future of cancer diagnostics - healthtech...analysis (e.g. ihc)* mammo-gram surgery chemotherapy...

All Materials copyrighted and can not be used without explicit permission

2008

Scientia Advisors, LLC

Boston ■ Silicon Valley

Scientia Advisors LLC

1 Broadway, 14th Floor

Kendall Square

Cambridge, MA 02142

www.scientiaadv.com

Future of Cancer Diagnostics

By Scientia Advisors

All materials copyrighted and can not be used without explicit permission2

Agenda

Oncology overview

About Scientia Advisors1

2

3 Influence of MDx on oncology

» Early Detection

» Prognosis

» Theranostics

Conclusion4

All materials copyrighted and can not be used without explicit permissionConfidential and Proprietary - Do not distribute

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with a concentration in life sciences. We have one mission, to ensure that our

clients consistently outperform the market and their competitors.


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Agenda



» Early Detection

» Prognosis

» Theranostics

Conclusion4

Oncology overview2


Cancer incidenceLung, Breast, and Colon are the most common cancers worldwide

WW Incidence and Mortalities of Most Common Cancer Sites

Colorectal

Lung

Breast

For cancers of high incidence rates such as breast cancer and colorectal

cancer, National Cancer Institute (NCI) recommends screening of the

general population for these cancers on a regular basis

Source: Cancer Journal for Clinicians

In thousands


Suspicious mass identified by imaging

Biopsy of suspicious mass

Positive Diagnosis & Staging

Surgery

Therapeutics

Node -

Screening

Diagnosis & Staging

Surgery & axillary lymph node

analysis

2nd line treatment

3rd line treatment

Radiation

Node+

Further surgery

Histology

The traditional treatment care cycle involves repeated trial-

and-error to find the right treatment regimen for each patient

Traditional Treatment Care Cycle for Breast Cancer

1st Line Treatment

2nd Line Treatment

3rd Line Treatment

Source: Scientia Analysis


Understanding the Cancer Treatment Paradigm


Histology

Post-menopausal ER +, Her2 -

Pre-menopausal ER +, Her2 -

Breast cancer (BC) traditional treatment paradigmComplex care cycle with most researched and developed treatment

options

Breast cancer identified by Histology

1.6 M biopsies215,000 BC cases in U.S per year

STAGE 0(LCIS /DCIS)

Suspicious mass/lump from mammogram, biopsy sample diagnosed +ve by Histology

STAGE I STAGE IISTAGE III(III A/B)

STAGE IV

Surgery

Radiation

Hormone Therapy

Localized Metastasized

52,000 women are in Stage 0

Source: Scientia analysis, Breast cancer.org, American cancer society, Genomic Health, Veridex press release on BC sentinel node assay, Medscape, WebMD, and 2004 DataMonitor report on BC

Note: All numbers are U.S. annual numbers

15,000 women are in Stage IV

First line of treatment

Second line of treatment

Third line of treatment

LCIS: Lobular carcinoma in situDCIS: Ductal carcinoma in situER: Estrogen ReceptorHer2: Oncogene for Herceptin ResponseIHC: Immunohistochemistry

Axillary lymph node removal (Surgery)

Node - Node +

Surgery

Hormone Therapy

AromataseInhibitor

ER -, Her2 - ER+/ER -, Her2 +

Chemotherapy Herceptin

163,000 tests for ER, Her2 status (IHC from biopsy)

107,000 women are Node –ve , Stage I/II

41,000 women undergo second surgery to remove lymph nodes

Radiation

Surgery (Pallative)


Colorectal cancer (CRC) treatment paradigmResearch and development of treatment options are second only to breast cancer

Colorectal cancer identified by Histology

1.4 M biopsies148,000 CRC cases in U.S per year

STAGE 0

Suspicious polyp from colonoscopy, biopsy sample diagnosed +ve by Histology

STAGE ISTAGE II(II A/B)

STAGE III(III A/B/C)

STAGE IV

Surgery

Radiation


Source: Scientia analysis, American cancer society, National comprehensive cancer network, colon-answeres.com


Surgery (Pallative)

Surgery


Node - Node +

Camptosar or Eloxatin

Erbitux or Vectibix

Chemotherapy (5-FU+Leucovorin)

Avastin

Radiation




Histology


Lung cancer identified by Histology

1.4 M biopsies174,000 LC cases in U.S per year

Suspicious mass from chest X-ray, biopsy sample diagnosed +ve by Histology

Source: Scientia analysis, American cancer society, Lungcancer.org, GSK & Lilly wellness community presentation


SCLC(1) NSCLC(2)

STAGE I(I A/B)

STAGE II(II A/B)

STAGE III(III A/B)

STAGE IVLimited Extensive

20% 80%

Chemotherapy

Radiation




(1)SCLC: Small Cell Lung Cancer (2)NSCLC: Non-Small Cell Lung Cancer

Chemotherapy (Taxol)

Tarceva or Erbitux

Chemotherapy (Cis

or Carboplatin)Alimta


Node - Node +

Surgery

Radiation

Histology

Surgery (Pallative)


Histology

Lung cancer (LC) traditional treatment paradigmComplex care cycle with few treatment options once cancer advances


Oncology overview

Agenda



» Early Detection

» Prognosis

» Theranostics

Conclusion4

2


Oncology has been an early adopter of MDx tests, pointing

the way for other diseases Multiple factors underlie the penetration of molecular diagnostic into cancer care

Medical NeedCancer remains a leading killer in the developed world, driving researchers, physicians, patients

and payors to seek solutions

Standard of Carehas always included sample biopsy of cancer

tissue, a requirement for effective personalized molecular diagnostics

High CostCancer treatment is expensive:

In 1999-2000, cancer accounted for $60.9 billion in direct medical costs and $15.5 billion for

indirect morbidity costs(1)

Lack of Effective Therapeutics: Overall,

only 25% of cancer treatments are effective(4)

Research EffortOver $200 Bn has been spent on cancer research

over the last 40 years(2) resulting in significant advances in understanding of pathway biology

Nature of DiseaseCancer is a heterogeneous disease, with over

200 types identified so far(3); each is unique and requires a different therapeutic approach

Sources: (1) Chang et al. (2004) J Clin Oncol. 22:3524. (2) Scientia analysis; the NCI alone has spent ~$112Bn over the last 40 years (inflation-adjusted; NCI, http://obf.cancer.gov/financial), the remainder consisting of other government sources, industry and charities; does not include basic science research not specifically targeted to cancer. (3) http://www.cancer.gov/cancertopics/alphalist (4) Spear et al. (2001) Trends Mol. Medicine.


Imaging Biopsy of suspicious mass

Positive Diagnosis & Staging

Surgery

Therapy (Chemo or Targeted)

Node -

Screening

Diagnosis & Staging

Surgery & axillary lymph node

analysis

2nd line of treatment

3rd line of treatment

Radiation

Node+

Further surgery




Histo*

* Histology

MDx Prognosis

MDx Predisposition

MDx Detection

MDx Theranostics

Test that screens for cases linked to familial cancer cases (e.g. BRCA)

Detection: Dx of cancer only when doctor suspects it

Test that predicts the aggressiveness of cancer (e.g.. Genomic Health’s Oncotype Dx)

Test that indicates patient’s response to prescribed therapy (e.g. HER2/Neu test for Herceptin)

MDx tests are having a large impact on oncology care cycle

and is likely to greatly influence treatment decisions


MDx Screening

Screening: large scale screening of general population periodically


Screening & Detection

Differential Diagnosis &Prognosis

Theranostics ManagementSurveillance &

Monitoring

MDx not only provides effective patient treatment, but also

assists in monitoring and management

MDx Intervention Points

Prognosis:Test that

predicts the aggressiveness of cancer (e.g.

Genomic Health’s

Oncotype Dx)

Screening & Detection:

Test that screens for cases linked to

familial cancer cases (e.g. BRCA) and

difficult to diagnose cancers (e.g. Agendia

CUP Print)

Theranostics:Test that indicates

patient’s response to prescribed

therapy (e.g. HER2/Neu test for

Herceptin)

Monitoring & Management:

On-going monitoring to

analyze recurrence of cancer (e.g.

AgendiaMammaprint for

recurrence of Breast Cancer)

Trad

itio

nal

Ap

pro

ach

Screening

Diagnosis & Staging

Surgery & axillarylymph node

analysis

2nd line treatment

3rd line treatment



E.g. Breast Cancer Care Continuum:

Biopsy Tissue Analysis (e.g. IHC)*

Mammo-gram

Surgery

Chemotherapy Targeted Therapy (e.g. Herceptin)

MDx MDx MDx

Early Detection Prognosis TheranosticsValue Proposition of MDx

Early detection of cancer missed by tissue analysis

Preventing unneeded chemotherapies

Tailored therapy leading to reduced adverse effects and high efficacy

* Immunohistochemistry

E.g. The breast cancer patient care continuum has been

enhanced by MDx tests

• MDx based early detection will dramatically increase the use of Rx and bundling with early detection tests will give pharma an opportunity to allow Rx to be introduced earlier in the cancer care paradigm

• The use of MDx in prognosis will reduce unnecessary therapies; thus reducing healthcare costs

• The use of MDx theranostics will lead to better drugs that can in turn command premium price



The overall MDx oncology tests landscape - 2005Numerous players emerging with novel biomarkers

Source: Scientia analysis

Detection/Staging

Theranostics

Prognosis

Pipeline/RUO

Lung

Close to Launch

ASR/Commercially available

CE Marked

Regulatory Phase

SG Celera Diagnostics Veridex

ColorectalAdnagen

TSX:CDG

Epigenomics

EXAS

GHDX

GPRO

Genzyme GeneticsMZT MGRM

MYGN NorDiag ASAOM Sciences

PI

PD

PS

Roche

TWTI

PI

Cangen Biotech

CIPH

TSX:CURGPRO Genzyme Genetics

NorDiag ASAO M SciencesVysis

Bladder Abbott/VysisCangen BiotechCPHD Ikonisys Roche

CIPH

Other

O M SciencesAviara

PICelera Diagnostics

DIGE

GPRO

MZT

RocheTWTITm Bioscience

VMSINorDiag ASA

GPRO

TSX:CUR

PD

MYGN

CPHD

diaDexus

Roche

Veridex AdnaGen

TWTI

MGRM

NGEN

Breast

bioMerieux AdnaGen

Celera Diagnostics-Abbott

CPHD

CIPHCytyc

Epigenomics

GHDX

IkonisysMZT

MGRM

MYGN

O M Sciences PI

PDI

PS

Roche

Roche

Veridex

TSX:CUR

Exagen

Aviara

Abbot/Vysis

VentanaAgendia

BEC PI

CPHD MGRMLeukemia

Asuragen Diagnostics

Quest DiagnosticsCPHD

GenzymeNGENRoche

TWTI

Veridex

Gen-Probe/DiagnoCureVeridexEpigenomics

ProstateTSX:CDG

CIPHMZTPIPD

Aureon Laboratories

FDA approved

WW Incidence (in 1000s)

1,352

1,151

1,023

679

357

301

Scientia Confidential


The overall MDx oncology tests landscape - 2007Numerous players emerging with novel biomarkers


Pipeline/RUO

Lung

Close to Launch

ASR/Commercially available

CE Marked

Regulatory Phase

PD

SGCelera Diag Veridex

ColorectalAdnagen

TSX:CDG

Epigenomics

EXAS

GHDX

GPRO

GenzymeMZT MGRM

MYGN NorDiag ASAOM Sciences

PD

PS

Roche

TWTI

A&G Pharm

Almac DxAmbrilla AMDLDgnplx

Oryzn

PD

OncnomEntrix

LabCorp

Artic DxOrion

NCI

Biosite

Exact sci

Gene News

GenoMD

BEC

BDX

AsymmetRx

PD

Cangen Biotech

CIPH

TSX:CURGPROGenzyme

NorDiag ASAO M Sciences Vysis

Inverness

Abt/Vysis

Bladder Cangen BiotechCPHD IkonisysRoche

Aviva

CIPH

Other

O M SciencesAviara

PD

Celera Diagnostics

Qiagen

GPRO

MZT

RocheHologicTm Bioscience

VMSINorDiag ASA

GPRO

TSX:CUR

PD

MYGN

CPHD

diaDexus

RocheVeridex AdnaGen

Hologic

MGRM

NGEN

Molecular Devices

Gen-ProbeCytoCore

Dyamics

Gynecor

MTM lab

GenoMD

Immunotyp

Polartchnx

CorrelogicGenoMD

Immunotyp

Genzyme

GenoMD

Immunotyp

MBIRnDance

Roseta Gen

AlethiaAlthea tech

Exagen

GHDX

CPHD

Breast

bioMerieux AdnaGen

Celera Diagnostics-AbbottCIPH

HologicEpigenomics

IkonisysMZT

MGRM

MYGN

O M SciencesPD

PDI

PSRoche

RocheVeridex

TSX:CUR Aviara

Abbot/Vysis

Ventana

Agendia

Veridex

Hologic

BD Dgnstc

Appl imagBioImagene

Biophy

BioView

Falcon Gen Fermiscan

GenoMed

Int Genetics

NeoM

Perlegen Ventana

bioMerieux

Response

CeMines

Menssana

Perceptronix

BEC PD

CPHD MGRMLeukemia

Asuragen Diagnostics

Quest DiagnosticsCPHD

GenzymeNGEN RocheHologic

Veridex

DakoDxS

SBI

Gen-Probe/DiagnoCure

TargtdDxTX

Epigenomics

ProstateTSX:CDG

CIPHMZT PDPD

Aureon Laboratories

Clarient

MacroArray

Panacea Pharm

FDA approved


1,352

1,151

1,023

679

357

301

Detection/Scr

Predisp

Theranostics

Prognosis

Therapy

Monitoring

American Diag

diaDexus

diaDexus

20/20 gene sys

ImmunArray



MDx Oncology

Significant growth expected due to novel biomarkers

Key Trends and Growth Drivers

• MDx has changed cancer management, by providing

critically information and by reducing expensive

downstream tests

• The market is entering a new phase of growth as

emerging tests achieve clinical validation and

regulatory approvals (e.g. Genomic Health, Veridex)

• With the exception of HPV screening; screening test

for all other cancer Dx has exceptionally high barriers

to entry

Key Success Factors

• Strong channel to pathology labs and oncologists

• Content is the most critical driver in the oncology.

Discovery and validation of content is essential,

Multiple clinical studies and publications for validation

• Platform with medium-high throughput, fully

automated, with high multiplexing capabilities

• Strong assay development skills, reg. & reimb.

expertise

Unmet Needs

• Huge unmet needs in early diagnosis, accurate

staging, and determining patient prognosis and

eventual response to therapy

The MDx Oncology Market ($ M)

* Based on Digene before merging with Qiagen


0

1000

2000

3000

4000

5000

2007 2012 2017Bladder cancer detection Bladder cancer prognosis Breast cancer detection Breast cancer prognosis

Lung cancer detection Colon cancer detection HPV PGx

Predisposition Other

$507 M

$1,939 M

$4,334 M

17%

31%

Scientia

Confidential


Early Detection Prognosis Theranostics

MDx oncology testsWe will focus on 3 types of tests : early detection, prognosis, and theranostics

MDx oncology tests include predisposition, screening, early detection, prognosis, and theranostics tests. We will focus on early detection tests that enable early and accurate detection of disease, prognosis tests that provide disease recurrence free survival information, and theranosticstests that enable increased treatment efficacy and reduced adverse events


Oncology overview

Agenda



» Early Detection

» Prognosis

» Theranostics

Conclusion4

2


Early detectionImproved methods of detection and better understanding of disease leading to

higher oncology Rx sales

• Detection of cancer is currently done using Pathology

» Based on an optical method of detection

» Only detects one cancer cell in 200 normal cells

» Can lead to mis-classification of tumors

• MDx personalized medicine test will improve the detection/staging of Cancer

» More sensitive than optical methods of detection, can detect one cancer cell in 10 million normal cells; leading to earlier detection of cancer

» More accurate classification of tumors

» Early cancer detection will not only lead to increased patient population implying higher oncology Rx sales, but will also give pharmaceutical companies access to a wider range of patients at an earlier point of the cancer care paradigm



Breast cancer detectionToday’s detection methods (Histology) may miss micro metastatic levels of cancer

leading to poor prediction of disease outcome and treatment

STAGE 0(LCIS /DCIS)

STAGE I STAGE IISTAGE III(III A/B)

STAGE IV

Surgery

Radiation

Hormone Therapy

Axillary lymph node removal, Radiation

Node - Node +

Surgery

Pre-menopausal ER +, Her2 -

Post-menopausal ER +, Her2 -

Hormone Therapy

Aromatase Inhibitor

ER -, Her2 -


ER+/ER -, Her2 +

Unmet Needs

Current methodologies may misclassify tumor as benign/localized based on histologic appearance (at least one cancer cell must be present in every 200 normal cells for detection) when the tumor could have micro metastatic levels of cancer cells

Unfortunately 30% of patients considered to have benign/localized cancer end up developing metastatic cancer (due to misclassification)

MDx detection assay

Source: Scientia analysis, J Am. Surg “Molecular detection of breast cancer”, NEJM “Molecular classification of breast cancer”

1.6 M biopsies in U.S. annually215,000 BC cases

Suspicious mass/lump from mammogram, biopsy sample diagnosed +ve by Histology

Breast cancer identified by Histology

Promise of MDx is very sensitive detection (ability to detect one cancer cell in 107 normal cells) and accurate quantification of clinically relevant micro metastatic cells

No clinically validated biomarkers available for detection yet


Oncology overview

Agenda



» Early Detection

» Prognosis

» Theranostics

Conclusion4

2


PrognosisA reduction in unnecessary therapies; thus reducing healthcare costs

• Predicts aggressiveness of cancer, which was not possible by traditional pathology

methods, thus addresses an unmet need in oncology today

• Identifies patients with high risk of recurrence who may benefit from adjuvant

chemotherapy (improved recurrence-free and overall survival)

• Applies only to early stage patients with inherently good chances of survival (who may

be cured with local/regional therapy alone)

• Will reduce unnecessary chemotherapies, leading to fewer adverse side effects

• Are not theranostic tests, but influence key therapy decisions


DNA MutationMutation inactivates tumor

suppressor gene

Uncontrolled Cell GrowthMutation inactivates DNA

repair gene and several more tumor suppressor genes

MetastasisTransfer from one organ or

part to another organ or part not directly connected with it


Breast cancer prognosisToday, surgeons are having difficulty in predicting tumor recurrence and MDx

is addressing this problem

STAGE 0

(LCIS /DCIS)STAGE I STAGE II

STAGE III

(III A/B)STAGE IV

Surgery

Radiation

Hormone

Therapy

Axillary lymph node

removal (Surgery)

Node - Node +

Surgery

Pre-menopausal

ER +, Her2 -

Post-menopausal

ER +, Her2 -

Hormone

Therapy

Aromatase

Inhibitor

ER -, Her2 -


ER+/ER -, Her2 +

Unmet Needs

No means to predict recurrence

free survival

Major challenge in determining

which women with early stage BC

will gain benefit from adjuvant

chemotherapy

No rapid means to predict if more

extensive surgery of lymph nodes

is necessary

Source: Scientia analysis, Genomic Health, Veridex press release on BC sentinel node assay

MDx prognosis

assay

MDx sentinel

node assay

Radiation

MDx based prognosis assay quantifies the likelihood of breast cancer

recurrence to assist in treatment planning (eg. Genomic Health)

MDx based sentinel node assay can rapidly and accurately tell surgeons

whether breast cancer has spread and requires more intensive surgery (eg.

Veridex)

Exagen with 3 gene panel for prognosis seems to be in final stages of

product launch

Celera / Labcorp are also developing a panel of Prognosis markers

Histology


Prognosis^ tests are high value* diagnostics that reduce

healthcare expendituree.g. Oncotype Dx from Genomic Health

Source: Scientia Analysis; Genomic Health company financials

• Predicts likelihood of recurrence and benefit of chemotherapy for early stage (N- ER+) breast cancer

• Test based on algorithm and proprietary 21-gene panel using quantitative RT-PCR

• Genomic Health Financials:

- ~$25M Revenue 2006, $110M expected by 2008

- $3,460 price per test

Key Features Drivers of Success

• 7 studies with over 2600 patients, published in peer-reviewed journals and presented at national meetings validate the correlation between test results and the need for chemotherapy

• Studies have been conducted with Kaiser Permanente to show economic benefit

• Sales modeled around sales for big pharmaceutical companies, with clinical validation to help secure reimbursement

• Increasing adoption and reimbursement

» Over 27,000 tests have been ordered by over 5,500 Physicians since 2004

» Approximately 80% of the population is covered for the test

^ Other breast cancer prognosis tests provided by Agendia, ABT-CRA,Ipsogen, Exagen, Aviara; with Veridex (JnJ) and Roche entering the market in the future

* Provide critical information that helps physicians make clinically relevant decisions; as a result command premium prices


Oncology overview

Agenda



» Early Detection

» Prognosis

» Theranostics

Conclusion4

2


Theranostics (Thx) definition

Theranostics (Thx) are therapy specific diagnostics that can be used to select patients for treatments that are particularly likely to benefit them and to minimize side-effects.

Thx can also provide an early and objective indication of treatment efficacy in individual patients, so that (if necessary) the treatment can be altered with minimum delay.

Thx

Therapeutics (Rx)

Small molecules and proteins for treatment of diseases

Diagnostics (Dx)

Reagents and instruments for the diagnosis of disease


DIAGNOSTIC COMPANIES

• Research advances in biomarker discovery and systems biology is translating into more Dx tests

• Many new companies are emergingthat are focused on Dx

• Potential for higher pricing due to higher efficacy

• Enables focused trials – smaller groups for shorter periods with better results

• Dx facilitates better Rx sales by enabling better market penetration and expansion

Major trends and drivers of theranosticsKey stakeholders see clear benefits to adopting personalized medicine

REGULATORS

PAYORS

PHARMACEUTICAL COMPANIES

• Greater integration of Rx and Dx for more efficient and safer clinical trials(e.g. critical path initiative)

• Increased vigilance on drug approvals• Increased approval of genetic tests that influence

safety and efficacy of drugs

• Payment for performance• Payors are pushing for Rx-Dx integration,

especially diagnostics that reduce healthcare expenditure e.g. Oncotype Dx

Personalized Medicine

PATIENTS AND PRESCRIBERS

• Increasing influence of patient advocacy groups

• Personalized medicine reduces unnecessary therapies, leading to fewer side effects



Regulators are pushing for theranosticsApproval of numerous MDx theranostics tests in recent years that improve

safety and efficacy of existing Rx

On Aug. 22 2006, the FDA approved UGT1A1 test, for use in identifying patients that may be at increased risk of adverse reactions to irinotecan HCl

On Dec. 24 2004, the FDA approved AmpliChip CYP450 test, the first FDA approved PGx test

On Feb. 6 2007, the FDA approved Agendia’s MammaPrint Dx for breast cancer recurrence, the first IVDMIA test

On Sept. 18, 2007the FDA approved the first genetic test for Warfarin sensitivity, “Verigene”

On Dec. 12, 2007the FDA relabeled Carbamazepine to Include Recommendation of Genetic Test for Patients with Asian Ancestry

FDA withheld approval of Zarnestra®

On May 2005, Zarnestra was not approved by the

FDA for AML because Johnson & Johnson did not

have evidence in their trial that the drug was more

effective than chemo. FDA’s Oncologic Drug

Advisory Committee on Zarnestra believed that the

trials would have more effective if a diagnostic was

utilized to determine patients that were not eligible

for chemotherapy


Plagued by low efficacy & safety, Oncology Rx will be one of

the chief adopters of theranostics tests

0%

20%

40%

60%

80%

Oncology AlzheimersIncontinence HCVOsteoporosis Migraine (prophylaxis)Rheumatoid Arthritis Migraine (Acute)

Oncology Rx problem: low efficacy & safety Current Oncology Rx unmet needs

Solution: Personalized medicine tests

• Fewer rates of adverse reactions

• Better response to Rx, with correct dosages

• Rx provided only when necessary; leading to reduced healthcare costs

• Faster approval of drugs, with smaller test population, in shorter period

• Faster rate of R&D with improved drug discovery targets

• Revival of drugs that failed in the past

• 50% of oncology Rx are not as efficacious for the entire population as prescribed

• Oncology Rx has the lowest efficacy compared to other Rx

» Historically, oncology compounds tend to have a significantly lower success rate in clinical development than compounds in other areas, such as cardiovascular disease

Source: Scientia analysis, Trends in Molecular Medicine, Journal of clinical oncology, CDC

Oncology Rx have low efficacy

Oncology

Oncology Rx have low safety profile

Cancer

“Cancer Rx, FentoraI is tied to

several deaths”

“London Cancer Rx Trial Goes Horribly Wrong”

“FDA severely limits access to

cancer drug Iressa”

“Smart cancer Rx Sunitinib may have

toxic effects on heart”


Growth in oncology therapeutics will be highly influenced by

targeted approaches

Source: Scientia analysis, 2007 Cowen report on therapeutics

Targeted oncology Rx has a higher CAGR as compared to traditional oncology Rx

$55B

$86B

13%

• Targeted oncology Rx have a higher growth potential than traditional oncology Rx

• Thousands of cancer patients are already benefiting from several targeted Rx such as Avastin and Gleevec, personalized medicine tests will enhance the safety and efficacy of these targeted Rx

• Targeted oncology Rx are most likely to be influenced by personalized medicine tests

» Example: BCR/ABL test enhances the efficacy of Gleevec

» Example: UGT1A1 test improves the safety of Irinotecan

• High growth potential of targeted Rx will in turn drive the growth of personalized medicine tests

• In addition to oncology, infectious disease Rx such as HIV Rx have also readily adopted personalized medicine tests (e.g. HIV viral load, resistance tests)

Key Takeaways

5%


Targeted therapies with theranostics have proven the

blockbuster potential

Drug Name

Drug Developer

Test Name

Test Developer

Details

Herceptin Genentech HercepTest

Dako-Cytomation

FDA approved test to identify breast cancer patients who over-express HER-2. Over-expression of HER-2 = candidate for Herceptin.

Erbitux/ Tarceva

ImClone/ OSIP+Genentech

EGFR pharmaDx kit

Dako-Cytomation

Detection of colorectal cancer patients whom may benefit from treatment with Erbitux/ Detection of non-small cell lung cancer patients whom may benefit from treatment with Tarceva

Gleevec Novartis Ventana Dx c-Kit

VentanaMedical Systems

Detect the presence of the c-Kit protein in GIST. c-Kit = asset in selecting patients who may benefit from treatment with Gleevec.

Tarceva/ Iressa

OSIP+Genentech/ AstraZeneca

EGFR GenzymeGenetics

For non-small cell lung cancer

Gleevec Novartis BCR/ ABL GenzymeGenetics

The test detects all secondary BCR-ABL mutations and therefore predicts resistance to Gleevec for CML

$5.2

$3.9

$2.6

$0.8

$2.1

Genentech Roche Novartis BMS Others

Source: Scientia Analysis; Kalorama Information, Feb 2007

Estimated Cancer Targeted Therapy Sales 2006 ($B)


The pharma oncology pipeline has begun to respond to

ongoing unmet needs and research efforts

Phase I

Lung

Phase II Phase III Submitted

Regulatory Phase


1,352

1,151

1,023

679

Breast

Colorectal

Prostate

Merck

Wyeth

Wyeth

Amgen

Merck

Wyeth

Abbott

J&J

Novartis

Sanofi-Aventis

Eli Lilly

Genzyme

GSK

Merck

Wyeth

J&J

Novartis

Biogen Idec

Eli Lilly

Genentech

Pfizer

GSK

Wyeth

J&J

Novartis

Abbott

Amgen

Biogen Idec

Eli Lilly

Genzyme

Genentech

Roche/Genentech

Pfizer

AstraZeneca

J&J

Novartis

Eli Lilly

GSK

Wyeth

Amgen

Biogen Idec

Roche

Wyeth

AstraZeneca

Bristol-Myers Squibb

Sanofi-Aventis

Schering AG

Abbott

Roche

Pfizer

AstraZeneca

Source: Scientia Analysis; SG Cowen & Co Report; Company Websites; ClinicalTrials.gov

Roche

Pfizer

AstraZeneca

Bristol-Myers Squibb

Sanofi-Aventis

Merck

Roche

Pfizer

GSK

AstraZeneca

J&J

Novartis

Schering AG

Amgen

Eli Lilly

GSK

Roche (submitted EU)

Roche

Receptor Tyrosine Kinase (RTK) Inhibitor*

Non-RTK Inhibitors^

Chemotherapy Agent

Unspecified MOA**

* Includes Her-2/Neu, VEGF, EGFR, SRC/Abl, etc.

Ph

ase

I n

ot

com

ple

te

* Includes HDAC, DR5-targeted pro-apoptotic receptor etc.

** Unspecified method of action



There are two types of theranostic testsBoth are essential for improved outcomes

• Identify people likely to have adverse drug reactions to particular drugs

• Adverse Drug Reactions are the 6th leading cause of death

• Includes drug metabolism tests, used to determine right dose

• One-time tests that cost between $300 and $800

• Examples: CYP450, UGT1A1

Adverse Drug Reaction Tests

• Distinguish between responders and non-responders to a specific drug or set of drugs

• Includes Targeted Therapy tests, focused on identifying suitable patient subsets for targeted therapies

• Most well-known category of personalized medicine tests

Drug Responder Category Tests

Source: Scientia Analysis; Jorgensen JT, Personalized Medicine (2008), 5:55.

When combined, these tests provide a comprehensive profile that can be used for treatment decisions

Theranostic Tests


MDx theranostic tests that have focused on identifying

suitable patient subsets for targeted therapies

Test Name Test Developer Drug Name Drug Developer Details

HercepTest DakoCytomation Herceptin Genentech FDA approved test to identify breast cancer patients who over-express HER-2. Over-expression of HER-2 = candidate for Herceptin.

EGFR pharma Dx kit

DakoCytomation Erbitux/ Tarceva ImClone/ OSIP+Genentech

Detection of colorectal cancer patients whom may benefit from treatment with Erbitux/ Detection of non-small cell lung cancer patients whom may benefit from treatment with Tarceva

Ventana Dx c-Kit

Ventana Medical Systems

Gleevec Novartis Detect the presence of the c-Kit protein in GIST. c-Kit = asset in selecting patients who may benefit from treatment with Gleevec.

EGFR Genzyme Genetics Tarceva/ Iressa OSIP+Genentech/ AstraZeneca

For non-small cell lung cancer

BCR/ABL Genzyme Genetics Gleevec Novartis The test detects all secondary BCR-ABL mutations and therefore predicts resistance to Gleevec for CML

Trofile™ Monogram Maraviroc/ Selezentry™

Pfizer For HIV. Identifies patients infected with the R5 virus, which should guide therapeutic use of maraviroc, a CCR5 coreceptor antagonist.

Targeted Therapy Tests

Most well-known targeted therapy tests are in oncology



MDx theranostics tests that identify patients with significant

adverse reactions to particular therapeutics

Test Name Test Developer Drug Name Drug Developer Details

AmpliChip CYP450

Roche/ Affymetrix Various Various Microarray scan for CYP2D6 and CYP2C19 gene polymorphisms that affect metabolism of common drug classes, including antidepressants and schizophrenia drugs.

Invader UGT1A1

Third Wave Irinotecan (Camptosar)

Pfizer FDA approved molecular assay used to identify patients who may be at increased risk of adverse reaction to the chemotherapy Irinotecan. Based on polymorphisms in UGT1A1 metabolism.

CYP2C9/ VKORC1 genetic test

PGLX Laboratories/ Tm Biosciences; Nanosphere

Coumadin Bristol-Myers Squibb Identify patients with Warfarin sensitivity, based on polymorphisms in metabolism of Warfarin. Used to adjust dosage and avoid severe bleeding.

TIM Test PharmaNetics Angiomax The Medicines Company

To monitor patients being treated for angina, myocardial infarction, stroke, and pulmonary and arterial emboli. The tests assess blood-clot formation and dissolution.

Adverse Event Tests

Current tests apply to both specific drugs and multiple classes of drugs, predominantly related to polymorphisms in common or important drug metabolism pathways



Oncology overview

Agenda



» Early Detection

» Prognosis

» Theranostics

Conclusion4

2


Conclusion

• Cancer is complex, multi-factorial disease comprising more than 100 similar diseases. Current diagnostic tools, including various blood marker based immuonoassays, imaging techniques, and biopsy analysis, provide valuable information but remain effective only when the tumor frequency is greater than 1% to 10%

• Molecular diagnostics (MDx) are a game changing innovation that provide previously unavailable patient and disease specific information to oncology treatment care cycle. This new paradigm will eventually change the entire healthcare ecosystem and has shown the greatest initial traction in oncology

• MDx tests are influencing oncology care cycle by:

» Improving the early detection of cancer

» Providing a method to predict prognosis of early stage oncology patients, hence helping reduce unnecessary Rx and adverse side effects

» Improving efficacy and reducing side effects of targeted therapies

• MDx oncology competitive landscape is robust teeming with players exploring competing approaches


CONTACT INFORMATION

Harry Glorikian

Managing Partner

[email protected]

Office: +1-617-401-2330 - Ext 1382

Mobile: 617-407-5093 Fax: +1-617-812-0315

1 Broadway, 14th Floor

Kendall Square

Cambridge, MA 02142

THIS PRESENTATION IS MEANT TO BE ACCOMPANIED BY COMMENTARY & VIEWPOINTS BY SCIENTIA ADVISORS

THIS IS NOT MEANT TO BE A STANDALONE DOCUMENT ON WHICH TO BASE THE FINAL VIEWPOINTS OF SCIENTIA ADVISORS OR ON WHICH TO BASE THE FINAL AND DEFINITIVE

GO-FORWARD DECISIONS

mailto:[email protected]

future of cancer diagnostics - healthtech...analysis (e.g. ihc)* mammo-gram surgery chemotherapy...

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