Oncolytics Biotech Inc. (ONCY)

[onco_investor]

AGM Transcript V2 Board Thanks iisfoo

Audio Webcast at
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Oncolytics Biotech, Inc 2013 Annual Meeting of Shareholders
Conference Call May 9, 2013 17:15 ET
Executives
[BT] Brad Thompson PhD — President & CEO
[MC} Matt Coffey, PhD – COO
[MAD] Mary Ann Dillahunty JD MBA – VP Intellectual property
[GG] George Gill MD – Senior VP Regulatory Affairs & Chief Safety Officer
[AJT] Alan J Tuchman MD MBA (FAAN) – Senior VP, Medical & Clinical Affairs, & CMO
[BT] Thank you all for coming today. It’s an absolute delight for us to be back in Calgary. This is our
home and many of our shareholders from the start and from the present are here today. And that’s
really, it’s a delight to have you all here and it’s a delight to be here. A comment on the room
geometry, it's a little unusual, so I’ll be doing a bit of game show hosting and moving back and forth a
bit.
After I've finished the presentation, I would urge you to direct anything of interest from a question
perspective to me and anything difficult towards my colleague Matt. And anything financial towards
Kirk. Unfortunately, Kirk, you’ll have to speak but this is fine. But thank you for that. And I might ask
you to leave your questions to the end of the presentation, I won’t be taking all that much of your
time.
What I wanted to do today is to give you a brief update of the year's achievements and take a little bit
of time to talk in more detail about three specific clinical studies - our two lung studies, and our head
and neck clinical study. I think those are things of interest that people should be brought their
attention to.
Before I begin, I would like to bring your attention to our forward-looking statements and I will do my
first walkabout here, where we draw your attention to our forward-looking statements and with the
SEC, our registration statements and with the 13 securities commissions in Canada, I believe; despite
Ontario’s best efforts to have a single securities commission we still have 13. I’m a big fan of the
Alberta Securities Commission so I’m actually a fan of keeping it the way it is. Aside: I had to just say
that, it's my one political statement for the day.
Today, I’ll be talking about the last year review, I’ll be talking about our financial status. I’ll be talking
briefly about some intellectual property developments, to talk about our manufacturing program,
which is a critical program, and to be talking and to get some more depth mostly about advances in
our clinical trial program. And I would encourage you to pay close attention to that particular part of
the conversation. I’ll also be talking briefly about the year ahead and then we’ll entertain questions
and comments.
So with respect to the year in financial. As many of you know, we are a development stage biotech
company, which means we don’t have revenues and certainly don’t have revenues to cover our cash
burn costs. And so it’s important for us to maintain sort of an ongoing financing activity that allows us
to fund the operations of the company. And it’s always been our sort of operation to attempt to have
at least a year of cash on balance at any time. And so when we drift down close to the year, we
always anticipate doing a financing to push that time envelope beyond that particular time.
So a year ago at this time or a year ago at the end of Q1, we had a little over $40 million in cash. We
spent money mostly on our Phase III study candidly. We had a very heavy expense year with respect
to clinical trial programs last year. And as a result of that we then kept our eyes open for
opportunities to do a financing and we did so earlier this year.
And so what you have is a cash balance that reflects very closely to where we were last year - it’s a
little higher - and that gives us cash operation certainly till the end of 2014, and arguably to early 2015
by the guidance that we've provided to the market. But it’s critical for everybody to remember that
that is how biotech companies operate until they actually have revenues from sales.
With respect to intellectual property, and this a very short slide for a very large amount of activity,
but we maintain a very vigorous and aggressive IP program inside this company. And this isn’t just
patents, it’s also trademarks, it’s also confidential information that’s kept that way - trade secrets.
And that's reflected in output, upfront what you see, which is patents being issued on a regular basis,
but not just here in North America and Canada and the United States, but around the world. We have
a very aggressive worldwide filing strategy and Mary Anne Dillahunty spearheads that program for us.
And I have to say, it’s a real strength in this company, it has been and always will be - we will continue
to maintain our efforts in this particular area.
Manufacturing – and it doesn’t do justice to give this one slide, but to do much more than that would
be telling things that we’re not supposed to talk about, candidly. But we’re very, very late in the
development stage of our manufacturing process. Again, we view this as a major strength of the
company. Imagine a scenario where we demonstrated that Reolysin works and then we can’t make it:
a little beyond embarrassing I would have to say; or can make it, but it doesn’t meet regulatory
scrutiny – also a problem.
And there are more products that fail registration at agencies like the FDA because of manufacturing
issues than there are because of clinical data issues. And so this is a program that we don’t talk about
that often, but I think it’s absolutely critical that we recognize the effort and the achievement of this
particular activity. In this coming year, we’ll see the last elements of that fall in place. And I have to
say that this is viewed as a major strength by other entities taking a look at Oncolytics on both noncommercial
and commercial.
With respect to the clinical program I think the thing, the highlight, is, from a major activity
perspective, is actually looking at the first stage of our REO 18 head and neck study. We completed
and expanded enrolment, which was about twice the original anticipated enrolment in this study,
quite expeditiously. And we actually released initial data off the very, very early preliminary data that
was available from the study just before Christmas last year. And I think this was a critical milestone
for us to anticipate and a critical milestone for us to look forward to in this particular study. And I’ll be
going into more depth about that data and I'll also be explaining why we did this analysis, because I
think it’s very important for people to understand how, I think, nuanced, the analysis of this particular
study has become.
This is our randomized clinical program, just as a placeholder to let you know what we’re doing. I
don’t have all the clinical studies that Oncolytics is involved with on this particular slide, that would
take another slide or two. We have a very broad-based clinical program now looking at a number of
different indications, different types of cancer. And I think the key thing for us in the last year has
been moving into a very broad randomized, which means we have a control and test group within the
same study program, looking at most of actually the major indications in oncology.
And this is a result, of course, of our belief that Reolysin actually is broadly active against most
cancers. And this is the result of that. This slide really just gives you an indication of the breadth of the
activity and the number of patients in each one of those studies. I'd just like to note that those last six
studies, those randomized Phase II studies, represent about as many patients as we’ve enrolled in
total for the entire history of the company in our previous studies including the REO 18 head and neck
study. And that most of those program costs are being supported by outside agencies. The equivalent
to that 600 plus patients is in essence the cost of a single study test as a corporation.
Now, what do those comprise of? There’s actually four randomized studies now ongoing in Canada.
These are actively enrolling in Canada and just very briefly, we are looking at castration-resistant
prostate cancer in a very interesting study. Our first study looking at what I think of as a new age
targeted therapeutic in combination with Reolysin, which is colorectal cancer, in combination with
Avastin and a drug combination called FOLFOX6.
Looking at actually both types of lung cancer both adenocarcinoma of the lung and squamous cell
carcinoma of the lung in a second line setting in a study here in Canada, randomized so it's in essence
two studies in one - there's actually four arms in the study. And finally, a study that’s I think very
important is to take a look at Reo finally in a randomized setting looking at breast cancer. And all
these studies are being run by NCIC here in Canada, it’s old name The National Cancer Research
Institute of Canada, which is now just NCIC, they've gone with the contraction of their official name.
We still have, and these are further advanced, two studies going on in the United States, one for later
stage ovarian and reproductive stage cancers in women. I have to tell the anecdote of a colleague
company of ours here in Canada, who was running an ovarian study many years ago and got a query
from Health Canada wondering about the gender imbalance in their study [laughter], but we have not
got that question about this particular study. Every time I look at that study, I think of Tony, I can't
help that. And a colleague of ours who unfortunately died of pancreatic cancer actually ran that
study.
And the other study being a very interesting study in pancreatic cancer, and just to note that these
are first line patients, but they are actually getting standard of care. Standard of care currently, (which
is about to change) is gemcitabine for first line patients in the United States and in Canada and we’re
not actually using that in first line patients, so it’s kind of an interesting study. And both of those are
sponsored for and mostly paid by the NCI, and the GOG, the Gynecologic Oncology Group, is actually
running the ovarian study.
So between those two jurisdictions, six studies which will either be substantially enrolled or
completely enrolled in this calendar year. And so next year when we are standing here, I’m hoping to
be able to be describing early data out of some or most of these studies. It’s a very significant step
forward for Oncolytics and it’s really, if you think of head and neck as the tip of the iceberg for
Oncolytics, this is the bulk of the iceberg underneath the water. These represent literally most of the
major indications from a numeric perspective for number of patients in oncology to date. Very critical
to be thinking in that term. This is Oncolytics future in these six studies.
Now, I want to talk briefly in more detail about three studies as I indicated and that’s our two lung
studies, single arm lung studies, one for adenocarcinomas of the lung and one for squamous cell
carcinomas of the lung. I think these are very critical, because they do lead into a number of our
existing studies, because we already have that second line study, but probably I think one of these
two studies is a candidate for our own next larger randomized study.
The first is looking at, and for different reasons, to take a look at these. First is the adenocarcinoma
lung or non-small cell lung cancer, and the primary objective of this particular study was to look at
response rates, but a unique feature of the study is us really getting for the first time into genotyping
patients, actually looking at their genetic makeup.
And as people are beginning to realize many of the cancers that we think of as one cancer, are
actually a number of different cancers. So I think, breast cancer now really is, what's the number,
Matt? six, eight diseases really, based on genotyping, and so if you don’t have balances of those in
clinical studies, your data is meaningless. It’s an issue. So you really need in certain indications to
understand the genetics.
Now, some cancers, you don’t have to, because we already understand that they are pretty
monolithic. Pancreatic cancer being I think the best example. The gene mutation that is linked with
pancreatic cancer is represented in over 90% of patients. That’s a pretty uniform patient population.
So you don’t have to do these sorts of things. Lung cancer, this type of lung cancer in particular, is one
that I think we’re going to have do that with.
This is just an example of actually metastatic disease and many of you have seen this slide before, this
is the same slide I showed last year, where you've got metastatic disease expressing. I’ll do it on both
hands, but the upper left is metastatic disease expressing through the lung wall and you’re seeing a
rather rapid reduction – post cycle two is only about four weeks out. And again in the lower and the
lung lobe there, for those at the other end of the room. I won't laser light you because I'll blind you.
And so, this is very typical of the responses we’ve seen in the studies, the key thing is however is this
rather crowded slide. I think the key element is that you will see there’s a number of different things
that can, that are associated with this – there are mutations at certain genotype or certain genotypes
due to mutation. There are certain things that we call over-expression, so the genetic makeup is the
same, but you’re actually getting more of something, so that's when we say it's over-expressed. You
can see it’s a pretty diverse set and sometimes you get more than one thing and you see BRAF and
EGFR amplified, over-expressed KRAF, all blended together and what we’re seeing is that there is
different patterns of response as a result of these different genotypes.
For example, if you have a KRAS involvement, you see a lot of stable disease, almost uniform stable
disease, which is almost unheard of honestly in this indication; and when you see EGFR involvement,
you’ll see a lot more partial responses, but you also see more progressive disease. So you’re getting
more aggressive responses but more aggressive failures, and so going forward into future studies we
will have to take this into account for entrance criteria, but this is honestly the future of some of
these diseases. It is this finer differentiation between the patient populations and it gets critical. So
you will see a lot more of this in future indications or future studies of Oncolytics when it’s warranted.
We are not going to do genotyping where it’s not warranted. Just, people ask us why we don’t
genotype head and neck, well, it's not necessary, they are pretty much, they are pretty uniform. It's
the same with pancreatic cancer.
The other one that’s interesting, on those Reo studies, I mean the really key thing I think for this first
one is looking at the stable disease or better in this relatively diverse patient population. The entrance
criteria they were all supposed to be stage 3B’s or 4’s, which is very late stage, it turned out all the
patients, except for one I think, were stage 4 and in this patient population you don’t expect to see a
90% or better stable disease rate by RECIST which is what we got out of the study It's probably,
arguably about twice, what you would expect to see with this particular patient population, these are
very late stage patients and we saw a very, very aggressive if you want to think of clinical benefit as
being stable disease or better.
The other thing that’s noticeable here, and this hasn’t actually been published yet, is that many of
these patients normally only get 3 or 4 cycle of therapy and we’re starting to see patterns beyond
that, so beyond the... we're starting to see duration of response become an issue, but that will be the
subject of a future... when the study is finally done.
The other lung cancer is squamous cell lung cancer. Sort of arguably about a third of lung cancers are
in this category and this of course was the subject of early disclosure of the very first patient who
showed up on a news article out of Texas. Actually Matt and I saw the first response of the study on
the TV screen when they actually showed it, and we were little unhappy with the investigator for that,
but the good news was that you had a very aggressive response in patients.
This one I want to highlight for a slightly different reason than the first one. The first one was looking
at genotyping, this one is looking at a somewhat different element of it. Again, you’re seeing, this is
actually patient one and with the circles, the top is the primary tumor and you can see, very rapidly,
post cycle two, it's just a few weeks out, and you’re seeing these very aggressive responses and this
actually is the 6th or 7th best response on this study.
There are six patients who are better than this with respect to this kind of response. And you also see
metastatic lesions which is represented in the lower slide. But the key thing to think about here isn’t
necessarily the response rate, which is impressive, but the speed of response. And I think – just keep
that in the back of your head about speed of response.
Anecdotally, for the last decade, George and Matt and other people associated with our clinical
program have been hearing reports about how patients quite often show tumor changes very rapidly,
often in the first week of therapy. It’s very unusual. So the speed of response is starting to be
interesting. And that’s the case here. You’re seeing post cycle 2, a few weeks out, you're seeing these
very aggressive responses. Now, if you look at – and this data just came out earlier this year – and this
is really a reflection of speed of response, not magnitude of response – this is what we call a waterfall
graph, where you actually graph the worst patient on the upper left at a certain timeframe and then
at (so these aren't in order of enrolment and have nothing to do with duration) but they're just
basically more or less at the same time – all but three of these patients were done at four cycles, a
couple were at two cycles and I think one was at six cycles. So it’s a pretty uniform timeframe, it’s not
absolutely pure.
But what you see is that 19 out of the 20 patients actually in that defined timeframe actually showed
shrinkage of tumors in a fairly short period of time. And we have this very bulky about a third of the
patients showing this rather aggressive speedy response. And so these waterfall graphs actually show
you a – are very handy, they are not a measure of response rate by RECIST as we call it, sort of
maximum response rate for a duration of time, but they are actually a reflection of speed of response,
if you want to think of it at that way. And so in this particular indication that’s quite interesting, and
this is one of the more impressive waterfall graphs honestly I have ever seen. So it’s quite interesting.
When you switch over to more standard measurements, which is looking at and this was announced
after the first, the final, we’re actually seeing more on the duration of response, which is response by
RECIST. This particular patient population again you don’t typically expect to see stable disease or
better numbers up in the 90%-ish range, but again, we saw this. So overall, when you combine both
our squamous cell and our non-small cell lung populations, it basically covers most cancers of the
non-small cell lung, together you are getting 9 out of 10 patients getting some form of clinical benefit
by RECIST. And that’s impressive I have to say, and that’s something that we’re certainly very
interested in and I think will figure largely in our clinical trial progression, the clinical trial program
progression, not the patients, my apology.
Honestly, this slide, if everybody pays attention to this slide and goes away and just remembers
what's on this slide today, I’ll be thrilled. This is the slide – this is my chance to act a little tiny bit
professorial. Normally, we look at something by, called best responses by RECIST, where you measure
the patient at time zero, you measure it at some time out there, and that you hope to have some
form of response and you measure the response and you measure the percentage shrinkage by the
addition of some of the longest tumor measurements and so on. And then you have to maintain that
until – for a certain period of time. And so, you see – let’s say you have a -50% at Cycle 4 in this case,
potentially at Cycle 6 when we scan again, we want to see if we maintained it: if it's maintained then
that’s a response by RECIST.
These kind of responses are standard. This is the standard way of measuring in clinical studies, but
they are relatively time independent because it doesn’t matter whether it's between Cycle 4 and
Cycle 6, Cycle 12 and Cycle 15 – you're really measuring the best response and seeing if it’s
maintained and it doesn’t matter how long it takes to get to that response.
And when you think about what that means to a patient, what it means for a patient is that if you
don’t really care when the response happened this is more important for patient outcomes if they are
actually going to able to live to that event. Think about that for a second. Now if you’re only going to
live six weeks if you have an agent that is going to cause a response at Cycle 12, out maybe 6, 8
months, that doesn't do you much good. But what this does do, so when you look at RECIST, you look
at things that are much predictive of patients who are going to have better prognoses coming into the
study from the start.
So it’s a magnitude think of it as can you make this response bigger, but you are not really caring
about how long it takes you, that’s what we do now, that’s the system. The layer on top of that and
this is where the new agents, the new targeted therapeutics, have some wrinkles and some nuances
that are quite interesting.
You also have to take into account with all these things when you stop treating. Honestly a lot of the
new agents when you quit treating, you quit getting benefit. So let’s say a patient is only getting four
months of therapy, wondering about a response out at 9 months or 10 months or progression free
survival at 10 months or overall survival, doesn’t mean so much because you quit treating six months
ago, how can it be better than your control arm, when you’re not treating anymore? So these things
are important and we’re also starting to see a number of therapies not just Oncolytics Reolysin
potentially, but a number of existing therapies like Avastin and others that you are actually starting to
see lots of activity over time. You’re seeing a tolerance issue coming up or perhaps in some cases
toxicity issues coming up, so you have to layer that over the top of this. So that’s the second element
when you’re looking at things.
The third one is one that virtually is untouched. And this is something I think it’s really critically
important – I’ll go back to my six week analogy. You come into a clinical study or into a clinic before
it's an approved product and you have a 6-week lifespan, you don’t know that yet. You have no idea
that you have a 6-week lifespan, and that’s often the case. And you’re treated with an agent that
gives you a response say -30% of your tumor volume in two weeks. Well, that’s interesting, that’s
probably going to give you some clinical benefit. And actually there have been studies in other
products like Nexavar, which have actually shown that the rapidity of response actually provides
clinical benefit. If that same agent would only give you a response at 16 weeks, which is 10 weeks
after you're dead – not so much clinical benefit to expect. So the speed of response really matters.
So you have this relative thing – speed of response matters, magnitude of response matters. And that
makes complete sense. I mean if you’re going to have a really rapid response in a tumor and you need
it now then that’s more important than maybe getting a better response later - two things. So just
keep that in mind for now and for the future. But I would urge people to take a look, if you’re
interested in looking at things like that, look at the Nexavar studies for squamous-cell carcinoma,
where they actually didn’t see any progression free survival benefit, nor overall survival benefit, but
they saw clinical benefit in a pretty significant patient population, because it was faster at getting to
the same point. So driving to [indecipherable] as opposed to walking to [indecipherable] - when time
matters, you drive.
How does this relate to Reolysin in our head and neck program? Our head and neck study now
currently is in essence the same as it was before. It’s a double-blinded placebo-controlled study
looking at patients with advanced head and neck cancers. It’s a two stage study, it was always
designed to be a two stage study, and what we had originally intended was to run the first stage with
around 80 patients, look at an adaptive approach looking at progression free survival to determine
the probability of success in the second stage and then move into the second stage, which is where
we would definitely prove the statistical outcome of that particular study.
Along the way we discovered we actually thought we had two patient groups by response. Patients
who had just metastatic disease in essence had about twice the progression free survival of patients
who had local regional involvement. So they might have metastatic lesions but they also, they have an
active head and neck cancer in the local regional area. And so when we discovered that, we thought
we were fairly unique at that time. We went to talk with our investigators, talk with the FDA, and
what we agreed as a group was that we would double up in essence on the patient side, and analyse
these two patient populations separately, and that’s what we did.
So we enrolled 167 patients in the first stage instead of 82, which is where we were at the start, and
then we would go into an analysis once we see the results of that data then we proceed into the
second stage just like before. The overall endpoint, before and now – a reminder – the primary
endpoint is overall survival, that is the registration endpoint, that is the endpoint that matters in this
particular case.
The secondary endpoints, which we will still report on are progression free survival, we’ll look at best
response, and we added in a specific additional one, which is looking at tumor-specific response at a
specific time, and I’d like to draw back to my comments on the last slide, when we take a look at that
data because that’s important. We are also looking at some other things like HPV status and where
we could get biopsies, and we knew we wouldn’t get very many, at Ras pathway status.
So the analysis, where we are right now, we’re still doing the analysis of the first stage and as I said
it's167 patients. We are still blinded to overall response rates. We are still blinded with respect to
progression free survival and we are still blinded with respect to overall survival.
The patients, we still don’t know who is in control and who is in test. We're blinded, that’s critical. Our
Data Monitoring Committee has now reviewed the data on the patient population now three times
and has continually just said continue on with the study. Now that we are not enrolling, we're not
treating patients anymore, their job is done, I mean that’s categorically concluded.
The data we announced just before Christmas is I think quite interesting from two perspectives: one,
the first piece of data we looked at was looking at a set time; now it was all at a set time here, we're
all looking at the same point in time, was to see what percentage of patients had actually had no
growth, so 0% growth or better and compare just those two percentages and we looked at the
patients and we looked at metastatic tumors specifically because there was enough data to actually
give you statistics and that’s an important thing to note with these studies is that you're looking at
fairly small patient sets and it doesn’t necessarily mean with these small patient sets that you'll
actually reach a statistical endpoint when you think about the size of studies that you look at. I mean
there is about probably arguably about 70 patients with just distal mets, there is about a little under
100 patients with local regional involvement, they are pretty small patient numbers and, as we
originally intended, they're used as guidance to move into the second stage.
I think we were a little surprised honestly that we reached statistical significance with this particular
endpoint where we were looking at just comparing those two gross numbers. So in the control arm,
you had 67% of the patients and their metastatic disease with that 0% or better and the test arm was
86% – that’s a pretty big increase in percent.
If you look at it on a more fine basis, which is looking at again, the comparative waterfall graphs. and
what this waterfall graph is actually, is every patient in those categories graphed on here from the
worst to the best, so the worst is up at the left, so if you take that one up in the upper left, that
patient's metastatic lesions actually grew 100% in six weeks, and that’s on the control arm, and on the
lower right you’ve actually got the best patient, which was on -80% and again, that same six weeks, in
this case on the test arm. And what you found is that, over that same time period, six weeks, it’s
roughly about between a 10% and 15% on each patient benefit increase in shrinkage over that
timeframe.
And so, if you’re expecting to get a -30 on the control, you could expect to get -45 on test, and if
you’re +15 on control, you could expect to get 0 on test, more or less. But what this is, is a measure of
rate of shrinkage – this is the velocity thing again, so this is the early patients, this doesn’t mean
they’ll actually have better responses in the end, what it means is they’ll get more response sooner.
And in the other studies, again I’ll refer you to the Nexavar study, this actually translated into clinical
benefit in this case being, living longer.
So we’re hopeful, I mean, this is the only data we have out of the study to date, but certainly it’s a
very good indication early on that we are hoping to see something based on this, and I mean, of
course, the best would be to have increased rate of shrinkage, and also have increased magnitude of
shrinkage, but we don’t know that yet, that’s still blinded - and that will be coming out in the coming
months.
We’re quite excited about being at this stage of this particular study and I think it’s really quite
significant that we were actually [able] to get a statistically significant outcome of anything with this
small dataset. Just as I’m mentioning about the timing of data, because I know I’ll get asked the
questions, what we did when we doubled up on the patient number and looked at those two patient
groups was go to a different statistical endpoint. And instead of doing it at a fixed time to do a
predictive analysis, we are going to basically an event-driven outcome and while we roll that off our
tongue quickly and wish that events would happen quickly, events in this particular case are deaths.
What we’re talking about here is we have to have a certain number of deaths on study to reach a
comfort zone that our statistics won’t change based on the rest of the people dying after that point.
And so we are actually in waiting mode. We are waiting for events to occur and once we cross a
critical number of events, then we will do this statistical analysis and that is not predictable. People
do not die on schedule and we’re all thankful for that. So when we have that percentage of events
occur then we will do the statistical analysis, and not a day sooner. Well, this is the comment on that.
So looking at the year ahead, I think I can very comfortably say that sometime between next week
and the end of this year – how's that for a timeframe? – that we will complete the first stage of the
analysis of the 167 patients on REO 18 and that will be overall survival data, progression free survival
data, magnitude of response data, which is actual RECIST-based response data, and that will tell us
which patient group, maybe one, it may be the other or maybe both will be the candidates for the
second stage of the study, which will then finish off the program.
Now there is a possibility, just as a side comment. We will be consulting with primarily our European
regulatory friends about looking at this dataset from this first stage because it is now large enough,
167 patients is large enough, that if the outcomes were to fall our way, it might be considered for
some form of regulatory approval. But we do not know that – it will be completely dependent on the
outcome of the data and it will completely depend on the outcome of Matt and his colleagues'
conversations with our European regulatory friends. I guess we can call them friends, they're actually
quite helpful. So that’s something to watch out for this year, and start watching from soon to later.
We expect some time before the next AGM to either be completed, (and I'm hedging a bit because
one study is a little slower starting up) but five of the six I'm pretty comfortable will certainly have
finished, completely finished, enrolment in those, which is the future for Oncolytics – those major
indications in those randomized studies coming in behind. We will also have selected, and I think,
much sooner in the year than near the end of the year, our next indication that we’ll be taking into
our later stage development ourselves. And I think you can guess where I would like to go on that.
And I'm expecting our manufacturing group to deliver on what they have committed to deliver, which
is to finish our manufacturing development this year, which is the result of many years of, I think, very
fruitful investigation. Again, I can’t emphasize [enough], and that’s why I am finishing up mentioning
manufacturing last, how important an asset it is to have backing up everything that we do having a
completed and very productive manufacturing program. So I am very pleased about that.
So that concludes my comments and meanderings for today. I appreciate your time and attention. I
appreciate the fact that many of you have been associated with Oncolytics as shareholders as long as
I've been associated with this program, and I think the only one who has a longer tenure with this is
Dr Coffey who we are all very thankful has maintained his interest and presence on this particular
program.
So, again thank you and what we would like to do is open for questions, we would like people to
identify themselves, we’re going to hand a mike out, am I correct? for those people who like to ask
questions because we are actually webcasting the questions so, if you could identify yourself and
speak into the microphone and if for some reason I don't get a microphone I’ll repeat the question
and Matt will answer all your difficult questions and I will answer the soft lobs. Thank you very much. I
appreciate it.
Question andAnswer Session
[35:09] Jon Tyson
[JT] Hi, I'm Jon Tyson. I have a question about slide 17, that graph of tumor response. When you say
50% shrinkage, is that 50% sum of lengths or is it 50% volume?
[BT] These are all sum of lengths which is the standard basis for er...
[JT] So, it’s really like it shrinks 7/8ths of…
[BT] Yeah, the volumetric is by the cube of the radius so ... if they were spheres ... so, I mean they're
much more dramatic on a volumetric progression, I mean a 50% regression length wise. And you also
have to think of it, if you have a tumor that's like a sausage, the long dimension is the sausage and
then you could shrink it like this all the way towards a fine pencil line and it's zero. I mean it’s not, I
mean the length is the best, honestly, that people have actually come up with. Dr. Eisenhower who
actually works with the NCIC, is the former Director of the NCIC, was the principal author of the new
RECIST criteria - I'll put a plug in for a Canadian component in global oncology - and it’s very difficult
doing the evaluations on these things from an overall perspective, because it’s very variable with the
tumor type, but I think we stuck... this is RECIST-like measurements - they meet RECIST standards. It’s
just not the duration of RECIST because we were after velocity not magnitude.
[36:40] Dean Bradford
[DB] My name is Dean Bradford. Can you tell me with regards to REO 18, how many patients continue
to survive?
[BT] No, I can’t. That’s... there are certain elements of the study that we do keep confidential and the
number of patients that are alive is but one of them, so I apologize, sort of, for not being able to tell
you that.
[37:13] Darrell Scott
[DS] My name is Darrell Scott. So rather than telling us how many patients are alive, can you tell us
what the trigger is that you would need to unblind at that particular point?
[BT] At this time, I can’t disclose what the trigger is, partly because we’re still working on it. With the
change of going from 82 patients with a single patient group to 167 patients representing two patient
groups, and having actually basically two measurements because you’ve got each of those two
patient groups, required basically a complete redefinition of the statistical plan with respect to when
the endpoint was going to be, going to event-driven on those two groups.
And you needed some sense of the progression free survival that you were seeing in the combined
groups actually to do that math and that’s what’s going on right now. We’re actually defining that as
we go. And just as a mention on that, it’s kind of we thought we were very unique in this last year. We
thought that we had actually – for the first time – observed these two patient groups and that turns
out not to be the case.
In the last year since that decision was made, we found out that another drug done by our former
colleague company of ours where the drug is called Erbitux, actually in the registration studies in
Europe, actually found the same thing, it just never showed up in the publications and it never
showed up in the label. So in the publication they were still treating the group as a monolith,
combining met patients and local regional patients together. In the label that’s for the treatment of
all, but when you dig into the regulatory stuff, you know the discussions at the regulators and the
presentations, they were seeing the same thing – they were seeing that the metastatic-only patients
as a group were doing much better than the local regional patients, but they just didn’t choose to
differentiate between the two.
So we weren’t quite as clever as we thought, I think, but there is certainly a track record of people
seeing with this and coping with this before, so I think it was reassuring for us that we actually did
that. I still think it was the absolute right thing to do once we figured that out to deal with it the way
we did. But certainly the analysis of this study is proving to be extremely interesting both with respect
from that and with respect to the now-dawning information that there's different components that
affect clinical benefit – you know, rates, magnitude, tolerance, those sorts of things. So we have an
interesting few months ahead of us.
[39:50] Don Siegler
[DS] My name is Don Siegler and I have two concerns on the Phase 3. Dr. Tuchman recently said the
data would probably be the end of the third quarter, I'd like your comments on that, and there is
something about a six month blackout on the V2 board. Anybody...?
[BT] Well, a) I don’t read the V2 board
[DS] I know, I don't...
[BT] And I would urge anybody not to read anything on a chat board but that would offend half the
people in this room so... I would urge people to either call us or read the stuff that we have to put out
because we have to put our hands over our hearts and warrant [indecipherable] whatever, but I am
not disparaging the V2 board because I think it’s a very good board. I don’t know about what a six
month blackout is, I don’t know what that reference is.
Does somebody have some texture on that or... Oh, yeah, that’s the, I’ll explain that – in the
information circular there was, we have a provision on our option plan that if we are inside an
internal blackout for whatever reason and a person’s options expire, of course, they can’t – they
could exercise, but they can’t sell them – which doesn’t seem to be particularly fair.
And so the provision is that if you have, if you are in a blackout period for any reason, financial, which
is often the case, we go into blackout every quarter for our financial statements from the time they
are prepared until the time they are actually, when Kirk prepares them or his colleagues prepare
them to when I read them, that’s when I get blacked out, when they are distributed to our board,
they get blacked out at that point in time.
And there’s other events that cause blackouts as well. If you have information about a clinical study or
you can have rolling layered ones like you might be talking about squamous cell and then you roll into
head and neck, and we were in, so you’re blacked out a lot of the time. We just don’t put a press
release for blackouts, blacked out, blacked out, blacked out, but if there – if your options actually
expire during, while you’re blacked out, what they do is, the options expiry is extended until 10 days
after the blackout period is lifted. So that’s all that refers to in that particular case - because there was
an information period and that’s when the financials actually deal with all those particular option
blackouts.
The other question was? [question repeated from the floor] Alan answered the question or made a
comment about end of third quarter and left out the word 'by' at the end of the third quarter. So, I
will plead Alan missing a word in his presentation and that is his opinion. We honestly don’t know
when the event threshold will be crossed, a) because we don’t know what that event threshold is, we
don’t know when people will die and b) so we don’t know that... that would be I think Alan’s probably
internal estimate in his own mind, that sometime between tomorrow, or last week, and tomorrow
and the end of Q3 because that’s really what his opinion was, but that’s a personal opinion not based
on any data because I don't have that data either.
[43:20] Bill Langford
[BL] My name is Bill Langford I had a question about the Phase 3 trial and you alluded to this yourself I
think, but given that there are two patient groups sample size is perhaps, in the metastatic group, 35
versus 35 ballpark, that’s not a large number, not a powerful statistical test which I believe means
that you have to have quite a substantial difference in performance to get a statistical significance.
Could you comment on that a bit Brad and the second thing would be what is the test for whether or
not they would be proceeding to the next stage. Thank you.
[BT] Matt? [laughter]
[MC] Awesome, this is fun, we’ve been kicking this around a bit as well. I was speaking with Wang
Chong who is the analyst over at Edison and it’s interesting because we obviously don’t have the data,
so I don’t sleep at nights and I worry about these things and drive my wife crazy.
If you look at the Erbitux study, the metastatic group lasted about 50% longer so not unlike ours
collectively, but what’s interesting if you look at the hazard ratio Erbitux in the metastatic only patient
has a hazard ratio of 0.99, which means basically 99% of the events on one arm happen on the other
one. So there is really no difference. But when you look at what they do in the local regional group,
it’s really quite an impressive outcome for those patients, they do really well. So that collectively as
you said, there is enough events for the entire study to say that the study was successful. Now if it
had gone the other way, they probably would not have had a successful study and would have had to
pick one patient population.
We are still at a point where we’ll be looking at the two groups and hopefully there's... When we
looked at the initial data, we reported there was a statistically significant trend in the metastatic-only
group. There was also a numerical trend in local regional. So it could be that the metastatic shrinks
more rapidly than the local regional, we don’t know at this point, the jury is out, but it looks like it’s
having an effect both in local regional and metastatic. I’m off to Europe Monday to talk to our
regulatory group because there is – I think there is some misunderstanding. In North America, there is
a requirement for two well-controlled randomized studies, you have to have two, and people are
going – Are you going to be selling this on Tuesday? It's like 'No!'. No – we have to do another study
and I think we’ve made that clear for the most part, but there is some confusion.
Europe is a little bit different. If you have one well controlled study in a very difficult to treat
indication, you can get a limited drug registration so we’re looking at that. So we are planning for
being successful in both groups or one group or the other. But as you said, the metastatic is probably
going to represent about 40% of the 167 patients. So you are going to have to see a bigger magnitude
to reach statistical significance. With the local regional as you said it's probably about 100, so you may
not have to have as big of a difference.
But then there is also the question of – if we ran a million patient study and we had a p-value of 0.003
and patients lived one day longer, it is statistically significant, absolutely it is. Are you going to spend
$100,000 for the one day, that’s really the question, so we’ll take a look at the data: statistically
significant is one thing, but you want the patients to derive a clinical benefit. Now, in this patient
population, their survival times are very well [documented?]; historically, if you look at it, their
median survival's about four months. so if you can extend that a month, for them, a 20 -, 25%
increase is going to be meaningful. Especially when you look at the tox profile – these patients aren’t
paying any real toxicology consequence, like they’re doing, really, really well.
So we don’t have kind of thing, but we are going to position ourselves to get a European opinion as to
what they feel about the product, how much of a difference they’re going to need to see pricing on
this type of agent. So I’m assuming that it’s going to hopefully work in both groups. Realistically
though, I think one group will show more pronounced effect than the other one and that will be what
we pursue in the second study.
[Inaudible question] It’s a small group, so I mean if we reach statistical significance I’d be over the
moon. and I'd probably quit and move to Jamaica. But it is, as you said, it’s probably like 100 versus 70
patients, what we'd look for then is a clear trend. I mean, you can look at some of these curves and
see, the curves are very descriptive of what the patients are doing. You can tell if it’s a delayed
immunological consequence, if there’s a more pronounced initial effect, if it’s a proportional effect
and they do better to the whole thing... You know, you could get a three, four, five-week advantage
and it's not statistically significant, but if you can see that much of a magnitude of response, we’ll
move it ahead.
[BT] You’ll need it [the microphone] again. Thank you, Matt. Interesting in your choice of successful
place to go being Jamaica. But they don’t have an advantageous tax regime. I thought that you should
just know that.
[48:35] Unidentified [Alf Conradi?]
[U1] I’d like to congratulate you on a very successful year building on the foundation and planting the
seed for future success, certainly is worthwhile, so congratulations. The question I have – I have two
questions. Can you elaborate on where pancreatic trials are at – both pancreatic trials, and secondly,
can you make a comment on where you’re at, if you’re talking about potentially approaching Europe
for registering the product, what sort of funding formula are you thinking about, if you could
comment on both of those, please?
[BT] Well, the randomized pancreatic study, we can’t comment on – they’re still enrolling, it’s ongoing
with many patients still on study. And so that’s the status. We don’t have interim data to discuss
about that. The single-arm gemcitabine/Reolysin combination pancreatic study, there are still several,
[to MC: a couple?] several patients still on study that are still being treated and that’s rather
remarkable on itself but I think the final-ish data on that will be presented later this year, if I had to
guess. [Inaudible interjection by MC] That’s good. So I mean that’s where we are on that. We’ve done
the interim releases on that data but I think we wait until we actually get later in the year to actually
do a final release on pretty much final data on that particular study. The funding part – referring to
like how we get reimbursed in Europe? or…
[U1] What sort of – Matt just alluded to $100,000 to get... for a day of life – I don’t understand that.
[BT] We actually had this conversation once with the FDA, which they're not supposed to have and
they said Well, you know, it's one thing to show a statistical significance. What’s clinically relevant or
however they... [interjection from MC] What’s clinically significant? And I said, so that means we’re
talking about pricing right, and they were like Yes, and I said, so if we want to charge $100,000 for a
month of life that’s probably not clinically relevant. How about if I charge a dollar for a month? And
they went, Oh yeah, you’re right. Oh, we can’t talk about this. I mean they’re not supposed to – the
FDA regulators aren’t supposed to consider that. Reimbursement is a completely different issue and
in different jurisdictions, you get different reimbursement regimes, like in England forget it.
[MC] Quality of life...
[BT] Yeah, quality of life here, there... In the United States are you not going to treat a patient and
give them four extra hours of life and potentially be sued? Of course not, which is why we have the
most aggressive pricing in the United States. I mean those sorts of things vary by jurisdiction all over
the place.
But in essence when you get down near to the end, I think we’re heading towards this in a general
trend worldwide. It’s that, however you prove clinical benefit, in the end quality of life will actually...
is becoming a mathematical art, and actually determines pricing more and more. And so, until we
actually know what kind of benefit we’re deriving for an indication... It kind of makes it a little fuzzy
talking about pricing candidly. I mean a rule of thumb in the air, I mean $40,000 for a six month
treatment course is cheap for a biologic and a 100 is getting pricey. Well, that’s kind of – there are
cases over a 100,000 but that’s just kind of the range that people talk about for therapies.
So, if you’re only going to treat somebody for two weeks, unlikely you’ll be getting $100,000 for it, if
that’s all they’re getting. If you extend their life, and quality of life, six, eight, nine months or
whatever time for a severe indication, you charge a $100,000. I mean that’s... Then you get quotas
where people, you know, if you get sick in October, they've run out of their money, so you don’t get
reimbursed at all, but if you are going to get cancer, get it in January or February or at the start of the
fiscal year. I mean those are the realities in our healthcare system, and that’s not just Canada, it’s
worldwide it’s different everywhere.
[52:55] Oliver Murtaugh
[OM] I'm Oliver Murtaugh. You’ve often said that you expect to partner before you go to market. This
is many years later now, do you still have that feeling or do you think we can go it alone on this
product?
[BT] Well, you know it was interesting, I mean as you refer it’s been many years that we’ve been
consistent in saying that and I’d like to happily report we’re still being consistent with that. I think
knowing what you are capable of and the organization is capable of is important and we're not a sales
and marketing organization, we don’t have that capability. And to build that capability would both be
time-consuming and extremely expensive and so I think it's our anticipation that we would continue
on with that course that we set on day one now many years ago, which would be to take it to fairly
late stage and then to seek out an affiliation however we wanted to call it with an entity that has
those capabilities. Whether that's worldwide or different jurisdictions or whatever would be that
case, and there is a variety of different relationships you can do for that, but that is consistent as
what, I mean we believe that our strength is doing what we do, not doing that.
[54:17] Andre Techine
[AT] Kind of another follow-up question on head and neck. So I think in the original plan for this study,
I think the plan was to look at the overall survival, but six months after enrolment?
[BT] The original, the primary endpoint in the original study plan was looking at overall survival, but
not at a fixed time. Again, you could look at it at six months, but that was in anticipation they’d all be
dead by six months, so that's a convenient timepoint, right. And that’s also the timeframe in which
you see about 8 cycles of therapy, which is the maximum number of cycles on study of the drug triplet
the carboplatin, paclitaxel and Reolysin together.
The endpoints are the same as they were at the start, it’s just different patient populations now and
that’s why we doubled up on the numbers.
[AT] So, I guess, as a kind of follow-up to that, right now if you’re looking at going out potentially to
12 months of the events, is there any indication or any concern that the control arm is doing
significantly better than originally expected? And is there any data from that Erbitux study that would
indicate how the control arm for mets-only went?
[BT] The control arm in the mets-only did much better than I think anybody expected in the Erbitux
study, but that didn’t affect the registration. Matt, I think, would be quite happy to go into detail
about that and probably could provide that?
[MC] Send me an email and I’ll send you the graphs and you can post them wherever, they’re public
documents. They are not easy to find public documents like really not easy to find public documents.
And actually to your question about pricing, in the discussion they talk about quality of life years and
pricing and how they come to it. So it’s kind of an interesting, because at the end of the day, NICE
didn’t actually... - they said, Oh, it doesn’t work at all for the metastatic group, so we’re not going to
reimburse for it. And it’s less than a quality life year so, you can't charge more than £30,000 and since
you’re assuming it’s going to be more, we’re not going to reimburse for that either. But it’s all very
medicinal how they go through it.
But it was interesting, I don’t... As people get more savvy with these clinical studies, as Brad alluded
to, breast cancer is kind of considered to be a number of different indications based on the genetic
phenotype of it. Head and neck cancer it was interesting that Erbitux did have this effect in the study
that it wouldn’t work in metastatic and would work in local regional, that the metastatic group lived
50% longer than the local regional, but George and I have been over this, over this, over this, and over
this because when we first saw this event we were just like…
[BT] and over this, over this, over this…
[MC] ...over this, over this. It’s interesting the patients die differently: if you have metastatic disease
to your lungs or to your liver eventually you will die of cachexia and just you'll waste. If you have a
massive lesion and that’s threatening your carotid or your jugular or your breathing or your air supply,
I mean all of the plumbing to your head and all the rest of it goes right up through that one little pipe.
So, if you have lesions threatening all of the structural integrity of those things, those patients die
catastrophically. So, they just have different risks, so maybe it’s not that surprising that they are
different. What’s surprising is that it didn’t end up on their package inserts, to me.
We’ve shared this with doctors and we said did you know this and they said 'No, and I was on the
study', but you can imagine when it's in a 14 patient, 14 country study you don’t get to see all the
data. And the companies collect it all and they share what they share and you can’t really see the
trends if that’s not what they're looking for. So, I think you know we made this discovery, but when I
went off to ITF or the Innovation Task Force in Europe I said, we are blinded still but we are seeing this
in this group, and this in this group and they said Oh we’ve seen it before.
But they are regulators, they can’t tell you where they’ve seen it before because it's under
confidentiality but we've had all kinds of conversations with the FDA where they go, out of the blue,
We want you to do this, and we were like Why? Mmmm.. we can’t really say, but just do it, and then
you will read in the popular press somewhere that someone had this problem, and you're like Oh,
that’s why we're doing that. So, you do get these little titbits from the regulators and in this particular
instance they came up and they said, We’ve seen this before. So we’re not unique. It just wasn’t
something that ended up, but if you send me an email, I'll send you those curves and if you want just
post them or post the link to where they are, it makes it very, very clear. But I think no-one... if there
wasn't a difference in the PFS and the OS, you could just group them all together and no-one would
care about where it is.
I mean statistically they do better. So it's very hard to run a study when you have two different
patient populations, it's like trying to run a colorectal and lung study in the same study, there is
different risk, different.... Surprising to us, certainly would have been surprising to the EXTREME
study, because they didn't stratify for it, it was an after type of effect as well.
[BT] Many of our investigators were the same investigators that were on that study and they didn’t
know.
[MC] No.
[BT] It’s interesting. Quick clear.
[MC]But send me an email, I will send you the curves.
[AT] So with regard to a follow-up study, will it be possible to use data from one of the other
randomized trials as justification for a follow-up study?
[BT] Yes, I think is the short answer; we're... There's some interesting kind of nuances and again
Matt’s going to be discussing this with our European colleagues in the very near future about lumping
and clustering different types of studies together for looking at approval paths, so... But until that's
settled, you can’t really…
[MC] We'll have to see the data too.
[BT] Yeah, that's right.
[AT] So, and one other question... any... There's been some discussion about the neoadjuvant type of
therapies?
[BT] Neoadjuvant is interesting. And part of my PhD is radiation biology, so I’m really interested in
neoadjuvant therapy, but that’s a different and very old story, sadly. But I mean neoadjuvant in its
purest form is treating patients prior to surgery in essence. And you are doing that for one of two
reasons, either to improve the outcome of the surgery by reducing the tumors prior to the surgery, or
potentially making the patient operable on when they were not operable before.
And so, the practical use of looking at a set timepoint in a short timepoint is if you could take... is 67%
of patients worth the surgeons treating somebody for six weeks prior?... Probably not, because that
means 33% of them grew, that’s not good. Is 87% shrinking over that timeframe or at least stable?
Mmmm yeah, it’s probably worth it for a surgeon because that actually gives them... And that’s how
they think – this has improved my outcome on surgery.
You get surgery, surgery is kind of the ultimate in velocity because you go in with a tumor and you
come out with a complete response, I mean in few minutes. But it’s the, [MC alive!] well hopefully
yeah, the duration of that response can vary rather markedly, but that’s, I think that’s a key
underpinning of all this stuff. I mean, you know in some of the lung cancers in particular if you could
reduce the tumor burden you would take a lot of patients who are inoperable into operable and you
take operable patients and give them a better outcome and so I think that’s something we will always
keep in mind in studies going forward.
[AT] Are there any plans to follow-up on that?
[BT] Well, if you incorporate the endpoints into further studies then you basically get that for free and
we’ll be doing that, and these velocity, these velocity type considerations are neoadjuvant endpoints.
I mean that’s what you are in essence measuring. So…
[MC] From December until March, April I had four unsolicited protocols in renal cell, [patA?] cell,
panc, and head and neck from various key opinion leaders around the world saying we saw your
results have you thought about using it here. So we got draft protocols coming from major key
opinion leaders saying you know, if you can cause that much shrinkage that quickly have you
considered using it for this. So, it is interesting because I think the scientific community... If you look
at biologics, biologics either work in the tail of the Kaplan-Meier curve like if you're trying to develop
an immune response, it takes a while to do that in the patients. You know IL2 – 10% of the patients
live forever – they have this long tail.
The other thing is if you look at things like Sorafenib, there's this bulbous, you know the curve goes
sigmoidal because everyone is deriving benefit for a finite period of time and things like Sorafenib
they will use it for four to six cycles followed by surgery. Because you get this massive effect, a very
profound initial effect and then you lose it over time because it’s a biologic. They don’t have... and
they generally have to use the cytotoxics.
Things like Avastin, the VEGF inhibitors, depending on the indication, have a period of activity lasting
from 4 months to 11 months typically. So it really is tied to that. So if you can go in and use something
that has really no side-effects to enhance the effectiveness of the cytotoxic, to get a more desirable
outcome, it is very attractive but like I said four different indications from four different people
unsolicited said Hey, can we look at this? So it's something we are obviously in discussions with a lot
of pharma partners. Those are the kinds of studies they tend to be larger, it would be nice to have
them pay for them, do them, so…
[AT] Actually one last question, then. With regard to any of the trials and data so far, any plans for
looking for applying for a big breakthrough therapy?
[BT] Yeah, I get asked about breakthrough therapy designation quite a bit. And I don’t think anybody
really understands what that means yet particularly. You get – you get a breakthrough designation,
what does that mean? It’s specific to you, so it’s not general and this isn’t a criticism but the FDA
keeps layering programs on top of each other to fix programs without changing the old program. The
Special Protocol Assessment was to fix the fact that they were approving Phase IIIs but they had no
intention of approving the product after the study, and things like that. And so I'm not sure, the
breakthrough therapy. what it means honestly. So until we actually figure that out...
[AT] It could help the share price...
[BT] Mmmm?
[AT] It could help the share price.
[BT] Well, I’ll give you another example about things, I mean people talk about... [To MC: Where's one
where they would say yes or no in a hurry?]
[MC] Fast track.
[BT] Fast track. We'll, get fast track designation. All that meant was that they had to review it within a
certain shortened review period, and if they weren’t prepared to say yes, they'd just say no. Well
that’s not a benefit and people were getting 'fast track' and their stock could go up and then they get
said 'no' fast, and you're like , that's not very helpful. So until we understand what breakthrough –
that designation – means, we won't be touching it, and I haven't had anybody able to demonstrate to
me that it means something defined, at least for our case.
I’d say the agency, the agency – I’m speaking of the FDA in particular – and this is a pattern back... if
they're faced with a therapy that is safe and highly efficacious in a disease like cancer, like AIDS,
anything that has bad outcomes they are very good about moving through their approval process.
They are extremely focused on things like that. So I'm not sure that program is absolutely needed
candidly.
[66:00] Doug Shoemaker
[DM] Metastatic cancer is that an actual designation by the FDA or is it that currently it's thought that
a particular kind of cancer metastasises and they're all different diseases? Can you comment on that?
[BT] George is shaking his head, correctly – it is not generally accepted as being a separate disease,
it’s the outcome of a sort of... you have metastatic head and neck, metastatic colorectal, metastatic
breast, the primary, what I think of as primary and George will correct me because I always misuse
the terminology and I apologize, but the initial occurrence is what you're characterized at. Many of us
think it should be otherwise.
[DM] OK
[BT] But, so what, that’s not the way it is. George is a...
[DM] So, to change that with the FDA would be a major…
[GG] The indications in the package insert are stage-specific in most cases so the package insert
doesn’t say this drug is approved for colon cancer. Period, that’s the end of the story. It’s approved in
the population that it was studied in, so if you do your trials in metastatic colon cancer, let's suppose
you limit your trial to only patients who have metastases in the liver, that’s what the indication will
say in the package insert when you get your approval. So when we study, when we write the protocol
and we write the inclusion and exclusion criteria, you've defined the population and that’s going to be
what you get an approval for if your trial is positive.
[BT] I mean the one case that I always refer to with people and that is Delcath's metastatic ocular and
melanoma where the primary is no longer there because they've taken the eye out already and that’s
an interesting disease because there are always mets it metastasizes to the liver, which I don't
understand, but their study was looking at actually specifically just at the liver mets resulting, but it
was liver mets resulting from primary of ocular and melanoma – that’s what the label says.
[GG] One addition to that comment is that that doesn’t mean that’s where the drug is restricted in its
use, out in the community. Oncology is probably the largest off-label specialty there is because what
happens is, good trials get published, the company may or may not have access to the data legally to
submit it. You have to remember trials are done by cooperative groups in Canada, the United States
and so forth. They often do it with approved drugs already, that are on the market, but they do it in
an indication or at a point or in a combination that’s new, and if it works well it gets published and as
soon as that data is out, the use begins all over the country in cancer communities everywhere, if you
see suddenly a new advantage.
The first trial I was ever involved in – just couple of months ago – [laughter] we were looking at
children with leukemia and looking at methotrexate as a remission – maintenance of remission drug -
which is how it was being used. And the trial looked at two different dosing regimens, that’s all: same
drug, different doses. And in fact the duration of remission on one arm was six months and on the
other was 18! You don’t see advances like that very often anymore, unfortunately, but the point is,
there is a big separation. People say, well if head and neck works, it’s just... there's not many patients,
although in truth if you look at the numbers worldwide, there is a lot of patients. The answer is, if it’s
out there and other positive information is coming out, clearly it's going to get used far beyond the
indication that’s in the package insert.
[70:20] Alf Conradi
[AC] So Alan, Alf Conradi again, I have two questions. The first has to do with what are your thoughts
with respect to the role for a potential maintenance therapy?
[AJT] And the second question?
[AC]: The second question is coming back to pancreatic, the carboplatin/paclitaxel study, where are
you at with enrolment for that study?
[BT] Well I can answer that one quickly - we don’t comment on enrolment in studies while they are
ongoing, so that will answer that question.
The first question – maintenance therapy is always an interesting thing, from two perspectives. One,
maintenance therapy doesn’t attract particularly good pricing so one has to be cautious one gets too
far into thinking about maintenance therapy. But secondly, to be candid an agent like Reolysin which
for a variety of good scientific reasons that we've disclosed really shouldn’t be expected to show that
much activity by itself. The agent by itself has difficulty penetrating tumors – the chemo and other
agents actually potentiate this activity within the tumor in a very specific way and there's some things
that Matt and his colleagues on the research side are demonstrating right now that will I think
enhance our understanding of that. So I think Reolysin should be viewed as yet another biologic that
does better when it's mixed with something else.
And I think that’s getting to be quite, almost the standard for biologics - the standalone biologics
either as primary therapy or as maintenance therapy just are unlikely to be used particularly a great
deal. Keep that in the back of your mind - if we prove it otherwise, wonderful, but that’s I think the
sort of standard operating line that we have to be thinking about.
[MC] What's interesting now if you look what’s happening in colorectal, typically you take a drug until
you fail it, then you don't see it again because they assume it doesn't work anymore. With biologics
that doesn't necessarily have to be the case because biologics enhance the effectiveness of other
cytotoxics.
So Folfox or Bevacizumab was approved in the first-line setting for colorectal cancer with FOLFOX. So,
you would take 6 or 8 or 9 months of this and you would progress and patients would go on to
irinotecan-based therapy. Some bright bulb decided to add Avastin back to FOLFIRI and they actually
increased the PFS again. So, Avastin actually now has approval for FOLFOX in the first-line setting and
FOLFIRI in the second-line.
So, reovirus, if you look at the biochemistry of it, it affects the cell kill a certain way with taxanes, if
you add it to something like VELCADE you get a different kind of cell kill, one around ER stress. So,
theoretically what we could potentially look at is an induction phase or an early treatment phase with
one cytotoxic or family of cytotoxics or platinum doublets or what have you. And then if toxicities
ensue or there is a problem, switch out that drug combination for another one and continue on with
the virus, because we actually have seen patients who failed a drug regime and you add the virus to it,
and all of a sudden they’re active again.
There has been reports even of on our crossovers it was on the news that the mayor of Bexley
actually had failed carbotax on the panc study, they added the virus to it and he had an objective
response, which is a fantastic internal control because you know he is resistant to the carbotax, but
when you add the virus it adds a unique cell kill mechanism. So, I agree with Brad, I don’t think
reovirus – it’s huge, it’s a bus, when you compare it to like a diffusible chemotherapeutic. It’s an
actual particle.
Our pathologists now can actually receive samples from the clinic in a blinded fashion so that you just
get the block of tissue, and he can tell us now whether or not that patient has received the virus as a
monotherapy or in drug combination based on the distribution of the virus, which is completely
different and the ratio of transcript to protein. So, I think there will be a role for reovirus in like longterm
maintenance therapy, but only in the context of a cytotoxic. It’s just, it needs to be delivered
effectively and the cytotoxics really do a very good job with that.
[AC] Thank you
[74:47] Jon Tyson
[JT] I have a question about blinding - what does that exactly mean, does that mean you know
everything about the patients?1
[BT] It means we know nothing about the patient. But blinding is – it’s awful and important, awful
from Matt's perspective because he doesn’t know, and very important for the doctor not to know I
think, and the patient not to know.
I mean imagine you come into a clinical study, and you’re a doctor, and you've got your favourite
patient, and you’ve got your less favourite patient, for whatever reason, and they're not going do
well. You are going to put the favourite patient on the test arm and because you have to balance out,
the less favourite patient, because they don't have the better outcome, on the control arm. You’re
just going to do that, it’s just human nature.
You have to blind the doctor from knowing what he’s treating the patient with, or she. And you have
to blind the patient, he or she, from knowing what they are getting, so they’ll stay on study because if
they know they are getting the control, they will go off-study. So it’s critical that they be blinded.
Now the company I would argue doesn’t need to be blinded, but my arguments don’t mean anything,
so we are blinded too, and that’s because then we can’t influence – but we can’t influence anyway –
but we can really not influence things if we don’t know either. It’s better when everybody is blinded,
our statistician is blinded, our data collection people are blinded, there’s people who know little slices
of things, but nobody knows enough for the whole picture, and that’s critical.
[JT] So on September, you knew that the metastatics were doing better than the…
[BT] But that was blinded, basically we knew – no just back up for a second. Last summer, when we
looked at the case report forms, you could see the case report forms for every patient, you just don’t
know what they are being treated with.
[JT] Right.
So I know, we know where the tumors are, we know whether they’re responding or not, I just don’t
know what they are being treating with.
[JT] All right. So you know everything except what they are being treated with?
[BT] Except what they are being treated with.
[JT] OK.
[BT] So you look at that and you go OK, well... somebody noticed - a couple of somebody actually -
noticed a pattern where patients with local regional disease were progressing quicker than patients
with just metastatic disease. But that was as combined groups. That’s what was noticed last summer.
[JT] OK. So if you…
[BT] Still blinded though.
1 I am informed that the full question here (inaudible on the recording because BT spoke over the end of
it and thus misinterpreted the question) was 'I have a question about blinding. Does that mean that you
know everything about the patients except whether they are controls or not?'
[JT] If you look at slide 23 then every patient whose tumor shrank by more than 50% is a test subject,
and every patient whose tumour...
[BT] No.
[JT] On slide 23.
[BT] No that’s a misreading.
[JT] Do you have the graph there?
[BT] No.
[MC?] That one.
[BT] No. These are individual patients. These are individual patient points and this is a waterfall graph,
so this is a patient – a single data point. And this is another single data point...
[JT] If you have a patient and you see his tumour...
[BT] But I don’t know, I don’t know who those patients are. I don’t have a clue who those patients
are. Our doctors don't know who those patients are; those patients don’t know who those patients
are!
[JT] But you said you had access to their medical data, except...
[BT] But I do not know, we do not know what they were treated with.
[JT] Right, right. If you knew here I have a patient whose tumors grew by 100%, and you have that
plot there, you now know that that patient is a control subject [inaudible background discussion
starting with "no you don't"] but none of the test subjects... [inaudible] ...No, but look... [Inaudible]
[BT] But honestly, honestly yes we could sit around and find a patient and maybe in an extreme case
find out what one patient was treated with.
[JT] [Inaudible interjection]
[BT] Please... But we didn’t — we don’t do that.
[JT] OK, OK.
[MC] Just when a patient gets randomized it goes to a group in California that has an algorithm that
says the patient – and this is to the pharmacists at the site – this patient will go on X or Y so that code
gets given to the pharmacists on that site. The pharmacist is the only person (because the pharmacist
has to make it up) so the pharmacist will either hand the physician a bag of saline or a bag of saline
with virus in it but even the doctors and the nursing staff don’t know. So, there is no bias from the
doctor’s point. So the only person who really knows who got what is the pharmacist but the
pharmacist has no contact with the patients so they wouldn’t be able to identify...
[BT] And that’s only one site out of 94.
[MC] Yeah, the 94. And the group in California who said this patient on this day gets randomized X or
Y, when that information went out, it went from that group in California to a group in Orlando and
bypassed the company. So we can see the case report forms as he said so we can see... and it’s all
patient identifiers, so we don’t know the patient's name, we know the sex and sometimes you know
the initials. But, we don’t know what the person's got and so the only way to finally unblind is to get
the unblinding codes from the group in California, but they can’t do that until a predetermined time
so we’re kept completely in the dark which drives me flipping crazy.
You're looking at these things and you're going – Oh, God I hope he's on the control arm, and then
you’re like Oh, that’s an awful thing to say, but I really hope that guy's on the.... So it’s scientifically
the best way of doing it. It’s driving me batty.
Because, it was a small study designed to create a bigger study, so you want to be able to have some
of that information to make the bigger, more expensive, study better. So, that’s the problem with it.
The NCIC studies and the NCI studies will guide us to design hopefully a Phase 3 study or Phase 3
studies based on generic markers that predict for success and patient characteristics like, you know,
the one thing that we were looking at there with the lung mets, is the lung mets do really, really well.
There wasn’t a big enough patient sample to say whether or not lymph node lesions do well or liver
mets although the liver looked good it was just the sample size was really small. There is a lot you can
learn from these studies. But when they're blinded you can’t learn anything until the blind's broken.
So it’s maddening as a scientist to be in this situation.
[JT] Thanks
[80:51] Andy Lee
[AL] Andy Lee, a question for Matt. Matt, concerning the Erbitux data. Obviously, when you saw it,
you were quite alarmed, I think, initially, I’m guessing here, but based on one or two of your
comments today, when I saw the data and I came across it in the fall of last year, I just chose to wish it
away. You I think...
[MC] Erbitux data or our data?
[AL] Erbitux data. The Erbitux mets data is what I’m referring to.
[MC] OK, yes.
[AL] Now, you’ve probably done quite a bit of an analysis and thought about this, had some time to
ponder over it – what can you say concerning your conclusions that would relieve my concerns at this
time, related specifically to the Erbitux mets data?
[MC] The Erbitux I mean – data is just data. I looked at it and it’s funny, if you actually read the NICE
arguments, they kind of explain why wouldn’t the mets work better and there was a few sort of things
in there. Erbitux is a great product. I mean it works in a lot of different indications. But it doesn’t work
in a lot of indications as well, so I think when we get information like that, it helps us refine the
patients who are going to derive the most benefit. And in refining the patients who derive the most
benefit we get the most competitive pricing.
So based on what we saw from early tumor changes it looks like we get more rapid and better
magnitude of response in the local mets, but we also see activity in the local regional disease, it's just
the kinetics could be potentially different. So when looking at the Erbitux data, I find it fascinating
that they’ve identified two different patient populations in the head and neck because trying to
explain it to somebody... Like there was a competent authority that said Well, has there ever been
another example of this? and you pull out the NICE document, when we sent in the protocol
submission and they went, Oh, OK, well, that’s just the case. Other people have reported it, it’s not
just you.
So those precedents, I don’t know, I was alarmed to see it because I know patients who have
metastatic disease are taking Erbitux and they are not deriving any benefit. And that’s what was
alarming to me. I thought, I’m a scientist through and through and yeah, I would love to treat every
single person with reovirus, and have it be a trillion dollar product, but at the end of the day, I don’t
want to give it to somebody who is not going to derive any benefit, it's awful to do that to the
patients, it's awful to do it to their families, it’s expensive, it’s a drain on their healthcare.
So I’d rather identify early which patients are deriving benefit. So in a way I was actually kind of
encouraged by the Erbitux data, although shocked that it wasn’t made available. And the one thing
that sort of stuck in the back of my head when reading that paper, they said, you know, there's 42%
male and 58% female and age of this and age of that... They do call out, they do say, 65 % of the
patients have local regional only and 35% only had mets. And then all the other analysis, it’s like here
is the response for females and here is the response... they never gave the curves for the local
regional versus metastatic and that... It must have twigged with NICE because NICE asked the
question, but it never ends up in a publication or the package inserts. So it is one of those things that I
was alarmed by not because it was a good bit of science, it was just the fact that it could have helped
a lot of other people design head and neck cancer studies to have pre-stratified for these patient
populations if there is an expectation they’re going to respond differently.
[BT] This is an add on though, I think it has absolutely no carry over to how or how not Reolysin will
work in either of those patient populations because the two drugs work quite differently.
[AL] I think my concern is that mets are only a subgroup. There is potential there that it’s a sweet
spot, that you’re seeing this extended PFS, doubling of the PFS, that there's a potential it's because of
the activity of Reolysin within that group, unblinded group. I think that with the Erbitux mets-only
data and their identification of this group…
[MC] Oh, I see what you're saying.
[AL] Yeah, that’s what I’m getting at. That I think is a concern and I’m wondering what you've thought
of over the past many months that may have relieved your concern with respect to that?
[BT] I’m missing what the concern is.
[MC] Erbitux demonstrated that the mets patients do differently.
[BT] Yeah.
[MC] And….
[BT] Which would have been nice to know three years ago.
[MC] Yeah because we could have stratified for it and it would have been nothing.
[BT] Yes.
[MC] But what he's saying is are you concerned the reason the met group does better is because they
do better anyways.
Looking at the early tumour changes, you know it's funny because someone said what does that
mean? Yes, there's an enhanced kinetic response, yes there's more patients that respond, yeah it
looks like it’s doing something but it's not RECIST. And I said OK but if it worked worse what do you
think the outcome would be on PFS and OS? Oh, it would be awful. I said so why can’t you think of it
in reciprocal terms – the fact that you’re getting more dramatic responses earlier isn’t that likely or
more likely to lead to benefits on the patients' prognosis. Well, yeah... And because we are seeing
changes in both local regional and metastatic, I don’t think the responses are going to be the same, I
think there is going to be a patient population that does better, like in the local regional versus the
mets, I think one of them is going to do better in the presence of the virus.
In terms of it being different one might have a four-week and one might have a two-week, or one
might have six weeks and one might be one week, I just think the early changes demonstrated that
there was a benefit for being on the viral arm on both local regional and metastatic at that six week
timepoint. So I think what it does do is it identifies two different patient populations, it identifies that
we have to change the second follow-on study to better treat the patients. But I’m not... The data's
blinded, I mean I can keep myself up all night by thinking oh mets is doing differently because of this.
The EXTREME study, the problem with it is it’s not looking at this patient population. So if it was the
exact same patient population, I’d be looking and comparing those numbers saying OK well they had
100 days, so we should have 100 days. The problem is those patients hadn’t failed platinum. So both
sets of them are doing better, so I can’t make a comparison, so I’m not overly fussed but you're right
– if it was the same patient population, I'd be drawing those curves out and comparing directly, but
our patients have a far worse prognosis.
[AL] Thanks, that’s what I needed to hear. Thank you.
[MC] Yes, no... it drove me bonkers...
[BT[ Yeah but I think we have to resist comparing apples to oranges – other agents have different
activity than our agent. And as they continue to demonstrate, it doesn't necessarily mean they
understand how those agents work, like Avastin. Our understanding of Avastin is quite different than
it was five years ago or three years ago.
[87:25] Mark Gray
[MG] Mark Gray. I have a couple of questions. Regarding the Phase 3, can you explain what stage two
is and regarding the second study that you need, when would you pursue that?
[BT] The study has always been – think it more of as a program – it’s always been designed to be two
stages, which is in effect two studies under the same umbrella, and the study originally was designed
to enrol 80 patients in effect in a single patient group. See how they were doing after a set period of
time and then use that as a predictor of success in the second stage and run a larger sample size in
the second stage and that would count as our two studies for filing in the U.S. That's how it was
designed.
In essence it's the same now, it's just that we're using different endpoints if you want think of that
way, we’re using an event-driven OS endpoint as the final endpoint in the first stage, with two patient
groups. So it’s a nuance really when you think about it and so the second stage is basically a second
study and it’s under the same umbrella of the program, that’s all.
[MG] Would you be looking for a partner at that point?
[BT] It depends. It depends on so many different things – how big is the study, how long is the study
going to take, how many countries we’ve run the study in, which patient population is benefiting, and,
and, and, and... There’s so many depends that, my board's nodding and smirking to themselves
because they've heard this story too many times from me – when they ask me questions, it depends, I
do it all the time.
But it does, it depends. I mean we have too many variables and because of all those variables you
can’t say whether you do a partner or not do a partner before you know anything about it. I don’t
know if it’s going to be a 100 patient study, a 200 patient study, a 5,000 patient study, don’t know,
don’t have a clue. I don’t know which patient population, don’t know if we run it in 2 countries, 14
countries, 30 countries, I mean all the things will really change how and when and with who, you
would run that study.
[MC] What we’re hearing from... I mean if you think about it any approval requires two well
randomized studies, so that 167 patient local regional metastatic accounts for one study, we still have
to do the other one. Keep in mind, we’re doing studies in lung, colorectal, panc, ovarian, prostate…
[BT] Breast
[MC] Breast, thank you. Those are all one half of your registration program as well. So it’s interesting,
we’re talking to pharma partners and some of them go – Listen, we really like what you're doing with
head and neck, it’s a niche market you could probably get an approval with a smaller number of
patients. Then you get the other spectrum going – Well, it’s not a billion dollar market, we would look
at it at proof of concept, and we would follow up with a lung program or colorectal or breast or one of
the larger indications you have. Even though, I mean if you look at the some of the lung studies
people have run... George, what's the largest lung study you've seen? I've seen them with over 1,200
patients
[GG] 5,000
[MC] 5,000. I mean some of these lung programs are huge, there's no way our organization could run
a program like that. But everyone's interested in the results, not everyone is interested in the
indication. So it comes into play I mean if we have a good response there, but then turn around and
have like a home run in the largest market, say, colorectal, pharma is going to invest where they get
the biggest rate of return and it’s going to be in the larger market place.
[BT] Well, the profile (this is a sidebar), but the profile of the disease really does matter. More women
die of ovarian cancer than breast cancer: where's the profile in womens' cancer? Breast. I mean,
profile matters, and head and neck does not have a favorable profile. It’s a self-induced disease in a
patient population that does not have sympathy generally.
[91:23] [OM] Going back to the concept of maintenance therapy, you once mentioned that when
somebody dropped off the test (off the product) the cancer returned aggressively. Of the current
Phase 3 and double-blinded Phase 2, how many of these tests are continuing Reolysin treatment
after, say, the initial six cycles or whatever it is that they're set up for?
[BT] All the randomized studies do not have a maintenance therapy component, the Phase 2s. The
Phase 3 study had the option for a patient to go after eight cycles to go on just Reolysin monotherapy
or saline if they were on the control arm -– they don’t know which – and again because we don’t
know who’s what, I don’t know how many patients went onto maintenance therapy on Reolysin or
not.
Again, you’re running into doctor perceptions and everything else. Many of the doctors in our head
and neck study thought that after eight cycles of carbotax and Reolysin or carbotax and saline that
that was pretty much it. So they weren’t really encouraging patients at that stage, you know they’re
getting closing to death, to stay on, come in for a week out of every month to get possibly saline all by
itself. So, I mean, you have I guess... a long-winded way of saying we don’t know yet, we will find out.
[MC] The panc study has a maintenance phase.
[BT] Just Reo?
[MC] No, it's Reo/platinum
[BT] Right. When I think of maintenance I think of Reo by itself, but you're right.
[MC] What they were seeing is patients would go up to eight cycles and they would go on to
monotherapy on some of these single arm studies that we’re doing and they would progress after a
cycle or two. And a few of the doctors have said – Listen it's interesting you know, we think based on
your biochemistry it has to be delivered with a cytotoxic. The problem with the platinum doublet like
a carboplatin/paclitaxel is it’s toxic as all get out. On lung studies, you typically only get four or six
cycles, even if you’re responding, because it is such a toxic intervention if you will. They typically get
neuropathies from the taxane, so one of the investigators at CTRC said – Listen, I’m just going to drop
the taxane and keep them on the platinum. And it looks like on these single arm studies you can stay
on platinum/reovirus for extremely long periods of time. And in some of the other indications we
have where like gemcitabine...
[BT] Gem... Gem/Reo, what’s the maximum [inaudible] almost two years with it...
[MC] So you can continue to treat with it.
[OM] So on the Phase 3 then, there are patients who are still alive and they're still being treated with
Reo or saline?
[BT] I cannot comment on that.
[OM] [inaudible]
[BT] No, because that would tell you whether they had progressed or not. We cannot talk about
whether patients have all progressed or not it's against... it's trial detail that has to remain
confidential. The patients are treated with whatever until they progress and if I were to say patients
were still being treated I would tell you that there were patients that hadn’t progressed which would
be like me telling you how many people were still alive on the study. That’s trial detail. Alan will come
and slap my wrists rightfully for saying this, and you're correct.
[94:45] Unidentified
[U3] Brad, I got quick question for you. You said maintenance therapy was only on the Phase III?
[BT] Reolysin monotherapy, maintenance therapy, was only for the Phase III that’s my narrow
definition, so yes.
[U3] I just wanted to make sure of that, for some reason I thought it was on the pancreatic
carbotax/Reo too.
[BT] No, that evolved into taking the taxane out of it and just doing a platinum/reo doublet, because
the platinum and reo seems to be...
[MC] [Inaudible interjection]
[BT] And ovarian has that too I think, doesn't it?
[MC] The NCIC studies and the ovarian studies are all... because we don’t have it they tend to be a
weekly taxane.
[BT] They dropped the taxane.
[MC] Well no, it's just weekly taxane so they don't get the acute effects. It's treatment until
progression.
[U3] OK that makes more sense on that. I want to expand just a little more on the pancreatic one
since we’re talking about that. This comment you made last year in the Needham Conference, so it’s a
year ago, and it says you said so it's your quote...
[MC] Where did that come from?
[U3] The Needham Conference last year.
[BT] And where did the quote come from?
[U3] It’s the transcript.
[BT] And who's transcripted it?
[U3] It’s mine.
[BT] So it’s an alleged quote. OK.
[Inaudible]
[BT] An unofficial transcript taken by not my official biographer.
[Laughter]
[U3] Well, I have a couple of 'em in here, which, er...
[BT] I do have an official biographer, but…
[U3] A couple would make them interesting, but it’s nothing, it's just more of an expansion hopefully
from last year, it says again people are actually starting to talk about second-line pancreatic patients
for the first time in my experience which is nice, it’s actually nice to be developing a patient group
that actually might be living long enough to be second line. We’re talking a year later; can you expand
at all on that?
[BT] No, I cannot.
[U3] OK, well I...
[BT] I'm firm in my alleged comment from last year – I would support that statement whoever may
have made it. And I don’t think, I mean it’s clear, I mean there has been news about at least one
crossover patient who failed in carbotax and went on to carbotax and Reolysin and then went on to
have a response. So I mean it’s not unusual to expect it, we’ve seen other ones like that, and that
would be the case. But I think that not just with potentially our program, but with some of the other
advances that are going on in pancreatic cancer that you are going to see a very large number for the
first time of what we think of as second line patients.
I mean there is some really – I mean the Gem/Abraxane study is looking kind of interesting and of
course that one is interesting that the Abraxane looks like the neuropathy caused by Abraxane is
actually recoverable after you've finished therapy and you can re-treat again which is a major
advance. And a colleague of ours, who was the principal investigator on that study and we’re quite
thrilled that his study came out so well. It’s a very important study.
But you got some of the other drug combinations that people are using outside of gemcitabine are
actually starting to show some fairly aggressive activity in patients – they don’t cause severe damage,
because they’re quite toxic – so you’re generating patient populations that are gem naïve that have
failed first line so they become second line. So it’s really – pancreatic cancer is changing. I don’t think
panc is going to be quite the death sentence it was very soon, which is nice. But I think Reo is part of
that and I think we’re consistent in that. I mean we've been open about the gem/reo data I mean
we're seeing a subset of patients that seem to be doing extremely well on gem/reo. And that’s
generating a second line patient population, I mean that's just by definition, so whoever said that, I
would support their statement.
[U3] I like that, you’re saying that whoever would support that statement. How many – I didn’t get it
this time – how many patients have you treated to date so far? I know last year it was about 700 –
500 in-house and 200 by…
[BT] We’re about… I don't know, about 640 or 650 in-house and I honestly between the NCIC doing
their data and everything else we're probably narrowing in on 900 would be my guess.
[U3] OK, so we’ve increased it quite a bit. I have another alleged statement – as we're talking a year
later it's more sort of general update on comments: 'I mean I can pretty well say confidently say now
if you have a KRAS mutation driven disease, I can almost guarantee you a stable disease or better on
Reo, it doesn't matter what it is, panc, non-small cell lung, colorectal it's interesting it's not statistical
yet, but it's getting there.' We're talking a year later and then I looked at your REO 021 up there with
all the people with KRAS, EGFR mutation, stuff like that.
[BT] REO 016.
[???] Pretty statistical.
[BT] I mean the lung data I think is looking quite intriguing, though it’s still a relatively small patient
population but if you have the KRAS mutation involved, you have an overwhelming preponderance of
stable disease by RECIST, it’s quite, quite remarkable. Matt I think would, I mean it’s…
[MC] Looking at that line if I'm not mistaken anyone who had KRAS mutation in the lung had stable
disease or better.
[BT] Well they had one PD.
[Inaudible discussion]
[BT] So I think that is a baseline. I think the whole KRAS story is becoming important, which is why
we’re focusing more time and attention, where it’s relevant, to do genotyping when it's appropriate.
So but I mean people are starting to find out the differences between the different RAS elements too
in other diseases you know. And I think for some indications it’s absolutely critical that everybody get
a handle on what genotype you're looking at and we don't even know the genotypes that are
important for a lot of subsets.
That’s a pretty large amount of effort being done by some pretty large groups on that, I mean some of
the big pharmas that we deal with have massive typing groups, hundreds of people, working on just
that one element. It’s... I think a lot of belief that that’s important, but 'asterisks' there's been cases
where people have run studies where they’ve done genotyping, where they think they have pure
patient populations coming in and maybe get one out of nine patients showing a response when
there should have been 100% – it doesn’t mean you know everything just because you have a couple
of markers.
[U3] One other one, it’s not directed to you. Mary Ann – there we go let somebody else do a little
talking. I understand, I could be wrong, might be mistaken, was there a couple of patent challenges
before? In regards to some of the intellectual property that you guys had, and if so, has it been
resolved?
[MAD] Well, we did have a challenge to one of our European patents, it was in our possession and yes
we resolved that, so that patent has granted and has been reregistered in all the states in Europe
where we had it. The only other patent challenges when we actually sued the commissioner of
patents in the United States for additional term and we won that one too, so we were real pleased
with that.
[U3] Thank you very much.
[BT] It should be called the Dillahunty exemption, not [inaudible]. There was not a lot of love in the
patent office for Mary Ann on that day.
[102:36] Unidentified
[U4] I will ask you another question...
[BT] Yes, if we could, we'll take just one more question and then we’ll, which will be official question
and then we’ll be available for a while to actually talk on one-on-one if we could please.
[U4] Now that you have clarified or told us again that the likely route for this company is eventually to
be bought out or partnered, hooking up with some larger entity in some way or other, what in your
mind are the events that have to happen to be in that position where a larger entity will make a
serious – what you would consider a serious offer for this company?
[BT] I would think that generally, I think at this stage of development that having relatively clear cut
randomized clinical data in one or more indications would be the trigger for something to happen
whether it would be M&A, or partnering, an association, along those lines. And I think we've been
pretty much settled in our own minds internally in the company that that was probably the trigger
probably for three or four year now, so…
[U4] So you’ve said that the Phase 3 unblinding will happen sometime by, before the end of the year.
When do you expect, or, of the six Phase 2 randomized trials, when do you expect that one or two of
them will release some results, either preliminary or final results?
[BT] I am going to decline to put a timeframe on timelines for the results from those other clinical
studies. Just, when the enrolment gets to a certain stage that the investigators are comfortable with
the data that's coming out of them, then we’ll talk about it and, you know, we'll leave that to them.
[U4] And for Mrs Dillahunty – or Miss, sorry – the strategy of the company I understand has always
been to keep on renewing and updating and expanding our patents, so that the 20-year patent
coverage is extended. Are you comfortable that we are doing that? If this process is going to take
more time that we are continuing to increase our intellectual property protection?
[MAD] Well, yes, as you’ve said that's really always one of our goals is to make sure that every
inventive aspect that we come up with whether that’s a formulation or a novel proprietary Reolysin
and those patents don’t expire until 2028. So, and we are, we continue to file patent applications
including some that have not yet published over aspects that we are discovering as we work through
all these things so.
[U4] Thank you.
[BT] OK, one more, one more.
[105:21] Bill Thompson
[BillT] Hi, I'm Bill Thompson. Brad, I was wondering if you could comment on that association with
that Russian company? I mean, there was a comment that they made, but then there was nothing
came from your office?
[BillT] Didn’t I cut-off the questioning a question ago? [laughter] And here I was, answering a question
because we share a common name. This is what you do to me.
We do not have an agreement with a Russian company and until we do have an agreement with a
Russian company that’s valid and going forth, we will not comment on it. That is as much as I could
say. We have all sorts of things on the go that are at different stages of development and sometimes
some people get enthusiastic about talking about things prior to them actually being concluded and
that would be my Russian friends.
So, if we do conclude something with somebody in Russia, and it becomes active then we’ll be talking
about it specifically. I didn’t mean to make fun of that, I just was like I got out of answering that
question and here I am answering it.
I mean, in all seriousness, we have relationships under different stages of development with different
types of entities all over the world. And they get to a certain stage when they become concrete, they
become real. For example, our NCIC relationships, which allow us to do those – now four randomized
clinical studies in Canada. I mean you can move along, and you cross a threshold when they’re real,
and then you talk about them.
And that’s the same for discussions and contract work with anything that we do, and whether it’s in
Russia or any other country in the world, we’re not at that stage, and so no. When we get to that
stage, we’ll talk about it. That's all I can say. I’m a little unhappy with my potential colleagues in Russia
for talking about something that didn’t exist yet, so we’ll leave it at that.
[107:40] Summing up
Well again, thank you for coming today, thank you for the questions, thank you for the time and
attention, and thank you for the many of you that have been following us as shareholders and just
following us generally here in our home base in Calgary for being there for us all these years and for
following us in what continues to be I think a very interesting program and I think we are near to the
end of about to find out whether Reolysin works or not in the way that matters and so there is many
years of work and many years of dedication that is about to liberate Matt from his insomnia, and we'll
leave it at that. As Matt descends into a number of addictions.
So again thank you for coming today and we will be around for a short period of time – we have
another meeting unfortunately we have to go to soon but for a while we’ll be here and again thank
you.