1. Advancing
Personalized Medicine
one cancer patient at
a time.
James Lim, Ph.D., Nelson Chan, Ph.D., Dale Fedun, Brian Feth
Mentor: John Feilders (CMEA Capital)
Lawrence Berkeley National Laboratory
University of California, Berkeley – Haas School of Business
*73 interviews
1
2. Team of scientists and MBA students
James Lim, PhD
Scientist
Experience: Seven years of cancer cell microscopy
Expertise: Live-cell microscopy and cancer cell biology
Dale Nelson James Brian
Nelson Chan, PhD
Scientist
Experience: Seven years of cancer research
Expertise: Biochemical and toxicological analysis mediating cancer cell death
Brian Feth
MBA
Experience: Five years in life sciences business strategy consulting and private equity
Expertise: Business model development and project management
Dale Fedun
MBA
Experience: Twelve years in creating and managing business IT programs
Expertise: Business model and IT system development
2
2
3. Circulating Tumor Cells (CTCs): Initial Idea
Circulating tumor cells Oncologists & Pathologists
Cancer cells that have Does my patient have any
detached from the CTCs?
tumor and are How aggressive are they?
circulating in the blood
stream
Capture and grow CTCs
Video technology to characterize aggressiveness
3
3
4. Testing our initial hypotheses: Focus on
customer segments and value propositions
Diagnosis/ Direct sales
Advocacy Groups Consultation
Prognosis: Conferences Clinicians
Regulatory Cell-
Cell validation MD office Adverts Oncologists
Agency Characterization
Patient mgmt Publications Pathologists
Oncologists Database building
Drug selection Patient Patients
Physicians Assoc Disposal
advertisements
R&D
Minimally invasive
Low cost
Specific
IP Fast
Patient Database Hospital MD
office, HMO
Advocacy Groups
Pharma
Variable: Media, plastic ware, personnel, computing
Service per time point (service/use)
storage, building space
Kits / Reagents (patients only)
Fixed: Centrifuge, microscopes, freezers, incubators,
and hoods
4
4
5. Get out of the Building! Talked to customers and
partners to test our hypotheses
• Visited local hospitals and
clinics
• Called nurses and patients to
get perspectives
• Spoke with physician and
patient advocacy groups
• Hit the rolodex, plan interviews
far in advance, daisy-chain to
new contacts
5
5
6. Key people we spoke to:
Dr. Leisha Emens
Dr. John Siebel
Dr. Ana Aguilar
Dr. Scott North
Dr. George Sledge
Dr. Alan Venook
Dr. Peter Eisenberg
Dr. Cassandra Lee
Dr. Balaram Puligandla
Dr. Ken Pritzker (CEO)
Dr. Doug Tkachuk (CMO)
Dr. Scott Minick (CEO)
6
6
7. Determining our customers
Oncologist Pathologist
Patient management Sample management
• Oncologists decide • Pathologists perform in-
what tests to order, house tests and
when, and how often facilitate contracts with
service providers
• Primary customer • Less important
7
7
8. Key messages from Oncologists:
Dr. Siebel
“Culturing a patient’s CTCs to test efficacy of therapies would be
valuable, if you could prove in vitro results are replicated in vivo.”
Dr. Sledge
“Don’t give us more data. Tell us which drug to use for
each patient.”
Dr. North
“Definitively knowing if a patient should get chemo
would be a major breakthrough in oncology.”
8
8
9. What we learned from similar companies:
RNA Diagnostics
“The space is crowded; there are
many start-ups enumerating CTCs”
LifeLabs
“The clinical setting is difficult and
can take years to get to market”
Bind Biosciences
“CTC enumeration is not as useful and provides a limited
sample. Your approach is unique and overcomes key
limitations.”
9
9
11. We are unique in our ability to culture CTCs
Technology Capability
Company Product Technology Channel
Isolate Count Analyze Culture
Parsortix Filter Kits
CellSearch Antibody Kits
Vita-Assays Substrate Kits
Mvs360 Antibody Device
OncoCEE Microfluidics CLIA labs
LiquidBiopsy Antibody CLIA labs
ISET device Filter Device
On-Q-ITY
chip
Microfluidics Device
ApoStreamTM
Technology
Microfluidics Device
- Substrate CLIA?
*This is an abbreviated list
11
11 Class 8 - Update 3.19.2012
12. Cell culture value proposition
Identify and
enumerate CTCs
Characterize
growth potential
Culture Test
Chemotherapies
CTCs
Test CTCs for
biomarkers
12
12
13. Updated business canvas
Consultation
Characterization Provide new data Direct sales
Advocacy Groups
Database building to improve Conferences
Regulatory
R&D treatment MD office Adverts
Agency Oncologists
decisions Publications
Oncologists Treatment
Patient
Physicians Assoc determination in
advertisements
vitro
Pharmaceutical
Researchers
IP
Patient Database Hospital MD
CLIA certification office, HMO
Advocacy Groups
Pharma
Variable: Media, plastic ware, personnel, computing
Service per time point (service/use)
storage, building space
Kits / Reagents (patients only)
Fixed: Centrifuge, microscopes, freezers, incubators,
and hoods
13
13
14. Alternative market model
• Urged by the teaching team to
Private
CMS
payer/MAC explore alternative markets
Hospital / Clinic • Interviewed clinical research
Lab Advisory
Commi ee
Oncologists ASCO / organizations, pharma/biotech,
NCCN
and academics
CanScan
Influence
Payment
Sets rate
14
14
15. Alternative market model
• Urged by the teaching team to
explore alternative markets
• Interviewed clinical research
organization, pharma/biotech,
and academics
15
15
16. Partnering with Quest Diagnostics
• Covers 130 countries
• 2000 sites in the US
16
16
19. Key people we spoke to:
Dr. Ming Tong
Dr. Brian Edmunds
Dr. Philip Tagari
Dr. Thomas Fare
Dr. Sal Russelo
Dr. Steve Labkoff
Dr. Lisa Hewitt
Dr. Zemin Zhang
Dr. John Sninsky
Dr. Scott Patterson
Dr. Lawrence LaPointe
Dr. Slyvie Sakata
19
20. New opportunity: Pharmaceutical drug testing
“A better human-like in vitro models
for high throughput screening”
Head Research Development
Amgen “This would be a powerful platform to
test personalized drugs”
VP Business Development
“Testing drug on circulating cancer cells Merck
could offer us better end-points to
evaluate drug candidate effectiveness”
Head Research Development “Come work with us, we will be
Abbott Laboratories your first customer!”
CEO
Clinical Genomics
20
20
22. Current business canvas
Cell charact.
Database dev. Provide new data Personal
Str. Alliances:
Product/IP Dev to improve assistance,
local hospitals -
Treatment sel. treatment Automated
Marin Gen Oncologists
In vitro screening decisions. services
Hospital, CHRC
Oakland. Consultation
Cell Line bank. Pharmaceutical
Cancer drug
Med Device – Researchers
efficacy screening.
Medtronic, Baxter
IP CTC biomarker
Tech Validation- discovery
Patient Database Sales force
Clinical Genomics
CLIA certification
CPT Code
Joint Venture:
Quest Diagnostics
Variable: IP Licensing, lab supplies, personnel, IT,
Usage fee per CTC scan, data/consulting
specimen transportation
sales, cell line sales, instrument/kits product
Fixed: Lab equipment, lab space, SG&A, R&D
model
22
22
23. Intellectual property progress
Who owns What is Patent New IP
the IP? patentable ? process generation
Progress
Spoke to Berkeley Initial meeting with Provisional and New IP for keeping
Tech Transfer IP lawyer Utility application competitors away
Provisional Utility Application International
Patent (US) Patents
12 months
Up to 30 months
23
23
24. Path to Revenues
Mechanistic
PoC
Concept • Cell culture
feasibility
Validation
• Mouse models ✓
Requirements • 20-30 human
blood samples
• $10-15K
Cost ($100K+ equip)
• Access to lab
Time 2-3 Months
24
24
25. Path to Revenues
Mechanistic Technology
PoC Scope
Concept • Cell culture • Proof of
feasibility Concept in
Validation
multiple cancer
types
• Reproducibility
• Mouse models • 100+ human
Requirements • 20-30 human blood samples
blood samples
• $10-15K • $50K+
Cost ($100K+ equip) • Incubator space
• Access to lab
Time 2-3 Months 3-6 Months
25
25
26. Path to Revenues
Mechanistic Technology Biomarker
PoC Scope Validation
Concept • Cell culture • PoC in multiple • CTC / tumor
feasibility cancer types characterization
Validation
• Reproducibility
• Mouse models • 100+ human • Genomic / Pharma
Requirements • 20-30 human blood samples Proteomic
blood samples • Morphology Sales
• $10-15K • $50K+ • Outsource
Cost ($100K+ equip) • Incubator space (~$20K)
• Access to lab • Service/kit dev.
Time 2-3 Months 3-6 Months 1-2 Months
26
26
27. Path to Revenues
Mechanistic Technology Biomarker Clinical
PoC Scope Validation Validation
Concept • Cell culture • PoC in multiple • CTC / tumor • Patient
feasibility cancer types characterization stratification
Validation
• Reproducibility
• Mouse models • 100+ human • Genomic / • Phase II trial Clinical
Requirements • 20-30 human blood samples Proteomic (~200 patients)
blood samples • Morphology • Treatment use
Sales
• $10-15K • $50K+ • Outsource • Outsource
Cost ($100K+ equip) • Incubator space (~$20K) ($500K-$1M)
• Access to lab • Service/kit dev. • CPT Code/CLIA
Time 2-3 Months 3-6 Months 1-2 Months 1-2 Years
27
27
32. Choosing Partners: Decision Matrix
LAB / Incubator Proof of Concept COST TIME IP issues ?
0
$
$
$$
$
Hospital Trial
$$
$$$
32
32
33. Next Steps
FDA Clinical
Trials
**Grants and
Investments
IP and
Patents
New IP
Hospital trial generation
Clinical **Grants and
Validation Investments Personalized
treatment of
LAB patients
Complete IP
Publications protection
Incorporating
CanScan
Proof of
Concept New IP Revenue from
**Grants and generation Pharma
Investments
Record of
Invention
Lab Certification Licensing
New IP
Patent filing (CLIA) royalties
generation
Grow cancer cells
April 2012 May 2012 July 2012 Dec. 2012 Spring 2013
33
33
36. The CanScan Vision: Personalized Diagnostics
Platform for:
New drug testing
Personalized
Chemosensitivity
testing
Biomarker
Discovery
36
36
37. Thank you!
James Lim, Ph.D., Nelson Chan, Ph.D., Dale Fedun, Brian Feth
Mentor: John Feilders (CMEA Capital)
Lawrence Berkeley National Laboratory
University of California, Berkeley – Haas School of Business
37
37
38. Appendix
James Lim, Ph.D., Nelson Chan, Ph.D., Dale Fedun, Brian Feth
Mentor: John Feilders (CMEA Capital)
Lawrence Berkeley National Laboratory
University of California, Berkeley – Haas School of Business
38
38
39. CanScan Technology: Background on CTCs
Collection of cells that have the
ability to ‘metastasize’ away from
the primary tumor
Enumeration of CTCs was a better
indicator of disease progression
than traditional imaging
techniques
CTCs are potentially a valuable
diagnostic and prognostic tool
39
39
40. Current CTC technologies: Limitations
Competitors
Marker-Dependent Marker-
INDEPENDENT
Method leads to Method allows for
cell death LIVE cells to move
and grow
Genomic and Easy to enrich cells
Proteomic analysis for genomic and
is difficult proteomic analysis
Technological Technological
DEAD-END HIGHWAY
40
40
41. Improving CTC detection and characterization
Invade
Current detection and
characterization methods for CTCs
fail to address the most intriguing
aspect of their biology:
Adhere
CTCs are programmed to
invade, adhere and
Proliferate proliferate.
41
41
44. Health insurance reimbursement is necessary
precondition for hospitals to use our service
Private insurance or Medicare reimbursement requires:
Evidence of
• Double-blinded, placebo controlled clinical trial with several
hundred participants will be needed
Clinical Utility
− Must demonstrate the detection is accurate and repeatable
− Must demonstrate improved decision-making ability for physician
linked to better patient outcomes
Assignment of
• Codes are assigned by the AMA (CPT code) and CMS (HCPCS
code) semi-annually with editorial panel approval (12-18 mo)
a Billing Code
− CanScan’s likely coding: HCPCS Level II or CPT category III*
− Veridex CellSearch received code in Nov. 2011 for CTCs
− CanScan will likley need new code (non-immunologic)
* Coding used for non-FDA approved service billed by suppliers other than physicians
44
44
45. CMS requires that all laboratory testing on human
specimens be CLIA certified
• CMS regulates all laboratory testing (except research) performed on humans in the
U.S. through the Clinical Laboratory Improvement Amendments (CLIA)
− CLIA certification requires accreditation from a CLIA-certified provider (e.g., CAP)
− CLIA covers approximately 5,500 independent labs (225,000 total labs)
− We will likely need to apply for CLIA certification for High Complexity tests *
• FDA regulates commercially marketed in vitro diagnostic tests under the Clinical
Laboratory Improvement Amendments (CLIA), not a requirement for CanScan
* Immunicon received approval as a High Complexity lab in 11/2006
45
45
46. The market size for metastatic cancer diagnostics in
the US is estimated to be $805 Million / year
Methodology: Value: Explanation: Source:
U.S. population size 313M Total U.S. population in 2012 U.S. Census
x Bureau estimate
U.S. incidence of all cancers 0.512% Treatment is typically given in ACS Cancer Facts
the first year following diagnosis & Figures 2011
=
Total U.S. cancer incidence 1.6 M
x
% diagnosed with regional Cancers that spread to local or NCI SEER 2011
39.4%
or distant cancers distant lymph nodes or organs data
=
Patients w/ regional or
628,420
distant cancers
x
Cost of diagnosis and Weighted avg. patient cost p.a. JAMA. 2010;
$1,285
monitoring (annually) for imaging procedures (2008) 303(16):1625-1631
=
Market size for metastatic
$805M
cancer Dx / monitoring
46
46
47. Technology: Capture and Culture CTCs
1. Draw blood 2. Separate blood through centrifugation
3. Plate cancer cells on S-SUBSTRATES, let them grow 4. Image cancer cells
47
47
48. Technology: Enrichment and Selection
Detailed comparison of
CTCs from a single patient
Determining the genetic and proteomic
makeup of CTC subgroups
48
48
Editor's Notes
Our team has a depth of scientific and business experience in our core markets
We initially believed we were a visualization company with a novel approach to characterizing cancer Create value by enumerating and characterizing the aggressiveness of CTCsTarget customers in hospital (i.e., pathologist, oncologist, patients) Use a CLIA-based service model to deliver value to customersUse direct sales channels to reach customers in the hospital
When we entered the class, we thought our target markets were physicians managing clinical trials, pathologists (traditionally the main cancer diagnostician at a hospital), oncologists, and patients. And we were fairly certain the patients might be interested in purchasing kits to look for cancer recurrence.
Interview summary slideShowwe had discussions with oncologists and competitors from these institutions(see mammoptics slide 10)
What oncologists do, what pathologists do. Focus on oncologists.Need a new approach to get interviews with oncologists. Hit the rolodex, plan interviews far in advance, daisy-chain to new contactsPathologists do not order tests, and usually don’t decide where to source a test from, so are less important to our business
key learnings from oncologists (value proposition)
Title and company for “quotes”
Leading up to this slide, we need to be developing the case for a pivot into a cell culture company. John didn’t seem clear on how/why we decided this.
Change technology column to: Dead vs live cellsThe point of this slide is simply that right now culturing is a unique proposition. Do not focus on all competitors or what they do or how we will compete. Make the simple point of for now we have a unique proposition.
Value Proposition of Cell CulturingCell culture node in the middleBubbles appearing around showing value prop of cell culturingSimilar to mammoptics slide 19
This is about "reimbursement“. Use our original slide, then on the next slide overlay “start-ups can die while waiting for a CPT code"(mammoptics slides 11&12)The point here is CPT Code
This is about "reimbursement“. Use our original slide, then on the next slide overlay “start-ups can die while waiting for a CPT code"(mammoptics slides 11&12)The point here is CPT Code
To Do:Quest logo, map to show they are national-what Quest does-they would build it for us-10% of revenues
To Do:Quest logo, map to show they are national-what Quest does-they would build it for us-10% of revenues
To Do:Quest logo, map to show they are national-what Quest does-they would build it for us-10% of revenues
Interview summary slideShowwe had discussions with oncologists and competitors from these institutions(see mammoptics slide 10)
They are willing to purchase the CTCS. Also they are willing to outsource the service to us. _____________AnimationThis is the far better than our cancer cell modelsThis would be a powerful companion diagnostic tool to support personalized medicinesThis can improve personalized medicineCulture CTC is good, this can change how we developWe need it, this is whyNo regulation to serve usWe’ll pay for it when you can prove itSame format as previous bubble slides: pharma has a large unmet need for better human-like in vitro HTS models (quotes).
We need it, this is whyNo regulation to serve usWe’ll pay for it when you can prove itSame format as previous bubble slides: pharma has a large unmet need for better human-like in vitro HTS models (quotes).
Development timeline (milestones)graph of costs over time Similar to mammoptics slides 57 – 63 (but less busy)
Development timeline (milestones)graph of costs over time Similar to mammoptics slides 57 – 63 (but less busy)
Development timeline (milestones)graph of costs over time Similar to mammoptics slides 57 – 63 (but less busy)
Average clinical trial cost per patient is $6,000, which would imply $1.2M for a 200 patient trial. However, the cost of trials is a range that we think we’re on the low end of since it would be existing drugs used
Average clinical trial cost per patient is $6,000, which would imply $1.2M for a 200 patient trial. However, the cost of trials is a range that we think we’re on the low end of since it would be existing drugs used
Average clinical trial cost per patient is $6,000, which would imply $1.2M for a 200 patient trial. However, the cost of trials is a range that we think we’re on the low end of since it would be existing drugs used
Average clinical trial cost per patient is $6,000, which would imply $1.2M for a 200 patient trial. However, the cost of trials is a range that we think we’re on the low end of since it would be existing drugs used
Average clinical trial cost per patient is $6,000, which would imply $1.2M for a 200 patient trial. However, the cost of trials is a range that we think we’re on the low end of since it would be existing drugs used
Overview of failed trials – most recent, one FDA approved device / comprehensive overview of CTCs in the clinical setting. TRY TO FIND TRIALS FOR PEDIATRICS – this might be the first of its kind… / emphasize that.
Overview of failed trials – most recent, one FDA approved device / comprehensive overview of CTCs in the clinical setting. TRY TO FIND TRIALS FOR PEDIATRICS – this might be the first of its kind… / emphasize that.
Overview of failed trials – most recent, one FDA approved device / comprehensive overview of CTCs in the clinical setting. TRY TO FIND TRIALS FOR PEDIATRICS – this might be the first of its kind… / emphasize that.
Historical significance, what are they, what are some of the unique attributes of these cells / cite tons of references
Marker/antibody based approaches have inherent limitationsLowsensitivity, specificity, and reproducibility.
Marker/antibody based approaches have inherent limitationsLowsensitivity, specificity, and reproducibility.
Overview of failed trials – most recent, one FDA approved device / comprehensive overview of CTCs in the clinical setting. TRY TO FIND TRIALS FOR PEDIATRICS – this might be the first of its kind… / emphasize that.
Average clinical trial cost per patient is $6,000, which would imply $1.2M for a 200 patient trial. However, the cost of trials is a range that we think we’re on the low end of since it would be existing drugs used
Overview of failed trials – most recent, one FDA approved device / comprehensive overview of CTCs in the clinical setting. TRY TO FIND TRIALS FOR PEDIATRICS – this might be the first of its kind… / emphasize that.
Overview of failed trials – most recent, one FDA approved device / comprehensive overview of CTCs in the clinical setting. TRY TO FIND TRIALS FOR PEDIATRICS – this might be the first of its kind… / emphasize that.
