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CSL Ltd. Investor Presentation 2015

Dec 9, 2015

17854_rns_2015-12-09_5673f59b-6075-405d-b868-ff68305f8dd0.pdf

Investor Presentation

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December 10, 2015

1

Global

Legal Notice

Forward looking statements

The materials in this presentation speak only as of the date of these materials, and include forward looking statements about CSL Limited and its related bodies corporate (CSL) financial results and estimates, business prospects and products in research, all of which involve substantial risks and uncertainties, many of which are outside the control of, and are unknown to, CSL. You can identify these forward looking statements by the fact that they use words such as “anticipate,” “estimate,” “expect,” “project,” “intend,” “plan,” “believe,” “target,” “may,” “assume,” and other words and terms of similar meaning in connection with any discussion of future operating or financial performance. Factors that could cause actual results to differ materially include: the success of research and development activities, decisions by regulatory authorities regarding approval of our products as well as their decisions regarding label claims; competitive developments affecting our products; the ability to successfully market new and existing products; difficulties or delays in manufacturing; trade buying patterns and fluctuations in interest and currency exchange rates; legislation or regulations that affect product production, distribution, pricing, reimbursement or access; litigation or government investigations, and CSL’s ability to protect its patents and other intellectual property. The statements being made in this presentation do not constitute an offer to sell, or solicitation of an offer to buy, any securities of CSL.

No representation, warranty or assurance (express or implied) is given or made in relation to any forward looking statement by any person (including CSL). In particular, no representation, warranty or assurance (express or implied) is given in relation to any underlying assumption or that any forward looking statement will be achieved. Actual future events may vary materially from the forward looking statements and the assumptions on which the forward looking statements are based.

Subject to any continuing obligations under applicable law or any relevant listing rules of the Australian Securities Exchange, CSL disclaims any obligation or undertaking to disseminate any updates or revisions to any forward looking statements in these materials to reflect any change in expectations in relation to any forward looking statements or any change in events, conditions or circumstances on which any such statement is based. Nothing in these materials shall under any circumstances create an implication that there has been no change in the affairs of CSL since the date of these materials.

Trademarks

Except where otherwise noted, brand names designated by a ™ or[®] throughout this presentation are trademarks either owned by and/or licensed to CSL.

2

Global

Agenda

  • Welcome

  • Introduction & Highlights

  • Research & Early Development

  • Immunoglobulins & Specialty Products • Clinical Development

  • Commercial Opportunities

Mark Dehring Andrew Cuthbertson Andrew Nash

Charmaine Gittleson

Bob Repella

  • Q&A

Break

  • Coagulation/Haemophilia

  • Clinical Development

  • Commercial Opportunities

Charmaine Gittleson Bob Repella

  • Breakthrough Medicines

  • CSL112 Clinical Development

  • Influenza Vaccines R&D

Charmaine Gittleson Andrew Cuthbertson

  • Summary

  • Q&A

3

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Introduction and Highlights
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4

Global

CSL Protein Therapeutics Technical Platform

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Breakthrough
Medicines
Immunoglobulins Specialty
Products
Haemophilia
Products
Plasma Recombinant
Fractionation Technology
Protein Science
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5

Global CSL R&D Strategy

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Breakthrough
Medicines
Immunoglobulins Specialty
Products
Haemophilia
Products
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  • Maintain commitment

to extracting maximum value from existing assets and supporting and improving current products

  • Develop new protein-based therapies for treating serious illnesses focusing on products that align with our technical and commercial capabilities

6

Global Commitment to Research & Development

R&D Investment* (US$ millions)

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New Product Development activities focus on innovative new therapies for lifethreatening diseases.

Market Development strategies seek to bring therapies to new markets and new indications.

Life Cycle Development ensures continuous improvement of existing products.

*FY14 / FY15 YoY growth 6% at constant currency

7

Global

Leveraging Global Capabilities

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1,100 scientists globally
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8

Global

R&D Portfolio – December 2014

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Research Pre-clinical Phase I Phase II Phase III Registration Commercial/
Phase IV
CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH
Immunoglobulins
Haemophilia
Life Cycle
Specialty
Management [# ]
Products
Influenza
Vaccine
Hizentra [®] CIDP Hizentra [®] Japan
Beriplex [®] Privigen [ ®] CIDP
Market Japan Hizentra [®] biweekly
Development Fibrinogen New CSL830
Indications C1-INH subcut Voncento [®] EU
PCC New Beriplex [®] NOACs Fibrinogen Kcentra [TM] US
Indications Daiichi Aortic EU Zemaira [®] EU Bleeding /Surgery
Novel Plasma
Proteins
Rec Coagulation CSL650 CSL689 rVIIa-FP CSL689 rVIIa-FP CSL627 rVIII-SC CSL654 rIX-FP
Factors rvWF-FP Congen Def Inhibitors
Partnered Vaccine Partnered Vaccine Partnered Vaccine
New Product Programs Programs Programs
Development P. gingivalis/POD FXIIa Antagonist CSL362 IL-3R
OH-CRC/Sanofi Janssen
CSL324 G-CSFR CSL112
Discovery
reconstituted HDL
Projects CSL346 VEGFB
CAM3001 Quadrivalent
CSL334 IL-13R GM-CSFR –AZ Flu Vaccine
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Core Capabilities:

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Immunoglobulins
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Haemophilia
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Specialty Products
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Breakthrough Medicines
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Vaccines & IP
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*Partnered Projects

9

LCM includes direct post marketing commitments as well as pathogen safety, capacity expansions, yield improvements, new packages and sizes for all registered products

Global

Progress through Stage Gates in 2015

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Privigen Hizentra [ ® ] US
Japan Flex Dosing
CSL640 CSL627 Voncento [ ®]
rIX-FP subct rVIII-SC US VWD EU
CSL650 CSL627
rVWF-FP rVIII-SC EU
CSL312 Respreeza [®]
Anti-FXIIa EU
CSL324
GCSFR
Quad Flu
Vaccine 18+
p.ging/POD CSL362
OH-CRC Janssen
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10

Global

R&D Portfolio – December 2015

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Research Pre-clinical Phase I Phase II Phase III Registration Commercial/
Phase IV
CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH
Immunoglobulins
Haemophilia
Life Cycle
Specialty
Management [# ] Products
Influenza
Vaccine
Hizentra [®] CIDP
C1-inh New
Privigen [®]
Market Indications Japan
Development Fibrinogen New Beriplex® Kcentra [TM] US
Indications Japan Bleeding /Surgery
PCC New CSL830 Respreeza [® ]
Indications C1-INH subcut EU
Ig Formulations
Rec Coagulation CSL650 CSL689 rVIIa-FP CSL689 rVIIa-FP CSL654 rIX-FP
Factors rvWF-FP Congen Def Inhibitors
CSL627 rVIII-SC
Partnered Vaccine Partnered Vaccine Partnered Vaccine
Programs Programs Programs
New Product
P. gingivalis/POD CSL334 IL-13R CSL362 IL-3R
Development
OH-CRC ASLAN AML Janssen
CSL312
CSL112
Discovery Anti-FXIIa
reconstituted HDL
Projects
CSL324 G-CSFR
CAM3001 Quadrivalent
CSL346 VEGFB GM-CSFR –AZ Flu Vaccine
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Core Capabilities:

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Immunoglobulins
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Haemophilia
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Specialty Products
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Breakthrough Medicines
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Vaccines & IP
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*Partnered Projects

LCM includes direct post marketing commitments as well as pathogen safety, capacity expansions, yield improvements, new packages and sizes for all registered products

11

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Research & Early Development
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12

Global

CSL’s Global Research Capability

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• Coordinated global project portfolio

Specialty Breakthrough Haemophilia Products Medicines

Immunoglobulins

  • Hub (Bio21, Parkville) & spoke model

  • Research excellence in therapeutic proteins

  • Plasma and recombinant manufacturing platforms

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13

Haemophilia Research Strategy

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Novel Strategies –
Coag Factor
Maximising Value
Addressing
and Performance
Inhibitors
of Existing Assets
Novel Strategies –
Non-Coag Factor
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  • Major focus on patient QoL

  • Extract maximum value and performance from existing assets

  • Develop new protein-based therapies and strategies for treating bleeding disorders

o Congenital

o Acquired

14

Haemophilia

Research – Half life extension

• Improved prophylaxis for haemophilia patients

Product Features Phase Manufacturer Half-life extension Half-life extension
Eloctate rFVIII fused to Fc Market Biogen Idec
N8-GP BDD FVIII O-linked pegyln Ph II/III Novo Nordisk
BAX 855 FVIII Lys-linked pegyln Market Baxter 1.1 - 1.5 fold*
BAY 94-9027 BDD FVIII site-specific pegyln Ph I Bayer
CSL627 rVIII-SingleChain Single chain BDD FVIII Submitted CSL Behring
Alprolix FIX fused to Fc Market Biogen Idec 3 fold
CSL654 rIX-FP FIX fused to albumin with cleavable linker Submitted CSL Behring 5 fold
GlycoPEGylated rFIX FIX N-linked pegyln Ph III Novo Nordisk 5 fold
CSL689 rVIIa-FP FVIIa fused to albumin Ph I CSL Behring 3-4 fold

• FVIII T1/2 extension limited by interaction with VWF Target VWF T1/2

15

Haemophilia

Research – FVIII half life extension

  • VWF – Albumin fusion protein (VWF-FP)

  • Haemophilia A patients have normal levels of VWF

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FP VWF FVIII
After 9 hrs the
majority of FVIII is
associated with
endogenous VWF
FP VWF FVIII VWF VWF FVIII
T1/2 3-4 days T1/2 16 hrs
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• Create novel modified VWF-FP to enable:

o Administration of higher doses without risk of thrombosis

o Higher affinity association with FVIII

  • Candidate product – modVWF-FP + CSL627

16

Haemophilia

Research – FVIII half life extension

  • modVWF-FP PK study in NHPs

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x
x
x
x
x
x
x
CSL627
Haemate [®] P
pd VWF + CSL627
modVWF-FP dose 1 + CSL627
modVWF-FP dose 2 + CSL627
modVWF-FP dose 3 + CSL627
D 'D 3 [ n g /m l]
modVWF-FP (ng/ml)
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modVWF-FP PK

  • Prolongation of FVIII exposure by modVWF-FP

  • Product development initiated

17

Haemophilia Research – Subcutaneous Delivery

Enabling more flexible and convenient prophylaxis in haemophilia patients

  • New, innovative and unique administration form

  • Patients with poor venous access

  • Reduction or avoidance of indwelling catheters & associated complications

  • Patients with fear for injections / needles

  • Maintain consistent trough levels (fewer peaks)

18

Haemophilia

Research – Subcutaneous Delivery

  • Subcutaneous delivery of rIX-FP (haemophilia B mice)

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250 100
rIX-FP 125 IU/kg s.c
rIX-FP 250 IU/kg s.c
200 80
rIX-FP 125 IU/kg i.v BeneFIX 250IU/kg s.c
150 rIX-FP 125 IU/kg s.c 60
100 40
50 20
0 0
0 20 40 60 80 100 0 20 40 60 80 100
Time [h] Time [h]
FIX activity (% norm)
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• s.c rIX-FP ~50% bioavailability* in haemophilia B mice

• s.c.rIX-FP ~8-fold higher AUC than BeneFIX**

Bioavailability 13-50% depending on species *TM of Pfizer. Inc.

19

Haemophilia

Research – Subcutaneous Delivery

  • rIX-FP s.c efficacy in haemophilia B mice

Total blood loss

Bleeding time

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400 2500
Vehicle
300 * n.s. CSL654 250IU/kg 2000 *
BeneFIX 250IU/kg
1500
200
1000
100
500
0 0
µL
Seconds
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  • rIX-FP reduces total blood loss and bleeding time following s.c administration to haemophilia B mice

  • Phase 1 to commence mid 2016

20

Breakthrough Medicines

Breakthrough Medicines

  • Leveraging clinical and technical insight in developing novel proteinbased therapies

o Significant unmet need

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Haemophilia
Products
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o Multiple indications

  • Key Focus

o CSL362 (Janssen)

o CSL324

21

Breakthrough Medicines

CSL362 – Acute Myeloid Leukaemia

  • Most common acute leukaemia in adults

  • Incidence increases with age

  • Untreated AML fatal: 3 – 4 months

  • Chemotherapy → 50-75% CR

  • ~70% will relapse

  • CSL362 MOA – targets CD123 overexpressed on leukaemic cells

    • engineered to recruit immune killer cells

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  • inhibits IL-3 activity

22

Breakthrough Medicines

CSL362 – Acute Myeloid Leukaemia

  • Licence Agreement with Janssen Biotech – June 2013

o CSL responsible for completing CSL362 AML Phase 1 clinical study

Milestone Date
Phase 1 Last Patient Last Visit July 2015

o Janssen responsible for all further oncology development

Milestone Date AML Phase 2 First Patient In* August 2015

*JNJ-56022473

23

Breakthrough Medicines

CSL362 – Acute Myeloid Leukaemia

  • CSL362 depletes biomarker pDC’s and basophils in patients

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24

Breakthrough Medicines

CSL362 – Acute Myeloid Leukaemia

Conclusions

  • Manageable safety profile:

  • Pre-medication with steroids required to prevent infusion reactions

  • PD effects confirming CD123-targeted ADCC

  • Rapid and full depletion of basophils and pDCs

o Sustained depletion at CSL362 dose levels ≥ 3 mg/kg

  • Saturation of CD123 receptor on monocytes at CSL362 dose levels ≥ 3 mg/kg (trough concentration > 3μg/ml)

  • Conversion of MRD seen in a subset of pts treated with CSL362

  • AML Phase 2 study commenced July 15 (Janssen partnership)

25

Breakthrough Medicines

CSL362 – SLE

  • pDCs contribute to a disease amplification loop in SLE

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CSL362
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Janssen to commence exploratory study in SLE patients 2H 2016

26

Breakthrough Medicines CSL324 – Chronic and Acute Inflammation

CSL324 – anti-G-CSFR mAb

  • Targeting the G-CSF receptor represents a novel approach to the treatment of neutrophil mediated pathologies

  • Efficacy in multiple animal models of inflammatory disease

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COPD exacerbations
Cystic Fibrosis
exacerbations
Acute Respiratory
Disease Syndrome
G-CSF G-CSF
Rheumatoid
arthritis
neutrophils
CSF’s, cytokines
Vasculitis
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27

Breakthrough Medicines CSL324 – Chronic and Acute Inflammation

  • Early clinical development strategy

Safe, well tolerated Determine dose & interval

Phase I FIH (SAD) Study

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Phase Ib Proof of Principle in Patients (Neutrophilic Dermatoses)

  • GLP toxicology completed, CSL324 safe and well tolerated

  • Phase 1 to commence mid-late 2016

28

Global

CSL Research Summary

  • Portfolio of early stage opportunities consistent with CSL commercial objectives

Immunoglobulins Haemophilia

Specialty Breakthrough Products Medicines

  • Delivery of high quality candidates for clinical development

o CSL362 (anti-IL-3R, partnered with Janssen Biotech)

o CSL324 (anti-G-CSFR)

o CSL312 (anti-FXIIa)

29

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Immunoglobulins
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30

Immunoglobulins

  • Maintaining leadership position through focus on:

Immunoglobulins

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Specialty
Products
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o New Indications

o Geographic expansion

o Delivery options

  • Key Focus

o Hizentra[® ]

o Privigen[® ]

31

Immunoglobulins

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Privigen [® ]
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Hizentra [® ]
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• The first and only 10% liquid intravenous immunoglobulin (IVIG) therapy that is proline stabilized with room temperature storage up to 36 months

• The first 20% high concentration low volume SCIG for convenient self administration providing steady-state Ig levels and an established longterm safety record with chronic administration

32

Immunoglobulins Progress in Neurology

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

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  • Build on Privigen[®] experience in CIDP

  • Introduce SC infusion method

o Ease of administration

  • Steady state levels, manages wear off effect

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33

Immunoglobulins PATH Program

  • Pivotal study

o Largest randomised placebo controlled study in CIDP (16 countries/69 sites)

o Study screening completed (n=289)

o 71 patients have completed the primary study

o Last patient completing Q4 2016

  • FDA and EMA submissions 2H 2017

  • PMDA submission 2018

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34

Immunoglobulins Subcutaneous Infusions Made Simple

  • 83% (n=100) patients said medication in its current form was easy to use (120 subject responses at week 9)

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35

Immunoglobulins

Subcutaneous Infusions Can Be Individualised

  • Clinical trial highest dose/volume required – 160mL in avg 80kg patient

  • 4 infusions sites/session/~120 minute infusion time

  • 2 infusion sites/session x 2 days ~60 minute infusion time

  • Infusion volume of 50mL/site well tolerated

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  • Infusion rate of 35 mL/hr tolerated

36

Immunoglobulins Portfolio Expansion in Japan

  • ~3,500 Primary Immunodeficiency patients in Japan PID network (2014)

  • Currently Hizentra[®] and 5% IVIG available to patients

  • CSL will bring first high purity room temperature 10% IVIG product to Japan

  • Commence Privigen[®] PID study Q3/4 2016

o Agreement on study design reached with PMDA

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37

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Commercial Opportunities
and Activities
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38

Global Plasma-proteins Therapeutics Market

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Immunoglobulin
$8.0B
Haemophilia
$10.5B Total Global
Market Value:
~$25.0B
Specialty
$2.9B
Albumin
$3.3B
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Sources: Company annual reports/financial schedules, MRB global Coagulation Factors Concentrate Market 2014 & 2015, MRB WW Plasma Fractionation Market 2014 interim report, CSL Actuals FY15

39

Global

CSL Plasma-proteins Therapeutics Portfolio

CSL FY15 Sales $5.0B

Immunoglobulin Haemophilia Albumin Specialty

$2,326M Immunoglobulin $1,026M Haemophilia $923M Specialty $754M Albumin

40

Immunoglobulins

Global Market

  • IVIG continues to hold largest share of market

  • Increasing acceptance and growth of SCIG

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Hyper
$1.0B
SCIG
$0.6B
Total Global
Market Value:
~$8.0B
IVIG
$6.4B
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Sources: Company annual reports, Markets and Markets Plasma Fractionation Report 2015, based on 2014 data, CSL Actuals FY15

41

Immunoglobulins CSL’s Global Performance

CSL FY15 Sales $2.326B IVIG SCIG Hyper

Key Brands:

42

Immunoglobulins

Continued Market Growth

US-PPTA Data (Kg, 000)

Per-Capita IG Use

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70
USA
Canada
Australia
65
Sweden
8.5% CAGR France
60 Spain
Italy
UK
55 Germany
Japan
South Korea
50 Hong Kong
Singapore
China
45 Poland
Chile
Malaysia
40 Argentina
Brazil
Taiwan
35
Russia
Thailand
India
30
2007 2008 2009 2010 2011 2012 2013 2014 2015 0 20 40 60 80 100 120 140
2015 estimated (grams, per 000 pop)
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Sources: PPTA. Note: PPTA reported incomplete data for 2011. MRB 2011

43

Immunoglobulin Today, Tomorrow, Future

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Today
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Future
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  • • •

  • Privigen[®] CIDP Hizentra[®] CIDP Approval of new growth in Europe and development program indications Canada • • Continued global Pursue new

  • • Hizentra[®] launches therapeutic areas individualized therapy • • Evaluating novel Develop additional

  • • Carimune for select delivery devices formulations markets

44

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Specialty Products
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45

Specialty

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Breakthrough
Medicines
Immunoglobulins
Specialty
Products
Haemophilia
Products
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  • Leveraging high quality broad product portfolio through:

o New markets

o Novel indications

o Novel modes of administration

  • Key Focus

o Beriplex[®] /Kcentra[® ]

o Berinert[®] , CSL830

  • Zemaira[®] /Respreeza[® ]

46

Specialty

Kcentra[®] / Beriplex[®]

  • Prothrombin Complex Concentrate = PCC (4FPCC)

  • Vitamin K-dependent coagulation factors (FII, FVII, FIX, FX)

  • Indicated as an agent to reverse the effects of vitamin K antagonists (e.g. Warfarin) for:

o Bleeding related to over-anticoagulation

o Patients needing urgent surgery

  • Expanding into new geographies

  • Explore utility in treating patients bleeding with receiving Novel Oral Anticoagulants (NOACs) – Factor Xa and Factor IIa inhibitors

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47

Specialty

Beriplex[®] Expansion in Japan

  • Clinical study evaluating vitamin K antagonist reversal in acute bleeding and for surgery

o Open label study almost completed

o Demonstrated effective INR reversal at 30 minutes

o No safety concerns

o PMDA submission Q2 2016

  • Availability of Beriplex[®] will address a high unmet medical need specifically highlighted by Japan Ministry of Health and Welfare

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48

Specialty

Potential New Usage for 4FPCC

Coagulation Cascade and Mechanisms of Anti-coagulation

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FII
FVII FIX
FX
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49

Specialty

Reversal of Anti-coagulation Effect in a Bleeding Patient

  • Antidotes being developed to reverse the anti-coagulation activity of Factor Xa or IIa inhibitors

o Studies demonstrate normalisation of clotting tests

o Bleeding studies not yet available

  • 4FPCCs in healthy volunteers also reverse prothrombin time prolongation

o 50IU/kg Beriplex[®] dose reversed the anticoagulant effect of edoxaban[1 ]

Can bleeding be stopped or controlled to allow for urgent medical or surgical care?

References: 1. Circulation. 2014;CIRCULATIONAHA.114.013445 published online before print November 17 2014

50

Specialty

4FPCC in the Control of Bleeding – Animal Data

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Data represent medial plus interquartile range. Shaded area represents sham treated control range.

References: Pragst et al. JTH 2012; 10(9): 1841-48. Herzog et al. Thromb Res 2014; 134(3):729-36. Dickneite and Hoffman 2014; 111(2):189-98. Herzog et al. Anaesthesiology 2015; 122(2):387-98. Herzog et al. Thromb Res 135 (2015) 554–560. Herzog et al. Critical Care 205; 19(1):P348.

51

Specialty

Kcentra[®] / Beriplex[®] in Treatment of Acute Major Bleeding Related to FIIa or FXa Inhibitor Use

  • USA and international expert groups recommend inclusion of PCC in guidelines as agent to reverse anticoagulant effect of NOACs[1,2,3]

  • Hospital treatment algorithms increasingly including PCC

  • Clinical program under consideration to assess control of severe bleeding

References: 1. Clinical Practice Guide on Anticoagulant Dosing and Management of Anticoagulant-Associated Bleeding Complications in Adults. American Society of Hematology 2011. 2. EHRA Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. European Society of Cardiology 2013. 3. Management of major bleeding complications and emergency surgery in patients on long-term treatment with direct oral anticoagulants, thrombin or factor-Xa inhibitors: Proposals of the Working Group on Perioperative Haemostasis (GIHP) 2013

52

Specialty Hereditary Angioedema (HAE)

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Berinert [® ]
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CSL830
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• • Plasma derived, pasteurised and Plasma derived, pasteurised and nanofiltered concentrate of C1 nanofiltered higher concentrated C1 Esterase Inhibitor indicated for the Esterase Inhibitor indicated for the intravenous treatment of acute routine prevention of Hereditary abdominal laryngeal or facial attacks Angioedema (HAE) attacks in adult of Hereditary Angeiodema (HAE) in and adolescent patients adults and adolescents

53

Specialty Complement Pathway and HAE

-ve -ve -ve

54

Specialty Clinical Presentation

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55

Specialty

The Impact of HAE on Patients

  • HAE is unpredictable

  • All body sites are associated with impairment; not just laryngeal attacks

  • It impacts people not just during attacks, but also in between attacks

  • Attacks are associated with significant anxiety: this anxiety is proportionate to the severity and pain of individual attacks

  • Results in missed opportunities in terms of school and career, as well as significant absences from work for both patients and carers

The HAE-Burden of Illness Study in Europe (HAE-BOIS) 2012-4

References: Caballero T. et al. Allergy Asthma Proc. 2013; Aygören-Pürsün E et al. ISPOR 2012; Bygum et al. Acta Derm Venereo l 2015.

56

Specialty

HAE attack frequency does not link with severity

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----- Start of picture text -----

1-24 25-52 53-104 >104
attacks/year attacks/year attacks/year attacks/year
~78% ~13% ~6% ~3%
Still has significant
disease burden
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57

Specialty

Subcutaneous Dosing Maintains Trough above Protective C1-INH Level

  • SC trough remains above predictive 40% threshold

  • Potential for reduced attack rate

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----- Start of picture text -----

SC l ow IU/kg 40 IU/kg
SC h igh IU/kg 1000 IU
IV 1 000 I60 I U /kg/kg
40%
activity
0 200 400 600 80
Time (hrs)
100
80
60
C1-INH functional activity (%)
40
20
0
----- End of picture text -----

References: Zuraw et al. Allergy 2015; 70: 1319-1328

58

Specialty

CSL830 Program Progress

  • Phase III study rapidly completed enrollment (n=90)

  • Patients moving into extension study

o Allowed for individualised dosing

o Well tolerated

o No withdrawals for lack of efficacy

  • Submission to FDA and EU anticipated 2H 2016

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59

Specialty

Bringing new technologies to the HAE space CSL312 – Anti XIIa monoclonal antibody

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FXIIa MAb
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60

Specialty

CSL312 Development Plan – HAE Therapy

  • New molecule and target – potential benefit:

o In refractive patients

o For HAE types I, II and III as well as ACE inhibitor induced oedema

o For subcutaneous delivery every 2 to 4 weeks

o Other indications

  • Commence first in man studies 2H 2016

61

Specialty

Respreeza[®] / Zemaira[®]

  • Respreeza[®] is a highly purified alpha-1 therapy approved by EMA for maintenance treatment to slow the progression of emphysema in adults with severe alpha-1 antitrypsin deficiency (AATD)

  • RAPID trial is largest placebo controlled study in patients with AATD (Chapman KR et al. Lancet 2015; 386: 360-368)

  • Respreeza[®] approved by EMA in August 2015

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62

Specialty

Alpha-1 Antitrypsin Deficiency (AATD)[1 ]

AAT coats the lungs, protecting them from NE Blood vessel AAT is released from the liver into the bloodstream, where it mops up NE NE is produced by neutrophils – a type of white blood cell – in response to infection / irritation White blood cell (neutrophil)

Lungs lack AAT coating and are open to attack from NE Blood vessel AAT accumulates in the liver, may cause liver damage in some patients Unchecked by AAT, NE attacks healthy lung tissue White blood cell (neutrophil)

References: CSL Behring Data on File. Alpha-1 Antitrypsin Deficiency Counseling Tool 2008

63

Specialty

AATD Leads to Lung Tissue Deterioration

Images from high-resolution computerised tomography scanning

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A B
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normal lung (left; A)

severe emphysema (right; B)

References: http://www.ctsnet.org/portals/thoracic/newtechnology/article-4

64

Specialty

RAPID Program – Respreeza[®] Slowed Rate of Lung Density Decline from Baseline

  • Difference in annual decline from baseline to Month 24 favours Early-Start

  • Lost lung density in the DelayedStart group could not be regained

  • Early-Start group maintained a therapeutic benefit for 4 years

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----- Start of picture text -----

0 A1- Placebo
PI
Annual rate of decline:
-1.37 g/L/year
-2
Annual rate of decline:
Annual rate of decline: -1.08 g/L/year
-4 -2.06 g/L/year
Annual rate of decline:
-6
-1.31 g/L/year
RAPID Trial RAPID extension Trial
(A,-PI N=50, Placebo N=47) (A,-PI N=50, Placebo N=47)
-8
0 12 24 36 48
Month of treatment
Change from baseline (g/L)
----- End of picture text -----

  • *The slopes were estimated based on data from the 50 Early-Start and 47 Delayed-Start subjects who had completed both the RAPID and RAPID Extension trials

References: 1. Chapman, KR et al. Lancet 2015; 386: 360-368. 2. CSL Behring. Data on File. Dec 2013 Interim Analysis of Extension Trial

65

Specialty

Estimate of Long-Term Clinical Benefit[1,2 ]

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Extrapolation of Respreeza [®] effect on the predicted time to reach terminal
respiratory function (data from the RAPID trial) [1,2 ]
•
RAPID program
Projected survival difference
demonstrates a
60
specific treatment A1- No treatment
PI
has been shown to 50
40
delay the -1.5
g/L/yr
30
progression of and
-2.2 g/L/yr
Terminal
modify disease in 20 value
~6 years
patients with severe 10
AATD 0 5 10 15 20
Time (years)
Lung density (g/L)
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Extrapolation based on: 1. Chapman, KR et al. Lancet 2015; 386: 360-368. 2. CSL Behring. Data on File. RAPID Trial Clinical Study Report. November 2013

66

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Commercial Opportunities
and Activities
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67

Specialty

Global Market

  • Orphan/rare diseases

  • Unmet medical need

  • Often under or misdiagnosed

  • Awareness and education

  • Significant patient value

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Other
~$0.3B
Acquired Bleed
~$0.6B
Total Global
Market Value:
~$2.9B
HAE
~$1.2B
AATD
~$0.8B
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Sources: Company annual reports/financial schedules, based on 2014 data, MRB WW Plasma Fractionation Market 2014 interim report, CSL Actuals FY15

68

Specialty CSL’s Global Performance

  • Increase demand

  • Geographical expansion

  • Appropriate diagnosis

CSL FY15 Sales $923M Key Brands: Acquired Bleeding Other HAE AATD

69

Specialty

Acquired Bleeding (Beriplex[®] /Kcentra[®] )

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Warfarin Reversal
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NOAC Reversal
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  • Indicated for patients with acute major bleeds, requiring urgent surgery or invasive procedure

  • Evaluating clinical development options

  • Data published in Lancet

  • Potential benefit in patients with significant bleeds

  • Utilised by over 2,000 hospitals in the US

  • Institutional guidelines, expert groups and scientific societies

  • Broad EU experience and expansion in emerging markets

  • Animal and human data published in peer-review journals

  • Japan clinical development program ongoing

  • Prospective registry data

70

Specialty

Hereditary Angioedema (HAE)

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----- Start of picture text -----

Berinert [® ]
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----- Start of picture text -----

CSL830
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----- Start of picture text -----

CSL312
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  • • •

  • C1-INH for acute C1-INH for prophylaxis Fully human, high treatment affinity mAb targeting • Phase III pivotal study FXIIa

  • • Fast relief of pain and fully enrolled •

  • swelling Activation of FXIIa is • Subcutaneous delivery key step in complement

  • • Short-term prophylaxis pathway in EU • Steady-state blood •

  • levels could reduce Effective in animal

  • • Geographic expansion breakthrough attacks models for HAE I, II and (Asia, LATAM) III and ACE inhibitor • induced oedema Eliminates need for patient IV ports • Subcutaneous delivery

  • • every 2 to 4 weeks US and EU filing targeted for 2016 • Phase I 2H 2016

71

Specialty

AATD (Hereditary Emphysema)

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----- Start of picture text -----

Zemaira [® ]
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----- Start of picture text -----

Respreeza [® ]
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  • •

  • Indicated in the US for chronic Approved in the EU for hereditary augmentation and emphysema 3Q2015 maintenance therapy

  • EU API market is ~$200M USD

  • Ongoing education programs to support appropriate diagnosis

  • DNA1 test kit to confirm known/unknown variants

  • Demonstrated to slow the progression of emphysema

  • Rapid data published in the Lancet

  • Geographic expansion in Latin America

  • Only highly purified formulation available in EU

72

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Q&A
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73

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----- Start of picture text -----

Break
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74

December 10, 2015

75

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----- Start of picture text -----

Haemophilia Products
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76

Haemophilia

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----- Start of picture text -----

Breakthrough
Medicines
Immunoglobulins Specialty
Products
Haemophilia
Products
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• Supporting and enhancing plasma products and developing novel recombinant portfolio with focus on:

o Scientific and product innovation o Patient benefit

  • Key Focus

o IDELVION[TM] (rIX-FP)

  • AFSTYLA[TM] (rVIII-Single Chain)

o Long acting rVIIa-FP

77

Haemophilia

PROLONG-9FP Clinical Development Program IDELVION[TM] (rIX-FP)

References: www.clinicaltrials.gov

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78

Haemophilia rFIX Albumin Fusion Protein

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----- Start of picture text -----

Activation cleavage sites
Factor IX Albumin
ASP PP AP Linker
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..NWIKEKTKLTPVSQTSKLTRAETVFPDVDAHKSEVAHR..

• rIX-FP is

o A recombinant protein purified from CHO cells

o Generated by the genetic fusion of recombinant albumin to rFIX

PROLONG-9FP PROGRAM

Prove longer duration of action of rIX-FP addresses existing unmet medical needs by providing less frequent dosing

79

Haemophilia

PROLONG-9FP Clinical Trial Program

Phase I

Phase I/II

Phase II/III

  • PK • PK

  • PK

  • Safety • Long-term safety

  • Long-term safety

  • Weekly prophylaxis • 7-, 10-, and 14-day prophylaxis

  • On-Demand treatment

  • On-demand treatment

  • Surgical prophylaxis

Phase III

  • In children

  • PK

  • 7-day prophylaxis

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Phase IIIb (extension)

  • 21 day prophylaxis

  • Surgical arm

  • PUPs arm

Study 2001

Study 2004 Study 3001 Study 3002 Study 3003 COMPLETED ONGOING

PK – pharmacokinetics; PUP – previously untreated patient

80

Haemophilia

Adult Study Flow Chart (Study 3001)

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----- Start of picture text -----

Period: Screening PK Treatment EOS
Up to 14 days
30 days
On-Demand
Group 2
On-demand 7-day prophylaxis
rIX-FP
Subject
Flow: PK 14-day prophylaxis
Prophylaxis 7-day prophylaxis 10-day prophylaxis
Group 1 7-day prophylaxis
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PK assessments were repeated in a subset of patients at Week 26; patients who met the switching criteria began a longer treatment interval EOS – end of study; PK – pharmacokinetics

81

Haemophilia

IDELVION[TM] shows sustained activity above 5% activity out to 14 days

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----- Start of picture text -----

80
70 Previous FIX 12-65y (n=12)
rIX-FP 50IU/kg 12-65y (n=46)
60
50
40
Day 7
30
13.8
Day 10
9.6
20 Day 14
6.1
10
5% activity level
0
0 24 48 72 96 120 144 168 192 216 240 264 288 312 336
Hours
FIX Activity (IU/dL, %)
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• Shifts patient from severe <1% to mild ≥ 5% FIX activity

*WFH Guidelines for the Management of Hemophilia. 2[nd] Edition. Hemophilia; Epub 6 July 2012

82

Haemophilia

rIX-FP prophylaxis reduced spontaneous and overall bleeding rate

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----- Start of picture text -----

Within-subject comparison (n=19)
rIX-FP
Adult On-Demand vs. AsBR
Prophylaxis On-demand Prophylaxis reduction
period period
~6 months ~12 months
15.43 0.0 100%
AsBR, median (IQR)
(7.98–17.96) (0.00–0.96) (p<0.0001)
Target joint(s), n (%) 10 (53) 0
Estimated total ABR 18.22 1.81
(95% CI) (15.38-21.58) (0.97–3.37)
----- End of picture text -----*

*Assuming Poisson distribution

ABR – annualised bleeding rate; AsBR – annualised spontaneous bleeding rate; CI – confidence interval; IQR – interquartile range

83

Haemophilia

rIX-FP Effective in 7 and 14 days regimens in Adults

Within-subject comparison Within-subject comparison
7-day
n=21		 14-day
n=21
AsBR, median (IQR) 0.0
(0.0, 0.0)		 0.0
(0.0, 1.0)
Median dose (IU/kg) 40 IU/kg 75 IU/kg

AsBR – annualised spontaneous bleeding rate; IQR – interquartile range

84

Haemophilia

Paediatric Reduction of ABR among previously on-demand patients

Subject Age AsBR AsBR Total ABR Total ABR Weekly rIX-
FP dose
(IU/kg)
Prior to study In study Prior to study In study
1 8y 31 3.5 39 5.9 65 IU/kg
2 7y 34 2.4 42 4.7 65 IU/kg
3 4y 15 0 19 1.2 50 IU/kg

ABR – annualised bleeding rate; AsBR – annualised spontaneous bleeding rate

85

Haemophilia

Low Bleeding Rates During Weekly Prophylaxis Treatment in Children

References: 1.Data include 3 subjects previously
receiving only on-demand treatment; 8 treated
nasal bleeds		 ABR Age <6 years
(n=12)		 Age 6-11
years
(n=15)
Spontaneous Median 0.00 0.78
IQR 0.00, 0.10 0.00, 1.99
Total Joint Median 0.5 1.13
IQR 0.00, 1.45 0.00, 2.36
Total Median 2.61 3.4
1
IQR 2.00, 6.48 0.76, 5.91
Prophylaxis
IU/kg		 Median 48.7 42.6
IQR 44.8, 56.2 40.4, 51

ABR – annualised bleeding rate; IQR – interquartile range

86

Haemophilia

Patients respond to long-term prophylaxis therapy (4.2 years) in PROLONG-9FP program

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----- Start of picture text -----

30
Spontaneous ABR
25
Total ABR
20
15
10
5
0
ODT 7-day PT 14-day PT
Mean Annualized Bleeding Rate
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Reduction in ABR and AsBR in patients moving from on-demand to long term prophylaxis

15 males (ages 15-46 years) with hemophilia B (FIX ≤2%) with a mean of 175 Exposure Days (EDs) (range 121-232) to rIX-FP over 4.2 years on rIX-FP

87

Haemophilia

PROLONG-9FP Program

  • Extension study ongoing EMA post marketing commitment

o Previously untreated patients being enrolled

  • Adult and pediatric indications under review by EMA and FDA

  • FDA and Canadian approval expected Q1 2016

  • EMA approval expected Q2 2016

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88

Haemophilia rVIII-SingleChain (CSL627)

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Me [++ ]
A1 A2 A3 C1 C2
rVIII-SingleChain
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89

Haemophilia AFFINITY Clinical Trial Program

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----- Start of picture text -----

Phase I/III Study 1001 - COMPLETED Phase III Study 3002 Extension Study 3001
• PK • Pediatric • Adult
• Long-term safety COMPLETED • Pediatric
• On-demand treatment • PUPs
•
Long-term prophylaxis
•
Surgical prophylaxis
Study 3001
Ongoing
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90

Haemophilia

AFFINITY Study demonstrated

  • Improved PK:

o Lower clearance, greater AUC and longer half-life compared with otcocog alfa

  • Well tolerated locally and systemically

  • Excellent efficacy controlling bleeds and for surgical procedures

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91

Haemophilia

rVIII-SingleChain effective in 2x and 3x weekly Prophylaxis Regimen

  • On demand arm (n=27)

  • median ABR = 19.64

  • Prophylaxis arm (n=146)

  • median ABR = 1.14

  • median AsBR = 0.00

  • Comparable ABR in the 2x and 3x week regimens

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ABR – annualised bleeding rate; AsBR – annualised spontaneous bleeding rate

92

Haemophilia

rVIII reported* Median ABR

Individualized
(mean 3.5 days)		 Individualized
(mean 3.5 days)		 3x Weekly 3x Weekly 2x Weekly 2x Weekly Weekly Weekly
ABR AsBR ABR AsBr ABR AsBr ABR AsBr
rVIIISC 1.14 0 1.14
(20-50IU/kg)		 0
Efmorotocog alfa1
(rVIII Fc fusion)		 1.6
(25-65IU/kg)		 3.6
(65IU/kg)
BAX8552
(rVIII pegylated)		 1.9
(40-50IU/kg)		 0
Octocog alfa3
(rVIII 3rdgeneration)		 4
Turtucog alfa4
(rVIII 3rdgeneration)		 3.7

*Not direct head to head clinical comparison

References: 1. Mahlangu, J et al. Blood 2014;123(3):317-25. 2. Adynovate full prescribing information Baxalta Nov 2015. 3. Kavakli K et al. J Thromb Haemost 2015;13:360-9. 4. Lentz SR et al. Haemophilia 2013;19(5):691-7

ABR – annualised bleeding rate; AsBR – annualised spontaneous bleeding rate

93

Haemophilia

rVIII-SingleChain AFFINITY Program

  • Extension study ongoing fulfilling EMA post marketing commitment

o Previously untreated patients being enrolled

  • Accepted by FDA June 2015, approval expected mid 2016

  • Filed to EMA December 2015

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94

Haemophilia rVIIa-FP (CSL689)

rFVIIa Linker rAlbumin

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95

Haemophilia

Congenital Haemophilia with Inhibitors (CHwI)

  • Occurs when patient develops inhibitory antibodies to the coagulation factor (FVIII or FIX)

  • Genetic predisposition / mutations

  • Occurs early, highest risk in previously untreated patients

o 34% inhibitor incidence, develop within 20 exposures

References: Peyvandi et al. https://ash.confex.com/ash/2015/webprogram/Paper82866.html

96

Haemophilia

Role of rVIIa-FP in CHwI

  • rVIIa-FP can lead to the formation of a stable hemostatic plug to control bleeding

  • works locally by binding to tissue factor exposed at the site of vascular injury

  • Also binds to factor X on activated platelets

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97

Haemophilia

CSL689 has longer half life than rFVIIa

  • CSL689 half-life = 8.5 hrs[1 ]

o Potential to dose 2-3 x weekly

  • Possibility of on demand and manageable prophylaxis regimen

  • rFVIIa (Novoseven) half life ~2-3hrs

o Indicated for treatment of bleeding episodes- requires dosing every 2-3 hours[2 ]

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References: 1. Golor G et al. J Thromb Haemosras 2013 Nov;11(1):1977-85. 2. NovoSeven Full Prescribing Information USA

98

Haemophilia

rVIIa-FP Clinical Development Program

Congenital Haemophilia with Inhibitors

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Phase I (Healthy Volunteers)
PK
Safety
COMPLETED
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----- Start of picture text -----

Phase III
Prophylaxis
Surgery
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• Pivotal Phase II/III trial in haemophilia A & B patients with inhibitors o Dose finding, safety & efficacy on-demand therapy o Commenced first half 2015

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o Bleeding episode successfully treated

99

Haemophilia PROLONG-7FP Clinical Development Program

Congenital Factor VII Deficiency

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----- Start of picture text -----

Phase II/III
Prophylaxis
On-demand
PLANNING
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EXTENSION

  • Phase I PK/PD study in congenital FVII deficiency patients

o PK and safety in patients

o Commenced December 2014

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10 0

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Commercial Opportunities
and Activities
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10 1

Haemophilia

Global Market

  • Trend toward recombinants in developed markets

  • New longer-acting product launches

  • 75% of patients with bleeding disorders are under/un-treated

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----- Start of picture text -----

VWD
$0.5B
Hem B
$1.3B
Total Global
Inhibitor Market Value:
Bleed
Therapy ~$10.5B
Hem A
$2.2B
$6.5B
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Sources: Company annual reports/financial schedules, based on 2014 data, MRB global Coagulation Factors Concentrate Market 2014 & 2015, Hemophilia World, December 2013, Vol 20. No 3, CSL Actuals FY15

10 2

Haemophilia CSL’s Global Performance

Grow range of differentiated pd and recombinant therapies

  • Broad portfolio presence

  • Growth in developed and emerging markets

  • Continued balance between recombinant and plasma derived portfolio

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CSL FY15 Sales $1,026M Key Brands:
Recombinant
Plasma
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10 3

Haemophilia

Key Growth Drivers

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----- Start of picture text -----

Breakthrough
Medicines
Immunoglobulins Specialty
Products
Haemophilia
Products
----- End of picture text -----

  • Successfully launch the new recombinant products globally

  • Position Idelvion[TM] (rIX-FP) as the new SOC for haemophilia B

  • Afstyla[TM] (rVIII-SingleChain) product profile highly competitive

10 4

Haemophilia

Idelvion[TM] (rIX-FP)

  • Unique recombinant albumin fusion protein molecule

  • Pharmacokinetic profile includes extended half-life and greater area under the curve (AUC) resulting in increased activity levels

Attributes of Albumin

Potential Differentiated Profile

  • Naturally occurring protein

  • Dosing interval up to 14 days

  • Binds endogenous components

  • Trough level ≥5%

  • Not associated with immune

    • Zero median AsBR

  • response

  • Long serum half-life

  • Well tolerated

  • No inhibitors in pivotal program

10 5

Haemophilia

Afstyla[TM] (rVIII-SingleChain)

  • Single chain design with most of B-domain deleted

  • Covalent link between heavy and light chains

Single Chain Design

Potential Differentiated Profile

  • Strong affinity to vWF

  • Twice-weekly dosing

  • Greater molecular integrity and stability

  • Effective bleeding control

  • Well tolerated

  • Improved pharmacokinetic profile

  • No inhibitors in pivotal program

10 6

Haemophilia

rVIIa-FP

  • Prophylaxis and treatment of adult, adolescent and pediatric patients with congenital haemophilia A or B with inhibitors and congenital FVIIa deficiency

Attributes of rVIIa-FP

Potential Differentiated Profile

  • Unique recombinant albumin fusion protein molecule

  • Fast, effective on-demand treatment in majority of patients

  • Significantly longer half-life

  • Extended dosing interval ~3 x per week

  • Therapeutic effect allows for more convenient prophylaxis

  • Major improvement to patient care

10 7

Haemophilia Today, Tomorrow, Future

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Today
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----- Start of picture text -----

Future
----- End of picture text -----

  • • •

  • Helixate[® ] Idelvion[TM ] rVIIa–FP

  • • • • Beriate[® ] Afstyla[TM ] Subcutaneous rIX-FP

  • • • Humate[® ] True long-acting rVIII

  • Mononine[® ]

10 8

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Breakthrough Medicines
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10 9

Breakthrough Medicines

  • Leveraging clinical and technical insight in developing novel proteinbased therapies

Breakthrough Medicines

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----- Start of picture text -----

Haemophilia
Products
----- End of picture text -----

o Significant unmet need o Multiple indications

  • Key Focus

  • CSL112 (Apo AI)

o CSL324 (anti-G-CSFR mAb) o CSL346 (anti-VEGFB mAb) o CSL312 (anti-FXIIa mAb)

11 0

Breakthrough Medicines

Acute Coronary Syndrome (ACS)

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11 1

Breakthrough Medicines

Reduction of Early Recurrent Cardiovascular Events – A High Unmet Medical Need in ACS

  • Recurrent CV events occur early, are associated with high mortality and are inadequately addressed by available therapies

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References: Figure adapted from PLATO Trial, Kohli P et al. Circulation 2013;127:673-680

11 2

Breakthrough Medicines

Cardioprotective Role of High Density Lipoprotein

  • HDL exerts cardio protective effect through cholesterol efflux

o movement of excess cholesterol from arterial-wall macrophages

o leads to reduction in plaque size and risk of rupture

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----- Start of picture text -----

Cholesterol Efflux Capacity (CEC)
Inversely Associated with
CV Events
Lowest CEC (quartile 1)
CV risk
67%
Highest CEC (quartile 4)
Years
Participants with event (%)
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References: Dallas Heart Study, New England Journal of Medicines, Nov 2014

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Breakthrough Medicines

CSL112 raises ABCA1 Cholesterol Efflux Capacity

  • Impaired cholesterol efflux, inflammation and plaque rupture, all exist in the setting of ACS

  • Contribute to the high incidence of early recurrent cardiovascular events

  • CSL112 results in a profound, immediate and sustained rise in ABCA1 specific cholesterol efflux capacity

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Phase 2a Study in patients with stable atherosclerotic disease

References: Gille et al. (2014) presented at AHA.

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Breakthrough Medicines

CSL112 – A Novel Therapy for Acute Coronary Syndrome

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Cholesterol removal from
atherosclerotic plaque
CSL112
infusion
Liver uptake
Biliary excretion
Atherosclerotic plaque lesion
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CSL112 has the potential to rapidly reduce the high rate of early recurrent CV events, addressing a significant unmet medical need in ACS.

References: Modified from Kingwell & Chapman. Circulation 2013;128:1112-1121

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Breakthrough Medicines

CSL112 Phase 2B

Proof of mechanism and demonstration of safety

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Randomisation
N = 1200
Four Weekly Infusions
High dose (6 gms) Low Dose (2 gms) Placebo
N = 400 N = 400 N = 400
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  • 1,258 patient post myocardial infarction trial fully recruited

  • Data Monitoring Committee has confirmed safety to date

  • Biomarker data to confirm mechanism of action – 2H 2016

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x Breakthrough Medicines x Clinical Program

  • Phase 2b Dose-ranging / POC Moderate RI safety (Ph2) • • ACS population Higher risk ACS population

  • • • Safety, efflux biomarker, pop PK Safety, pop PK

  • • • Normal and mild RI Start up stage

  • • Enrollment completed LPLV Q2 2016 Phase 3 Pivotal Trial • ACS treatment target population

  • • CV event benefit (MACE) and safety risk

  • • 1[0] endpoint: MACE

  • • Design and planning stage

• Planning for Phase 3 commenced

o Strategy in place for inclusion of high risk patients in Phase 3 o Anticipating commencement in 2H 2017

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Influenza Vaccines R&D
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Vaccines

Core Flu Products

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  • Differentiated, adjuvanted influenza vaccine for 65yr+ and young children

  • • Elderly indication approved in >30 countries (US approval Nov 2015)

  • Paediatric indication in Canada

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  • World’s first cell-culture flu vaccine

  • • Currently registered for 18yr+

  • QIV 4yr+ anticipated in 2016

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  • Traditional egg-based vaccine

  • • Currently indicated for 5yr+

  • • QIV 18yr+ anticipated in 2016

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  • First and only intravenous influenza anti-viral

  • Currently registered in the US for 18yr+

  • Plans for global rollout[1] and paediatric indication

1. Seqirus rights exclude Japan, South Korea, Taiwan, Israel and US Government stockpile

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Vaccines Key R&D Programs

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TIV Filed • Expanding age indication to 4yr+
Cell culture QIV Filed • Filed for US approval
Anticipate launch in 2016
Adjuvanted QIV Phase III • Filing in 2016
QIV Filed • Age ≥ 18 yrs
Anticipate soft launch in 2016
QIV Phase III • Age ≥ 5yrs, filing 2016
QIV Phase III • Age ≥ 6mo, filing 2017
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Summary
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12 1

Global

R&D Portfolio – December 2015

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Research Pre-clinical Phase I Phase II Phase III Registration Commercial/
Phase IV
CLINICAL DEVELOPMENT REGISTRATION / POST LAUNCH
Immunoglobulins
Haemophilia
Life Cycle
Specialty
Management [# ] Products
Influenza
Vaccine
Hizentra [®] CIDP
C1-inh New
Privigen [®]
Market Indications Japan
Development Fibrinogen New Beriplex® Kcentra [TM] US
Indications Japan Bleeding /Surgery
PCC New CSL830 Respreeza [® ]
Indications C1-INH subcut EU
Ig Formulations
Rec Coagulation CSL650 CSL689 rVIIa-FP CSL689 rVIIa-FP CSL654 rIX-FP
Factors rvWF-FP Congen Def Inhibitors
CSL627 rVIII-SC
Partnered Vaccine Partnered Vaccine Partnered Vaccine
Programs Programs Programs
New Product
P. gingivalis/POD CSL334 IL-13R CSL362 IL-3R
Development
OH-CRC ASLAN AML Janssen
CSL312
CSL112
Discovery Anti-FXIIa
reconstituted HDL
Projects
CSL324 G-CSFR
CAM3001 Quadrivalent
CSL346 VEGFB GM-CSFR –AZ Flu Vaccine
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Core Capabilities:

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Immunoglobulins
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Haemophilia
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Specialty Products
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Breakthrough Medicines
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Vaccines & IP
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*Partnered Projects

LCM includes direct post marketing commitments as well as pathogen safety, capacity expansions, yield improvements, new packages and sizes for all registered products

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Global

Expected Progress in next 12 Months

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Privigen
Nebulised Ig
Japan
CSL640 rIX-FP rIX-FP
rIX-FP subct Japan US Approval
Mod VWF rVIII-SC rIX-FP
LA rVIII Japan EU Approval
Haptoglobin/ rVIII-SC
Hemopexin US Approval
CSL312 CSL830 rVIII-SC
Anti-FXIIa C1-INH s.c. EU Approval
CSL324 Beriplex [® ]
G-CSFR Japan
Afluria [®] QIV
CSL362
18+ years
Janssen SLE
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Global

Significant Target Launch Dates

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2015 2016 2017 2018 2019 2020
Voncento™ CSL654 CSL654 CSL689 rVIIa-FP
V WD EU rIX-FP US rIX-FP Japan Inhibitors
CSL654 CSL627 rVIII -SC
rIX-FP EU EU/Japan
CSL627
rVIII-SC US
Respreeza [®] CSL830 C1-INH
EU SubCut
Beriplex [® ]
Japan
Hizentra [® ]
CIDP
Cell Culture Privigen [® ]
QIV Japan PID/SID
Fluad US Afluria/Fluvax Adjuvanted
Elderly+ QIV 18+ QIV
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Core Capabilities:

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Immunoglobulins
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Haemophilia
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Specialty Products
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Vaccines & IP
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  • Calendar Years

12 4

Global

2015 Highlights

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Immunoglobulins
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  • Hizentra[®] flexible dosing registration in US • Hizentra[® ] CIDP pivotal study recruitment completed

  • Respreeza[®] registration in Europe

  • Specialty Products • Berinert[®] s.c. pivotal Phase III recruitment completed

  • rIX-FP effective in 7-14 day dosing regimens & MAA submitted

  • •

  • Haemophilia rVIII-SingleChain effective 2x weekly prophylaxis & MAA submitted • rVIIa-FP inhibitor Phase I/II commenced •

  • Breakthrough CSL112 (Apo A-1) Phase IIb study recruitment completed •

  • Medicines Anti-FXIIa mAb pre-clinical development completed

  • Licensing & Fluad registration in the elderly in the US •

  • Vaccines CSL362 Phase II AML study commenced by Janssen

12 5

R&D Briefing

12 6

Global

Further Information

Presentation Playback

A playback of the Research and Development presentations will be available for a period of two weeks following R&D Briefing. Investors wishing to listen to these presentations should contact CSL Investor Relations to arrange access. Contact: [email protected]

Investor Relations:

Mark Dehring Head of Investor Relations CSL Limited Phone: +613 9389 2818 Email: [email protected]

Media:

Sharon McHale Head of Public Affairs CSL Limited Phone: +613 9389 1506 Mobile: +614 0997 8314 Email: [email protected]

12 7

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