In this 2nd wave of our precision oncology pulse survey, we explore how recent clinical, commercial, and regulatory events have impacted the adoption of emerging precision oncology biomarkers and diagnostic tools. We also examine the key technological trends likely to impact the landscape in the near-mid term.

1. 1
Update On The Adoption And Utilization Of Emerging Precision
Medicine Biomarkers And Technologies In Routine Clinical Care
DeciBio Consulting, LLC
10203 Santa Monica Blvd., Ste. 400
Los Angeles, CA 90067
Phone: (310) 451-4510
Email: info@decibio.com
www.decibio.com
DeciBio Contacts:
Andrew Aijian: aijian@decibio.com
Companion Diagnostics Forum 2020 – October 28
Disclaimer
Some of the companies listed in this document may be
DeciBio Consulting Clients or Customers; However, this
project is entirely self funded by DeciBio Consulting

2. 2
• 06/16/2020 FDA
approves Keytruda
in advanced
patients with TMB-
H tumors, with
F1CDx as a CDx• 05/2020 Lilly’s
Retevmo and NVS’
Tabrecta approved
for RET fusion and
METex14 skipping
NSCLC, respectively
• 03/07/2019 Paige.AI
receives FDA
breakthrough device
designation for its AI-
based dig. path tools
The precision oncology landscape continues to evolve at a rapid pace; in the past 2 years, multiple
clinical, technological, commercial, and regulatory developments have impacted cancer care
Select Key Precision Medicine Developments; 2018 – 2020 YTD
• 03/16/2018 CMS
finalizes LCD for
NGS testing in
advanced cancer
patients
• 07/30/2020 Tagrisso
granted Breakthrough
Designation for
adjuvant treatment of
pts. with stage IB-IIIA
EGFR-mut. NSCLC
• 09/2020 CMS grants
LCD for Natera’s
Signatera for CRC
MRD and a draft
LCD for
immunotherapy
monitoring
• 04/21/2020 FDA
expanded
authorization for use
of digital pathology
during the COVID-19
pandemic • 07/2020 Guardant’s
Guardant360, then
FMI’s F1Liquid CDx
become the first FDA-
approved liquid
biopsy CDx tests
• 10/13/2020 Caris
launches its
CODEai real-world
data clinico-
genomic database
with >215,000
patients
• 04/01/2020 FDA
approves Sectra’s
and Leica’s digital
pathology solution
for primary diagnosis
• 12/19 – 01/20 ArcherDx
announces development
of personalized MRD
assay; receives
breakthrough device
designation
• 01/07/2019 Guardant
launches its LUNAR-1
MRD assay to
biopharma and
academic researchers
• 03/30/2018 Foundation
Medicine announces
commercial availability
of FoundationOne CDx,
the first FDA-approved
CGP assay
• 07/12/2018 Guardant
announces Medicare
coverage of Guardant360
assay in NSCLC under
Palmetto GBA, coverage
later expanded to all
solid tumors
2018 2019 2020

3. 3
Dx
Specialist
VP /
CXO
To evaluate how emerging / next-gen Dx tools are being integrated into routine cancer care, we
conducted a pulse survey of >140 oncology stakeholders as a follow-up to a 2018 survey on this topic
Source: DeciBio Dexter Expert Network
Oncologists were asked about adoption /
utilization of emerging biomarkers /
modalities in routine clinical care (not in
trials) and overall trends
Pathologists / Lab Directors were asked
about technology adoption / capabilities,
assay volumes (in routine clinical care),
and overall trends
0%
25%
50%
75%
100%
Setting Role CDx Experience
Academic
Community
N = 58 N = 58
0%
25%
50%
75%
100%
Setting Role Lab Type
Academic
Lab
Community
Lab
MDx Lab
Anatomic
Path. Lab
Other
Comm. Ref.
Lab
Other
Molecular
Path. Lab
Central /
Core Lab
Oncology Lab
Lung
Leukemia /
Lymphoma
Breast
Prostate
CRC
Melanoma
Glioblastoma
Head & Neck
Other
Ovarian
Med. Onc.
Heme-Onc.
Surg-Onc.
Rad-Onc.
Other
N = 58 N = 84
Pathologist
Lab
Director
Other
N = 84 N = 84
25% of respondents were repeats from the 2018 survey33% of respondents were repeats from the 2018 survey

4. 4
This analysis indicated significant changes and trends in precision medicine adoption, practices,
and capabilities in just the past two years; five key themes emerged from the data and analysis
1 Adoption of biomarker testing has increased significantly, though stakeholders largely feel comfortable with the surge
2
NGS is becoming the standard method for molecular testing across cancer types; though broad decentralization of NGS
(and especially other emerging biomarkers and modalities) is not expected in the foreseeable future
4
Digital pathology (DP) use is growing, but the full clinical and workflow value propositions are yet to be realized; expectations
for the value of DP remain high with increasing development and use of artificial intelligence
3
Confidence and adoption in liquid biopsies (LBx) is increasing; LBx is expected to be the most significant driving force of
change in pathology / biomarker testing
5
The role of the pathologist is changing, and pathologists of the future will need an entirely new skillset than today’s
pathologists
Key Takeaways

5. 5
Paths / LDs:
Adoption of precision medicine is increasing rapidly in routine clinical care, though stakeholders
largely feel comfortable with their ability to accommodate this growth (for now)
Average Number of
Adv. Cancer patients:
~40%
(50 → 70)
Number of Different
Biomarkers Ordered:
~25%
(7.5 → 9.5)
Share of Patients
Tested:
~7%
(56% → 60%)
Biomarker Lab Tests
Offered per Lab
~15%
(13 → 15+)
Biomarker Testing
Volume >110%
1 4 7
1 4 7
1 4 7
I feel adequately informed about the
current CDx testing guidelines
I am familiar with all of the companion
diagnostic assay options available
It is easy for me to implement testing for a
new biomarker into my care protocol / lab
Strongly
Agree
Strongly
Disagree
Strongly
Agree
Strongly
Disagree
Strongly
Agree
Strongly
Disagree
…However, oncologists and pathologists / lab directors seem to be
managing the surge moderately effectively, generally showing slightly
higher familiarity, knowledge, and ease of integration since 2018
The precision medicine load on oncologists and
pathologists / labs is growing in mid-high double digits
annually, both in patient volumes and number of markers…
1 4 7
1 4 7
1 4 7
There is room for improving new assay /
technology implementation in labs
Oncologists: 2018 2020
2018 2020
Changes in adoption / utilization from 2018 - 2020
Oncologists
Pathologists
Respondent agreement / disagreement with the following statements
51 2 3 4

6. 6
+5% +4% +2%
+5%
+7%
+2% +3%
+1%
+11%
+8%
+10%
+2%
-1%
+11%
+18%
-2%
+17%
+11%
+34%
+6%
+3%
+6%
+1%
-5%
+3%
+20%
+13%
+19%
+4%
-10%
0%
10%
20%
30%
40%
Much of the increase in precision medicine adoption is driven by recent drug / CDx approvals,
demonstrating relatively rapid uptake of new markers and the expanding precision medicine arsenal
While guideline recommendations are required to drive broad
adoption, many cited clinical utility (as presented at conferences)
and diagnostic availability as key drivers of early adoption of new
markers into clinical practice
In NSCLC, where many of the new markers
are approved, overall adoption rates range
from ~55% (TMB) to ~75% (RET, ROS1,
MET) to ~95% (ALK, EGFR)
Changes in Biomarker Adoption Rates (Absolute Difference From 2018 to 2020)
51 2 3 4
Pan-tumor, last-
line, TMB-H
(Jun 2020)
ROS1+
mNSCLC
(Aug 2019)
RET Fusion+ lung
and thyroid
(May 2020)
Last-line NTRK
Fusion+ tumors
(Aug 2019)
Last-line NTRK
Fusion+ tumors
(Nov 2018)
Last-line MSI-H tumors
(May 2017); 1L MSI-H
mCRC (Jul 2018)
2L MSI-H mCRC
(Jul 2018)
METex14 skipping
mNSCLC
(May 2020)
Share of Oncologists
AMG510 Fast-
Tracked for KRAS
G12C+ NSCLC
(Sep 2019)
Final LCD
covering CGP
issued
(Mar 2018)

7. 7
A key consequence of the penetration of precision medicine is the shift in genetic testing from single-
marker methods (e.g., FISH, PCR) to panels (e.g., NGS), and the moderate centralization of testing
0%
25%
50%
75%
100%
2018 2020
Single
Biomarker
Assays
Disease-
Specific
Panels
Hotspot
Panels
Comp.
Genomic
Profiling
~13%
~25%
~55%
~8% 20182020
1 4 7 10
NGS testing will be
distributed across all
hospitals / sites that
evaluate cancer
patients
NGS testing will be
widely distributed
across all AMCs as
well as reference labs
Major cancer centers and
reference labs will conduct
the vast majority of NGS
testing
Reference labs will
conduct an outsized
majority of NGS testing
While NGS is widespread (~65% of labs surveyed have an NGS platform in house, and
~90% of all molecular path. labs); the expertise and costs required to deploy NGS for routine
CDx testing in-house is still limiting (only 40-60% of NGS adopters consider themselves
capable of implementing tissue-based NGS CDx testing in their lab in the near term)
Projections of future NGS decentralization remain unchanged, with respondents
anticipating that the majority of clinical NGS testing will be conducted at advanced
AMC labs, major cancer centers, and reference labs
Oncologists estimate that genomic profiling now
represents >50% of their genetic biomarker testing
volumes, driven in part by tumor-agnostic markers
Estimated Share of Genetic
Biomarker Testing by Method
Expected Degree of NGS Decentralization Among Lab Stakeholders
Fully
Centralized
Fully
Decentralized
“…The expansion of molecular targets and genomic understanding of carcinogenesis is redefining precision medicine to the extent that protein/gene analysis is
being performed for nearly every advanced cancer. NGS is at an inflection point, where it no longer serves as a last resort when all standard therapies
have failed but is required before initiating the first systemic therapy for a metastatic cancer…”
- Oncologist, Private Community Practice
51 2 3 4
2018 2020
Routinely
prior to 1L
Occas. <1L
Occasionally
at 2L+
No plans
to adopt
~36%
~12%
~29%
~10%
Routinely at
2L+
~14%
Testing Approach for Tumor-
Agnostic Biomarkers

8. 8
27%
27%
19%
17%
14%
14%
13%
11%
11%
11%
10%
10%
8%
8%
7%
7%
7%
15%
13%
20%
29%
21%
15%
21%
13%
20%
10%
17%
13%
7%
10%
15%
8%
14%
24%
17%
23%
18%
17%
18%
22%
33%
20%
23%
24%
18%
18%
15%
18%
18%
20%
33%
43%
38%
37%
48%
52%
43%
43%
49%
57%
50%
59%
67%
67%
60%
67%
58%
Tissue CGP
Multiplex flow cytometry
Tissue TMB
Digital pathology
WES
TCR repertoire analysis
Liquid Biopsy
Multiplex IHC
ctDNA load analysis
Immune cell population profiling
Blood TMB
Gene expression profiling
Multiplex cytokine profiling
IGRA / ELISPOT
Whole transcriptome sequencing
Neoepitope burden analysis
CTC analysis
We already offer this test in-house
We would likely offer this test in-house, regardless of IVD availability
We would likely offer this test in house if there was an IVD available
We would not likely offer this test in-house
Contrary to prior expectations, outsourcing of testing slightly outpaced insourcing over the past two
years; the expectation to adopt emerging biomarker technologies in-house remains limited
Over the next 2 years, I plan to decrease the amount of testing I
send out to reference labs (due to bringing tests in-house)
Strongly
Agree
Strongly
Disagree
For current / established biomarker assays, labs retained a largely
stable in-house vs. send-out ratio since 2018, though send-out
testing grew slightly faster…
1 4 7
…Outsourcing for emerging / new markers, however, may be high,
as many labs do not expect to bring emerging modalities in-house
due to equipment capital costs, and validation and requirements
0
25,000
50,000
75,000
100,000
2018 2020
In House Send-Out
(Hospital / Clinic / Private Practice Labs)
Δ = ~175%
Δ = ~190%
Paths / LDs: 2018 2020
200 – 250 tests / year
is the average
threshold at which
respondents consider
in-housing a new test
Assay Volumes, In-House vs. Send-Out 2018-2020
Expected Adoption of a Hypothetical CDx on Emerging Platforms
51 2 3 4
An increased preference for IVDs may
be driving testing to single-site PMA labs 3%
7%
3%
7%
Avg. Δ vs. 2018

9. 9
Respondents cited liquid biopsy as the overall most impactful trend in precision medicine, while
pathologists cite digital path as especially impactful; perspectives vary by clinical care setting
Oncologists
Pathologists
AMC
Community
AMC
Community
Ref Labs
LBx -
Biomarkers
Clinico-
Genomic RWD
Integration
LBx –
Early
Detection
Digital
Pathology
Single-Cell
Analyses
Digital
Biomarkers
Multiplex
Spatial
Analyses
Advances in
Radiography
1 2 3
1 1 3
2 3 1
1 3 2
2 3 1
Stakeholder Rankings of Most Impactful Precision Oncology Trends
Many respondents
called out AI / ML as a
powerful tool driving
many of these trends
Other disruptive trends
highlighted by
respondents include
MRD, and any
technologies that
reduce testing
turnaround time
51 2 3 4
= Normalized Impact Rating

10. 10
The impact of liquid biopsy in precision oncology is already being felt in routine clinical care today
driven by the reduced sampling burden on patients and simpler workflow for clinicians
Confidence in LBx for biomarker testing / CDx is
relatively high, while the use of LBx for monitoring
is not yet considered as actionable as imaging
Strongly
Disagree
Strongly
Agree
Neither
Agree /
Disagree
I consider the results of liquid-biopsy testing to be as
clinically actionable as those of tissue-based tests
~58% indicate some
level of agreement
Strongly
Disagree
Strongly
Agree
Neither
Agree /
Disagree
I consider liquid-biopsy based monitoring (e.g., ctDNA
loads) to be as clinically actionable as imaging methods
~35% indicate some
level of agreement
Overall, the share of blood-based testing has
increased by nearly ~140% since 2018, but
remains <15% of volumes across all markers
85%
79%
5% 12%
6% 5%
4% 3%
0%
25%
50%
75%
100%
2018 2020
Other
Peripheral Blood Cells
Peripheral Blood (Soluble Markers)
Tissue
Among solid tumor markers / assays, CGP, MSI,
MET, NTRK, PIK3CA and TMB all showed
moderate increases in blood-based testing
Assay Volume Distribution by Sample Type
Interest in LBx remains high, however,
due primarily to reduced invasiveness
and ease of sampling
51 2 3 4
“…Less invasive and more precise testing
is needed to limit the burden on patients,
so liquid biopsies, followed by single cell
analyses, will most likely have the
edge…”
“…Liquid biopsy, if sensitive and specific
enough, should provide non-invasive and
maybe more accurate results of mutations
due to e.g., tumor heterogeneity…”
“…Less invasive procedures such as
liquid biopsy will become the norm for
testing. Easy collection and testing
process…”
“…I hope that liquid biopsies are
ultimately proven to be as actionable as
they are so much more convenient…”

11. 11
Digital pathology is recognized as a transformative technology with significant clinical potential,
though its clinical, financial, and workflow value propositions are still being determined
51 2 3 4
Approximately half of all labs have digital slide
scanners; adoption of computational image
analysis solutions is limited (<25% of labs)
52%
23%
Adoption of Digital Slide Scanners (% of labs)
Adoption of Computational Image
Analysis Solutions (% of labs)
While most lab stakeholders use digital pathology for
clinical applications, it is generally used in a minority
of cases; non-clinical uses are also common
27%
16%
16%
25%
32%
50%Non-clinical applications
Specialty stain analysis –
minority of cases
Specialty stain analysis –
majority of cases
Primary diagnosis –
minority of cases
Primary diagnosis –
majority of cases
Other clinical applications
Remote consultations / second opinions and use in
tumor boards were commonly cited key use cases for
digital pathology; it was also cited as particularly useful
for breast-cancer markers and FISH analyses
0%
20%
40%
60%
80%
100%
The financial, clinical, & workflow
benefits of dig. path are largely
perceived to be neutral to mod. positive
Financial
ROI
Clinical
Impact
Ops /
Workflow
Impact
Many respondents have relatively recently
implemented dig. path. (partly due to COVID)
and are still evaluating the full extent of its utility
Significantly
Negative
Moderately
Negative
Significantly
Positive
Moderately
Positive
Neutral
Digital Pathology Use Cases

12. 12
There is high consensus among pathologists that technology is irreversibly changing the field and
their role; most are optimistic and nearly all cite a critical need for new skill development in pathology
51 2 3 4
Optimistic – Increased Role
in Precision Medicine
(~41% of Respondents)
Pessimistic – Decreased
Role in Precision Medicine
(~11% of Respondents)
Neutral – New skills will be required
for pathologists to succeed
(~48% of Respondents)
“…I think that pathology will become more
digital soon and computers will replace the
humans…”
“...At some point, all surgical pathologists
will have left is checking margins, and
digital pathology will streamline that
process…Pathologists need to evolve our
value proposition. We should also
probably stop training so many
pathologists…”
“…I feel that general and surgical
pathology will have a decreasing role as
time goes by due to molecular testing. I'm
glad I'm not starting out in Pathology right
now, since morphology is what drew me to
pathology.…”
“…Pathologists who know molecular
will replace the ones who don’t...”
“…Pathologists must be on board
with the changes in technology,
especially with respect to AI
applications…”
“…With highly multiplexed analysis of
tumor slides, pathologist are adapting
to a new multidimensional reality…”
“…As technology becomes more
complex it is critical to have subject-
matter experts who understand both
the test and clinical entity provide
thoughtful interpretation. This is the
key role for molecular pathologists
and our job is only becoming more
important, not less, no matter how
good AI gets! (At least for now)...”
“…A clear and rational integration of
clinical, histopathologic, and molecular
data is the key challenge for
pathologists in the next few years…”
“…Now is the hour of the
pathologist, I constantly say. All of
the complex testing that lies in the
lab drives major clinical decisions...”
“… It [role of pathologist] is rapidly
changing - increasing responsibilities
with clinical, regulatory, financial,
administrative duties…”
Pathologist Perspectives on the Future Role of the Pathologist in Precision Oncology

13. 13
Based on the trends identified in these data and analyses, we have identified key takeaways for
precision oncology market participants and stakeholders to bear in mind when looking to the future
Theme / Trend Implications for Stakeholders
Surge in precision medicine
adoption
• While stakeholders feel comfortable today, education and familiarity gaps remain, and will only grow (and may
accelerate) as new biomarkers and integrated data comes online; continued investment in stakeholder
education is essential
NGS becoming standard of
care; expectation of
centralization of emerging Dx
modalities
• Clinical stakeholders need to be prepared to handle increasingly more data; simplified data management and
analysis will become a point of differentiation among NGS providers
• Higher utilization will put cost and TAT pressures on NGS providers
• Developers of emerging Dx modalities need to consider a service model strategy to maximize accessibility
Increasing confidence and
utility of LBx
• Many molecular markers (and any other marker for which spatial context is not essential) may shift to liquid-
first testing; the establishment of a robust liquid biopsy testing infrastructure will facilitate the adoption of
emerging use cases (e.g., screening, monitoring)
• Histology will remain a staple of diagnosis / staging, but tissue-based biomarker analyses may become more
focused on spatial context than biomarker quantification
Moderate adoption of digital
pathology with full potential still
to be realized
• Digital pathology likely to remain more of a workflow convenience than an essential tool until clearer clinical or
operational utility can be established; AI-based computational image analysis expected to be a catalyst for the
broader transition to digital
Evolving role of the pathologist
• Pathologist education, both in medical school and ongoing education, needs to feature advanced molecular
and digital technologies as a core element of training; currently practicing pathologists need to take the
initiative to develop these capabilities
• It will be incumbent upon emerging biomarker / Dx technology vendors to target pathologists for training and
education to maximize clinical adoption
1
2
4
3
5

14. 14
Thank you for your time and attention!
Special Thanks To:
• The PlanetConnect team
• Colleagues at DeciBio who contributed to this analysis
o DeciBio Analytics’ Dexter Platform
• All those who participated in primary research
For more information about DeciBio, visit us at www.DeciBio.com;
These slides will be made available via PlanetConnect; Please connect directly with us for additional insights

15. 15
?
+5% +4% +2% +5% +7%
+2% +3% +1%
+11% +8% +10%
+2%
-1%
+11%
+18%
-2%
+17%
+11%
+34%
+6%
+3%
+6%
+1% +3%
+20%
+13%
+19%
+4%
-5%
15%
35%
55%
75%
Much of the increase in precision medicine adoption is driven by recent drug / CDx approvals,
demonstrating relatively rapid uptake of new markers and the expanding precision medicine arsenal
Changes in Biomarker Adoption Rates (Absolute Difference From 2018 to 2020)
51 2 3 4
OncologistAdoption%Δ%ofOncologists
47%
5%
17%
45%
29%
3%
21%
47%
16% 19%
41% 40%
17% 19% 22% 16% 10%
41% 38%
9%
43% 48%
26%
41%
59%
21% 24%
12%
24%
16%
36% 38%
47%
29%
0%
25%
50%
75%
100%
NSCLC
MEL
Breast
NSCLC
Breast
L/L L/L
CRC
NSCLC
CRCCRC
CRC
NSCLC
L/L
Breast
Breast
NSCLC
NSCLC
Overall Adoption
Tumor-Specific Adoption