novellus dx

Enabling Precision Cancer Care TM

Dr. Michael Vidne

Sep, 2016


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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


The Unmet Need

3NovellusDx proprietary information


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


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.



Each dot is a cell

‘Clusters’ expresses a specific patient-gene &

reporter-gene

The Technology



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




Case Study


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



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



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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




Thank You

Reducing treatment cost by eliminating the guesswork

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