Presented to the International Plasma Protein Congress Amsterdam March 2019

1. INTERNATIONAL CHALLENGES FOR ALL STAKEHOLDERS OF THE
PLASMA THERAPEUTICS INDUSTRY
Albert Farrugia PhD
International Plasma Protein Congress ,Amsterdam
19-20 March 2019

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ALL THE OPINIONS EXPRESSED IN THIS PRESENTATION ARE SOLELY MY OWN

3. Kedrion Biopharma |
 Current status and projections
 Barriers to globalisation
 Access issues
 Emerging and disruptive therapies
 Towards the future
3
OUTLINE

4. Kedrion Biopharma |
 Current status and projections
 Barriers to globalisation
 Access issues
 Emerging and disruptive therapies
 Towards the future
4
OUTLINE

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THE CONTINUING IMPORTANCE OF IG

6. -
2 ,000
4 ,000
6 ,000
8 ,000
10 ,000
12 ,000
14 ,000
16 ,000
18 ,000
20 11 20 14 20 17 20 25
7,136
9,437
12,618
16,863
7,070
7,868
8,767
9,132
The Growing Discrepancy bet ween t he Domest ic Supply of
Plasma and t he Needs t o meet IgG Demand from 2011 t o 2025
Plasma
Needed
Plasma
Supply
The Domest ic Plasma Procurement does not
cat ch up wit h t he growing need for plasma
t o make IgG in Europe

8. Kedrion Biopharma |
 Current status and projections
 Barriers to globalisation
 Access issues
 Emerging and disruptive therapies
 Towards the future
8
OUTLINE

9. HUNGARY - 439/2015. (XII. 28.) GOVERNMENT
DECREE GOALS OF THE DECREE
The Hungarian National Blood Transfsusion Service
(HNBTS) is
-responsible for the blood supply in Hungary,
coordinates the blood collection based on the annual
plan,
-maintains and improves the donor register with
cross deferral register covered the donor data with
plasmapheresis centres.
To improve the attitude of the plasmadonors
into the whole blood donation, so the
plasma centres monitorize their donors’
whole blood donation (the minimum
request once whole blood donation per
year).
Klara Baroti-Toth, Sandor Nagy Plasma Supply Management, EDQM, Strasbourg, 29-30 January, 2019.

10. Goal of the contract among the HNBTS
and plasmapheresis centres
To be safer procedure for the donors (with same
requirements) and same quality of the recipients.
To prepare a unique donor register, with cross deferral
register (The validation periode should be finalized at the
end of March 2019.).
To prevent the TTI.
To find the donors to give blood again or at first time.
Every 6 month they should send their procedure’s data (it
is confidential), but their donor deferral riports are
implemented into the eProgesa, unique donor register to
improve the blood safety.
To prepare a max. limit for donor
expenses in the plasma centres.
Klara Baroti-Toth, Sandor Nagy Plasma Supply Management, EDQM, Strasbourg, 29-30 January, 2019.

11. COLLECTED WHOLE BLOOD
Unit
450,000
400,000
350,000
300,000
250,000
200,000
150,000
100,000
50,000
0
2010 2011 2012 2013 2014 2015 2016 2017 2018
Klara Baroti-Toth, Sandor Nagy Plasma Supply Management, EDQM, Strasbourg, 29-30 January, 2019.

12. Plasma Supply Management, EDQM, Strasbourg, 29-30 January, 2019.

13. • coexistence of „standard“ blood transfusion service and
commercial plasma-collection centers didn´t harm national self-
sufficiency in blood components during last 10 years
• over 60 liters of plasma / 1000 inhab. can be collected
respecting CoE limits for donation frequency / volume
• over 20 liters of plasma for fractionation / 1000 inhab. are
collected from voluntary non-remunerated donors (plus 5 litres /
1000 inhab. for clinical use)
Czech experience ….
P. Turek, Plasma Supply Management, EDQM, Strasbourg, 29-30 January, 2019.

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PLASMA FOR FRACTIONATION - CHINA
Volume of plasma collection and number of
plasmapheresis centers from 2011 to 2016. Proportion of registered donors by occupation

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MORE ON CHINA

16. Biotest is supporting Shanghai RAAS in selling first Shanghai
Raas product in Hungary
First cooperation with Shanghai RAAS on a European level
• Gammaraas (Liquid 5% IVIG) from Shanghai RAAS
• first patient successfully treated with Gammaraas on 1
October 2018
Marketing & sales activities
Company Presentation Biotest AG
http://www.equitystory.com/Download/Companies/biotest/Other%20Information/20181114_Biotest_Analyst_Presentation.pdf
.
Biotest Analyst call - Nine months 2018
14 November 2018

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YET MORE ON CHINA
www.thelancet.com Vol 392 August 4, 2018

18. Kedrion Biopharma |
 Current status and projections
 Barriers to globalisation
 Access issues
 Emerging and disruptive therapies
 Towards the future
18
OUTLINE

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ACCESS ISSUES – HTA/REGULATOR COLLABORATION

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DISPARATE OUTCOMES
“The drug received marketing authorization from the European Medicines
Agency for use in the UK in February 2018. On July 7, NHS England
announced its decision to reimburse Hemlibra; the date that patients will be
able to access this new treatment is expected to be announced shortly.
Medicines for hemophilia do not require approval from the medicines cost
effectiveness watchdog the National Institute for Health and Care Excellence
(NICE), and are instead directly commissioned by NHS England.”
The drug manufacturer postulated an added benefit based, among other things, on
a randomized controlled comparison between emicizumab and as-needed
treatment with conventional preparations in the framework of the HAVEN 1 study.
However, the G-BA had explicitly specified routine prophylaxis as ACT because,
according to the current state of knowledge, this treatment has advantages over as-
needed treatment. Hence no added benefit could be derived from the HAVEN 1
study. The indirect comparisons additionally presented were also unsuitable for this.

21. Kedrion Biopharma |
 Current status and projections
 Barriers to globalisation
 Access issues
 Emerging and disruptive therapies
 Towards the future
21
OUTLINE

22. NOVEL THERAPEUTICS FOR HEMOPHILIA
Valder R. Arruda et al. Blood 2017;130:2251-2256
(
(
(
Extended
half-life
(EHL)
coagulation
factor
concentrates
CFCs
Non-CFC
based
treatments
Gene therapy

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IG USAGE BY SPECIALITY IN 2012
23
Rheumatology/Nephrology 2%

24. SELECTED NEXT GENERATION BIOLOGICS CURRENTLY UNDER INVESTIGATION.
Molecule Description Preclinical data Indications Stage Institution
GL2045;
Stradomer™
Fc multimerized by
IgG2 hinge
Animal models: CIAa,
ITP, MG
In-vitro: FcγR avidity
↑
CIDP (Orphan Drug Status
Granted, US) MG, RA
Preclinical Gliknik/Pfizer
HexaGard™
IgG1 Fc with IgM
tailpiece and
mutations
[L309C/H310L]
In-vitro: FcγR avidity
↑; no binding to FcRn
Autoimmune or inflammatory
disease
Preclinical
Liverpool
School of
Tropical
Medicine
SIF3 (M230)
CSL730
IgG1 Fc based
trimer
Animal models:
arthritis, ITP
In-vitro:
ADCP ↓, FcγR avidity
↑
Autoimmune disease Preclinical Momenta/CSL
ARGX-113
Mutated IgG1 Fc
with high affinity for
FcRn
Not known MG Clinic Phase I argenx
SM101
Recombinant
soluble FcγRIIB
Animal models: CIA,
SLE
SLE, ITP Clinic Phase II
Suppremol/Bax
alta/Shire
HL161 Anti-FcRn mAb Not known
Pemphigus, NMO, MG, lupus
nephritis
Preclinical
HanAll
BioPharma
Autoimmunity Reviews 15 (2016) 781–785

25. INTEREST FROM THE ESTABLISHED PLASMA COMPANIES
 CSL – Acquired Momenta (50% of SIF3)
 Grifols – Acquired GigaGen (44%) (?Polyclonal recombinant Ig)
 Baxter – Acquired SuppreMol

26. Kedrion Biopharma |
 Current status and projections
 Barriers to globalisation
 Access issues
 Emerging and disruptive therapies
 Towards the future
26
OUTLINE

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PLASMA FRACTIONATION ECONOMICS (SIMPLIFIED)
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First to last litre fractionated

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 The plasma industry continues to show growth, robustness and interest from global investors.
 The industry is dangerously geared to the USA for its main revenue stream, and for its supply of
raw material.
 Efforts to increase access to plasma outside the USA continue to be obstructed by the
protectionist efforts of the transfusion sector in some countries.
 Increasing and promising expectations of the entry of China into the global plasma therapeutics
environment are tempered by issues of adequate compliance and oversight.
 The convergence of market approval and reimbusement pathways in some landscapes should be
viewed with concern, particularly against a background of disharmony in payment systems.
 Disruptive technolgies have pushed plasma-derived haemophilia therapies outside the high price
markets, and there are indications that some indications for IG may follow a similar route.
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REFLECTIONS