Recording_HerO_Pam Ward_04Aug17

INTERVIEWER: That was very nice of you. So, I did see him. I told him that we’re exceptionally
honored to have you as our newest MCOE member and we had a great meeting in June in
Indianapolis. So, I’m just going to go ahead and turn it over to Josh and let him spend the
next 45 minutes with you.

RESPONDENT: Okay. Thank you, Vivian.

INTERVIEWER: Thank you.

INTERVIEWER: Yes, thank you very much, Dr. Ward, and as Vivian said, so I’m an international
product manager at Roche and my area of responsibility is genetics and infectious disease and
one of the areas we’re doing a deeper dive on right now is the area of hereditary oncology,
trying to understand – so we’re talking to clinicians, we’re talking to genetic counselors and
also of course speaking to lab directors and we’re really trying to understand the dynamics in
this area because it is a very complicated space. So that was kind of the conversation we
were hoping to have with you today. Now, is your lab currently performing any hereditary
testing?

RESPONDENT: No. So well, the only thing we do is Lynch syndrome. So we do

microsatellite instability and then we do IHC and if we get MSI, microsatellite instability-high
and we have lots of it at IHC, mismatch repair genes, and we don’t currently do the
sequencing. We send that out. So that’s the only sort of – and then we do BAP1-B on a CA1-
associated protein sequencing for uveal melanomas and that’s the Sanger sequencing
approach. So we haven’t moved into NGS or do hereditary panels so they get sent out from
here and I guess they go to MyRisk. Is that to Myriad?

INTERVIEWER: That is Myriad, yes.

RESPONDENT: It goes to Myriad on their 26-gene panel. I don’t think any of them to go
Foundation. So basically, they’ll have a patient who has found a history of malignancies and it
if we ruled out Lynch syndrome and they don’t think it’s a BAP1-associated malignancy then
they’ll just send them out to Myriad.
INTERVIEWER: That’s perfect. So you’re going to be a great person for us to speak with. So a
couple of things you said kind of helped me give you a little more background to orient you.
So, as we’re having this discussion, what I’d really like – I think a lot of the conversation is
going to be around kind of what would it take to get you to adopt the test, right? I know in a
vacuum that you’re not the one that is responsible for making that decision in a whole, right,
but it’s kind of that, “Hey, what would it take for you as a lab director to say, ‘Yes, I’m
willing to adopt this type of test”? When we say this type of test, we’re really considering a
mid-to-large panel, right?

RESPONDENT: Right.

INTERVIEWER: So 20 to maybe 100 genes, that type of thing run on an NGS platform, right? To
some extent, consider it to be technology agnostic, right? So whatever the platform is going
to be, it’ll be a reliable platform, yes?

RESPONDENT: Right.

INTERVIEWER: This is 100% about clinical samples as well, really nothing related to research.

RESPONDENT: Right. So I mean from any next-gen sequencing panel that we’re looking
at, the wet bench part, I wouldn’t say it’s easy, but it’s relatively easy for us as laboratories
to adopt because this is what we do. We validate and bring tests online. So the challenge for
us is the bioinformatics part because we don’t have a bioinformatics division. We don’t have
any bioinformaticists. Because we are Children’s Hospital of LA, we are associated with that
facility so we are in conversations with using their bioinformatics because obviously, they do
a lot of germline testing for children and so their bioinformatics goal is substantial, so there
are conversations ongoing for us to start to exploit their bioinformatics. So right now, that’s
been a bottleneck particularly when we get into hereditary, it’s about ownership of the
databases and resolving results and if you’ve got the database and for me, databases might
not be public, if you have content, then you’re the king.

INTERVIEWER: Well, yes. So you just came out guns blazing, right, and touched on…

RESPONDENT: Yes.
INTERVIEWER: …a lot of the stuff that we’re interested in getting to the bottom to and
certainly, the informatics piece is definitely one of those. So maybe can we take on step
back? Maybe can you describe your lab to me…

RESPONDENT: Yes, sure. Yes.

INTERVIEWER: …in terms of what you’re currently doing in sequencing? I’ve heard you mention
Sanger. I think Vivian mentioned in her earlier talk that you do have some NGS platforms
onboard and maybe you’re even bringing some more onboard. So could you just kind of
describe the lab and what equipment you have currently available? Then as you’re describing
that for what you currently have and maybe if you are going to bring some other stuff
onboard, really maybe go into the psychology a little bit about why you adopted it and what
some of your criteria were for adopting it versus maybe a different solution either an older
technology, Sanger or microarray or something, or a different even NGS platform.

RESPONDENT: Okay. So, in the lab, we have the Sanger sequencing for BAP1 which is
BRCA-associated protein. So that will be for screening uveal melanomas and mesotheliomas
and that went on to Sanger sequencing because it’s a single-green target and it’s relatively
simple to validate and get the results off and plus those tests come in as a single gene
screening order. We are validating a somatic-targeted cancer panel on the MiSeq. We chose
use the ThunderBolts panel for that. So the ThunderBolts is digital droplet PCR so the library
preparation is on a digital droplet PCR instrument or is digitized and then on regular PCR. The
idea why we chose that is because if we want to customize a panel, just the approach of
having single molecules and droplet [Unintelligible] with individual PCR reactions ongoing,
there will be less competition between primer sets and it might be easier to custom an
existing panel with a droplet format than a single PCR format so that’s why we chose
ThunderBolts. Then we chose the MiSeq because at that time, there was a lot of discussion
about, “Do you use MiSeq? Do you use Ion Torrent?” It seemed that some of their called preps
were more robust coming out of the MiSeq. That’s primarily I guess due to the higher-inputted
DNA requirement into that system compared to the Ion. So anyway, we went with the MiSeq.
So ThunderBolts Somatic Cancer Panel is on the MiSeq and we brought this panel in mainly to
capture all of the individual tests that are going out right now. So tests will go out for c-Kit,
they’ll go out for MET, they’ll go out for EGFR, they’ll go out for extended RAS testing and
BRAF and so on down the list. So our idea was to then have one test, one platform, and then
just do multiple tumors as each of these were requested from pathology or from our clinical
oncologist in order to achieve this testing. Then once this targeted somatic solid tumor panel
is online, then we’ve got plans to move into HemOnc. Our HemOnc services is much smaller
than solid tumors as is with most people and so that is a secondary pass at NGS to bring
HemOnc online and then also we need to start to look at translocations as well. So we’ve
been looking at the Archer panel. Illumina has a translocation panel, but again, bottleneck is
informatics. We’re looking at different companies to do the reporting for us and annotation of
variant calling. So it’s just difficult to know exactly which way to go with these companies.
They’re not inexpensive and then at this 11th hour, we’ve now got this [Unintelligible] from
Children’s LA that we might be able to exploit their bioinformatics and that will be a much
better option for us than using some commercial company. We also have the Ion Torrent in
the lab. So we’re working with a company called Vela Diagnostics and so there, we’re looking
at doing cell-free DNA and lung patients and colorectal cancer patients. So the idea they’re
going on to the Ion platform is that it needs so much lower inputted DNA in order to get a
result and so it’s cell-free DNA. So if you [have a tumor] that DNA would fit better on an Ion
platform than a MiSeq. Then also we’re working with Vela to do HCV genotyping and variant
calling for drug resistance with NS3, NS5A and B. So right now, that’s all we have either
ongoing in a lab [hole] or on the boiler plate to come up not to the front.

INTERVIEWER: So that’s really interesting. So I may…

RESPONDENT: So what it – what? Go on.

INTERVIEWER: Go ahead. No, you please, go ahead.

RESPONDENT: No, that’s sort of what I meant, but I think you’ll tell me.

INTERVIEWER: So what I was going to ask you is it seems like you’re using assays from – so it
doesn’t seem like you’re using Illumina assays or Thermo Fisher assays that you’re getting
those assays from third-party companies and putting those on a platform. How come you’re
doing that?

RESPONDENT: Right. How come?

INTERVIEWER: Yes. Why not the use the…?

RESPONDENT: Yes, so first, let’s go the somatic genome panel. So, we bought the
RainDrop digital droplet PCR instrument. So this affords a high level of detection of low copy
numbers of allelic variants. So for monitoring of CML patients looking for BCR-ABL. In order to
determine somebody is complete molecular response, we need to come down by 4.5 logs. So
if you’re using classic qPCR, the imprecision of the low end is enormous and that’s just at the
end of the spectrum for me to have precision in order to call somebody complete molecular
response. So we decided not to use the FDA-approved qPCR BCR-ABL assays, but to actually
develop one on a digital droplet to get the high level pf precision at that very low end to call
somebody either negative or whatever value it’s going to be. Because we had the digital
droplet instrument in the lab, the company then started to talk to us about their next-gen
sequencing cancer panels, which has the library prep in PCR following digitization. So you
take your single PCR reaction and you digitize it into 10 million droplets and so now each
primer set in the panel, in the next-gen sequencing panel is individually amplifying the
individual molecule in that droplet. So we don’t have competition between primer sets and
template. So there is sort of a better overall coverage using that approach than if you don’t
use a digitized approach. So that’s why we went with a ThunderBolt RainDance chemistry and
put it onto the Illumina platform. Now in terms of the Ion Torrent, Vela or Vela Diagnostics – I
don’t know which way you really pronounce it – they had a licensed agreement with Life
Technologies to develop next-gen sequencing assays on the Ion Torrent. So Life Technologies
was then acquired by Thermo Fisher and so Vela actually has a very desirable license to
design assays on the Ion Torrent and no other company other than Fisher can do that. So
we’ve been working with Vela for some time and so then they just approached us to start to
work on their cell-free assays, cell-free circulating tumor DNA assays for long and called
direct [rotations] on the Ion. So that’s what we’re doing and because we’ve got that platform
in the lab then we’re using the Vela HCV Genotyping Assay on that instrument as well.

INTERVIEWER: Thank you. No, that all makes a lot of sense. Can I just ask one quick favor? My
pen just ran out of ink so I’m just going to run out of this conference room quickly to grab
another pen. Please forgive me.

RESPONDENT: Okay, that’s fine. [Laughter] Yes. [Pause]

INTERVIEWER: Sorry about that. I just raided someone’s cube and stole a pen. Appreciate it.
So, I’m trying to think of the best way to go around. So maybe we’ll stick with your
healthcare system. So how are samples coming into you? What I’m trying to get at is samples
that would come in to your lab for a hereditary oncology are likely different than the samples
that would come in to your lab for a somatic oncology piece. So I’m trying to understand
where your samples are currently coming from and how they’re processed versus what the
difference would be if you were to have a hereditary test in the lab. Does that make sense?

RESPONDENT: Right. Yes. So once the clinician has identified a patient as having
family history of malignancy, so that person then is deferred to our genetic counseling office
and then the request for those hereditary tests would come through the genetic counselor. So
right now, that’s where we get some of our microcephaly have been syndrome testing from is
because they’ve identified a patient who has family history and is likely to be Lynch
syndrome. So the genetic counselor determines as to what level of testing this patient will
have as first pass. So if they consider it’s likely to be Lynch and it comes to us for
microcephaly instability and immunohistochemistry, mismatch repair genes and then
depending on those results, if it’s loss of IHC MLH1, it’ll go out for methylation, MLH1
methylation and if not, depending on which IHC, gene has been lost is whether then it goes
out to sequencing of MSH2, MSH6, et cetera. So then if all of that comes back negative and
there’s still obviously a family history then it will be determined that sample will then go to
Myriad for the more extensive panel of 26, but 26 is not a big panel as you’ve alluded to. I’ve
looked at a few different companies. So Ambry has a hereditary cancer panel, which has got
34 genes. So I’ll see some differences between Ambry and Myriad. Then InVitae up in the Bay
Area, they have another panel that there seems to be very specific. They’ve got succinate
dehydrogenase genes on there. You’ve got four of those and TSC1, 2 suppressor genes. So
their panel, there seems to be a slightly different, skewed panel which maybe based on
population of patients when they started developing the test. We don’t see all of the reports
when they come back from Myriad, but a lot of times, somebody’s going to offer hereditary
testing and it comes back negative. So the need for a larger panel I think is there and I guess
even then we’ll have some negatives, but at least we could try and eliminate some of the
patients having a negative answer in the case of family history.

INTERVIEWER: So maybe just a little interest for you. So we’ve been looking at this space,
right and we’ve taken a look. So as you’ve alluded to, Myriad, Ambry, InVitae, there was also
a company called Color. There’s another company called Counsyl. There are quite a few that
have these panels.

RESPONDENT: Yes. I haven’t seen all them, right.

INTERVIEWER: When you look at all of them, there are about 50 genes that all of them run in
some combination, but of all 50, I want to say it’s only five genes appear in all of them. It’s
really, really – and it’s BRCA1, BRCA2. I think ATMt, P53, and maybe P10 or something like
that, but other than that, all of their panels are completely different…

RESPONDENT: Different, right.

INTERVIEWER: …which is really interesting. So you mentioned if your IHC comes back positive
then you’re going to go to the MSH – where is that MSH sequencing done or the other – the
smaller Lynch-only sequencing done?

RESPONDENT: Well, our reference lab is ARUP so anything that goes to them really
goes to ARUP.

INTERVIEWER: Oh, okay. There you go. Perfect. Then so maybe going back to Myriad a little
bit, how did you guys land on that? Why Myriad? Why not the Ambry or InVitae or whoever
else?

RESPONDENT: Well, that’s not my – we don’t get to decide that.

INTERVIEWER: Okay.

RESPONDENT: That’s I guess in the genetics counselor’s office. I guess they looked at
different panels and they choose where they send it. I have actually…

INTERVIEWER: So it’s not exclusive then? So your GCs might be sending them out to Ambry or
InVitae or what-not.

RESPONDENT: Right. That said, I haven’t seen any InVitae reports and I haven’t seen
any Ambry reports, but I don’t think – well, we don’t so things exclusively. When I’ve looked
at whatever goes out to next-gen sequencing, Foundation is one of the players and preventing
her without their [Unintelligible], but I don’t think I’ve seen enough hereditary reports to rule
out that they can’t go anywhere else. I guess if there maybe choices and it’s Myriad, they
made that choice for a reason, but it may be dependent upon the patient. Because this one
from InVitae, I guess if you’ve got a patient with a GIST-type tumor, you might send there
because there’s a subset of GIST patients that have succinate dehydrogenated mutations and
not c-Kit or PDGFR.
INTERVIEWER: Interesting. So maybe another question, do you have any idea on what
percentage of the tests that are getting sent out on patients who’ve been diagnosed with
cancer versus a family member who’s worried about it because mom or dad or uncle or
whoever had cancer and they think they might be susceptible?

RESPONDENT: Well, I don’t know for sure but I’m guessing every case here that goes
out is a patient who’s already been diagnosed. At least they’re the only reports that I see
because there’s a pathology report. To my knowledge, I don’t know if we have a screening
program per se when you have a diagnosis or to get a diagnosis.

INTERVIEWER: So, one of the arguments we’re looking at is – or I shouldn’t say argument, but
one of the areas we’re exploring is – you seem to be pretty well-informed, but a lot of lab
directors we’ll talk to and we’ll ask them, “Well do you know where your…?” Because the
salesforce for Myriad, Ambry, InVitae can go directly to the clinician, right? They can
completely circumvent the lab.

RESPONDENT: Right. What they do – they don’t come to the lab. They go to the
clinician, right.

INTERVIEWER: Right. You seem to be fortunately kind of looped in on that at least as it relates
to those who are maybe at risk for Lynch. So I guess [Laughter] for lack of a better term, how
does that make you feel? Is that something that you’re comfortable with? Would you rather it
go to your lab? What does that look like for you?

RESPONDENT: So, right now, because we haven’t moved into hereditary testing, I’m
quite comfortable with it going out and we have so many other things that we are still trying
to bring online in terms of finishing off our validation for our solid tumor panel and then doing
HemOnc next-gen sequencing, and then doing our translocations. We have even gotten to
bring hereditary testing onto our list because I don’t know what the volume is. So everything
we do is volume-driven and so therefore, we would have to see a significant volume that
would indicate that we need to do this testing in-house. So what I don’t like is that when our
tissues get sent out, obviously the clinician has to contact the surgical pathology department
and they identify the block and they send it out. So we’re out of that loop so we’re not
notified that anything is going out and I’m trying to change the policy so that we are notified
so that we have a better understanding of the molecular testing that is being performed
because as we are in molecular pathology, I think we have some expertise to provide some
input, but perhaps you’re not asked.

INTERVIEWER: Yes, that’s unfortunate. [Laughter]

RESPONDENT: Yes.

INTERVIEWER: So, going back to the volume question, how would you find out? So I guess if
that volume is going out, do you know who it’s going out from? Is it OB/GYNs? Is it oncologists?
Is it some other…?

RESPONDENT: Yes, it’s mainly from the oncologists. We don’t have an OB/GYN service
here. USC Keck Hospital is limited service that we don’t have obstetrics or GYN. No,
unfortunately, our surgical pathology department is not as efficient in electronic capture of
send outs. This is something that we’ve struggled with them and we’re trying to implement a
change. They are going through a – they’re going to be changing their reporting system. I
don’t know if they’re going to Sunquest, but they are going to change their whole MIS system
and so hopefully then we’ll be able to capture in electronic format sample tumors that are
blocked that are sent out and where they’re sent out for testing because right now,
everything’s on a piece of paper and it’s in a folder so it’s just very difficult to capture that.
The only way we incidentally find it, if we haven’t seen something come through for Lynch
and part of our validation for NGS would be go in and pull out certain reports so we can do
some cross-validations and we’ll find all of those that have been out to either Myriad or
Foundation. So it’s sort of an incidental capture as opposed to a, “Give us an electronic
capture,” but that’s just the failing of our facility.

INTERVIEWER: Yes. No, that’s a difficult – well, yes, in the absence of a robust...

RESPONDENT: Yes.

INTERVIEWER: …system, it’s a difficult problem to overcome. Okay. So maybe let’s go back to
that bioinformatics piece. So you guys are doing some clinical annotation and interpretation
and granted it’s on a relatively small number of genes and relatively easy to understand
areas. So, you’re doing it, right? What’s the big deal to scale up for a broader hereditary
panel?
RESPONDENT: So right now, we’re doing a targeted panel. So we’re going after
targeted mutations. So most would be at the variance that we’re finding are that were
already documented, but they’re novel. They don’t need a full, powerful bioinformatics
workup and we’re not going to see that many unknown variances. The thing is try not to
report a variance of unknown significance because that’s not going to help anybody, but at
the same time, if there’s no information out there then you have no choice but to call it a
variance of unknown significance. When you move into hereditary cancer, it scales out the
whole level of bioinformatics, but if we start to be able to exploit our bioinformatics at
Children’s, I mean they are already working on germline mutations. That’s what obviously all
of the screening is over there for children with disabilities. So they get up for that and I don’t
see much difference for them to go from a cancer-related germline mutation then to a
physical or mental disability.

INTERVIEWER: Yes, it’s about whatever database you’re going to use as your backbone, right?

RESPONDENT: Yes, right.

INTERVIEWER: Then you curate and you put your confidence intervals on a given call and then
when you get a VUS, you get a VUS and you start chasing it down.

RESPONDENT: Right.

INTERVIEWER: So what would you relationship with them look like not from a business or
financial perspective, but from a workflow perspective? Would you do the sequencing in your
lab and then just kind of send them the electronic data and they would use their database or
whatever?

RESPONDENT: Yes, I think so. Right. That would be the plan, yes.

INTERVIEWER: So it would essentially be a cloud-based relationship. Can I call it that?

RESPONDENT: Right, yes.

INTERVIEWER: Okay. You’re comfortable with that? You don’t mind data in the cloud. That’s
all okay.
RESPONDENT: Well, I mean the [trick is just] to identify it. That’s the way we work.
It’s reality, right?

INTERVIEWER: I’m with you, but it’s a US-centric view of the world, right?

RESPONDENT: Right.

INTERVIEWER: When we go and we start talking to Germany and France and some others, it’s
verboten, right? No way that’s happening, but it’s also interesting, even within the US there’s
a lot of varying levels of comfort with doing that. So you seem to be pretty comfortable with
it.

RESPONDENT: Yes.

INTERVIEWER: Okay. So let’s say Roche does have a test, right and let’s say for argument’s
sake that we can run it on existing workflows. You’re not going to have to adopt a bunch of
frontend stuff or whatever. So how much of the bioinformatics – and I know this is a hard
question, but how much of that bioinformatic burden would we have to take off you right now
in order for you to adopt that test, right? So is it, “Hey, if we needed one full-time person,
okay we can live with that,” or, “No, we can’t have any personnel in here. We need every
call to be ‘absolute”? Where would it be on that scale?

RESPONDENT: So, right now, we would need full support because we don’t have any.
So either a person or sending it through the cloud, but we would need full support to do the
annotation.

INTERVIEWER: Again, a cloud-based solution could also be an option, right? So if we had…

RESPONDENT: Yes.

INTERVIEWER: …where you would just send us the data and we would send you back a report
that would work as well?

RESPONDENT: Right, yes.

INTERVIEWER: If you were going to bring a test in-house, how important would regulatory
status be for you? So if we had an IVD kit box that you could bring in-house, is that important
for you or is it relatively irrelevant?
RESPONDENT: Well, we work in the LDT world so it doesn’t have to have the IVD and
in fact, in some respects, it gets to be challenging to put some of these panels on IVD because
once you’ve gone through that regulatory pathway, you should’ve fixed it now and it’s going
to be very costly to change it. So at least in the LDT world, you can just come out with a new
version and then it’s just the lab to revalidate it. So we’re perfectly fine with the LDT world.
In fact, that’s all our NGS right now and that’s what most labs are doing. So it doesn’t
determine at all because Roche will know that oncology tests can quickly become outdated.
You have a very simple KRAS test on the z480, which is now kind of out-of-date I guess
because we’d be doing extended RAS testing and using [NPAS] as well as the codons 146 and
117 and 61 and not just 12 and 13.

INTERVIEWER: So I think it’ll be really interesting to see what happens over the next three to
five years with sequencing. So I’m not sure if you saw Thermo recently got approval for a
somatic oncology panel, an IVD approval…

RESPONDENT: I did see that.

INTERVIEWER: You did or did not?

RESPONDENT: Yes, I did.

INTERVIEWER: You did.

RESPONDENT: I did, yes.

INTERVIEWER: Well, so what they did is really interesting, right? So they have IVD claims on – I
don’t know if it’s two, three, four genes and they’re putting analytical claims on another 10,
15, 20 genes that they’re going to report out on, and then they have another 20, 30, 40 in
there that are going to be completely masked, right? To your point, it’s going to be really
interesting to see how Roche and Thermo and Illumina and all of these other manufacturers,
“Is that the path that we’re going to follow, right? We’re going to make claims on a couple,
we’re going to have some analytical on others, and then masked in the background and then
as the biology catches up with the science, we can bring forward the claims that we’re
applying on some of the genes that are in there.”

RESPONDENT: Well, I mean I guess I don’t see that as a good approach. I see it as a
[Unintelligible].
INTERVIEWER: Oh, that’s interesting. Why not?

RESPONDENT: What is it, it’s like Band-Aid approach and then how do the insurance
companies deal with it? So you’ve got the different levels of oversight of these targets all in
one panel. In the insurance world, how do they deal with that?

INTERVIEWER: Yes. I think it’s the same. So I think you’re basically going to get paid for that
which has validation and the other ones are going to kind of be freebies. So it’s not dissimilar
to what we’re seeing today in hereditary, right? At the end of the day, what really pays for
hereditary is BRCA1 and BRCA2, right?

RESPONDENT: Right, yes.

INTERVIEWER: To some extent, some of the stuff in the Lynch as you well know, but the rest
of the stuff is kind of, “We’ll throw it in for you,” and you do that. Is it smart, good,
responsible approach? I think the jury’s still out on that, but that’s the way I would tend to
see things evolve, right? So you’re going to get paid on something very specific within the
panel and you get the rest of the stuff “for free.”

RESPONDENT: Right, yes. So I guess pragmatically, that’s the only way to move
forward because otherwise, nothing will ever become IVD labeled. It would always stay in
that LDT world, but is there anything wrong with that? Is there anything wrong with staying in
an LDT world?

INTERVIEWER: Yes. It’s hard for me to answer that question coming from Roche. We’re an IVD
company, right so I’m like [Laughter]…

RESPONDENT: Right, yes. That’s right, yes.

INTERVIEWER: Yes. For us, we’re big and we’re slow so having a regulatory wall to kind of
hide behind is helpful for us. Having said that, we do believe there is a lot of comfort in
standing behind the result and alleviating some of that burden off of the lab.

RESPONDENT: Yes. So to counter my own argument, the good thing about having an
IVD test is that you do introduce a standard approach and I think a standard approach is very
worthwhile because we do need to be able to have commutable results so that does afford
that level of standardization. So yes, I could convince myself to argue in the opposite
direction, yes.

INTERVIEWER: Well, good. Hopefully, we’ll have something to help nudge you along the way
at some point in the near future as well.

RESPONDENT: Also, the other thing, yes clinicians, they put more confidence in an
FDA-approved assay. That’s just a way to say what they feel. Being a laboratorian, that just
isn’t a true statement, but I think it depends on the level of expertise that you have in your
particular molecular lab as to how good the LDTs are that are coming out of that lab and we
know there’s a huge variation in that and so perhaps then again, the FDA approach does give
a more even playing field and standardize everything. Particularly in the quantitative world,
as you know, for viral loads, it’s important that we all work on this international unit scale so
results are commutable.

INTERVIEWER: Yes, absolutely. So maybe let’s peel back something you just said a little bit
further as well. How much influence do the clinicians have on a test that you would adopt,
right? So one of the clear challenges we’re going to have is we’re used to selling into a lab,
right as Roche. We definitely have physician-facing salesforce as well, but that’s not our
bread and butter so to speak. So right now, the decisions on what test to do, what genes to
use in the test and everything are being made by a physician and/or a genetic counselor. So
you, as a lab person, how influential is that going to be? So in other words, even if we had this
test, right and you thought it was the greatest thing ever and you went out to your clinicians,
would they say, “Okay, sure. We’ll use your test. We trust you”? Or what level of comfort do
they need to have with it? Because you’re going to go to them and say, “Stop sending this to
Myriad,” right? So how does dynamic work?

RESPONDENT: Yes. So right now, Myriad has 26 genes and you’ve spoken about going
up to 100. So, although while they say I’m not getting less content, they are not going to put
a roadblock. If they get more content, then they’ll be happy. So you can add to what they are
currently getting. We cannot take away because by taking away, they’ve already reached a
level of comfort with what they’ve got and they’re not going to accept less, but they will
accept more.

INTERVIEWER: Interesting.
RESPONDENT: So if you have a larger panel that’s more inclusive because as you say,
there’s such a huge heterogeneity of tumors that are heterogenous then the landscape of
testing reflects that same heterogeneity. If you can come up with a more comprehensive
panel that covers more different centrums where we have less negative results then that’s
going to make the clinician happy because he’s going to be able to give a positive result, if in
that positive result he’s going to be able to give a useful result to his patient or her patient.
So you have to go big other than small.

INTERVIEWER: Yes. One other thing that just dawned on me, so when you’re sending these
samples out to Myriad, financially, how does that impact you? Are you guys responsible for –
who’s paying for the test? Maybe that’s the best way to ask the question.

RESPONDENT: Yes. Any send-out test in pathology is paid by pathology. So we pay the
lab, Myriad or Foundation or wherever it goes and then the hospital is responsible for
collecting whatever it can to recover the cost from a patient.

INTERVIEWER: So do you ever run into problems with the 14-day rule thing then?

RESPONDENT: So I’m not a billing person.

INTERVIEWER: Okay.

RESPONDENT: That’s a billing question, right?

INTERVIEWER: That is and essentially, there’s going to be a bundled payment for all the tests
in the hospital and then the hospital’s going to decide where the money is going to go.

RESPONDENT: Right. Is that when the patient is in the hospital? Because a lot of
pathology tests are actually done as an outpatient basis because that way then it’s not
bundled into the hospital.

INTERVIEWER: Right. Unless they’ve been admitted because of the cancer. That’s kind of
where it is.

RESPONDENT: Even so then, they wouldn’t probably have the hereditary testing while
they’re in the hospital. They’d come back as an outpatient and have that. They would try not
to bundle it in a hospital test.
INTERVIEWER: No, they would definitely try not to bundle it, clear.

RESPONDENT: Because they don’t get paid.

INTERVIEWER: Sometimes it does – I was just wondering if that was – so either way. So you’re
responsible for paying all of those. Yes, I wonder if what your…

RESPONDENT: So yes, so when we look at send-outs to bring in-house, we look at

volume and we look at cost. This comes back to the fact that somehow, the surgical
pathology department needs to do a better job of capturing all of the send-outs electronically
because I don’t think any of us really know how much gets sent out and how much we’re
spending. I certainly don’t know.

INTERVIEWER: Well, so that’s what I was just going to get at. So there has to be a way in your
system because somebody from your system is writing a check to Myriad or Ambry or InVitae,
whatever it is so there has to be a way to know exactly what that volume is.

RESPONDENT: Yes.

INTERVIEWER: That would be fascinating to get down because one of the things I think we –
one of the arguments we would make if we were going to ask you to adopt a test would
clearly be an economic one, right where it’s like, “Look, here’s the volume that you’re
sending out,” but it’s been incredible in these discussions that I’ve been having. In fact, I
haven’t spoken to one laboratory person who’s not doing hereditary that any idea on the
volume that they’re sending out. To a person they’re like, “We have no idea what are
clinicians are sending out, what that volume looks like,” none whatsoever. That’s been
fascinating for me because there could be a potential big…

RESPONDENT: Yes, shocking actually. [Laughter]

INTERVIEWER: Well, it is because that’s potentially tens of thousands, hundreds of thousands

of dollars just walking out the door, right? Millions even, so anyway…

RESPONDENT: Yes.
INTERVIEWER: Well, I know we’re up against the time and I apologize for that. I’ve gone a
little bit over. So is there anything that you would like to ask me or any questions I can
answer for you?

RESPONDENT: So in your timeline then, where are you in your development of this
panel?

INTERVIEWER: So I think from an internal development perspective, we’re very much in the
exploratory phase. We’re really trying to understand because this is such a mature market,
what would be the best way if at all for us to enter it.

RESPONDENT: In the US?

INTERVIEWER: Yes. The piece that we keep running up against is exactly what you said in our
opening dialogue that the bioinformatics piece is so critically important and it’s so difficult,
so how we would manage that and how we would be able to do that. Again, if we went with
an IVD for example, how much of the burden could we reduce on the lab with that type of
result? So we’re really in that type of exploratory function again for a test we would develop
in-house.

RESPONDENT: Yes. Because all the pathology labs are in the same juncture where w
suddenly now have to introduce a whole new service into our operations. I mean we’ve done
flow cytometry, we did blood banking, we do autopsy, all the different pathology services and
now, for the first time ever, we have to do bioinformatics. Just being able to mesh those two
services together and the fact that there’s not that very many bioinformaticists out there.
Those who are out there are only going to go to facilities that they feel are strong in
bioinformatics. So we could never attract a decent bioinformaticist to come as a single person
to work for us because that’s just not attractive for them. So we even have to partner and
collaborate with our Children’s Hospital or we just stick with sending through cloud going
through different commercial companies.

INTERVIEWER: Yes.

RESPONDENT: Right now, we just can’t offer anything else.

INTERVIEWER: So let me…

RESPONDENT: I hope in 10 years’ time it’ll be different.

INTERVIEWER: So let me ask you one question. Wat would be the top three things you would
have a bioinformatics person do for you?

RESPONDENT: Well, they’re going to have to be responsible for doing the filtering of
VCS, the annotation of those variants, and then just presenting the variants that we would
then sit down with the pathologist to determine which ones ultimately go in the report. It
doesn’t sound a lot but [Laughter] that’s a lot of work.

INTERVIEWER: No, it is a lot of work, but I’m always – I’ve asked that question a few times
and I haven’t always gotten the [Laughter] same answers from that.

RESPONDENT: Yes. Then the other point that I’d like to make is that each of these
different platforms with their different chemistries, they all have their own unique sense of
false-positives, right?

INTERVIEWER: Sure.

RESPONDENT: So it is always great if a company would – because they know what the
false-positives are, but they don’t tell you. So you have to go through this discovery process
of false-positives. So again, if it’s IVD, you would have that information and we would know
that information. So that would eliminate some of the bioinformatic headaches right upfront
because you know that these are just system-generated artifacts. So that’s something that
we’ve discovered more of those than we first thought are system artifacts.

INTERVIEWER: No, good to know. Okay. Vivian, do you have anything else?

INTERVIEWER: No, I think this is – and thank you, Pam for a very nice…

RESPONDENT: Well, I hope this was useful because yes, we don’t do the testing, but I
sort of have some knowledge of what’s going on in that space.

INTERVIEWER: Yes.

INTERVIEWER: Honestly, you’re the most useful, right? I mean I’m not going to walk in and sell
a test to Myriad, Ambry, or InVitae, right? [Laughter] So I need to know what it’s going to take
to get a person like you to adopt so it’s incredibly helpful so thank you.
RESPONDENT: Yes, okay. Very good.

INTERVIEWER: Yes. It’s very generous of you to give us the time and then I learned a lot too,
just the thinking, right because we talked about it briefly when I was in your office and this is
a huge area and we’re continuously trying to seek advice to see how we would prioritize our
resources. So, I thank you again and I hope you have a wonderful – again, we’ll get dinner for
this precious hour. So hopefully, I would be able to schedule something with you soon and I’ll
see you face-to-face.

RESPONDENT: All right. Thank you, Vivian and good to meet you, Josh [as well].

INTERVIEWER: You as well and thank you for your support of Roche and MCOE and all that
stuff. We really appreciate it.

RESPONDENT: Yes. I should [meet you].

INTERVIEWER: [Laughter] Have a good weekend.

RESPONDENT: Okay. Thank you, guys. Yes, thanks. Bye.

INTERVIEWER: Thank you.

RESPONDENT: Yes, bye.

INTERVIEWER: Bye-bye.