NovellusDx provides functional testing of cancer mutations to guide treatment decisions and avoid ineffective therapies. It analyzes mutations from next generation sequencing reports using a high-throughput clinical lab with proprietary technology. This identifies whether variants of unknown significance are driver mutations and which drugs they respond to or develop resistance against. A case study showed a BRAF variant was highly oncogenic but resistant to an ERBB2 inhibitor, and responded to a BRAF inhibitor instead, changing the optimal first-line treatment.

1. Enabling Precision Cancer Care TM
Dr. Michael Vidne
Sep, 2016

2. Enabling Precision Cancer Care TM
2
Get the FACTs:
Functional Annotation for Cancer Treatment
NovellusDx proprietary information
Characterize VOUS mutations
Measure the response to drugs
Avoid unhelpful treatments & save cost
Only requires a NGS report as input
Certified international & NY state CLIA and ISO
35 multidisciplinary, full time employees
High-throughput clinical lab
>20 collaborations with hospitals & pharma

3. Enabling Precision Cancer Care TM
The Unmet Need
3
NovellusDx proprietary information

4. 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

5. Enabling Precision Cancer Care TM
Partial ID of Driver Mutations Restricts Agent
Success
5
• 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
1
1
1
11
1
1
1
1
1
1
2
3
4
5
67
8
9
10
11
12
NGS finds in average
1-4 drivers
Remaining mutations are
uncharacterized
Source: 1 Vogelstein, Bert, et al. "Cancer genome landscapes." Science, 2013: 1546-1558.
NovellusDx proprietary information

6. Enabling Precision Cancer Care TM
Each dot is a cell
‘Clusters’ expresses a specific
patient-gene & reporter-gene
The Technology
6
NovellusDx proprietary information

7. Enabling Precision Cancer Care TM
NovellusDx Precision Cancer Analysis: Automated,
Quick, Thorough and Personalized
7
• 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
NovellusDx proprietary information

8. Enabling Precision Cancer Care TM
8
NovellusDx proprietary information
Case Study

9. Enabling Precision Cancer Care TM
Characterizing VOUS That Can Guide Treatment
And Clinical Trial Enrolment
9
Case Study #4 : NGS finds ERBB2 driver mutation and a BRAF VOUS
NovellusDx Finds the BRAF VOUS is an highly oncogenic
Found mutated by NGS
Signaling proteins
Tested gene
Drugs affecting pathway
WT
1.2
1.3
1.4
1.5
1.6
1.7
4*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
NovellusDx proprietary information

10. Enabling Precision Cancer Care TM
BRAF VOUS Mutation Is Resistant To Neratinib
10
• 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
ERK2medianN:Cratio
ERBB2
MTOR
BRAF
ERK
MEK
Neratinib
AKT
Reporter
NovellusDx main findings – resistance to Neratinib
KRAS PI3K
NovellusDx proprietary information

11. Enabling Precision Cancer Care TM
11
• 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
ERK2medianN:Cratio
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

12. Enabling Precision Cancer Care TM
12
NovellusDx proprietary information
Thank You
Reducing treatment cost
by eliminating the
guesswork