Dr. Stefan Müllner - BioTech Pharma Summit...2020/07/06 · Psoriatic Arthritis (MEASE 2004, 24weeks, PsARC and ARC50) 30 - 63 M Rodgers et. All Health Technology Assessment 2011;

Dr Stefan MuumlllnerPorto October 26 2017

Options for Biomarker based Patient Stratification

in NON-ONCOLOGY Clinical Development

Dr S Muumlllner Porto 26102017 wwwfundamentade

The Current Status in Pharma


3

What if the FDA decides tomorrow that all new drug

approvals require Companion Diagnostics (CDx)


Response Rate of Standard TherapiesDisease

Average of

non-

Responders

Author Citation

Rheumatoid Arthritis (ACR20) 28 - 58 Craig Beavers et alOrthopedics

January 2010 - Volume 33 middot Issue 1

Ankylosing spondylitis (ASAS

20)40 C McLeod et al Health Technol Assess 2007111ndash158

Psoriatic Arthritis (MEASE

2004 24weeks PsARC and

ARC50)

30 - 63 M Rodgers et All Health Technology Assessment 2011 Vol 15 No 10 p19

SLE (EULAR 2009) 45 Merrill EULAR 2009 Benlysta BLISS 52 and 76

Lupus Nephritis 44 - 47 G Apple JAm Soc Nephrol 2009 Cellcept vs Cyclophosphamide

Multiple Sclerosis 50Communication of DMSG on

Fingolimod

httpwwwdmsgdemultiple-sklerose-

newsindexphpw3pid=newsampkategorie=therapienampanr=

2310

Crohns Disease - Primary non

responders to anti TNF-alpha30 - 40 Remo Panaccione MD FRCPC

Advanced Therapy of Inflammatory Bowel Disease

Volume 2 IBD and Crohns von Theodore

BaylessStephen B Hanauer

Crohns Disease - Secondary

non responders to anti TNF-

alpha

30 - 40 Remo Panaccione MD FRCPC httpwwwmedscapeorgviewarticle578444_3

Ulcerative Colitis 41 - 50 Walter Reinisch et al Gut 201160780e787 Results of NCT00385736

Epilepsy (Lacosamide) 59 - 67 E Ben-Menachem Epilepsia 2007 48 (7) 1308-17

Epilepsy (Zonisamide) 50 MJ Brodie Epilepsia 2005 46(1)31-41

Parkinsons Disease

(Rotigotine)52 RL Watts et al Neurology 200768(4)272


The Pharmaceutical Industry needs to

change


Anti-Rheumatics Top 10 Pharmaceutical


Market Size

In 2016 Global anti-rheumatic drugs sale $533 billion in 2016

Abbvie a global pharmaceutical company still dominates the anti-rheumatic

market with the market share of 302 and Humira from Abbvie

with $165 billion in sales

Connective Tissue Diseases

Rheumatic diseases are chronic diseases involving the inflammation and severe

pain in joints tendons ligaments bones and muscles Hence medical

researchers have devoted their time and efforts to develop effective drugs for

the treatment of these diseases

Epidemiology

Clinical research has identified that people with the age between 40 and 50

suffer mostly from rheumatic diseases However elderly patients and children

may also suffer from these conditions According to a study around 30 percent

of people of the world suffer from rheumatic diseases more than 46 million

Americans

7

Market of Anti-Rheumatics

Not yet any CDx on the market or required for approval


Patient Stratification Benlysta (SLE) Case Study

Quantifiable Benefits for Patient Stratification

Clinical savings already represent a strong driver to use biomarkers

4000 patients

screened for

eligibility in

Phase III based

on AAB

Regulatory Approval

2500 patients

enrolled with

positive

outcome

Phase II Phase III

Phase II failed

but association

between

outcome

and AAB was found Approval

First drug in Lupus

in last 50 years

1500 patients

(not enrolled)

30000 $patient

(fully loaded

costs in Phase III)

Savings

45 M $


The Chance and the Challenge

VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx

Fingerprinting Blood provides Big Data Opportunities


Precision Medicine - Current Status


Following a successful Example

Oncology Dx and CDx

1Source Frontiers in Oncology 16th May 2014 lsquoCompanion Diagnostics for Targeted Cancer Drugs ndash Clinical and Regulatory Aspectsrsquo and Jasen2Pharmgenomics Pers Med 2015 8 99ndash110Published online 2015 Mar 31 rsquoThe current and future state of companion diagnosticsrsquo 1

11

Genomic solutions for Oncology dominate

the molecular Dx amp CDx market

Autoimmune Diseases are 10-20 years behind

Regulatory Requirements and Guidelines will come soon

Genomics ndash Current Bench Mark in Precision Medicine

Microbiome

analysis

Detection

of disease risks

Personalization

of therapiesIdentification

of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response

Companion Diagnostics (CDx) Development

bull More than 46 of all therapies are linked to biomarkers

bull Immuno oncology will generate a 30$B market and guidance

for treatment is required

bull Chronic diseases are at the start for targeted patient

stratification

bull More than 25 companies are actively developing therapies

targeting the microbiome across 13 diseases turning into a

relevant CDx area

bull Liquid biopsy testing is seen as a major growth driver

bull Stratification of patients enables economic clinical trials

smaller in size with faster success and lower attrition rates

bull Next-Gen Sequencing (NGS) is rapidly adopting and will

further expand to clinical genomic testing

bull Transformation from sample prep to bioinformatics analysis

will revolutionize future clinical testing and data reporting

Scope of Companion Diagnostics

The challenge The demand

Biomarkers confirmed

Diagnostic partner technology identified

Attrition and timelines of clinical program

Complete CDxtoolbox workflow

Cost-effective Efficient to operate

Many barriers hampering CDx development bdquoOne Stop Shop Sellingldquo partner requested

Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance

Key Areas in Precision Medicine

Relevance () ndash Next 5 Years

95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends

Immuno OncologyCombinatorial Drug Testing

Patient MonitoringFrequent Testing

Human MicrobiomeSurrogate biomarkers

Data ReportingEnabling Bioinformatics

GI Gastro Intestinal ID Infectious Diseases Source Hanson Wade Survey Analysis


bull Pharmaceutical companies developing targeted therapies

choose an external diagnostic partner to access

technology and in vitro diagnostic expertise

bull More than 300 company press releases about CDx

relationships Partnership types were

bull 51 Development developing a companion diagnostic

product for a companyrsquos pre-existing drug candidate

bull 21 Licensing exclusive license between 2 companies

on CDx development and commercialization

bull 16 Commercialization agreement on Rx-Dx co-

commercialization in various market regions

bull 15 RampD Collaboration permission to use a

diagnostic test for drug candidates or funding from the

Pharma company for RampD on a CDx

16

Types of Partnerships between

Pharma and Diagnostic Industry

Biomarkers are Key and fueling the

CDx Program

Full biomarker use

(100 of trials)

Moderate biomarker use

(20-50 of trials)15

Heavy biomarker use(50-99 of trials)

Low biomarker use

(lt20 of trials) 26

21

38

47

Number of biomarkers in clinical Phase III trials

SOURCE ClinicalTrialsgov httpwwwnaturecomnrdjournalv14n12fullnrd4759html

Number of biomarkers by Pharma companies

Clinical Trial Programs

- Cumulative success rates of oncology trials from Phase I to launch remain le12

- Attrition rate is defined by percentage of likelihood of moving to next clinical phase

- Inconsistently achieving superior reimbursement for use of Companion Dx

A challenge remains the high attrition rate of trials amp superior reimbursement

Majority

of CDx

programsAttrition rate ~60

Attrition rate ~40

AR ~32

How to develop a better CDx

Example Gene ndash EGFR) | Variant ndash L858R | Therapy ndash Iressa

bull Test 1 Limit of detection 1261 ndash Qiagen ndash PCR Technology

bull Test 2 Limit of detection 82 ndash ThermoFisher ndash NGS Technology

Both FDA approved Both Technologies have high Sensitivity

Needs for development

1 Specific and sensitive Technology

2 Regulatory Approval with reference material and clinical studies

1 therascreen EGFR RGQ PCR Kit

2 The Oncominetrade Dx Target Test FDA Summary of Safety and Effectiveness Data

Details provided on this slide from wwwsens-idcom

Patient material Engineered Reference Material

Source comparable to human Human or Bacteria (plasmids)

Allelic frequency variable controlled and specific

RNA Expression variable controlled

Protein Expression variable controlled

Certified No YesNo (Depending on provider)

Any Biomarker No Virtually yes

The earlier you can treat the better

-Consequences for Test1 and 2-

The more sensitive your CDx the better for the patient

Details provided on this slide are wwwsens-idcom assumptioins

Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late

Treatment Possibility

0 41 2 3

LOD (Test 2)

LOD (Test 1)

LOD = Limit of detection


The Current Status in Precision Medicine

Autoimmune

Autoimmune Diseases and CDx Development

The auto-immune market is forecasted at $75bn (2018) with RA 45 followed by MS

At the edge to enter into clinical testing

- first clinically relevant biomarkers are emerging

- huge diagnostic potential deriving from CDx and monitoring testing

RA Rheumatoid Arthritis MS Multiple Sclerosis


DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are

bull a constitutive and dynamic components of the immune system

bull present in blood of diseased and healthy individuals

bull changing specifically with the development of diseases and treatment

bull useful for diagnostics patient stratificationCDx and precision medicine

bull enable retrospectiveprospective studies

-23-


Arbuckle et al (2003) Development of autoantibodies before the clinical onset of systemic lupus erythematosus

N Engl J Med 349(16)1526-33

Retrospective case study in systemic lupus erythematosus (SLE)

bull using US Dept of Defense Serum Repository samples

bull detection of established diagnostic SLE-autoantibodies

bull autoantibodies present many years prior to diagnosis

Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon

Expression Libraries bull High-throughput production

of human proteins

Protein Arraysbull Nitrocellulose or

bead-based arrays

Informationbull Measurement of patientsrsquo

polyclonal antibody pool

High-Throughput technology with human proteins as analytes

Serum based no need for tedious sample preparation

-25-


Challenges in CDx Development

Other Indications and Technologies

Proteomics ndash Protein Biomarkers in Serum

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4


Adapted from Leigh Anderson 2002 Randall Nelson 2008

Protein Analytes in Serum and Plasma


bull Variability exacerbated by disease heterogeneity and

sample complexity

bull Generally little to no routine use of internal standards or

reference materials

bull Candidate qualificationvalidation remains a significant

barrier to adoption of biomarkers

bull Many (including underpowered ill designed) studies

made it into the scientific peer review literature

bull Cited in subsequent (including underpowered and ill-

designed) studies as confirmatory fact (pseudo-validation

by literature)

S The Biomarker Dilemma

Over 1200 proteins are published as biomarker candidates

for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4

Proteomics Technologies


The ldquoBlack Holerdquo Validation of Protein Biomarker Candidates

Adapted from Leigh Anderson PPI

Biomarker Development



Liquid Biopsy

Longitudinal testing becomes Reality

Initial diagnosis Monitoring helliphellip Monitoring hellip Monitoring hellip


Liquid Biopsy is a significant Market Opportunity

Sources JP Morgan estimates

Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant

Liquid biopsy is a potentially disruptive

approach that can guide physicians in

choosing the appropriate course of therapy

We segment the market opportunity into four

distinct applications

Key Focus Area


Reality or Hype Only few people benefit

from Cancer Immunotherapy

69

bull Immunotherapy a new form of cancer therapy uses

the bodyrsquos own immune system to fight cancer

bull The first checkpoint inhibitor (CPI) was approved in

2011 this class of drugs unleashes the bodyrsquos

immune system against cancer and is the subject of

much enthusiasm

bull The percent of cancer patients who might actually

benefit from immunotherapy is much smaller

surprising given the way these drugs are described

bull The low percentage of people benefiting from cancer

immunotherapy may not change greatly

bull Doctors researchers the pharmaceutical industry

reporters patient advocates mdash all use sensational

language to describe these drugs

bull Navigating the waters of accurate information and

reasonable hope is a big challenge for oncology

Not approved

Checkpoint inhibitors(IO specific compounds)

Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology


A new Concept introduced by the FDA

bull Companion Diagnostics bull Complementary Diagnostics

bull Provides information that is essential for the safe and effective use of a corresponding therapeutic product

bull Identify biomarkers that can be used to stratify the likely outcomes for individuals exposed to therapy

bull Provide additional information about how a drug might be used or whether someone should receive a class of drugs

bull Potential to be used more broadly with a class of drugs and not confirmed to labeling

bull A new concept introduced by the FDA




Epigenetics


Epigenetics - Definition

Epigenetics refers to a gene activity state that may be stable over long periods of time persist through many cell divisions or even be inherited through several generations all without any change to the primary DNA sequence

DNA methylationbull cytosine residues in DNA

bull Transcriptional silencing

bull catalyzed by DNA methyltransferases (DNMTs)

Histone Modificationsbull post-translational modifications alter chromatin activity

bull Diverse modifications complex regulatoin little understood

Non coding RNA regulationbull Small interfering RNA (siRNA)

bull Piwi-interacting RNA (piRNA)

bull Mircro RNA(miRNA)


Development of Autoimmne Diseases

It is currently assumed that epigenetic mechanisms affect the immune system

mechanisms or the target organ of the of autoimmunity

Environmental Influence =gt Epigenetic Dysregulation =gt Autoimmunity

Genetic Predisposition plays a central role

Susceptibility

Initiation

Manifestation

Propagation

Tissue Specific Systemic

autoreactive T Cells

Autoantibodies

Phases


Challenges for CDx Development

Multiplexing and Multimodality


Multiplexing

Values of individual readouts for multiple markers feed into an algorithm to calculate the diagnostic result

- Read-out technology or platform with low CV for single marker values

- Logical and synergistic combination of 5-10 single markers measured with the same technology

- Trade off between validation costs and diagnostic improvement

- Special demand in NON-ONCOLOGY indications


Multimodality


- Logical and synergistic combination of values created by different technologies and technologybias

- Extremely robust technologies required to guarantee low CVs for single marker values

- Novel biostatistic concepts necessary

- Multimodal Cross-OMICS technologies will revolutionize Precision Medicine


Refining the Autoimmune Landscape

Kohonen maps create a landscapes of based on biomarkers and

their relationship to each other

with specific disease clusters for novel targeted Tx development

41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases

Identification of patient

subsets provide specific

targets for therapeutic

development amp CDx

Increases probability of

success and approvals

for novel drugs amp

therapies

New Biostatistic Models will enable Multimodality

Self organizing map according to Teuvo Kohonen Finnish engineneur


The Digital Challenge

Future healthcare will be built on digital multi-modality not just in

oncology

Understanding

disease on the

molecular level

Combining data

repositories for novel

therapy approaches

Defining biological

pathways drug targets

and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond


Challanges in CDx Development

Regulatory Aspects and Consequences


Timeline for Drug Development starting today

bull Treatment cost per patientindicationyear will be restricted premium

reimbursement only for proven personalized therapies

bull Regulatory bodies worldwide require gt 75 responder rate for approval of any

innovative new drug

bull No approval of novel drugs without companion diagnostics in major markets

bull EMACFDA and other Regulatory Bodies follow with own Guidelines

bull FDA issues General Guidelines for Companion Diagnostics

bull Subgroup definition by molecular diagnostics will segregate syndromes

into distinct diseases

bull Novel concepts integrating novel and trusted biomarkers by multiplexing and

multimodality define disease subgroups on the molecular level

44

2016

2017

2018

2020

2023

2028

2030

The Future starts today Precision Medicine is able to shape it

Details provided on this slide are the fundamenta assumptions

2018

2019

2020

2022

2025

2030

2032


bull more biomarkers

bull more standards and standartization

bull more precise discovery platforms

bull more and dedicated Biobanks with exactly described patient samples (serum plasma liquor urine tissue etc) and disease parameters (clinical scores IHC staging etc)

bull more precision driven biomarker research and specific government funding for biomarker validation under industrial standards for SMEs and Academia

bull more sophisticated and technology aligned biostatistics

bull more multiplexing

bull more multimodality approaches

Precision Medicine needs hellip


Consulting for Innovative Companies in Challenging Markets

Company Strategy ndash Business Development ndashTechnology assessment ndash Financial Transaction

There is no blueprint for a targeted development of a life science company to market and

financial success Identification of the right market segment with the right product idea in life

science is challenging and a high financial risk

Therefore it is our mission to minimize the risks for our clients by employing the synergistic

industrial experience of the fundamenta management partners

About us


Explore Terra Incognita


The Current Status in Pharma


3





Average of

non-

Responders

Author Citation







ARC50)





Fingolimod



2310








alpha





Parkinsons Disease




change




Market Size










Epidemiology





Americans

7







4000 patients

screened for

eligibility in

Phase III based

on AAB

Regulatory Approval

2500 patients

enrolled with

positive

outcome

Phase II Phase III

Phase II failed

but association

between

outcome


First drug in Lupus

in last 50 years

1500 patients

(not enrolled)

30000 $patient

(fully loaded

costs in Phase III)

Savings

45 M $



VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx






Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




3





Average of

non-

Responders

Author Citation







ARC50)





Fingolimod



2310








alpha





Parkinsons Disease




change




Market Size










Epidemiology





Americans

7







4000 patients

screened for

eligibility in

Phase III based

on AAB

Regulatory Approval

2500 patients

enrolled with

positive

outcome

Phase II Phase III

Phase II failed

but association

between

outcome


First drug in Lupus

in last 50 years

1500 patients

(not enrolled)

30000 $patient

(fully loaded

costs in Phase III)

Savings

45 M $



VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx






Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





Average of

non-

Responders

Author Citation







ARC50)





Fingolimod



2310








alpha





Parkinsons Disease




change




Market Size










Epidemiology





Americans

7







4000 patients

screened for

eligibility in

Phase III based

on AAB

Regulatory Approval

2500 patients

enrolled with

positive

outcome

Phase II Phase III

Phase II failed

but association

between

outcome


First drug in Lupus

in last 50 years

1500 patients

(not enrolled)

30000 $patient

(fully loaded

costs in Phase III)

Savings

45 M $



VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx






Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





change




Market Size










Epidemiology





Americans

7







4000 patients

screened for

eligibility in

Phase III based

on AAB

Regulatory Approval

2500 patients

enrolled with

positive

outcome

Phase II Phase III

Phase II failed

but association

between

outcome


First drug in Lupus

in last 50 years

1500 patients

(not enrolled)

30000 $patient

(fully loaded

costs in Phase III)

Savings

45 M $



VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx






Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us






Market Size










Epidemiology





Americans

7







4000 patients

screened for

eligibility in

Phase III based

on AAB

Regulatory Approval

2500 patients

enrolled with

positive

outcome

Phase II Phase III

Phase II failed

but association

between

outcome


First drug in Lupus

in last 50 years

1500 patients

(not enrolled)

30000 $patient

(fully loaded

costs in Phase III)

Savings

45 M $



VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx






Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




Market Size










Epidemiology





Americans

7







4000 patients

screened for

eligibility in

Phase III based

on AAB

Regulatory Approval

2500 patients

enrolled with

positive

outcome

Phase II Phase III

Phase II failed

but association

between

outcome


First drug in Lupus

in last 50 years

1500 patients

(not enrolled)

30000 $patient

(fully loaded

costs in Phase III)

Savings

45 M $



VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx






Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us







4000 patients

screened for

eligibility in

Phase III based

on AAB

Regulatory Approval

2500 patients

enrolled with

positive

outcome

Phase II Phase III

Phase II failed

but association

between

outcome


First drug in Lupus

in last 50 years

1500 patients

(not enrolled)

30000 $patient

(fully loaded

costs in Phase III)

Savings

45 M $



VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx






Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





VALUABLE

MOLECULAR

INSIGHTS

BIOLOGICAL

SAMPLE

MULTI PURPOSE

MULTI MODALITY

NOVEL

DxCDxTXVx






Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us







Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





Oncology Dx and CDx


11






Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




Microbiome

analysis

Detection

of disease risks

Personalization


of drug

targets

Understanding

disease

mechanisms

Monitoring of

disease progression

Prediction of

therapeutic

response






stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us








stratification



relevant CDx area
















Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us











Project

Scope

Workplan

IP Access

Biomarker

Technology

CDx Track

Record

Approval

Commercial

Collaboration

Agreement

Project

Management

Governance



95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





95Oncology

Disease Areas

21CNS Cardio

45Immunology

18Other GI ID

68

Technologies

45NGS

54

Liquid Biopsy

28Multiplexing

Bioinformatics

Emerging trends





















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us


















16




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




CDx Program

Full biomarker use

(100 of trials)


(20-50 of trials)15


Low biomarker use

(lt20 of trials) 26

21

38

47









Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us








Majority

of CDx


Attrition rate ~40

AR ~32























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us

























Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us







Tu

mo

rsp

ecific

ge

ne

tic a

lte

ratio

n

Time in

years

Surgery Onset of

disease

relapse

Relapse

Identification

Early Late

Early Late


0 41 2 3

LOD (Test 2)

LOD (Test 1)




Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





Autoimmune








DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us










DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




DiseaseNon-disease

Arbuckle et al 2003

Autoantibodies are






-23-



N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





N Engl J Med 349(16)1526-33





Autoantibodies

detected

in this study


Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




Autoantibodies

Brain

Lung

Liver

Colon


of human proteins


bead-based arrays





-25-





H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us







H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4






sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us








sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





sample complexity


reference materials







by literature)



for cancer

H L21 1a AA5

1000 2000 3000 4000 5000 6000 7000 8000 9000 10000Time0

100

07231-04_b 1 TOF MS ES+

BPI

176e3

6 96 9

5 02 3

50 2 3

6 31 9

6 74 4

6 44 4

5 89 3

9 24 4

13 66 6

76 7 9 7 25 9

61 73

65 74

6 31 8

7 20 459 53

7 99 9

65 5 4

5 36 3

6 93 9

8 83 4

63 64

69 3 9

69 39

79 69

6 29 4

71 44

6 29 4

78 8 0

6 94 4

69 69

6 96 9

67 29

7 44 8

7 25 4

8 62 0

67 3 9

6 64 9

799 4

65 99

6 89 4

77 54

8 66 563 9 4








Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us









Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





Liquid Biopsy






Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us








Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





Companion Dx

Companion

Diagnostics

combines targeted

therapeutics with

diagnostics

Prognosis

predicting

recurrence

Monitoring therapy

tracking

drug-

resistant






Key Focus Area




69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





69






much enthusiasm











Not approved


Cancer Patients

26Drug Benefit

Cancer Patients

IO Immuno Oncology












Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us













Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us





Epigenetics


















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




















Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us









Susceptibility

Initiation

Manifestation

Propagation



Autoantibodies

Phases





Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us







Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




Multiplexing







Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us




Multimodality











41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us








41

Novel proprietary

biomarkers enable

differentiation of

autoimmune diseases




development amp CDx



for novel drugs amp

therapies






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us






oncology

Understanding

disease on the

molecular level

Combining data


therapy approaches

Defining biological


and mode-of-action

Improving the

effectiveness of

healthcare

1990 to 2002

2004 to 2010

2010 to 2020

2020 and beyond









innovative new drug








44

2016

2017

2018

2020

2023

2028

2030



2018

2019

2020

2022

2025

2030

2032



















About us











innovative new drug








44

2016

2017

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Documents

Dr. Stefan Müllner - BioTech Pharma Summit...2020/07/06 · Psoriatic Arthritis (MEASE 2004, 24weeks, PsARC and ARC50) 30 - 63 M Rodgers et. All Health Technology Assessment 2011;