novellus dx

Enabling Precision Cancer Care TM

Dr. Michael Vidne

Sep, 2016

Enabling Precision Cancer Care TM

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Get the FACTs: Functional Annotation for Cancer Treatment

NovellusDx proprietary information

Characterize VOUS mutationsMeasure the response to drugsAvoid unhelpful treatments & save costOnly requires a NGS report as input

Certified international & NY state CLIA and ISO35 multidisciplinary, full time employeesHigh-throughput clinical lab>20 collaborations with hospitals & pharma

Enabling Precision Cancer Care TM

The Unmet Need

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Enabling Precision Cancer Care TM

Low Response Rates to Cancer Targeted Therapies, High Economic Burden

NGS guided therapies still have similar:• Response rates• Progression-free survival

Current state-of-the-art tech’ don’t support:• Actionable report for the

physicians• Response to drugs• Combination therapy

Progression-free survival in Mol’ Targeted and physician choice1

Source: 1 – Le Tourneau, Christophe, et al. "Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial." The Lancet Oncology 16.13 (2015): 1324-1334.

NovellusDx proprietary information 4

Enabling Precision Cancer Care TM

Partial ID of Driver Mutations Restricts Agent Success

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• Majority of mutations are not characterized by current Dx technologies

• These mutations:•Hamper response•Are responsible for resistance

mechanisms

• Oncogenic functional assay for these genes will tackle the problems

8-12 driver mutations operate in parallel within a given tumor1

1 1

11

111

111

11

12

3

4

567

8

9

10

1112

NGS finds in average1-4 drivers

Remaining mutations are uncharacterized

Source: 1 Vogelstein, Bert, et al. "Cancer genome landscapes." Science, 2013: 1546-1558.

NovellusDx proprietary information

Enabling Precision Cancer Care TM

Each dot is a cell

‘Clusters’ expresses a specific patient-gene &

reporter-gene

The Technology

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Enabling Precision Cancer Care TM

NovellusDx Precision Cancer Analysis: Automated, Quick, Thorough and Personalized

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• Physician send the NGS report

• NDX synthesizes the mutations into genes

Sample processing:• Chip printing• Transfection of genes

into cells

Automatic high content image analysis of signaling pathways activation

Proprietary algorithms help the physician tailor a treatment

Repeat process with drug incubation

1 2 3 4

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Enabling Precision Cancer Care TM

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Case Study

Enabling Precision Cancer Care TM

Characterizing VOUS That Can Guide Treatment And Clinical Trial Enrolment

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Case Study #4 : NGS finds ERBB2 driver mutation and a BRAF VOUS NovellusDx Finds the BRAF VOUS is an highly oncogenicFound mutated by NGSSignaling proteinsTested gene

Drugs affecting pathway

WT

1.2

1.3

1.4

1.5

1.6

1.74*10-5

0.01

0.03

G464V V600E

• NGS recommended treatment – ERBB2 Afatinib• NovellusDx BRAF mutation assay - extremely oncogenic – extremely

active • BRAF oncogenic activity abolishes Afatinib effect• BRAF inhibitor critical to first line treatment

VOUS mutation

ERBB2

MTOR

BRAF

ERK

MEK

AKT

Reporter

KRAS PI3K

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Enabling Precision Cancer Care TM

BRAF VOUS Mutation Is Resistant To Neratinib

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• Drug specificity, BRAF responds to Regorafenib, but not to Neratinib BRAF activity confers resistance to ERBB2 treatment

WT

1.1

1.2

1.3

1.4

1.5

1.6

VOUS Mutation

ERK

Neratinib

1

ERK2

med

ian

N:C

ratio

ERBB2

MTOR

BRAF

ERK

MEK

Neratinib

AKT

Reporter

NovellusDx main findings – resistance to Neratinib

KRAS PI3K

NovellusDx proprietary information

Enabling Precision Cancer Care TM

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• BRAF mutation is highly oncogenic – extremely active • BRAF mutation efficiently inhibited by Regorafenib

WT

1.1

1.2

1.3

1.4

1.5

1.6

VOUS MUTATION

ERK

Regorafenib

1

ERK2

med

ian

N:C

ratio

ERBB2

MTOR

BRAF

ERK

MEK

Regorafenib AKT

Reporter

NovellusDx main findings – sensetivity to Regorafenib

KRAS PI3K

BRAF VOUS Mutation Is Inhibited By Regorafinib

NovellusDx proprietary information

Enabling Precision Cancer Care TM

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Thank You

Reducing treatment cost by eliminating the guesswork