL)
* Hb increase >
1 g/dL and Hb >11.0 g/dL at end of treatment
DESIGN
•
Anemic Pre-dialysis Patients
not Receiving ESA
•
Randomized to Placebo or
Roxadustat TIW
–
Two Tier Weight-based Doses
–
8 Weeks Dosing
•
Statistically Significant,
Dose-dependent Hb Increase
for Both Cohorts
•
93.1% Hb response rate at
highest dose
*n at baseline
8
9
10
11
12
0
1
2
3
4
5
6
7
8
Study Weeks
PATIENTS
WITH HB
INCREASE >
1
G/DL
P-VALUE VS
PLACEBO
P-VALUE
VS
PLACEBO
MAX
CHANGE
IN HB
BASELINE
HB
N
TREATMENT
-
High Dose
31
8.9
2.4
<0.0001
93.1%
<0.0001
Low Dose
30
8.8
1.6
<0.0001
88.5%
<0.0001
Placebo
30
9.0
0.4
25.9%

Studies 048 and 040a: ESA Comparator Study in Stable
Dialysis Patients when Switched from Epoetin
(Conversion)
OBSERVATIONS
–
Study
048
OBSERVATIONS
–
Study
040a
(6
wks)
•
Hemodialysis Patients with Hb Corrected on Stable Doses of ESA
-
For Study 048, approximately 50:50 split between SC and IV
•
Randomized to Roxadustat TIW or Continuation of EPO for 6 Weeks of Treatment
DESIGN
Studies 048 and 040
•
Roxadustat Maintained Hb in All Cohorts
•
Hb Response Rates*
-
Low Dose (59.1%), Mid Dose (88.9%), High Dose (100%)
-
EPO (50%), p=0.005 (Mid Dose), p=0.0002 (High Dose)
•
Successful in Wide Range of Patients, Includes EPO
Hyporesponsive Patients
Study Weeks
* % of Patients Maintaining Hb Level No Lower than 0.5 g/dL below
Baseline at Both Week 6 and Week 7
Low-dose, 1 mg/kg (n=9)
Medium-dose, 1.5 mg/kg (n=10)
High-dose, 2 mg/kg (n=9)
Epoetin a
(n=9)
Study Weeks
18
18

19
Phase 2B Program

Study 040b: ESA Comparator Study in Stable Dialysis
Patients when Switched from Epoetin    (Conversion)
Mean (±SE) Hemoglobin (g/dL)
DESIGN –
Stable Dialysis
Conversion from ESA
•
Hemodialysis Patients with Hb
Corrected on Stable Doses of
ESA
•
Randomized to Roxadustat
TIW or Continuation of EPO
•
19-week Treatment Duration
•
Mean Baseline EPO Doses:
168 U/kg/wk IV (Dosed TIW)
•
Low and High EPO Users
•
Roxadustat Maintains Hb
Levels Without IV Iron
•
Roxadustat Maintains Hb
Levels with Lower Cmax  EPO
Levels than IV Epoetin
OBSERVATIONS
Roxadustat (n=61)
20
20

21
21
Study 041: Dose Finding in Pre-dialysis
Different Targets, Different Correction Rates, Single Maintenance Algorithm
•
92% Response Rate
•
Correction Achieved and
Maintained to Ends of
Treatment, Regardless of
Starting and Maintenance Dose
•
Reduction in Serum Hepcidin at
Week 9 vs Baseline, p=0.0003
•
CKD Patients not on Dialysis
•
Roxadustat Starting Doses
-
TIW or BIW
-
Tier Weight Dosing: 3 Sizes
•
Dose Titration to Achieve Hb
-
Dose Adjustment Every 4
Wks
•
Maintenance Dosing Upon
Achieving Hb 11 g/dL
–
TIW, BIW or QW
•
Dual Endpoint
Hb
1 and
Achieved Hb
11 g/dL
•
16 or 24 Week Treatment
DESIGN
OBSERVATIONS
Mean (±SD)  Hemoglobin (g/dL)
Source: Besarab et al. 2011, J Am Soc Nephrol 22:196A
21
21
9.5
10.0
10.5
11.0
11.5
12.0
12.5
13.0
0
2
4
6
8
10
12
14
16
18
20
22
24
Duration of Treatment (Weeks)
Target Hb
Cohorts A,B,E & F
Target Hb,
Cohorts C&D
Cohort A (tiered, TIW-TIW, n=23)
Cohort B (tiered, TIW-BIW, n=24)
Cohort C (fixed, 50 mg, TIW-TIW, n=23)
Cohort D (fixed, 100 mg, TIW-TIW,   =24)
Cohort E (tiered, BIW-QW, n=24)
Cohort F (fixed, 70 mg, TIW-BIW-QW, n=25)

Study 053: Roxadustat Corrects Anemia in Newly
Initiated Dialysis Patients without IV Iron
Besarab, et al., J Am Soc Nephrol 23:428A and 24:91A.
* p<0.05 compared to IV iron and oral iron
*
*
Weeks on Treatment
DESIGN
OBSERVATIONS
•
Incident Dialysis (Newly Initiated
Dialysis) Patients with Low Hb
Levels and not on ESAs
•
All Received Roxadustat
•
Comparison of Treatment
Response Under Different Iron
Supplementation Conditions
•
HD
(Hemodialysis)
Randomized
to
–
No Iron
–
IV Iron
–
Oral Iron
•
PD (Peritoneal) Received Oral Iron
•
Roxadustat Raised Hb as
Efficiently with Oral Iron as
with IV Iron
•
Oral and IV Iron Arms Had
Similar Hb Responses in PD
and HD
•
1 g/dL Hb correction in >90%
patients at Week 12
Mean (±SE) Hemoglobin (g/dL)
22

Conclusions: Phase 2 Studies
•
Evaluated Broad Range of CKD Patient Population: Stable Dialysis,
Incident Dialysis and Nondialysis; ESA Hyporesponders
•
In Dialysis and Nondialysis: Consistent, Dose-Dependent Hb
Response with Roxadustat
•
In Nondialysis: Both Tiered and Fixed Dosing Regimens Produced
90% Response Rates and Maintained Stable Hb
•
In Nondialysis and Dialysis: Substantial Reduction of Hepcidin
Observed in All Cohorts
•
In Incident Dialysis: No Increased Level of Roxadustat Dosing
Required (Study 053)
•
In Dialysis: Oral Iron is Comparable to IV Iron in Achieving and
Maintaining Hb Correction with Roxadustat in Patients on Dialysis
23

Roxadustat Safety Review
•
No Overall Safety Signal
–
An independent data monitoring committee reviewed data
–
Frequency and type of AEs expected in CKD patients
•
No Cardiovascular Signal
•
Lowers
Cholesterol
Levels
•
No Increase in Blood Pressure
•
Reduction in Blood Pressure at End of TIW Dosing
•
Platelet Reduction in Patients with High Platelet Count
•
No Cardiac Conduction Effect (TQT Study Negative)
•
No Drug Related Renal Toxicity
•
No Liver Safety Signal, No Special Liver Monitoring Requirement in
Phase 3
SAFETY
OBSERVATIONS
IN COMPLETED
PHASE 1 & 2
STUDIES
Roxadustat Exposure
~1,100 Subjects
16 patients > 1 year
9 patients > 3 years
EXTENSIVE
PRECLINICAL
EVALUATION OF
CANCER RISK
•
Carcinogenicity Studies Complete
•
No Clinical Evidence of Tumor Risk to Date
24

Treatment-Emergent Serious Adverse Events
Protocol 017
4 Weeks
Protocol 047
8 Weeks
Roxadustat
Placebo
Roxadustat
Placebo
Number of subjects
88
28
61
30
SAEs
4 (4.5%)*
1 (3.6%)
8 (13.1%)*
4 (13.3%)
Cardiovascular SAEs
0
1 (3.6%)
0
1 (3.3%)
CSE**
0
0
0
1 (3.3%)
Protocol 048
6 Weeks
Protocol 040b
19 Weeks
Roxadustat
EPO
Roxadustat
EPO
Number of subjects
74
22
66
23
SAEs
0
0
15 (22.7%)*
4 (17.4%)
Cardiovascular SAEs
0
0
1 (1.5%)
2 (8.7%)
CSE**
0
0
8 (12.1%)
4 (17.4%)
EPO-Controlled Phase 2 Trials (Conversion study in dialysis patients)
Placebo-Controlled Phase 2 Trials (Anemia correction in non-dialysis patients)
*No SAEs were attributed to roxadustat in completed trials. No statistically significant differences from comparators.
**CSE=death, myocardial infarction, congestive heart failure, subendocardial ischaemia, cerebrovascular accident,
thrombosis (fistula), arteriovenous fistula occlusion, angina pectoris, and vascular graft thrombosis.
25

Roxadustat Submissions for Marketing Approvals:
US, Europe, and China
•
Indication
–
Treatment
of
Anemia
Associated
with
Chronic
Kidney
Disease
(CKD)
in
Patients
on
Dialysis
and
Not on Dialysis
•
Primary
Efficacy
Endpoints
-
Based
on
Hemoglobin
(Hb)
Measurements
–
Change in Hb from Baseline, or % Hb responders
–
US
&
EU:
pre-specify
primary
endpoint
by
region
–
Dialysis (DD) -
in addition to stable dialysis, include incident dialysis, a high-risk population
–
Nondialysis (NDD) –
first placebo-controlled pivotal study for this population
•
~ 8,000
Subjects
in
10
Studies*
(8
ex-China,
2
China)
* Excludes Japan where Phase 2 studies are being completed and Phase 3 plans will be finalized in 2015.
** Plan to support  US regulatory approval with 7 studies (4 DD and 3 NDD), 5 of which (3DD and 2 NDD) will also be used in the European
package that contains a total of 6 studies (3 DD and 3 NDD).
26
REGULATORY AUTHORITIES
US
EUROPE
CHINA
# of P3 Studies to Support Regulatory Approval
7**
6**
2
# of P3 Patients to Support Regulatory Approval
~7,500**
Up to 4,000**
450
Minimum Duration
52+ weeks
36+ weeks
26-52 weeks
(100 for 1 yr)
Average Duration
1.3 to 1.5 years
1 year
6-12 months
Estimated Patient Years
~10,000
~4,000
~275
Mandatory Post-Approval Safety Study (China)
None at this time
None at this time
~2,000 patients
Pharma Partners
AstraZeneca
Astellas
AstraZeneca
•
Safety Assessment Focused on Cardiovascular Events, Large Phase 3 Program for CKD Anemia

Roxadustat Phase 3 Program
STUDY
NUMBER
COMPARATOR
RANDOM-
IZATION
N
STUDY
LOCATIONS
CHINA
EUROPE
US
STUDY
SPONSOR
PHASE 3 STUDIES TO SUPPORT REGULATORY APPROVAL
Stable Dialysis
CL-613
1
Epoetin
/Darbe
376/200/174
750
EU, MEA
3
36+ wks
52+wks
Astellas
FG-064
1
Epoetin
1:1
Up to 750
US+/-Global
36+ wks
52+wks
FibroGen
FG-806
Epoetin
2:1
300
China
26-52 wks
FibroGen
Incident Dialysis
FG-063
1
Epoetin
1:1
Up to 750
Global
36+wks
52+ wks
FibroGen
Incident and Stable Dialysis
AZ-002
Epoetin
1:1
1425
Global
52+ wks
AstraZeneca
Non-Dialysis
FG-060*
Placebo
2:1
Up to 600
US, LA
2
, APAC
3
36+ wks
52+ wks
FibroGen
CL-0608*
Placebo
2:1
450-600
EU, MEA
4
36+ wks
52+ wks
Astellas
FG-808
Placebo
2:1
150
China
26-52 wks
FibroGen
AZ-001
Placebo
1:1
~2,600
Global
52+ wks
AstraZeneca
EUROPEAN REIMBURSEMENT STUDY
CL-0610
Darbepoetin
2:1
570
EU, MEA
36+ wks
N/A
Astellas
1
Plan to support US regulatory approval with 7 studies (4 DD and 3 NDD), 5 of which (3DD and 2 NDD, highlighted) will
also be used in the European package that contains a total of 6 studies (3 DD and 3 NDD)
27
2
LA
-
Latin
America;
3
APAC
-
Asia-Pacific;
4
MEA
-
Middle
East
&
Africa

28
28
Roxadustat Has Potential to Address Unmet Need
in Multiple Markets
¹
FibroGen estimate
Disease
Dialysis
Pre
-Dialysis
Limitations
on ESA
Treatment
Clinician
Nephrologist Where
ESA
Is Avail Now
36% Anemic¹
20% Anemic¹
Endocrinologist/
Diabetologist
Cardiologist/
IBD, Lupus, RA,
etc.
GI/Rheumatologist/
Internist
JAPAN
CHINA, ASIA, ex-Japan
US
EU, CIS
FDA Safety
Issues
Not Referred to Nephrologists
‘Delayed Referral’
Safety Issues
(Higher ESA doses
required v CKD)
Transfusion Mkt
ESAs Not
Demonstrated
to Work
Generic
ESAs
Partnered with
Astellas
Costly
Treatment
Internist
CKD
DIABETES
HYPERTENSION
CANCER
INFLAMMATORY
Secondary CKD
28
28
Myelodysplasia
Chemotherapy
Induced Anemia
Oncologist

Potential Multiple Global, Multi-Billion Dollar
Markets for Anemia
DIABETES
HYPERTENSION
Secondary CKD
New Market:
First-in-Class Oral Therapy
in Secondary CKD
EU, CIS
US
JAPAN
Existing and
New Markets:
Cost Effective
Re-Establish
Market:
Safer Option
CANCER
New Market:
Treat in Presence
of Inflammation
INFLAMMATORY
1
2
4
3
6
¹
FibroGen estimate
5
Mainly New Market:
Opportunity to Become
Standard of Care for
Serious Unmet Need
CHINA, ASIA, ex-Japan
5
29
Disease
Dialysis
Pre-Dialysis
Roxadustat
Market
Opportunity
Clinician
Nephrologist
Where
ESA Is Avail Now
36% Anemic
¹
20% Anemic
¹
Endocrinologist/
Diabetologist
Cardiologist/
Myelodysplasia
Chemotherapy
Oncologist
IBD, Lupus, RA,
etc.
GI/Rheumatologist/
Internist
Internist
Induced Anemia
CKD
Existing Market:
Superiority to ESAs

Roxadustat Competitive Profile
•
Most advanced HIF-PHI in development: Global Phase 3 program
underway
•
Extensive clinical experience: >1,100 patient exposures in Phase
1 & 2
•
3 year maximum exposure duration
•
Intermittent dosing
•
Phase 3 dosing regimen based on extensive testing in Phase 1 and
Phase 2
•
Completed End of Phase 2 meetings with regulators
–
Phase 3 MACE-based safety endpoints based on end of Phase 2
discussions with FDA
–
Planned US NDA submission for both dialysis and pre-dialysis
30

Study 041 –
Competitive Highlights
Roxadustat Study 041 (pre-dialysis)
Sample size
145
Completion Rate
92%
Definition of Hb response
Achievement of Hb 11 g/dL and
Hb
increase
1 g/dL
Renal SAEs and/or dialysis initiation
5.5% (8)
Dialysis initiation while on study
3.4%
(5=4
SAEs
+
1
non-SAE)
With no dialysis
2.1% (3)
SAEs –
probably or possibly related
0
Deaths –
probably or possibly related
0
SAEs –
related (angioedema, severe
allergic reaction)
0
SAEs –
related (liver abnormality)
0
31

Phase 3 Dosing Regimen
Optimized for Hb Effect and Convenience
Starting dose: non-dialysis (1 study)
Starting doses: non-dialysis and incident dialysis (3 studies and 1 study, resp.)
Starting dose: stable dialysis (3 studies)
Conversion from baseline EPO dose to roxadustat dose, based on conversion factor data from
two Phase 2 studies
3x per week (TIW) dose frequency
•
Except a subset of 2 non-dialysis studies
•
BIW 2x/ week n~ 60  in study FG-060, n=20+ in CL-608, also testing in CL-610
•
QW 1X/ week n~ 60 in study FG-060, n= 20+ in CL-608, also testing in CL-610
Dose adjustments every 4 weeks, tested in five Phase 2 studies
Experience from Phase 1 and Phase 2 supports Phase 3 dosing regimen
Phase 2
•
Several hundred patients dosed at doses being utilized in Phase 3
Phase 1:
•
> 300 subjects dosed between 0.4 to 3 mg/kg
•
Dose-limiting toxicity not reached at highest dose of 5 mg/kg
Body weight (kg)
<70 kg
70 kg
Roxadustat dose
70 mg
100 mg
Roxadustat dose
70 mg
32

China Opportunity
•
Unique Positioning as a Domestic
Chinese Company
•
CFDA Green Pass Status
•
AZ, Our Commercial Partner,
2nd Largest Multinational
Pharmaceutical Company by
Sales in  China
•
1st Phase 3 Results with
Roxadustat –
Potential 1st Launch
Country
•
Potential Entry into #2 Pharma
Market in the World
•
Platform for Rapid Entry into
China
–
Corneal
Implants
•
Mean Hb 9.1 Achieved
with Use of ESA
•
300,000-400,000 Patients,
Reaching Size of US
Dialysis Population
•
20% to 30% Annual
Growth in Dialysis Capacity
Since 2007 and Expected
to Continue Near Term
•
Growth Driven by Severe
Disease Reimbursement
Policy and Demographics
NON-DIALYSIS
DIALYSIS
DIALYSIS
STAGE 4 PRE-DIALYSIS
Dialysis Eligible Population,
1-2 million
Progression
to End Stage
Renal
Disease
•
Very Sick, Highly
Anemic, Dialysis Stage
Population
•
Very Limited ESA Use
Graphic not to scale
33

Corneal Implants –
FG-5200 (China)
Proprietary Recombinant
Human Type III Collagen
•
Integration of Implants with Host Tissue
•
Encourages Nerve Regeneration
•
Allows for Clearer Vision and No Rejection
Central corneal scar
covering entire pupil
Most of pupil
is blocked
URGENT,
SEVERE UNMET
MEDICAL NEED
•
Approximately 4 to 5 Million Patients with Corneal Blindness in China
•
100,000 New Cases per Year, Approx. 3,000 Corneal Implant Surgeries
•
Cadaver Transplants Very Limited by Cultural Restriction
PLATFORM TO
FOCUS ON
CHINA FIRST
•
FG-5200 Targets Patients Treatable with Partial Thickness Implants
•
60-month Proof of Concept Data with Prototype in 10 Patients in Sweden
•
Possibility to Address Major Unmet Need –
Science Translational Medicine
•
Opportunity to Expand Outside China
•
Plan to Meet with CFDA on Clinical Program
34
34

Roxadustat Global Partnerships
$ Millions
JAPAN,
EU, ETC.
U.S., CHINA,
ROW
CASH RECEIVED
TO DATE*
Equity Investment
in FibroGen
$81
$20
$101
Upfront,
Non-Contingent
$360
$402
$360 + $220
Development & Reg.
Milestones
$543
$571
$103+ $0
Commercial
Milestones
$15
$653
$0
POTENTIAL TOTAL
$918 M
$1,626 M
$683 M of $2,543 M
Low 20% (Astellas) –
Low-Mid 20% (AstraZeneca)
Net Sales Royalty / Transfer Price
FibroGen ex-China Costs Capped at $116.5 M
(Cost-Share < 50% of Planned CKD Anemia Development Costs)
Commercialization Costs Are Covered by Partners
in All Territories Ex-China
PAYMENTS TO
FIBROGEN
China
Partnership:
50% Profit Sharing
and 50%
Development and
Launch Cost
Responsibility
DEVELOPMENT
FUNDING
LAUNCH
FUNDING
* As of November 2014
35

FG-3019
Monoclonal Antibody to Connective Tissue Growth Factor (CTGF)
36

FG-3019 Improved Fibrosis in Mouse Model
and in Human Disease
Reversal of Lung Fibrosis by
High Resolution CT at Week 48
Subject
NORMAL
WEEK 18
Two Weeks of FG-3019
WEEKS 16
Pre-Treatment
Week Post-Irradiation
Radiation-Induced Mouse Lung Fibrosis
Phase 2A IPF Clinical Trial
Reversal of Fibrosis by Micro-CT Imaging
Reversal of Fibrosis by Histology
Improved / Stable Fibrosis Correlates
with Improved Lung Function
Improved/
Stable Fibrosis
Worse
Fibrosis
Improved/Stable
38
%
37
37

38
38
Relationship of 1-Year Survival to Dose
Percent 1 Year
Survival Rate
•
Dose-Related Increase in Survival
•
Day-15
Minimum
FG-3019
Plasma
Level
150
µg/mL
-
2x
Median Survival (9.4 vs. 4.8 Months) (p=0.025)
-
3x
One-Year Survival (37% v 11%) (p=0.01)
Phase 2 Dose-Dependent Survival in
Advanced Pancreatic Cancer
Relationship of Survival to FG-3019
Day-15 Plasma Levels
Percent Overall Survival
Overall Survival Time (Months)
FG-3019 Combined with Gemcitabine and Erlotinib (n=75)
22.5
35
45
25
15
10
3
17.5
KEY
FINDINGS
Weekly
mg/kg
Biweekly
mg/kg
FG-3019  >
150 µg/mL; n=38
FG-3019  < 150 µg/mL; n=37
p=0.025
0%
0%
10%
30%
30%
31%
31%
25%
0%
5%
10%
15%
20%
25%
30%
35%
5
10
15
20
25
30
35
40
45
0
20
40
60
80
100
0

Phase 2 Trials in IPF and
Pancreatic Cancer
•
Main goal: convert to operable state
•
40 patients to be enrolled, with potential to expand
•
Randomization 1:1 up to 6 months of
•
Endpoint: complete tumor removal
•
Currently enrolling
LOCALLY
ADVANCED
INOPERABLE
PANCREATIC
CANCER
•
Combination of FG-3019 and Chemotherapy
•
~240 patients
•
Randomization 1:1 , treat to progression
•
Endpoints: CA19.9, tumor response (PET & CT scans), disease control
•
Study design under development
METASTATIC
PANCREATIC
CANCER NOT
PREVIOUSLY
TREATED
•
Randomized placebo-controlled clinical trial
•
136 patients
•
Naïve; previously treated; pirfenidone / nintedanib failures
•
Key endpoints
–
Pulmonary function: change in FVC from baseline
–
Fibrosis by HRCT
•
Currently enrolling
IPF
39
–
FG-3019, gemcitabine, nab-paclitaxel
–
Gemcitabine and nab-paclitaxel
–
FG-3019, gemcitabine, nab-paclitaxel
–
Gemcitabine and nab-paclitaxel

Duchenne Muscular Dystrophy (DMD) and CTGF
Blockade
•
DMD –
rare hereditary disease: ~1 in 3,500 boys in the US
–
No FDA/EU approved treatment to date
–
Progressive muscle weakness and respiratory failure (age 5-18)
–
DMD leads to muscle fibrosis and loss of muscle function: muscles
replaced by fibrotic tissue in advanced disease
•
CTGF:
Directly
impacts
not
just
fibrosis
but
muscle
cell
phenotype
–
Strongly associated with fibrosis in skeletal muscle of human muscular
dystrophy (MD)
–
Strongly associated with fibrosis in heart of mouse (mdx) MD
–
Induces de-differentiation of skeletal muscle cells
–
Over-expression in normal mice transiently induces features of skeletal MD
–
Reducing CTGF reduces mdx mouse MD
1
Au
(2011);
Morales
(2011);
Morales
(2013);
Pessina
(2014);
Vial
et
al
(2008)
40
1

41
41
FG-3019 Decreased Fibrosis and Increased
Muscle Strength in mdx Mice
FG-3019 significantly reduced collagen
content/fibrosis in muscle (mdx mouse)
FG-3019 increased Isometric Force by 50%
(mdx mouse)

42
42
Decreased CTGF Increased Skeletal Muscle
Function in mdx Mice
CTGF hemi-zygous or FG-3019-treated mdx mice exhibited increased isometric force
WT-
wild type, normal mice;
mdx -
disease model

43
43
FG-3019 Increased Muscle Endurance in mdx Mice
5-min treadmill exercise tolerance test:
•
Morales, Hum Mol Genet-Suppl Data (2013)
mdx mice treated with FG-3019
stopped fewer times to rest than
untreated mice (mdx-control) and
were more similar to normal mice

44
44
Investment Highlights
IPF: idiopathic pulmonary fibrosis
DMD: Duchenne Muscular Dystrophy
•
Three broad technology platforms generating multiple product candidates
•
Roxadustat –
a novel oral treatment for anemia in Phase 3
•
Targeting the multi-billion dollar global anemia market
•
IP protection expected through 2033 and potentially beyond
•
>1400
subjects
evaluated
in
P1
+
P2;
P3
to
enroll
~
7500
to
8500
subjects
globally
•
Global collaborations: Astellas and AstraZeneca
•
$2.5 billion in potential payments ($683 million received through 9/30/14)
•
Plus royalties, transfer prices, and clinical development support
•
Regulatory filings anticipated 2016 (China), 2018 (US)
•
Funded through expected global commercialization
•
FG-3019 –
a novel anti-CTGF Ab for treating fibrotic disease
•
Phase 2 proof of concept established in IPF and pancreatic cancer
•
DMD clinical trial design reviewed by expert body of TREAT-NMD and pre-IND
activities underway
•
FG-5200 –
collagen type III replacement cornea & scaffold for corneal blindness
•
$343
M
-
$348
M
cash,
cash
equivalents,
investments,
receivables
as
of
12/31/14
(unaudited)
44
44
TREAT-NMD is an EU-based network aiming to advance treatments and care for patients with neuromuscular disease; TACT, the TREAT-NMD Advisory Committee for
Therapeutics, is an expert multidisciplinary body that provides the neuromuscular community with guidance on advancing new therapies for neuromuscular diseases

February 2015
Discussion Materials