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CAPITAL MARKET DAY
2018
RADISSON BLU, ZURICH AIRPORT
4 OCTOBER 2018
PRESENTATION
CREATING THE FUTURE
Etienne Jornod
Executive Chairman
CAPITAL
MARKET DAY
2018
© Vifor Pharma
MILESTONE 2020
WHAT IS NEXT?
WE ARE ON THE WAY
Central purchasing organisation
for pharmacists
Worldwide
pharmaceutical company
4 October 2018 3
© Vifor Pharma
WE ARE BUILDING A FAST GROWING COMPANY
3 DRIVERS WITH BLOCKBUSTER POTENTIAL
4
Ferinject® Exploit the potential
Veltassa® Drive to blockbuster
Vifor Fresenius Medical Care Renal Pharma Launch products and enhance value
4 October 2018
© Vifor Pharma
PHASE 1 PHASE 2 PHASE 3 COMMERCIAL PHASE 4
Vadadustat4)
Avacopan
CCX140
CR845
Ferroportin
inhibitor1)
AFFIRM-AHF
HEART-FID2)
Paediatric
AMBER
DIAMOND Anti-infectives
PIPELINE & LIFE CYCLE MANAGEMENT
DE-RISKED INVESTMENTS
20193)
2019
OW
N P
RO
DU
CT
S
IN-L
ICE
NS
ING
PR
OD
UC
TS
5 4 October 2018
1) Iron overload; leveraging iron metabolism expertise 2) Daiichi Sankyo clinical trial 3) Assumes CMA approval 4) U.S. Filing expected by the end of 2019
© Vifor Pharma
WE KNOW HOW TO CREATE A
NEW MARKET!
4 October 2018 6
FERINJECT®
4 October 2018
© Vifor Pharma
1) Excluding the market share of Vifor Pharma products (0.6%).
Source: IQVIATM MIDAS® Quarterly panel, GERS, Insight Health, DN, DLI, Q2-2018. Average 2017 exchange rates have been applied.
GLOBAL I.V. IRON IN-MARKET SALES
MAT Q2-19961)
4 October 2018 8
© Vifor Pharma
GLOBAL I.V. IRON IN-MARKET SALES
MAT Q2-2018
4 October 2018 9
Source: IQVIATM MIDAS® Quarterly panel, GERS, Insight Health, DN, DLI, Q2-2018. Average 2017 exchange rates have been applied.
VELTASSA®
4 October 2018
© Vifor Pharma
GLOBAL POTASSIUM BINDER IN-MARKET SALES
MAT Q2-20151)
4 October 2018 11
1) Excluding the market share of Sorbisterit (1.6%)
Source: IQVIATM MIDAS® Quarterly panel, GERS, Insight Health, DLI, Q2-2018. Average 2017 exchange rates have been applied.
© Vifor Pharma
GLOBAL POTASSIUM BINDER IN-MARKET SALES
MAT Q2-2018
4 October 2018 12
Source: IQVIATM MIDAS® Quarterly panel, GERS, Insight Health, DLI, Q2-2018. Average 2017 exchange rates have been applied.
© Vifor Pharma
GLOBAL I.V. IRON IN-MARKET SALES
MAT Q2 WORLDWIDE 1996
96 MILLION CHF
MAT Q2 WORLDWIDE 2018
1,698 MILLION CHF
VIFOR PHARMA
1,219 MILLION CHF
= 71.9%
4 October 2018 13
© Vifor Pharma
175 MILLION CHF
225 MILLION CHF
VIFOR PHARMA
63 MILLION CHF
= 28%
GLOBAL POTASSIUM BINDER MARKET
MAT Q2 WORLDWIDE 2015
MAT Q2 WORLDWIDE 2018
4 October 2018 14
VFMCRP
15
4 October 2018
© Vifor Pharma
THE JOINT COMPANY
UNIQUENESS OF THE BUSINESS MODEL
THIS IS WHAT DIFFERENTIATES VIFOR PHARMA
FROM A TYPICAL PHARMA COMPANY.
REGULATORY CLINICAL R&D MEDICAL
AFFAIRS
4 October 2018 16
DIRECT ACCESS
TO THE PATIENT COMMERCIAL
Vadadustat
Avacopan CCX140
CR845
PRODUCTION
© Vifor Pharma 17
1) Fresenius Kidney Care (FKC): Fresenius Medical Care North America dialysis provider organization
INCREDIBLE PENETRATION IN FKC CLINICS1)
AND OTHER CLIENTS
4 October 2018
FINANCIAL AND CAPITAL
MARKET CONSIDERATION
18
4 October 2018
© Vifor Pharma
4'540%
3'444%
2'657% 2'537%
2'236% 2'107% 2'022% 1'995%
1'060% 1'017%
Vifor Pharma AG LogitechInternational SA
Tecan Group AG Sika AG Kuehne + NagelInternational AG
Schindler HoldingAG
ChocoladefabrikenLindt & Spruengli
AG
Sonova HoldingAG
LEM Holding SA Cie FinanciereRichemont SA
VIFOR PHARMA VS. TOP SPI PERFORMERS
THE HIGHEST SHARE PRICE RETURN SINCE 1995
Source: Bloomberg
Note: share price increase from 01.09.1995 to 31.08.2018; excludes market capitalization below CHF 100m as of 01.09.1995.
4 October 2018 19
© Vifor Pharma
OBJECTIVE 2025
WE ARE CONFIDENT TO DELIVER ON “MILESTONE 2020”
THE OBJECTIVE 2025 IS TO CONTINUE
TO GROW AT ONE OF THE FASTEST RATES IN
THE PHARMACEUTICAL INDUSTRY…
• NET SALES
• EBITDA
• NET PROFIT
«WE HAVE BEEN GROWING
EVERY YEAR
FOR 22 YEARS1)!»
1) Net profit before minorities, excluding non-cash one off effects and launch and ramp-up costs of Veltassa® in 2016 and 2017
4 October 2018 20
STRATEGY 2025
Stefan Schulze
President of the Executive Committee & COO
CAPITAL
MARKET DAY
2018
© Vifor Pharma 4 October 2018 22
STRATEGY 2025
EXPLOIT OUR COMPETITIVE ADVANTAGES
EXISTING GROWTH DRIVERS
Ferinject® – Exploit the potential
Veltassa® – Drive to blockbuster
VFMCRP – Launch products and enhance value
© Vifor Pharma 4 October 2018 23
FERINJECT® / INJECTAFER
®
EXPLOIT THE POTENTIAL
2019 2025
HEART-FID
completion U.S. Post-approval study
FAIR-HF2
completion Post-approval study
China launch
2021
AFFIRM-AHF
completion Post-approval study
EU guidelines1)
update based on
AFFIRM AHF
U.S. guidelines1)
update based on
HEART-FID
1) Targeted guidelines:
Focus on cardiology, patient blood management, nephrology and gastroenterology
> CHF 2 billion
in-market sales
potential
Japan launch
H2 2019
U.S. label
update
© Vifor Pharma
PATIENT BLOOD MANAGEMENT (PBM) – EU51)
4 October 2018 24
COMMENTS
• Patient focused approach to
blood management
• Medical benefit: i.v. iron
improves outcomes, including
mortality
• Economic benefit: reduction in
length of hospitalisation and
blood transfusion
• In-market sales opportunity of
> CHF 200m in EU5
IRON DEFICIENCY
SIGNIFICANT PBM OPPORTUNITIES
1) France, Germany, Italy, Spain and UK
Not treated Other i.v. iron Ferinject®
1’160K
96K
109K
1’365K1
With iron deficiency
© Vifor Pharma
FERINJECT® IN-MARKET SALES
4 October 2018 25
A LEADING PRODUCT
• Most extensive clinical evidence
with 28 published RCTs1) and
7’034 patients treated in RCTs
• More than 8 million
patient-years experience2)
• Unique non-dextran-based
carboxymaltose shell
• Only high-dose i.v. iron to
demonstrate efficient iron
utilization in the body3)
LIFE CYCLE MANAGEMENT
SUPPORTING FUTURE GROWTH
1) Randomized clinical trials 2) Vifor Pharma analysis as of August 2018 3) Beshara, S et al. Br J Haematol 2003; 120:853-9
Europe U.S. ROW
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025
© Vifor Pharma 4 October 2018 26
VELTASSA®
DRIVE TO BLOCKBUSTER STATUS
2019 2025
DIAMOND
completion Post-approval study
AMBER
completion Post-approval study
Label updates based on
DIAMOND results
Blockbuster
status
Guideline1)
updates based on
AMBER results
Guideline1)
updates based on
DIAMOND results
1) Targeted guidelines:
European rollout
Japan launch
Zeria
© Vifor Pharma
U.S. – 3.0 MILLION PATIENTS
Total population: 327 million
4 October 2018 27
EU5 – 3.1 MILLION PATIENTS
Total population: 320 million
JAPAN – 1.3 MILLION PATIENTS
Total population: 127 million
HYPERKALEMIA MARKET OPPORTUNITY
BUILD MARKET AWARENESS
Source: Saito Y et al. PLoS ONE 12 (9): e0184402.. 2008 ESC Heart
Failure 2016; 3: 145–151
Source: from House AJKD Vol 72 | Iss 2 | August 2018 . De Nicola et
al Nephrol Dial Transplant (2016) 31: 335–336
Source: USRDS 2013 ADR, CDC
10.7
4.7
2.3 1.7
0.8 0.5
0
2
4
6
8
10
12
CKD 3-4 only CKD 3-4 with HF HF only
Total prevalence With hyperkalemia
11.5
4.8
2.4 1.8
0.8 0.5
0
2
4
6
8
10
12
14
CKD 3-4 only CKD 3-4 with HF HF only
Total prevalence With hyperkalemia
10.3
0.5 0.8 1.1
0.1 0.1 0
2
4
6
8
10
12
CKD 3-4 only CKD 3-4 with HF HF only
Total prevalence With hyperkalemia
© Vifor Pharma
RESULTS EXPECTED
CLINICAL OBJECTIVES
STUDY
4 October 2018 28
LIFE CYCLE MANAGEMENT
UNLOCK FULL POTENTIAL WITH CLINICAL DATA
Strengthen evidence
of RAASi enabling
Beneficial effect on
blood pressure
AMBER DIAMOND
Beneficial effect on
morbidity and mortality
STRATEGIC OBJECTIVES Guideline updates U.S. label change &
guideline updates
H1 2019 2022
© Vifor Pharma
EXPECTED GLOBAL MARKET EVOLUTION FOR PHARMACEUTICALS IN NEPHROLOGY
4 October 2018 29
PRESENCE IN NEPHROLOGY
BECOME A GLOBAL LEADER IN A FAST-GROWING MARKET
Source: EvaluatePharma 2017-22 CAGR of 10.3%, 2022-25 CAGR assumed unchanged, Vifor Pharma analysis
2.7%
2017
~$20bn >$40bn
2025
VFMCRP current market share
Rest of the nephrology market
© Vifor Pharma 4 October 2018 30
1) Assumes Conditional Marketing Authorization approval
VFMCRP
BECOME AN INNOVATION LAUNCH ENGINE
2019 2025
RetacritTM
launch
Avacopan
launch1)
Additional launches in
nephrology
Vadadustat
launch
CR845
launch
CCX140
launch
CCX140 / FSGS Phase II trial
completion
CR845 / Uremic Pruritus Phase III trial completion
Avacopan / C3G Phase II trial
completion
Avacopan / ANCA AV Phase III trial
completion
Vadadustat Phase III trials
completion
Rayaldee®
launch
> CHF 1bn
reported sales
© Vifor Pharma
CURRENT INDICATIONS
4 October 2018 31
NEPHROLOGY
NUMEROUS OPPORTUNITIES REMAIN
Polycystic kidney disease
Metabolic acidosis
Vascular calcification
Kidney stones
Hypernatremia
Fabry
aHUS
Diabetic nephropathy
Acute kidney injury
β-Thalassemia renal disease
FSGS
ANCA associated vasculitis
Uremic pruritus
C3G
Secondary hyperparathyroidism Hyperphosphatemia
Hyperkalemia
Anaemia
Iron deficiency
PIPELINE INDICATIONS POTENTIAL INDICATIONS
© Vifor Pharma
COMMERCIAL
4 October 2018 32
NEPHROLOGY
LEADERSHIP ON THE WHOLE NEPHROLOGY CHAIN
CLINICAL PRE-COMMERCIAL
IN-LICENSING DEALS AND PARTNERSHIPS
Avacopan
Vadadustat CR845
CCX140
PRE DIALYSIS DIALYSIS
COMMERCIAL
PRE CLINICAL
DA
TA
GE
NE
RA
TIO
N
PARTNERSHIP
TRANSPLANTATION
COMMERCIAL
© Vifor Pharma 4 October 2018 33
STRATEGY 2025
EXPLOIT OUR COMPETITIVE ADVANTAGES
1) Therapeutic areas
EXISTING GROWTH DRIVERS
Ferinject® – Exploit the potential
Veltassa® – Drive to blockbuster
VFMCRP – Launch products and enhance value
Licensing/acquisition across geographies & TAs1):
• Nephrology & Cardio-renal
• Gastroenterology
• Patient Blood Management
INORGANIC GROWTH – ADJACENT INDICATIONS
• Leverage U.S. commercial infrastructure
• Become EU partner of choice for non-European growth
companies
EXISTING INFRASTRUCTURE
• Exploit data & pay-for-performance (anaemia and
bone-mineral metabolism management, etc.)
• Replicate VFMCRP structure in other therapeutic areas
• Ferroportin inhibitor
NEW TECHNOLOGIES AND BUSINESS AREAS
© Vifor Pharma
FERROPORTIN
INHIBITOR
4 October 2018 34
© Vifor Pharma
• Diagnosis soon after birth
• Death at around 5 year old if left
untreated
• Approximately 13 to 15 million
patients worldwide
4 October 2018 35
• Bi-weekly blood transfusions
associated to unwanted iron load,
treated with iron chelators
• Iron chelators therapy bound with
potentially fatal chelator-
associated toxicities
• Current chelator market size of
approximately USD 1 billion,
expected to double by 2022
• VIT-2763 binding to ferroportin
expected to prevent excessive
iron release
• Iron transporter ferroportin key in
regulating and controlling iron
level in the blood
• Clinical Phase I started in March,
results expected at the end of
2018
FERROPORTIN INHIBITOR VIT-2763
HIGH UNMET NEED IN BETA-THALASSEMIA MAJOR
BETA-THALASSEMIA MAJOR CURRENT TREATMENT NEW APPROACH – VIT-2763
© Vifor Pharma
2018 2027
4 October 2018
FERROPORTIN INHIBITOR VIT-2763
EXPECTED DEVELOPMENT TIMELINE
2023 2019 2020 2021 2022 2024 2025 2026
Filing
Launch
Phase III Phase II Phase I
36
Part I – Ferinject®
FERINJECT®
EXPLOITING THE POTENTIAL
Dario Eklund
Chief Commercial Officer
CAPITAL
MARKET DAY
2018
© Vifor Pharma
GLOBAL I.V. IRON MARKET (MAT Q2 2018)1)
• Market totalled CHF 1’698 million, +15% versus prior year period
• Ferinject® growth represented 88% of the total market growth, with +32% versus prior year period
• Global market share of Ferinject® in value is 47% (54% in our top 10 markets)
16 38 58 81 123 163
240
374
535
692
850-880
4 October 2018 39
MAT = Moving annual total 1) Based on Quarterly IQVIATM MIDAS® panel, GERS, Insight Health, DLI, historical data at constant exchange rate (average 2017) 2) Estimate based on IQVIATM
FERINJECT®
BLOCKBUSTER BY 2020
Europe U.S. ROW
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018E2)
IN-MARKET SALES1)
CHF MILLION
© Vifor Pharma
Switzerland
Australia
New Zealand
Sweden
Germany
Spain
France
UK
Italy
U.S.
Japan
China
5%
33%
47%
16%
16%
39%
16%
22%
53%
45%
0%
0%
40
Source: Quarterly IQVIATM MIDAS® panel, GERS, Insight Health
Launch Date
2008
2011
2012
2008
2007
2009
2011
2008
2012
2013
2019
2021
FERINJECT®
SIGNIFICANT MARKET OPPORTUNITY REMAINS
4 October 2018
Ferinject® Volume Per Capita (MAT Q2 2018) 100 mg eq./1’000 population
Ferinject® In-Market Volume Growth (MAT Q2 2017-18)
253
107
51
36
34
29
22
22
22
12
0
0
© Vifor Pharma 4 October 2018
FERINJECT®
THE BLOCKBUSTER PLAN
41
Therapeutic
areas
• Heart Failure
• Patient Blood Management
• Nephrology
• Gastroenterology
Strong
partnerships
• Partnering with leading
companies
Geographic
expansion
• Japan
• China
• Key pharmerging markets
Life Cycle
Management
• AFFIRM-AHF
• HEART-FID1)
1) Daiichi Sankyo clinical trial
Therapeutic area focus
© Vifor Pharma
PATIENT DROP-OFF - EU5
4 October 2018 43
1) IRONOUT HF trial, JAMA. 2017;317(19):1958-1966
Source: CapSys patient drop-off analysis, April 2018, Countries included: DE, ES, FR, IT, UK
CHRONIC HEART FAILURE
HUGE OPPORTUNITY REMAINS
1
Not treated Oral iron Other i.v. iron Ferinject®
1’415K
386K 47K
84K
1’932K
With iron deficiency
Ferinject® addresses only
4% of all patients
Further generate and exploit
clinical data
Fastest growing indication in
Europe
Oral iron ineffective1)
Sales opportunity of
> CHF 450m
© Vifor Pharma
Ferinject® addresses only
8% of all patients
Medical benefits for the
patients
Economic benefits for the
providers
Sales opportunity of
> CHF 200m
PATIENT DROP-OFF - EU5
4 October 2018 44
Source: Vifor Pharma analysis, Q1 2018, Countries included: DE, ES, FR, IT, UK
PATIENT BLOOD MANAGEMENT
OVER 1 MILLION PATIENTS OPPORTUNITY
1
Not treated Other i.v. iron Ferinject®
1’160K
96K 109K
1’365K
With iron deficiency
© Vifor Pharma
STUDIES SHOW CONTRIBUTION TO IMPROVED OUTCOMES1)
4 October 2018 45
PATIENT BLOOD MANAGEMENT
ECONOMIC BENEFIT
1) Froessler B et al, Ann Surg. 2016 Jul;264(1):41-6; German costs data
1
Transfusions
EUR 76 Savings per patient
Hospital stay
EUR 1’050 Savings per patient
Iron therapy
EUR 340 Cost per patient
-
Strong partnerships
© Vifor Pharma 47
• 20+ year partnership with Daiichi
Sankyo
• Injectafer® high dose segment
sales leader
• 44.5% MAT1) Q2 2018 growth
of Injectafer® in local currency
• 2025 goal: blockbuster franchise
in the U.S. with Venofer® and
Injectafer®
U.S. I.V. IRON MARKET
GROWTH DRIVEN BY INJECTAFER®
Source: IQVIATM NPA Audit from 2013 to 2018 1) Moving annual total
4 October 2018
U.S. I.V. IN-MARKET SALES
$169 $184 $188 $195 $208 $214
$324 $318 $324 $322 $321 $320
$0 $24 $89
$181 $252
$364
0
250
500
750
1'000
MAT Q2-2013 MAT Q2-2014 MAT Q2-2015 MAT Q2-2016 MAT Q2-2017 MAT Q2-2018
Mil
lio
ns
Other i.v. irons Venofer Ferinject ® ®
US
D m
illio
n
Injectafer®
© Vifor Pharma 4 October 2018 48
1) 3 months rolling share 2) Including low dose i.v. iron
Source: IQVIATM, volume in 100mg equivalents, data as of 09.2018
DAIICHI-SANKYO PARTNERSHIP
STRONG SUPPORT TO INJECTAFER® GROWTH
• Injectafer® is the fastest growing
i.v. iron in the U.S. market
• Injectafer® has gained volume
share from Feraheme® and
INFeD®
• INFeD® product shortage in Q2
2018
HIGH DOSE U.S. I.V. IRON PRODUCTS VOLUME SHARE
Vo
lum
e s
hare
1)
0%
10%
20%
30%
40%
50%
60%
70%
201
5-0
3
201
5-0
4
201
5-0
5
201
5-0
6
201
5-0
7
201
5-0
8
201
5-0
9
201
5-1
0
201
5-1
1
201
5-1
2
201
6-0
1
201
6-0
2
201
6-0
3
201
6-0
4
201
6-0
5
201
6-0
6
201
6-0
7
201
6-0
8
201
6-0
9
201
6-1
0
201
6-1
1
201
6-1
2
201
7-0
1
201
7-0
2
201
7-0
3
201
7-0
4
201
7-0
5
201
7-0
6
201
7-0
7
201
7-0
8
201
7-0
9
201
7-1
0
201
7-1
1
201
7-1
2
201
8-0
1
201
8-0
2
201
8-0
3
201
8-0
4
201
8-0
5
201
8-0
6
201
8-0
7
INFeD®
Shortage
Injectafer®
Feraheme®
INFeD®
Injectafer®2) January
2017
July
2018
Value share 29.5% 44.6%
Volume share 10.5% 20.5%
© Vifor Pharma 4 October 2018 49
MAT = Moving annual total
Source: IQVIATM, U.S. claims data from 09.2018
SOURCE OF GROWTH IN THE U.S.
INJECTAFER® EXPANDING IN ALL THERAPEUTIC AREAS
VOLUME PER THERAPEUTIC AREA
Gastroenterology Hematology / Oncology Nephrology Ob / Gynecology Cardiology
0
100
200
300
400
500
600
700
800
MAT Q2 2017 MAT Q2 2018
Vo
lum
e in
th
ou
san
d 1
00m
g e
qu
ivale
nts
+57%
+38%
+41%
+74% +70%
© Vifor Pharma 4 October 2018 50
INJECTAFER® AND VENOFER
®
BUILD A U.S. BLOCKBUSTER FRANCHISE
Maintain Venofer® leadership in dialysis and hospital
Strengthen Injectafer® market share leadership with hematology and oncology
specialists
Expand Injectafer® use with gastroenterology, cardiology, ob / gyn and
nephrology specialists
Execute clinical studies to create future growth opportunities
1
4
3
2
Geographic expansion
© Vifor Pharma 4 October 2018 52
1) Below 14ng/mL: National Health/Nutrition Survey conducted in 2009 in Japan (based on publication dated 23 July 2018)
FERINJECT® IN JAPAN
THE NEXT MAJOR LAUNCH
2018 2019
Expected launch by
Zeria Pharmaceuticals
Market access negotiation
in preparation
Two phase III clinical
trials completed
Ferinject® will have IDA label
(excluding dialysis)
Significant unmet patient needs in
Women’s Health and
Gastroenterology
Oral market
Only one i.v. low dose drug
Approx. 50% of women below 50
years old have low ferritin levels1)
Build awareness around high-dose
i.v. iron as the new standard therapy
Market access / pricing
MARKET OPPORTUNITIES CHALLENGES
© Vifor Pharma 4 October 2018 53
1) Based on Quarterly IQVIATM MIDAS® panel, GERS, Insight Health, DLI 2) Southeast Asian J Trop Med Publi Health 2015 46(2) 306-21 3) As per Vifor Pharma internal research
FERINJECT® IN CHINA
SIGNIFICANT OPPORTUNITY IN PBM
2018 2019 2021 2020
Phase III clinical
trial initiation
Partner
selection
Phase III clinical
trial readout
Expected
launch
Significant medical unmet need
in patient blood management
~3-5 Mio patients per year with
IDA undergoing elective surgery3)
Second largest iron market globally
~ USD 200m1)
Estimated anaemia prevalence in
central and eastern China2) is
13.4% (so up to 180 Mio people)
Very competitive market
Fast changing environment
2017
MARKET OPPORTUNITIES CHALLENGES
Life cycle management
© Vifor Pharma 55
COMPREHENSIVE CLINICAL DATA GENERATION
CONTINUED FOCUS ON KEY DISEASE AREAS
Source: Vifor Pharma
> CHF 300m
invested so far in company-
sponsored trials
Two major heart failure trials
with > 4,000 enrolled patients
on-going
Additional 45 interventional
clinical studies completed
& 11 on-going
4 October 2018
FERINJECT®
SERVING HEART FAILURE PATIENTS
Antonio Jordao
Regional Head Southern Europe
CAPITAL
MARKET DAY
2018
© Vifor Pharma
PATIENT DROP-OFF EU5
1’932K
4 October 2018 57
Source: CapSys patient drop-off analysis, April 2018, countries included: DE, ES, FR, IT, UK
IRON DEFICIENCY IN CHRONIC HEART FAILURE
MAJORITY OF PATIENTS ARE LEFT UNTREATED
Not treated Oral iron Other i.v. iron Ferinject® With iron deficiency
1’415K
386K 47K
84K
© Vifor Pharma
INCREASED MORTALITY2)-5)
4 October 2018 58
OTHER CONSIDERATIONS
• Up to 50% of patients with chronic
heart failure are iron deficient3)
• Iron deficiency in chronic heart failure
is associated with:
o Reduced quality of life1)6)7)
o Increased risk of hospitalisation2)
IRON DEFICIENCY IN CHRONIC HEART FAILURE
POOR OUTCOMES FOR THE PATIENTS
1) Enjuanes C et al. Int J cardiol 2014;174:268-75. 2) Martens P et al. Acta Cardiol 2018;73(2):115-23. 3) Klip IT et al. Am Heart J 2013;165(4):575-82. 4) Jankowska EA et al. Eur Heart J 2010;31:1872-80. 5) Yeo JT et al.
Eur J Heart Fail 2014;16:1125-32. 6) Wienbergen H et al. Am J Cardiol 2016;118(12):1875-80. 7) Comin-Colet J et al. Eur J Heart Fail 2013;15(10):1164-72.
100
80
60
40
20
0
0 1 2 3 4 5 6 7 8
Patients without iron deficiency
Patients with iron deficiency
P = 0.001
Time in study (years)
Cum
ula
tive s
urv
ival (%
)
Numbers at risk
Iron deficiency absent: Iron deficiency present:
753
753
386
343
104
100
63
49
40
33
© Vifor Pharma
META-ANALYSIS – PATIENTS WITH EVENT
INCIDENCE PER 100 PATIENT-YEARS AT RISK
OBSERVATIONS
• Improves heart failure symptoms2)-4)
• Improves quality of life and exercise
capacity2)-4)
• Significant risk reduction in chronic
heart failure hospitalisations
4 October 2018 59
1) Anker SD et al. Eur J Heart Fail 2018;20(1):125-33 2) Ponikowski P et al. Eur Heart J 2016;37:2129-200. 3) Ponikowski P et al. Eur J Heart J 2015;36:657-68. 4) Anker SD et al. NEJM 2009;361:2436–48.
FERINJECT® USE IN CHRONIC HEART FAILURE
CLEAR CLINICAL BENEFITS TO PATIENTS
20
15
10
5
0 Placebo
34 (15.1)
Ferinject®
19 (6.3)
58%
hazard ratio
reduction1)
© Vifor Pharma
4 October 2018 60
FERINJECT® EXPANSION IN CARDIOLOGY
THE SPANISH APPROACH
Awareness campaign
Education on diagnosis
and appropriate treatment
Focus on Ferinject®
differentiation
2014 – 2015
2015 – 2016
2017 onwards
© Vifor Pharma
IN-MARKET SALES IN CARDIOLOGY IN SPAIN
96
207
360
0
50
100
150
200
250
300
350
400
450
MAT Q2-2016 MAT Q2-2017 MAT Q2-2018
Ferinject Venofer Other IV Iron
4 October 2018 61
FERINJECT® EXPANSION IN CARDIOLOGY
SUCCESSFUL APPROACH IN SPAIN
Source: Farma&Cia, Q2-2018, Vifor Pharma Data Analytics
Ferinject® CAGR
94%
® ® Other i.v. irons
Vo
lum
e in
th
ou
san
d 1
00m
g e
qu
ivale
nts
© Vifor Pharma 4 October 2018 62
Source: CHF Psychodrama Market Research, K&A Brand Research, November 2017
FERINJECT® EXPANSION IN CARDIOLOGY
SPAIN AS A MODEL TO UNLOCK POTENTIAL IN EUROPE
Iron Deficiency Awareness Ferinject® Differentiation
Fe Ferinject®
Diagnosis and Treatment
Fe
50% prevalence of iron deficiency in
chronic heart failure patients
Focus on important heart-related
issues; iron deficiency perceived
as harmless by Cardiologists
Oral iron as easy and convenient
choice, even if ineffective
in chronic heart failure patients
© Vifor Pharma
IMPORTANCE OF IRON IN HEART FAILURE
IRON DEFICIENCY AWARENESS
COMMERCIAL PROGRAM ROLLED OUT IN Q2 2018
4 October 2018 63
1) Hoes MF et al. Eur J Heart Fail 2018;20(5):910-19
IRON DEFICIENCY IMPAIRS CONTRACTILITY
OF HUMAN CARDIOMYOCYTES1)
Normal Cardiomyocytes
(in vitro)
Iron-deficient cardiomyocytes
(in vitro)
© Vifor Pharma
Continuous online medical education on iron deficiency
4 October 2018 64
Integrated promotional program through digital channels
DIAGNOSIS AND TREATMENT
TARGETED INITIATIVES STARTED IN MAY 2018 IN EUROPE
MEDICAL EDUCATION DIGITAL AMPLIFICATION
7’500
Cardiologists
2018E
15’000
Cardiologists
2019E
8’500
Cardiologists
17’000
Cardiologists
2018E 2019E
© Vifor Pharma
EFFICACY-HF
CURRENT EVIDENCE GENERATING NEW EVIDENCE
4 October 2018 65
FERINJECT® DIFFERENTIATION
GENERATING EVIDENCE OF UNIQUE BENEFIT
INCREASED
QUALITY OF LIFE
IMPROVED
EXERCISE CAPACITY
REDUCED RATE OF
HOSPITALISATION
DECREASE IN
MORBIDITY
DECREASE IN
MORTALITY
BENEFIT IN ACUTE
HEART FAILURE
FAIR-HF
CONFIRM-HF AFFIRM-AHF
HEART-FID
FAIR-HF2
EFFECT-HF FAIR-HFpEF
© Vifor Pharma
IN-MARKET SALES IN CARDIOLOGY IN EU51)
239
467
740
0
200
400
600
800
1'000
1'200
MAT Q2-2016 MAT Q2-2017 MAT Q2-2018
Ferinject Venofer Other IV Iron
NEXT STEPS
• Awareness campaign rolled out
in Q3 2018
• Medical education and digital
amplification programs to accelerate
diagnosis and treatment
• Further strengthen guidelines with
clinical trials
4 October 2018 66
FERINJECT® DRIVING GROWTH IN CARDIOLOGY
EARLY STAGE OF A SUCCESS STORY IN EUROPE
1) France, Germany, Italy, Spain and UK
Source: Farma&Cia, Q2-2018, Vifor Pharma Data Analytics
Ferinject® CAGR
76%
® ® Other i.v. irons
Vo
lum
e in
th
ou
san
d 1
00m
g e
qu
ivale
nts
Professor Aryeh Shander
Emeritus Chair, Department of Anesthesiology, Critical Care Medicine, Hyperbaric Medicine and Pain Mngmt, Englewood Hospital, NJ, USA
Adjunct Clinical Professor, Department of Anesthesiology, Medicine and Surgery at Icahn School of Medicine at Mount Sinai, NY, USA
Clinical Professor, Department of Anesthesiology, Rutgers New Jersey Medical School, NJ, USA
PBM – A CALL FOR ACTION TO
IMPROVE PATIENT OUTCOMES
67
• PBM extends to all patient populations
• PBM offers appropriate therapy for a disease or condition
• Anaemia management is central to PBM
• Modifiable risk factor
• PBM is based on improving patient outcomes
• All consistent with “Clinical Care” and “Good Clinical Practice”
68
WHY PATIENT BLOOD MANAGEMENT?
TRANSFUSION IS THE ‘DEFAULT’ TREATMENT FOR
ALL ANEMIC PATIENTS
One treatment for all patients
One size (does not) fit all
Transfusions are associated with worse clinical outcomes
High risk with low benefit
Expensive therapy with low benefit = poor efficacy
Cure vs. Treatment
Transfusion a short term therapy
I.v. iron – a cure!
69
248 203 192 149
1'183
726 606
507
3'514
2'694 2'579
2'070
0
500
1'000
1'500
2'000
2'500
3'000
3'500
4'000
EHMC RIH CHUV AKH Linz
US
D
Mean RBC product cost Mean cost per RBC txn Mean txn cost per surgical pt txed
70
AKH Linz, General hospital Linz; CHUV, Centre Hospitalier Universitaire Vaudois; EHMC, Englewood Hospital and
Medical Center; pt, patient; RIH, Rhode Island Hospital; txed, transfused; txn, transfusion
ACTIVITY-BASED COST OF TRANSFUSION
FROM A PROVIDER’S PERSPECTIVE
Shander A et al. Transfusion 2010;50:753–65
Anthes E. Evidence-based medicine: Save blood, save lives. Nature. 2015;520(7545):24-6.
«TRANSFUSION ARE ONE OF THE MOST OVERUSED TREATMENTS
IN MODERN MEDICINE AT A COST OF BILLIONS OF DOLLARS»
71
Johns Hopkins Health System PBM Program across five hospitals
Approximately 400% return on investment for PBM efforts (alone with blood product cost savings)
72
Frank SM et al. Anesthesiology 2017;127:754–64
POSITIVE IMPACT OF PBM IMPLEMENTATION
ON HOSPITAL COSTS
• Across the entire health system changes in
utilization (number of units per 1000 patients) are
shown over time
• Financial results
o $2,120,273 blood acquisition cost savings
o Reductions in transfused units per 1000 patients
– RBCs 455 to 365 ( 19.8%; P<0.0001)
Blo
od u
tilis
ation
(units/1
000 p
atients
)
500
400
300
200
100
0
RBCs
2014
2015
2016
2017
A CALL FOR ACTION
TIME TO LOOK BEYOND TRANSFUSION
73
Management of Iron
Deficiency Anaemia
Managing the patient‘s own blood
to correct anaemia and improve care
Resorting to donor blood
to correct hemoglobin values
Patient Focus
• Physician driven
• Evidence based
• Outcome driven
• Quality of care
• Patient safety
Product Focus
• Manufacturer driven
• Behavior based
• Revenue & profit
• Growth
• Product safety
Model of
CARE
BUSINESS
Model
74
Menitove J. Hematologist 2018;15(3)
THE WORLD IS CHANGING!
… due to patient
blood management!
RB
Cs u
nits,
mill
ions
18
1992
17
16
15
14
13
12
11
1994 1997 1999 2001 2004 2006 2008 2011 2013 2015
RBCs distributed RBCs transfused
75
“Is the scientific use of safe and effective
medical and surgical techniques designed
to prevent anaemia and decrease bleeding
in an effort to improve patient outcome”
“
”
PATIENT BLOOD MANAGEMENT
Patient and medical condition (disease) focused
76 Hofmann A. Oncologist 2011;16 Suppl 3:3-11; Spahn DR, Goodnough LT. Lancet 2013;381:1855–65; Isbister JP. Best Pract Clin Anaesthesiol 2013;27:69–84; Goodnough LT, Shander A. Anesthesiology 2012;116:1367–76
THE ANSWER: 3 PILLARS CONCEPT OF PBM!
Optimise red cell
mass
Minimise
blood loss &
bleeding
Optimise
reserve of
anaemia
Anemia
ID
Blood Loss
&
Bleeding
Transfusion
3. Optimise anaemia tolerance 2. Minimise Blood Loss 1. Optimise RBC Mass
Sixty-third World Health Assembly
Date: 17-21 May 2010
Location: Geneva, Switzerland
WHA63.12 adopted by resolution May 21, 2010:
„Bearing in mind that patient blood management means that before surgery every
reasonable measure should be taken to optimize the patient’s own blood volume, to
minimize the patient’s blood loss and to harness and optimize the patient-specific
physiological tolerance of anaemia following WHO’s guide for optimal clinical use
(three pillars of patient blood management)“
© Vifor Pharma
GBD 2013 Mortality and Causes of Death Collaborators. Lancet 2015;385:117–171
1990 2013 1990 2013 Year Males Females
0.0
0.1
0.2
0.3
Pre
vale
nce (
pro
port
ion)
Malaria
Hookworm disease
Schistosomiasis
Other infectious diseases
Other neglected tropical diseases
Maternal haemorrhage
Uterine fibroids
Other gynaecological diseases
Sickle cell disorders
Thalassaemias
G6PD deficiency
Other haemoglobinopathies and haemolytic
anaemias
Iron-deficiency anaemia
Other endocrine, nutritional, blood and
immune disorders
Gastritis and duodenitis
Peptic ulcer disease
Chronic kidney disease (due to
diabetes mellitus)
Chronic kidney disease (due to
hypertension)
Chronic kidney disease (unspecified)
THE GLOBAL BURDEN OF ANAEMIA
In 2010, 68.36m YLD or
8.8% of all conditions were
attributable to anaemia
4 October 2018 77
© Vifor Pharma
Up to 28 Million
anemic surgical patients
78
4 October 2018
ESTIMATION OF GLOBAL VOLUME OF SURGERY
Source: Thomas G Weiser, Scott E Regenbogen, Katherine D Thompson, Alex B Haynes, Stuart R Lipsitz, William R Berry, Atul A Gawande
Fowler A.J. et al. Br J Surg (2015) 102: 1314
949’449 patients of 24 studies analyzed
39% of patients were anemic (WHO definition)
Anaemia was associated with Perioperative mortality - Odd Ratio (OR) 2.90 (2.30 – 3.68, p< 0.001) Acute kidney injury - OR 3.75 (2.95 – 4.76, p< 0.001) Infections - OR 1.93 (1.06 – 1.55, p< 0.01) Stroke in cardiac surgery - OR 1.28 (1.17 – 3.18, p< 0.01) RBC transfusion - OR 5.04 (4.12 – 6.17, p< 0.001)
META-ANALYSIS OF THE ASSOCIATION BETWEEN
PREOPERATIVE ANAEMIA AND MORTALITY AFTER SURGERY
Systematic review
79
48
5
50
8
37
5
11
36
21
3
27
4
76
4
60
7
79
4
46
2
83
4
10
43
44
8
19
8
0
1
2
3
4
5
6
0
200
400
600
800
1000
1200
# o
f ca
se
s
OMR
n = 8108
NJ OMR - 2.89 %
3.54
1.51
1.23
PBM
COMPARING CORONARY MORTALITY RATES
80
Observed
Mortality
THE BENEFIT OF PBM AND OPTIMAL ANAEMIA TREATMENT
EXAMPLE OF A STATE-WIDE PBM IMPLEMENTATION
81
Leahy MF et al. Transfusion 2017;57:1347-58
Clinical results/patient outcomes:
• In-hospital mortality 28%
• Length of hospital stay 15%
• Infection 21%
• Stroke 31%
Financial results over 6 years:
• $18’500,000 blood acquisition cost savings
• $80’000’000 to 100’000’000 activity-based cost
savings
Key measures indicators:
• Proportion admitted anaemic decreased from 20.8% to
14.4% (P=0.001)
• 41% reduction in blood product usage (P<0.001)
Improving outcomes while saving costs :
PBM in all emergency and elective medical and surgical patients in four tertiary hospitals in Western Australia
n=605,046
REVIEW ARTICLE
Improving outcome of
trauma patients by
implementing patient
blood management Füllenbach C, Zacharowski K, and
Meybohm P
Curr Opin
Anaesthesiol. 2017,
30 (2):243-249
EDITORIAL
Promoting Safety,
Quality, and Value
through Patient
Blood Management Waters MD
Anesthesiology 2017,
127(5):738-740
REVIEW ARTICLE
Patient Blood
Management Equals
Patient Safety Zacharowski K. Spahn, DR
Anesthesiology 2016,
30(2):159-169
82
SPECIAL
COMMUNICATION
Promoting High-Value
Practice by Reducing
Unnecessary
Transfusions with a
Patient Blood
Management Program Sadana D, Pratzer A, Sher LJ, Saag
HS, Adler N, Volpicelli FM, Auron M,
Frank SM
JAMA Intern Med.
2018, 178(1):116-122
• Addresses the high prevalence of anaemia
• Identifies Iron Deficiency Anaemia (IDA) as number one condition
• Strongly recommends the treatment with i.v. iron
• Oral iron ineffective in this population
CONSENSUS STATEMENT
International Consensus Statement on the Peri-Operative management od Anaemia and
Iron Deficiency
Munoz M et al
Anaesthesia. 2017, 72(2):233-247
83
OPTIMAL ANAEMIA TREATMENT AND
THE BENEFIT OF PATIENT BLOOD MANAGEMENT
84 Source: references added in the notes
Pre-operative iron deficiency anaemia treatment
> 700 patients treated with Ferinject®
Post-operative iron deficiency anaemia treatment
> 500 patients treated with Ferinject®
Iron deficiency anaemia treatment in the intensive care unit
> 100 patients treated with Ferinject®
Key findings
Reduction of transfusion rate
Increase of Hb and iron store levels
Reduction of length of stay
Reduction of infection rates
Well tolerated treatment
Treatment of perioperative IDA with Ferinject® has been studied in 16 major studies with more than
1’300 patients, incl. RCTs, single-arm studies and observational studies
OPPORTUNITIES FOR VIFOR PHARMA
• Become a leader in PBM through championing the anaemia cause
• Deliver a compelling message to regulators and payers
• Be on the forefront of this REAL change in paradigm
• Develop relationships with other non competing industry partners to
develop a comprehensive disease management approach
85
Part II – Veltassa®
VELTASSA® UPDATE
Patrick Treanor
President ad interim, Relypsa
CAPITAL
MARKET DAY
2018
© Vifor Pharma 4 October 2018 88
VELTASSA®
OVERVIEW OF KEY FEATURES
1) SmPC = summary of product characteristics
RAASi enabling
Included in SmPC1) in Europe
Room temperature storage
U.S.: 3 months / EU: 6 months
High safety profile
Limited undesirable effects
Mode of action
Calcium-based, non-absorbed
Broad use
Acute & Chronic
52-weeks data
AMETHYST-DN study
© Vifor Pharma
U.S.
4 October 2018 89
© Vifor Pharma
VELTASSA® DEMAND PER BUSINESS DAY1)
NUMBER OF 30 COUNTS EQUIVALENT BOXES
HIGHLIGHTS
• One of the fastest growing drugs
in nephrology in last 10 years2)
• Year over year demand growth
of +81% (H1 2017 vs. H1 2018)
• All time high in demand reached
in August
0
100
200
300
400
500
600
700
Jan
-16
Fe
b-1
6
Ma
r-1
6
Ap
r-16
Ma
y-1
6
Jun
-16
Jul-
16
Au
g-1
6
Se
p-1
6
Oct-
16
Nov-1
6
Dec-1
6
Jan
-17
Fe
b-1
7
Ma
r-1
7
Ap
r-17
Ma
y-1
7
Jun
-17
Jul-
17
Au
g-1
7
Se
p-1
7
Oct-
17
Nov-1
7
Dec-1
7
Jan
-18
Fe
b-1
8
Ma
r-1
8
Ap
r-18
Ma
y-1
8
Jun
-18
Jul-
18
Au
g-1
8
4 October 2018 90
VELTASSA® DEMAND PER BUSINESS DAY
CONTINUOUS INCREASE
1) Internal data 2) EvaluatePharma
© Vifor Pharma 4 October 2018 91
1) Sodium polystyrene sulfonate
Source: IQVIATM MIDAS® Quarterly panel Q2-2018, average 2017 exchange rates have been applied.
VELTASSA® U.S. MARKET SHARE
67.4% OF POTASSIUM BINDER MARKET
MAT Q2 2015
MAT Q2 2018
SPS1)
100%
32.1 Million CHF
86.1 Million CHF
© Vifor Pharma
VELTASSA® PAYER COVERAGE
U.S. LIVES COVERED, %
HIGHLIGHTS
• ~24M lives added or
improved coverage for
Veltassa® since early 2018
• 55% of U.S. lives covered
without prior authorization
• Recent coverage expansion
increased Medicare Part D
coverage to 64%1)
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
No
v-1
5
De
c-1
5
Jan-1
6
Feb
-16
Ma
r-1
6
Apr-
16
Ma
y-1
6
Jun-1
6
Jul-1
6
Aug-1
6
Sep-1
6
Oct-
16
No
v-1
6
De
c-1
6
Jan-1
7
Feb
-17
Ma
r-1
7
Apr-
17
Ma
y-1
7
Jun-1
7
Jul-1
7
Aug-1
7
Sep-1
7
Oct-
17
No
v-1
7
De
c-1
7
Jan-1
8
Feb
-18
Ma
r-1
8
Apr-
18
Ma
y-1
8
Jun-1
8
Jul-1
8
4 October 2018 92
VELTASSA® MEDICARE COVERAGE INCREASED
STRONG INCREASE FROM 44% TO 64%
1) Increase to at least 67% expected as of 1 January 2019
All lives 88%
Medicare 64%
© Vifor Pharma
OUT-OF-POCKET (OOP) COSTS
IN PERCENT OF U.S. LIVES COVERED
HIGHLIGHTS
• Median OOP is $6 for all
approved claims
• ~50% of Veltassa® Medicare
claims are Low-Income
Subsidy (LIS)
75%
25%
$0-25
$26+
4 October 2018 93
VELTASSA® OUT-OF-POCKET COSTS
75% OF PATIENTS PAY $25 OR LESS
Source: Symphony Source Health Analytics Primary-Final Plan Benefit Design Report (July 2017-June 2018)
© Vifor Pharma 94
NEPHROLOGISTS FEEDBACK
POSITIVE EXPERIENCES WITH VELTASSA®
Rated very highly by Nephrologists
Prescribers continue to expand usage
of Nephrologists believe
VELTASSA® is appropriate for
long-term treatment of
Hyperkalemia 94% 93%
89%
of Nephrologists believe
VELTASSA® is effective in
restoring K+ levels to target range
of Nephrologists have prescribed
VELTASSA® in the past three
months
Source: Relypsa data on file.
Over 10,750 physicians have
treated nearly 65,000 patients with
VELTASSA® since launch 65K
4 October 2018
Source: Based on a survey of 100 nephrologists conducted in August 2018 by Putnam Associates. Source: Based on a survey of 100 nephrologists conducted in August 2018 by Putnam Associates.
Source: Relypsa data on file.
© Vifor Pharma
3 MILLION HYPERKALEMIA PATIENTS IN THE U.S.
4 October 2018 95
U.S. MARKET OPPORTUNITY
• 3 million potential patients
• Gross price of USD 820 per month
• Targeted duration of treatment: 6 months
• 10% treated with Veltassa®
= USD 1 billion in net sales (blockbuster)
Key drivers of success:
• Awareness ✓
• Access ✓
• Duration of treatment ✓
VELTASSA® U.S. RAMP-UP
KEY CONSIDERATIONS
Source: USRDS 2013 ADR, CDC
10.7
4.7
2.3 1.7
0.8 0.5
0
2
4
6
8
10
12
CKD 3-4 only CKD 3-4 with HF HF only
Total Prevalence With hyperkalemia
Pati
en
ts (
in m
illio
n)
© Vifor Pharma
EUROPE
4 October 2018 96
© Vifor Pharma
PATIENTS TREATED
4 October 2018 97
PATIENT FEEDBACK
VELTASSA® ROLLOUT IN EUROPE
OVERVIEW OF FIRST ACHIEVEMENTS
1) Pre-License Access Program
0
250
500
750
1000
Mar-18 Apr-18 May-18 Jun-18 Jul-18 Aug-18 Sep-18
Commercial & PLA1)
“Being diagnosed with high
potassium changed my life
completely. I was so scared
in the beginning, but now
there is hope.”
© Vifor Pharma
Scotland Finland
4 October 2018 98
COMMERCIAL LAUNCH & REIMBURSEMENT
CURRENT STATUS
Switzerland Germany United Kingdom
Spain Italy France
Sweden Denmark
Norway Austria
REIMBURSEMENT
OBTAINED
REIMBURSEMENT
SUBMITTED
LAUNCHED
AVAILABLE
DELAYED
INITIAL
REJECTION
© Vifor Pharma
GLOBAL APPROACH
TO DATA
GENERATION
4 October 2018 99
© Vifor Pharma
RESULTS EXPECTED
ENROLLMENT
STUDY
4 October 2018 100
1) Chronic heart failure
LIFE CYCLE MANAGEMENT
UNLOCK FULL POTENTIAL WITH DATA
Enrolment of 290
patients completed
AMBER DIAMOND
Expected enrolment of
2’400 patients starting
Q1 2019
STRATEGIC OBJECTIVES
Increase accessible
patient pool U.S. label change
H1 2019 2022
Increase access to
patients with CHF1)
Guideline updates for
the management of
arterial hypertension
Guideline updates
© Vifor Pharma
COMPETITIVE
UPDATE
4 October 2018 101
© Vifor Pharma 4 October 2018 102
1) Veltassa® SmPC En. 2017 2) LokelmaTM SmPC En. 2018 3) Sanofi-Aventis, Resonium A SmPC, 2014, Kayexalate PI, 2010
* hypokalaemia, oedema ** 2 hours separation in FDA label *** U.S. PI advise 3-6 hour drug separation
VELTASSA®
A COMPELLING SAFETY/EFFICACY PROFILE
Novel therapeutic options Existing treatments
Veltassa® (patiromer)1) Sodium Zirconium
Cyclosilicate2)
Sodium Polystyrene
Sulphonate3)
No sodium content
Consistently well tolerated *
Drug-drug interactions 3 hours None** 3-6 hours***
Robust evidence for onset of effect
in 4-7 hrs
Onset of action 4-7 hours 2.2 hours 1-2 hours
1yr prospective data showing high tolerability
and efficacy
RAASi enablement in SmPC
Once-daily oral dose
Available dosages 8,4 g, 16,8 g, 25,2 g (sachets) 5 g, 10 g (sachets) 15 to 60 g per day (powder)
© Vifor Pharma 4 October 2018 103
1) Stifel, Vifor Pharma Company Update, 22.05.2018
VELTASSA ®
FROM AN OUTSIDE PERSPECTIVE1)
LABEL FEATURE ANALYST’S PREFERENCE
Indication No difference
Limitations No difference
Mechanism Veltassa® - calcium exchange mechanism preferable to sodium
(concerns about increasing sodium levels, particularly in cardiology)
Dosage and
administration
Veltassa® - focus is on chronic management, clearer proposition, not convinced by
3x daily acute phase with LokelmaTM (potential confusion on positioning)
Dosage forms LokelmaTM (just) – slight preference, on lower volume of water, appears to be more
miscible powder
Storage LokelmaTM - no need for cold chain distribution
Warnings and
precautions
Veltassa® - similar potential impact on GI motility, but edema issue (sodium-related)
with LokelmaTM a key concern, requires more monitoring, changes to diet, diuretics
Adverse reactions No difference - more apparent GI issues with Veltassa®, offset by edema issues
with LokelmaTM
Drug interactions LokelmaTM – 2h interval better than 3h, although drug-drug interactions more
theoretical according to lab experiments
Clinical data No difference
© Vifor Pharma
U.S.
• Strong demand continues
• Access improved to 88% of covered lives (Medicare 64%)
Product specific
• Extremely high satisfaction level from clinicians
• Uniquely differentiated versus competition
• Continued focus on building awareness
• Clinical studies focused on promoting benefits in cardiology
Europe
• Successful commercial launch in five countries
• Fragmented pricing & reimbursement process being systematically addressed
4 October 2018 104
VELTASSA® SUMMARY
Importance of RAASi for HCPs and patients - Benefit of Veltassa® from a cardiologist point of view
Stefan D. Anker, MD PhD
Division of Cardiology & Metabolism:
Heart Failure, Cachexia and Sarcopenia
Dept of Cardiology & BCRT, Charité (CVK), Berlin, Germany
The world of potassium
Nyirenda MJ, et al. BMJ 2009;339:bmj.b41114
• The most abundant cation in the body
• 98% intracellular
• Complex regulation of intracellular/extracellular
• Long-term K+ homeostasis mainly governed by renal
excretion
• Normal plasma K+ is tightly regulated despite variable
intake
• Disorders of K+ levels profoundly affect membrane
excitability and nerve, muscle and cardiac function
Serum K+ Values
1. Rastegar A, et al. Postgrad Med J. 2001;77:759–64; 2. Einhorn LM, et al. Arch Intern Med. 2009;169:1156–62; 3. Kovesdy CP. Am J Med. 2015;128:1281–7.
K+, potassium.
Serum K+ levels (mEq/L)
3.0 3.5 4.0 4.5 5.0 5.5 6.0
Hypokalemia Normokalemia Hyperkalemia
MILD MODERATE SEVERE
6.5
Hypokalemia Normokalemia Hyperkalemia
Mechanisms causing hyperkalemia
Causes
Excess potassium intake Potassium supplement
Enteral nutrition (e.g. whole protein formulas with high electrolyte content)
Potassium redistribution
Acidosis Hyperglycemia Insulin deficiency or resistance
Certain drugs, such as digoxin (toxicity) and succinylcholine
Strenuous exercise Hemolysis
Damage to tissue from rhabdomyolysis, burns, or trauma
Tumor lysis syndrome
Reduced potassium excretion
Impaired renal function Diabetes mellitus Heart Failure Obstructive uropathy
Diseases with low levels of or lack of response to aldosterone
Renin-angiotensin-aldosterone system (RAAS) inhibitors
Major causes of hyperkalaemia
www.stedmansonline.com (accessed 28.8.2015) www.nlm.nih.gov/medlineplus/mplusdictionary.html (accessed 28.8.2015)
What are the risks associated with hyperkalaemia?
1. Alfonzo A, et al. UK Renal Association Clinical Practice Guidelines. 2014;
2. Xi L, et al. J Geriatr Cardiol. 2015;12:119–26.
* p=0.021
ECG, electrocardiogram.
Elevated K+ is associated with an increase in all-cause mortality
Collins AJ, et al. Am J Nephrol. 2017;46:213–21.
An evaluation of medical records
demonstrated an increase in all-cause
mortality with elevated K+ in those
patients with comorbidities*
Co-morbidities included DM, HF,
CKD Stages 3–5, CVD or hypotension
Baseline serum K+ level (mEq/L)
Hyperkalaemia Normokalaemia Hypokalaemia
CKD, HF, DM CKD, HF DM Control group N=911,698
Shading surrounding lines indicates 95% confidence limits. *Evaluated through de-identified medical records (2007–2012) of individuals with ≥2 serum K+ readings (Humedica, Cambridge, MA). Spline analyses were performed to assess mortality at 0.1 mEq/L increments of serum K+ after adjusting for covariates and interactions. Patiromer clinical trials were not designed to measure mortality outcomes. CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus; HF, heart failure; K+, potassium
Predicted probability of mortality
Patients with or without CKD who experience hyperkalaemia once, are at greater risk of recurrent hyperkalaemia events
Einhorn LM, et al. Arch Intern Med. 2009;169:1156–62.
50%
of patients with hyperkalaemia* had
2 or more recurrences within 1 year
Some patients experienced
>20 recurrent episodes within 1 year†
*Hyperkalaemia was defined as serum K+ ≥5.5 mEq/L (1 mEq/L = 1 mmol/L); †70 individuals (0.21%) had more than 20 episodes in 1 year. CKD, chronic kidney disease.
Hyperkalaemia in heart failure patients increases as renal function declines
Go AS, et al. N Engl J Med 2004;351:1296–305.
eGFR: estimated glomerular filtration rate; MRA: mineralocorticoid receptor antagonist; WRF: worsening renal function. * Randomized Aldactone Evaluation Study: Double-blind trial in 1,658 patients with NYHA functional Class III or IV heart failure and ejection fraction ˂35% randomized to spironolactone 25mg (which could be titrated to 50mg) or placebo daily.
Ra
te o
f h
yp
erk
ala
em
ia
(% o
f p
atie
nts
)
6.08.5
6.7
13.315.4
25.6
18.2
30.2
0
5
10
15
20
25
30
35
Baseline eGFR ≥60 Baseline eGFR <60 No WRF WRF
Placebo Spironolactone
Intra-study change in renal function
Analysis based on RALES trial*
Baseline renal function
All RAAS inhibitors increase serum K+ levels
dRi
ACEi
ARB
MRA
K+ retention
Na+/water uptake
Angiotensin I
AT1 receptor
Angiotensin II
Aldosterone production
Mineralocorticoid receptor
Angiotensinogen
ARNi
Rossignol P, et al. Circ Heart Fail 2014;7:51–58.
ACEi, angiotensin-converting-enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor; dRi, direct renin inhibitor; HF, heart failure; MRA, mineralocorticoid receptor antagonist; RAAS, renin-angiotensin-aldosterone system.
Hyperkalaemia is common with RAASi
Hyperkalemia Prevalence
(% of Patients)
Clinical Trials EMPHASIS-HF1 PARADIGM-HF2 SOLVD3 CHARM-Added4 RENAAL5 IDNT6
Serum K+ Level > 5.5 mEq/L > 5.5 mEq/L > 5.5 mEq/L > 6.0 mEq/L ≥5.5 mEq/L >6 mEq/L
Patient Population
HF with reduced EF HF with EF of 40%
or less HF with EF of 35%
or less
HF with EF of 40% or less and were treated with
ACEi Diabetic nephropathy Diabetic nephropathy
Pts were also taking spironolactone at baseline
11.8
16.0
6.4
4.0
10.8
18.6
7.2
17.0
2.5
1.0
5.1 6.0
0.0
5.0
10.0
15.0
20.0
EMPHASIS PARADIGM SOLVD CHARM-Added RENAAL IDNT
Eplerenone Placebo Enalapril LCZ696 Enalapril Placebo Candesartan Placebo Losartan Placebo Irbesartan Placebo
ACEi, angiotensin-converting enzyme inhibitor; EF, ejection fraction; HF, heart failure; Ks , potassium; Pts, patients; RAASi,renin-angiotensin-aldosterone system inhibitor.
1. Zannad F, et al. N Engl J Med. 2011;364:11-21. 2. McMurray JJ, et al. N Engl J Med. 2014;371:993-1004. 3. SOLVD Investigators, et al. N Engl J Med. 1991;325:293-302.
4. McMurray JJ, et al. Lancet. 2003;362:767-771. 5. Miao Y et al. Diabetologia. 2001;54:44-50. 6. Avapro [package insert]. Bridgewater, NJ: Sanofi-Aventis US LLC; 2014.
RAASi
Placebo
Guidelines strongly recommend all RAASi to improve mortality and morbidity in HFrEF
HfrEF, heart failure with reduced ejection fraction; RAASi, renin–angiotensin–aldosterone system inhibitor.
EUROPE USA CANADA AUSTRALIA GLOBAL
Hyperkalaemia frequently causes RAASi to be discontinued
In a quarter of patients with a serum K+ of >5.5 mEq/L ACEis/ARBs were reduced in dose or discontinued in a study of 194,456 patients*
*Geisinger Health Care database, retro-spective analysis of patients with outpatient visit and a blood pressure measurement in 44 counties in Pennsylvania in the time period of January to October 2011 ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; RAASi, renin–angiotensin–aldosterone system inhibitor. Chang AR, et al. Hypertension 2016;67:1181-8.
Maximum RAASi dose is associated with a reduced incidence of mortality in the cardio-renal setting*
40
20
0
9.8%
20.3% 22.4%
13.7%
27.7% 30.1%
4.1% 8.2%
11.0%
CKD stages 3–4 Heart failure Total population
Pe
rce
nt
of
pa
tie
nts
(N=43’288 total patients
across dose categories)
(N=20’529 total patients
across dose categories)
(N=201’655 total patients
across dose categories)
Maximum dose
Discontinued
Submaximum dose
Epstein M, et al. Am J Manag Care 2015;21:S212–20.
* A large US database study including over 200’000 patients with the requirement of 1 RAAsi prescription within 12 months prior to July 1, 2009 CKD, chronic kidney disease; RAASi, renin-angiotensin-aldosterone system inhibitor.
Guidelines recommend RAASi dose modifications with increasing serum K+
1. Yancy CW, et al. Circulation. 2016;134:e282–93; 2. Yancy CW, et al. Circulation. 2013;128:1810–52; 3. Ponikowski P, et al. Eur Heart J. 2016;37:2129–200;
4. Heart Failure Society of America, et al. J Card Fail. 2010;16:475–539; 5. KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3;
6. National Institute for Health and Clinical Excellence. Chronic kidney disease (partial update): Early identification and management of chronic kidney disease in adults in primary and secondary care. 2014;
7. National Kidney Foundation. Guideline 11. http://www2.kidney.org/professionals/kdoqi/guidelines_bp/guide_11.htm. Accessed February 17, 2015.
Serum K+ threshold before change in RAASi guideline recommendation
>6.0
>5.5
>5.0
Serum K+ (mEq/L)
Most conservative Most aggressive
K/DOQI7: Discontinue ACEi/ARB if >5.5
ESC HFA3: Discontinue ACEi/ARB if >5.5;
Halve dose of MRA if >5.5
ACC/AHA HF2 and HFSA HF4:
MRA not recommended >5.0
K/DOQI7:
Halve dose of RAASi if >5.0
NICE CKD6: don’t routinely start
RAASi if >5.0
NICE CKD6: Stop RAASi if >6.0 ESC HFA3: Stop MRA if >6.0*
ACC/AHA/HFSA HF1, ESC HFA3:
ACEi/ARB use with caution >5.0
KDIGO Guidelines do not provide recommendations.5 *ESC HFA: Management of acute hyperkalaemia (>6.0) may require a short-term cessation of K+-retaining agents and RAASi, but this should be minimised and RAASi should be carefully reintroduced as soon as possible while monitoring K+ levels.3 ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; MRA, mineralocorticoid receptor antagonist; RAASi, renin-angiotensin-aldosterone system inhibitor.
Patients who benefit the most from RAASi therapy are the patients at greatest risk of hyperkalaemia
Palmer BF et al. N Engl J Med. 2004;351:585-92.
CARDIO-RENAL PROTECTION
Prescribe or continue RAASi and accept the
presence of hyperkalaemia?
MANAGEMENT OF HYPERKALAEMIA
Avoid, discontinue or down-titrate RAASi
and lose the benefits on clinical outcomes?
RAASi, renin-angiotensin-aldosterone system inhibitor
Why is the recognition and treatment hyperkalaemia increasingly important?
The incidence of hyperkalemia is increasing, and this is exacerbated by RAAS inhibitor use1–3
2010 2030
5.7M
8M
CHRONIC KIDNEY DISEASE
2009 2022
26M
46M
HEART FAILURE
US
Pa
tien
t N
um
be
rs
Reduced kidney function is the most
common cause of uncontrolled K+
Poor cardiac output leads to renal
insufficiency
A serum potassium level of ≥4.5 mEq/L is associated with mortality and arrhythmias
Unfortunately, current treatment have limitations
1. Einhorn LM, et al. Arch Intern Med 2009;169:1156–62; 2. Desai A, et al. Curr Heart Fail Rep. 2009;6:272-80; 3. Raebel MA, et al. J Gen Int Med 2010;25:326–33
Patiromer is a novel, non-absorbed K+ binder
Li L, et al. J Cardiovasc Pharmacol Ther. 2016;21:456–65.
GI, gastrointestinal; K+, potassium.
Patiromer is a novel, spherical, non-absorbed polymer – High-capacity K+ binder – Average bead size (100 μM) is too large for Patiromer to be absorbed – Site of action is primarily from the colon where K+ is the most abundant cation
and residence time of the polymer is the longest – Calcium is the counter-exchange ion
High-capacity polymer Uniform, spherical patiromer beads
Patiromer clinical studies
1. Huang I-Z, et al. J Am Soc Nephrol. 2010;21(Suppl):482A(F-PO1615); 2. ClinicalTrials.gov. NCT02033317. 3. Pitt B, et al. Eur Heart J. 2011;32:820–8;
4. Buysse J, et al. Future Cardiol. 2012;8:17–28; 5. Pitt B, et al. ESC Heart Fail. 2018;5:257−66; 6. Bakris GL, et al. JAMA. 2015;314:151–61;
7. Weir M, et al. N Engl J Med. 2015;372:211–21; 8. Weir M, et al. Presented at the American Society for Hypertension 2015, New York, NY: Abstract#LB-P-01;
9. Bushinsky DA, et al. Kidney Int. 2015;88:14–27; 10. Lesko LJ, et al. J Cardiovasc Pharmacol Ther. 2017;22:434–46; 11. Pergola P, et al. Am J Nephrol. 2017;46:323–32.
Proof of Concept
Prevention Treatment Post-US Approval
HF with/without CKD3,4
202
PEARL-HF
HK, CKD, T2DM, HTN6 205
(52-week safety & efficacy)
AMETHYST-DN
HK with CKD9
103
Effect of patiromer taken with or
without food11 401
(TOURMALINE)
CKD with HF5
204 HK with CKD7,8
301 (Phase 3 pivotal)
OPAL-HK
DDI Studies10
Healthy volunteers1
101
Haemodialysis subjects2
201
Healthy volunteers1
102
2008 2009 2010 2011 2013 2014 2015 2016
CKD, chronic kidney disease; DDI, drug–drug interaction; DN, diabetes nephropathy; HF, heart failure; HK, hyperkalaemia; HTN, hypertension; T2DM, type 2 diabetes mellitus.
Populations studied in Patiromer trials
1. Data on file. Relypsa, Inc. Redwood City, CA; 2. Weir MR, et al. N Engl J Med. 2015;372(3):211–21;
3. Bakris G, et al. Poster presented at: ASN Kidney Week 2014; Philadelphia, PA; November 11-16, 2014; Poster SA-PO1099; 4. Vifor. Veltassa® Summary of Product Characteristics 2017.
*88% had ≥stage 3 CKD (29% had stage 4 CKD) **K+ 5.1 to <6.5 mEq/L ***60% >65 years of age (20% ≥75 years) CKD, chronic kidney disease; K+, potassium; RAASi, renin-angiotensin-aldosterone system inhibitor.
97% Hypertension1 88% CKD*1 49% Heart Failure1
73% Diabetes Mellitus1 60% over 65 Years***1,2 99.4% taking RAASi4
Wide range of severity of hyperkalaemia** 42% of subjects had a serum K+ ≥5.5 mEq/L at baseline2,3
8% of subjects had a serum K+ ≥6.0 mEq/L at baseline1
Summary of Patiromer clinical studies
1. Bakris GL et al. JAMA. 2015;314:151-61; 2. Weir MR et al. N Engl J Med. 2015;372:211-21. 3. Pitt B et al. Eur Heart J. 2011;32:820
CHF, chronic heart failure; CKD, chronic kidney disease, DN, diabetic nephropathy, HF, heart failure; HK, hyperkalaemia; K+, potassium,; RAASi, renin-angiotensin-aldosterone system inhibitor; T2DM, type 2 diabetes mellitus * eGFR 15-59 mL/min/1.73 m²
• Lowest starting doses effective with minimal titration required • Long-term safety and efficacy data to support chronic use
• Significant and clinically meaningful serum K+ reduction, with maintenance
of serum K+ control and ability to keep patients on RAASi medications • Recurrence of HK on treatment withdrawal demonstrated need for long-
term chronic treatment
• In normokalaemic patients with CHF at risk of HK starting spironolactone
therapy, administration of patiromer compared with placebo: • Significantly reduced mean K+ levels
• Prevented hyperkalaemia
• Allowed a significantly greater percentage of patients to increase spironolactone doses to 50 mg/day
AMETHYST-DN (Phase II)1 52-week, open-label, randomized, dose-ranging study in patients with T2DM, CKD* and HK on ≥1 RAASi
OPAL-HK (Phase III):2 12-week, two-part, single-blind randomized withdrawal study in patients with HK and CKD* on ≥1 RAASi
PEARL-HF (Phase II):3 4-week, double-blind, randomized, placebo-controlled study in patients with HF and CKD* on ≥1 RAASi or with a history of HK with discontinuation of ≥1 RAASi
Design Results
New studies for more evidence – AMBER
100% Resistant Hypertension 100% CKD 51% Heart Failure
47% Diabetes Mellitus 71% over 65 Years 99.3% taking RAASi4
Enabling spironolactone in
in patients with resistant hypertension for prevention of hyperkalaemia
Agarwal R et al. Am J Nephrol 2018;48:172–180
Baseline characteristics of first 146 patients Results are projected to be available in H1 / 2019
Conclusion
• Elevate K+ levels are associated with poor outcome
• Hyperkalaemia is common and recurrent in CV diseases
• Current treatments for hyperkalaemia have limitations, in particular in the long-term management
• RAASi therapy is the cornerstone treatment in CV diseases
• Patiromer can treat hyperkalaemia and shows promise to enable optimal use of life-saving RAASi therapy
CV, cardiovascular; K+, potassium; RAASi, RAASi, renin-angiotensin-aldosterone system inhibitor .
Part III – Vifor Fresenius
Medical Care Renal Pharma
THE JOINT COMPANY
David Bevan
CEO, Vifor Fresenius Medical Care Renal Pharma
CAPITAL
MARKET DAY
2018
A UNIQUE PARTNERSHIP
© Vifor Fresenius Medical Care Renal Pharma 4 October 2018 129
1) Pre-commercial products
THE JOINT COMPANY
THE RATIONALE
STRONG IRON AND PHARMA EXPERTISE
GLOBAL LEADER IN DIALYSIS
Avacopan1) CCX1401)
55% Stake
45% Stake
Vadadustat1)
CR8451)
© Vifor Fresenius Medical Care Renal Pharma 4 October 2018 130
THE JOINT COMPANY
HIGHLY REPUTABLE DIRECTORS
1) Fresenius Medical Care North America
Etienne Jornod Executive Chairman
Stefan Schulze President of the Executive
Committee and COO
Colin Bond Chief Financial Officer
Rice Powell Chief Executive Officer
and Chairman
Michael Brosnan Chief Financial Officer
Frank Maddux Chief Medical Officer
FMCNA1)
David Bevan Chief Executive Officer
VFMCRP
© Vifor Fresenius Medical Care Renal Pharma
Focus on pharma needs of nephrology patients – Global Leader
Access to patient data. Faster clinical trial execution
Faster uptake and utilisation
Partnership technically controlled by Vifor Pharma
Registered in Switzerland
Sourcing of innovation
Evaluation of clinical assets
Acceptance of clinical risk
Regulatory and market access expertise
4 October 2018 131
Managed care expertise
Patient access (>300k patients)
Validation of innovation
Medications in FKC clinics1) become SoC2)
THE JOINT COMPANY
VALUE BEYOND FINANCIALS
1) Fresenius Kidney Care (FKC): Fresenius Medical Care North America dialysis provider organization 2) Standard of care
© Vifor Fresenius Medical Care Renal Pharma
CURRENT INDICATIONS
4 October 2018 132
NEPHROLOGY
NUMEROUS OPPORTUNITIES REMAIN
Polycystic kidney disease
Metabolic acidosis
Vascular calcification
Kidney stones
Hypernatremia
Fabry
aHUS
Diabetic nephropathy
Acute kidney injury
β-Thalassemia renal disease
FSGS
ANCA associated vasculitis
Uremic pruritus
C3G
Secondary hyperparathyroidism Hyperphosphatemia
Hyperkalemia
Anaemia
Iron deficiency
PIPELINE INDICATIONS POTENTIAL INDICATIONS
© Vifor Fresenius Medical Care Renal Pharma 133
1) Fresenius Medical Care North America
THE SCIENTIFIC ADVISORY BOARD
A JOINT FOCUS ON INNOVATION
Frank Maddux Chief Medical Officer
FMCNA1)
Prof. Dr. Michel Burnier Vifor Pharma Board Member
Dr. of Internal Medicine and Nephrology
Stefan Wohlfeil Chief Medical Officer
Vifor Pharma
Andrin Cerletti Head Global Business Development
Vifor Pharma
Robert Kossman Chief Medical Officer
Renal Therapies Group, FMCNA1)
Ravi Thadhani Professor of Medicine
Harvard Medical School
4 October 2018
© Vifor Fresenius Medical Care Renal Pharma 4 October 2018 134
THE SCIENTIFIC ADVISORY BOARD
INVOLVED IN ALL STAGES
External opportunities Pipeline products Marketed products
• Database screen of approx.
380 clinical stage assets per
year
• Pre due diligence on approx.
10 to 15 assets per year
• Full due diligence on approx.
5 to 6 projects per year
• Negotiations on approx. 1 to 3
deals per year
• Ensure VFMCRP operates as
a highly efficient launch engine
• Avacopan
• CCX140
• CR845
• Rayaldee®
• Vadadustat
• Optimise existing marketed
products
• Ferinject ®
• Mircera®
• RetacritTM
• Velphoro®
• Veltassa®
• Venofer ®
© Vifor Fresenius Medical Care Renal Pharma
VIFOR
PHARMA
4 October 2018 135
UNIQUE PARTNERSHIP
PROCESS OF A SUCCESSFUL TRANSACTION – CR845
Pro
ject In
itia
tion
Due diligence
Unmet
need
analysis
Data
insights
Sharing of
experience
BD&L process
Commercial
insights
Ongoing oversight through
SAB1) members
FRESENIUS
MEDICAL
CARE
VFMCRP
Sig
nin
g
Joint Steering Committee &
Joint Development Committee
2017 2018 2019 2016
Key interaction with partner
1) Scientific advisory board
SHAPING INNOVATION
Dr. Frank Maddux
Chief Medical Officer, Fresenius Medical Care North America
CAPITAL
MARKET DAY
2018
© Vifor Fresenius Medical Care Renal Pharma
EMPLOYEES
Q2 2018
111,263
(-1% yoy)
of which ~70,000 in the U.S.
137
PATIENTS
Q2 2018
325,188
(+3% yoy)
of which ~201,000 in the U.S.
DIALYSIS CENTERS
Q2 2018
3,815
(+3% yoy)
of which 2,500 in the U.S.
FRESENIUS MEDICAL CARE
RENAL DISEASE POPULATION AND TRENDS
4 October 2018
© Vifor Fresenius Medical Care Renal Pharma
EXPECTED TREND
4 October 2018 138
KEY DRIVERS
• Age, lifestyle and higher life
expectancy
• Increasing wealth and access
to medical treatments
• 10% of the U.S. population with
Chronic Kidney Disease
• Recognized as a public health
condition since 2006 by Centers
for Disease Control in the U.S.
• Strong growth in pharmerging
markets
CHRONIC KIDNEY DISEASE
GROWING PATIENT POPULATION
Note: based on FMC market and competitor survey 2015
3.5
6.0
2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025
Mil
lio
n o
f p
ati
en
ts
CAGR
5.5%
Actual FMC forecast VFMCRP Projection
Europe U.S. ROW
© Vifor Fresenius Medical Care Renal Pharma
Chronic kidney disease (CKD) still highly prevalent:
• 10% of the world’s population is affected by CKD
• CKD kills more people than breast or prostate cancer
• Diabetes is the leading cause of kidney failure (44% of new cases)
• Obesity is linked closely with CKD (30% of people worldwide in 2018)
VFMCRP is best positioned to drive innovation and help patients live better lives.
4 October 2018 139
INSIGHT INNOVATIONS
RECLASSIFYING KIDNEY DISEASE
© Vifor Fresenius Medical Care Renal Pharma
VIFOR FRESENIUS
MEDICAL CARE RENAL
PHARMA (VFMCRP)
140 4 October 2018
© Vifor Fresenius Medical Care Renal Pharma 4 October 2018 141
1) Standard of care
VFMCRP
GROW AND ENHANCE VALUE
2010 2020 2015 2025
ESTABLISH BUILD PORTFOLIO ENHANCE VALUE
55% 45%
IDEA SOC1)
DRIVE INNOVATION
© Vifor Fresenius Medical Care Renal Pharma
ESTABLISH
4 October 2018 142
© Vifor Fresenius Medical Care Renal Pharma 4 October 2018 143
VFMCRP
THE RATIONALE
55% 45%
STRONG IRON AND PHARMA EXPERTISE GLOBAL LEADER IN DIALYSIS
© Vifor Fresenius Medical Care Renal Pharma
VENOFER® MARKET SHARE AT FKC CLINICS1)
4 October 2018 144
1) Fresenius Kidney Care (FKC): Fresenius Medical Care North America dialysis provider organization
VENOFER®
FIRST STEP IN BUILDING A SUCCESS STORY
50%
75%
100%
2008 2009 2010 2011 2012 2013 2015 2017 2018
HIGHLIGHTS
• >23m patient years experience
• Gold standard in dialysis
• Exclusivity for FMCNA in dialysis
in the U.S. since 2008
• Expected to remain a key part
of the dialysis treatment protocol
• Sold to other dialysis clinics
• Currently no iron sucrose similar
in the U.S.
© Vifor Fresenius Medical Care Renal Pharma
PATIENTS TREATED WITH MIRCERA® AT FKC CLINICS BENEFITS OF MIRCERA®
Improved logistics
Easier dose preparation
90%+ of doses per electronic
algorithm
More patients in target range than
any other short acting ESA
Smoother path to stable dosing
Fewer dosing changes required
Adverse event rates low
4 October 2018 145
FMCNA Data from Clinical Data Analytics Assessment – Ofsthun, Stennett 2018
MIRCERA®
AT FKC CLINICS
UNPRECEDENTED SPEED OF CONVERSION
© Vifor Fresenius Medical Care Renal Pharma
BUILD
146 4 October 2018
© Vifor Fresenius Medical Care Renal Pharma 4 October 2018 147
1) Pre-commercial products 2) Only in dialysis
3) Profit sharing agreement in FMCNA dialysis clinics
VFMCRP
BUILD PORTFOLIO
2016 2015 2017
Mircera®/Roche U.S. License2)
Veltassa®/Relypsa License
(ex-U.S./Japan)
CCX140/
ChemoCentryx1) License (ex-U.S.)
RetacritTM/Pfizer U.S. License2)
Avacopan/
ChemoCentryx1) License (ex-U.S.)
EU Affiliates Acquisition from FMC
Rayaldee®/OPKO1) License
(Europe and other)
Vadadustat1) U.S. License for
FMC dialysis clinics
2018
CR845/Cara
Therapeutics1) License (ex-
U.S./Japan/South
Korea)3)
© Vifor Fresenius Medical Care Renal Pharma
Breakthrough designation by FDA; Phase-III study ongoing in Uremic Pruritus
First sales expected in 2021/2022.
60%-70% of dialysis patients affected Primary target: Uremic Pruritus
No opioid addiction
Global rights except U.S., Japan and South Korea, profit share for the sales to FKC clinics1).
148
1) Fresenius Kidney Care (FKC): Fresenius Medical Care North America dialysis provider organisation
DIFELIKEFALIN/CR845 INJECTION
CKD-ASSOCIATED COMPLICATIONS
0.8
1.7
4 October 2018
© Vifor Fresenius Medical Care Renal Pharma 4 October 2018 149
1) Pre-commercial products
VFMCRP
CURRENT PORTFOLIO
CARDIO-RENAL
MANAGEMENT
MINERAL & BONE
MANAGEMENT
ANAEMIA
MANAGEMENT
KIDNEY
PROTECTION
Avacopan1)
1)
Vadadustat1)
CR8451)
CCX1401)
CKD-ASSOCIATED
COMPLICATIONS
© Vifor Fresenius Medical Care Renal Pharma
ENHANCE VALUE
150 4 October 2018
© Vifor Fresenius Medical Care Renal Pharma 4 October 2018 151
VFMCRP
VISION
Global Leader in Nephrology
innovative patient-focused solutions.
The partner of choice
for renal pharmaceuticals and
© Vifor Fresenius Medical Care Renal Pharma
SPEEDING UP THE IDEA TO STANDARD OF CARE PROCESS
4 October 2018 152
THE VFMCRP INNOVATION ECOSYSTEM
IDEA STANDARD
OF CARE
BASIC
RESEARCH
CLINICAL
TRIALS
REGULATORY
APPROVAL
© Vifor Fresenius Medical Care Renal Pharma
[]
4 October 2018 153
RANDOMIZED CONTROL TRIAL (RCT)
VS. REAL WORLD EVIDENCE (RWE)
Pharma data
(RCT, observational)
Electronic medical and
health records
Pharmacy
data
Mortality,
other registries
Hospital visits,
Service details Test results,
lab values,
Pathology results
Claim
databases
Social
Media
Consumer
Data
Real-World
Data (RWD)
Meaningful
questions
Fit-for-purpose
Validated
findings
Externally
Validated
findings
© Vifor Fresenius Medical Care Renal Pharma
FMCNA CONVERTED PATIENTS TO VELPHORO®
JULY 2018 TO SEPTEMBER 2018
COMMENTS
• Program to migrate from calcium
based phosphate to non-calcium
based binders
• Referencing guidelines and
Velphoro® studies on the impact
of pill burden on adherence
• Panel Discussions and webinars
for nurses and dietitians
• Evidence base communications
with prescribing physicians
• Electronic algorithm to migrate
patients
4 October 2018 154
VELPHORO®
We
ek
ly c
on
ve
rsio
n d
uri
ng
ro
llo
ut
of
pro
gra
m
0
200
400
600
800
1000
1200
1400
28 29 30 31 32 33 34 35 36
Week number
© Vifor Pharma
The Vifor Partnership: New Ideas, New Medicines.
Thomas J. Schall, PhD. President and Chief Executive Officer
October 2018
© Vifor Pharma
FORWARD-LOOKING STATEMENTS
156
This presentation contains forward-looking statements from ChemoCentryx.
These statements relate to future events or our future financial performance or condition and involve known and unknown risks, uncertainties and other factors that could cause our actual results, levels of activity, performance or achievement to differ materially from those expressed or implied by these forward-looking statements.
These risks, uncertainties and other factors are described more fully in our periodic reports filed with the SEC, including our Annual Report on Form 10-K for the year ended December 31, 2017 filed with the SEC on March 12, 2018, particularly in the sections titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations”.
This presentation also contains estimates, projections and other information concerning our industry, our business, and the markets for our drug candidates, as well as data regarding market research, estimates and forecasts prepared by our management. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information.
© Vifor Pharma
CHEMOCENTRYX (CCXI): A DIFFERENTIATED APPROACH TO INHIBITING DISEASE-DRIVING CHEMOATTRACTANT SYSTEMS
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Founded in 1997 by Dr. Thomas Schall, early
discover of ‘chemoattractant cytokine’
(chemokine) superfamily
Envisioned an entirely new approach for
autoimmune and inflammatory disease therapy
Precise mechanism; precision medicine:
inhibition of specific chemoattractant receptors
with orally-administered small molecules
Based in Mountain View, CA
NASDAQ listed since 2012
© Vifor Pharma
NOVEL PRECISION THERAPEUTICS BY INHIBITING CHEMOATTRACTANT RECEPTORS
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© Vifor Pharma
A DIFFERENTIATED APPROACH TO INHIBITING DISEASE-DRIVING CHEMOATTRACTANT SYSTEMS
Highly Selective
Leaves Rest of Immune System Intact
Exclusive Focus
Small Molecules Highly-Selective
Broad Applicability
Leaves rest of immune system intact; No immunosuppression
Orally-administered, convenience, greater patient compliance
ChemoCentryx is a leader in chemoattractant system science
Approach applicable to Inflammatory, autoimmune diseases and cancer
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Establishing Strong Global Commercial Capabilities
CCXI retains commercial rights in the U.S.
Strategic commercial alliance with Vifor Pharma
Advanced Programs Focused on Orphan Diseases
Enrollment complete in landmark Phase III ADVOCATE trial in ANCA vasculitis
Extending the reach of avacopan –C3G trials ongoing; initiating clinical studies in hidradenitis suppurativa (HS) in US
Broad Pipeline of Unique, Orally-Administered, Small Molecule Therapeutics
Targeting indications with clear regulatory pathways and multi-billion dollar market potential
Robust clinical data generated with avacopan and CCX140
FROM BASIC SCIENCE TO COMMERCIALIZATION
Precision Approach Leads to Better Medicines
Leaves rest of the immune system intact
CCXI drug candidates selectively target a specific chemoattractant or chemokine receptor
© Vifor Pharma
CCXI’S BROAD PIPELINE - DISCOVERY TO LATE STAGE DEVELOPMENT FROM NOVEL PLATFORM
THERAPEUTIC AREA INDICATION PHASE III PHASE II PHASE I PRECLINICAL
CKD, INCLUDING ORPHAN FOCAL SEGMENTAL GLOMERULOSCLEROSIS Chronic and Orphan Kidney Diseases
ANCA-ASSOCIATED VASCULITIS
Complement Inhibition in Orphan Diseases
C3 GLOMERULOPATHY
DRUG/ TARGET
Avacopan (formerly CCX168)/ C5aR
CCX140/CCR2
DIABETIC NEPHROPATHY, SUCCESSFULLY COMPLETED PHASE II
Other Inflammatory and Autoimmune Diseases
IBD: ULCERATIVE COLITIS
TH17 DRIVEN DISEASE, e.g. PUSTUALAR PSORIASIS
OTHER ONCOLOGY INDICATIONS
Immuno-Oncology ADVANCED PANCREATIC CANCER CCX872/ CCR2
CCX507/CCR9
CCX587/CCR6
HIDRADENITIS SUPPURATIVA
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© Vifor Pharma
AVACOPAN
Targeted Approach to Complement Diseases: A ‘Pipeline in a Drug’
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AVACOPAN: THE ONLY ORALLY-ADMINISTERED SMALL MOLECULE C5AR INHIBITOR
Targeting the Complement Pathway ‘Downstream’ is Best
Avacopan
Reason for black box warning for eculizumab
Does not block production of C5b-9 leaving host defense mechanism (MAC) in place
Preserves beneficial functions of C5L2 pathway
Avoids long-term biological consequences of upstream complement inhibition
C5aR
1.
2.
3.
1.
2.
3.
C5a Antibodies
© Vifor Pharma Ltd.
Rationale for Avacopan Auto Antibodies → Activation of Complement Cascade → Generation of C5a → C5a Binds C5a Receptor (C5aR) on Neutrophils C5aR-Activated Neutrophils Destroy Blood Vessels
Status Phase 3 ADVOCATE trial fully-enrolled; Top-line data expected in Q4 2019
ANTI-NEUTROPHIL CYTOPLASMIC AUTO-ANTIBODY (ANCA) VASCULITIS: A COMPLEMENT C5A ACTIVATED NEUTROPHIL-DRIVEN DISEASE
40K
~4,000 new cases per year in U.S.
Overview Prevalence
~5,000 new cases per year in EU
• Highly inflammatory and progressive autoimmune disease caused by the over-activation of the complement system; generation of C5a
• Kidney is a major target organ
• Characterized by recurring flares, accruing into irreversible organ system damage (end-stage renal disease) and death; relapse is common
• Significantly impacts multiple aspects of physical function, emotional well-being, and overall productivity
50K
Current Treatments
High-dose steroids for 6 months
Prednisone Methylprednisone
Immuno-suppressants
Cyclophosphamide OR Rituximab
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URGENT NEED TO MODERNIZE SOC IN ANCA VASCULITIS
Rapid induction of remission
Reduced side effects
Major Unmet Needs:
• Prevent damage and preserve renal function
• Prevent glucocorticoid-related toxicity and infection
Durable remission • Majority of patients at risk for
relapse for many years
* Little et al, 2010 Ann Rheum Dis 69:1036–1043, Flossmann et al 2011 Ann Rheum Dis 70:488–494.
Current ANCA Vasculitis High-Dose Steroid Standard of Care (SOC)
11-16% die within 1st year of diagnosis*
Greatest risk to patients in first year comes from steroid-induced infections
Current treatments contribute ~60% of the mortality rate*
Need to taper steroid = high relapse rate
Irreversible organ damage with relapse (especially in the kidney)
Steroids for 6 Months
Prednisone Methylprednisone
Cyclophosphamide
Rituximab
or
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AVACOPAN PROFOUNDLY INHIBITS COMPLEMENT-DRIVEN NEUTROPHIL ACTIVATION
1Birmingham Vasculitis Activity Score 2Estimated Glomerular Filtration Rate
o EMA PRIME designation and orphan medicinal product
designation
o SwissMedic orphan drug designation
o FDA Grant and orphan drug designation
o Intractable disease designation in Japan
ANCA Vasculitis Regulatory Designations for Avacopan:
Primary endpoint achieved
Rapid onset of action with avacopan treatment
Marked improvements in renal parameters
Patients feel better
Multi-center, randomized (1:1:1), double-blind Phase II trial in patients with newly diagnosed or relapsed ANCA Vasculitis
A. SOC Control Group = Placebo + High Dose Steroid (+ CYC/RTX)
B. Avacopan + Low Dose Chronic Steroid (1/3 of SOC) (+ CYC/RTX)
C. Avacopan + No Chronic Steroid (+CYC/RTX)
Significant lowering of proteinuria and shedding of kidney inflammation markers; decrease in eGFR2
Reduction in vasculitis activity score (BVAS1, a signs and symptoms index) at week 12 with avacopan
Disease remission by BVAS week 4
Statistically significant enhancement in quality of life; favorable safety profile
Phase II CLEAR Trial
Avacopan Efficacy Established in Phase II CLEAR Trial
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AVACOPAN PHASE II “CLEAR” TRIAL MET PRIMARY ENDPOINT
* Thickness of line indicates multiple patients achieved 100% improvement in BVAS
High Dose Steroids SOC Avacopan Treatment Groups
9 pts* 1 pt
BVAS individual participant data shows more rapid response and remission with avacopan compared to SOC
Rapid Remission (BVAS = 0):
29% avacopan + no steroid BVAS = 0 by week 4
Only 5% on steroid standard of care therapy
Treatment Groups # Patients
BVAS (Vasculitis Activity Score)1
Statistical Significance2
Total Avacopan Patients 36/43 -84% P = 0.002
Avacopan + low dose steroid
19/22 -86% P = 0.002
Avacopan + no steroid 17/21 -81% P = 0.01
High dose steroid standard of care (SOC)
14/20 -70% N/A
Primary Endpoint: Proportion of patients with BVAS response at week 12
1BVAS response defined ≥ 50% from baseline, and no worsening in any body system 2P values refer to comparison of avacopan to SOC for non-inferiority
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AVACOPAN: RAPID IMPROVEMENT IN RENAL PARAMETERS
Jayne et al, 2017 JASN doi: https://doi.org/10.1681/ASN.2016111179
Neutrophil counts normalize within days
**** P < 0.0001, *** P < 0.001, ** P < 0.01, * P < 0.05 for superiority of avacopan vs. steroid control group; LSM change from baseline
No requirement for chronic high dose steroids to stabilize kidney function
** P < 0.01, * P < 0.05 for avacopan vs. control
Proteinuria improves faster and at greater magnitude in avacopan groups vs. control
*** P < 0.001, ** P < 0.01, * P < 0.05 for superiority of avacopan vs. steroid control group; LSM change from baseline
© Vifor Pharma
1 Prednisone / Methylprednisone
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AVACOPAN ENHANCES QUALITY OF LIFE IN ANCA VASCULITIS
Quality of Life After 12 Weeks of Avacopan Almost Same as General Population Controls
All Avacopan
Physical Functioning
General health perception
Vitality
Mental health
Bodily pain
Social functioning
Role emotional
Role Physical
Vitality
Avacopan + no steroid vs. general population controls2
Physical Functioning
Role Physical General health
perception
Mental health
Bodily pain
Social functioning
Role emotional
High-dose steroid1 group
Role Physical General health perception
Vitality
Mental health
Bodily pain
Social functioning
Role emotional
Physical Functioning
Significant improvement over 12 week dosing course 2Basu et al, 2014 Ann Rheum Dis 73:207–211
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AVACOPAN: LANDMARK PHASE III ADVOCATE TRIAL
Fully-enrolled, top-line data expected in Q4 2019
Avacopan, 30 mg twice daily
Placebo avacopan twice daily
RTX, 4 weeks or CYC, 12 weeks followed by AZA
RTX, 4 weeks or CYC, 12 weeks followed by AZA
Prednisone, 60 mg/day tapered to 0 over 21 weeks
Placebo to Prednisone Test Group
(N = 158)
Control SOC Group (N = 158)
52-week treatment period
Remission (based on BVAS)
at 26 Weeks
Sustained remission (based on BVAS)
at 52 Weeks
Two primary endpoints: (both analyzed after 52 weeks)
Time
1Potentially leading to greater separation of BVAS between SOC and Avacopan groups
+
B
VA
S R
em
issi
on
Sco
re
-
26 Weeks 52 Weeks
Avacopan Treatment (Test Group)
Control SOC Group
26 Weeks: Numerical Superiority / Non-Inferiority
Difference in Relapsed Patients
52 Weeks: Superiority
High rates of relapse over time associated with SOC1
4 Weeks
Rationale Behind ADVOCATE Design
1. Demonstrate effective,
rapid and sustained
remission of ANCA
vasculitis by BVAS
2. Eliminate need for
corticosteroids in standard
of care and associated
toxic side effects
Goals:
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OTHER OPPORTUNITIES FOR AVACOPAN
C3 Glomerulopathy (C3G) • Rare, life-threatening disease; affects young people; renal transplant not curative • Uncontrolled activation of the complement system leading to complement protein deposition in the kidney
(glomeruli), disrupting kidney function • No approved therapy • Huge economic burden on health care systems
• Potential registration-supporting trial with avacopan underway
Hidradenitis Suppurativa (HS): • Chronic disabling skin autoimmune disease that relentlessly progresses; with extremely painful
inflammatory nodules, boils or abscesses
• Neutrophil-driven disease where C5a involvement is validated
• C5a blockade with avacopan via C5aR offers a strong potential to control neutrophil activation
• Current incumbent therapy widely regarded as inadequate, yet sales in HS approach $1Bn US
© Vifor Pharma
CCR2 INHIBITOR CCX140
Targeted Approach to Orphan Kidney Diseases Such as FSGS
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40K ~5,400 new cases
per year in U.S.
Overview
Rationale • Histologic lesion from glomerular injury affecting specialized kidney
filtering cells, especially podocytes; new science shows CCR2 in FSGS kidney and role for CCR2 in renal cell (podocyte) protection
• CCX140 has demonstrated a statistically significant reduction in proteinuria in previous Phase II clinical trial in DN patients
CCX140 FOR FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)
Prevalence
Current Treatments
40K
• Orphan disease of the kidney’s filtering units (glomeruli), and is characterized by serious scarring that leads to permanent kidney damage
• Presents with proteinuria, in which protein is found in the urine due to a breakdown of the normal filtration mechanism in the kidney
• One of the causes of a serious condition known as Nephrotic Syndrome and often leads to ESRD; Primary FSGS often associated with genetic mutation
No Approved Therapies • Non-specific treatment approaches include steroids to
control proteinuria or immuno-suppressants
Number of FSGS cases are rising more than any other cause of Nephrotic Syndrome
Status Two registration-supporting clinical trials underway
~1,500 new cases per year in EU
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CCX140: CLINICAL DEVELOPMENT IN FSGS
Trial #1: Nephrotic Syndrome Primary FSGS: • ≥ 3 gram/day baseline proteinuria
• First presentation or new flare following prior effective treatment
• *Significant decrease in proteinuria from baseline approvable endpoint
Trial #2: Sub-Nephrotic Primary FSGS • At least 1 gram/day baseline proteinuria
• Decrease in proteinuria from baseline anticipated accelerated approval endpoint
• Reduced in decline in eGFR anticipated full approval endpoint
Screening
(Biopsy-proven primary FSGS & assess proteinuria levels) 0
CCX140, Dose range from 5 mg QD to 15 mg BID (n=6 to 13)
12 24
Study Assessments – Reduction in Proteinuria from Baseline (weeks)
Trial #1: Nephrotic syndrome primary FSGS (≥ 3 gram/day baseline proteinuria)
Trial #2: Sub-nephrotic primary FSGS (at least 1 gram/day baseline proteinuria)
• Stratify by level of proteinuria and immunosuppressant treatment (yes/no)
Rescue if no partial response; otherwise continue
Expand to 30-50 patients for pivotal part 21
CCX140, 5 mg QD (n=10)
Placebo (n=10)
CCX140, 10 mg BID (n=10)
CCX140, 15 mg BID (n=10)
Highest safe dose ( 12 weeks open label)
1Pending favorable results
Screening
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EXCITING MOMENT IN THE EVOLUTION OF CCXI
EMA validates CMA application for avacopan in ANCA Vasculitis
Positive OS results with CCX872 in Pancreatic Cancer
Launch of Late-stage trials of avacopan in c3G and CCX140 in FSGS
Phase III ADVOCATE trial fully enrolled
Recent Achievements
Near-Term
o Continue to support Vifor market readiness activities in their territories
o Continue to promulgate development in ANCA, C3G, FSGS
o Initiate comprehensive placebo-controlled clinical program with avacopan in HS
o Strong cash reserves (>$200M Q2 2018 cash and investments)
Over the next 2 years
o Data from ADVOCATE, C3G, FSGS, HS clinical trials 2109-2020
o Potential commercial launch of avacopan in U.S.
o Continued expansion of pipeline into additional indications
o Cash through ADVOCATE pivotal data and filings
© Vifor Pharma
The Vifor Partnership: A Formula for Success
October 2018