Final Event Transcript of REGN conference call, 7-Oct-03 10:00am
2003-10-10 13:06 (New York)
Regeneron Pharmaceuticals Conference Call To Report Phase II Results for IL-1
Trap Clinical Program in Rheumatoid Arthritis
Boston, Oct 10, 2003 (CCBN StreetEvents) -- Event Transcript of Regeneron
Pharmaceuticals conference call, 7-Oct-03 10:00am ET.
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Corporate Participants
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* Charles Poole
Regeneron - Vice President, Investor Relations
* Leonard Schleifer
Regeneron - President, CEO
* Merdad Parsey
Regeneron - Director of Immunology
* Murray Goldberg
Regeneron - CFO, Senior Vice President Finance and Administration
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Conference Call Participants
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* Michael King
Banc of America Securities - Analyst
* Raymond Myers
Princeton Institutional - Analyst
* Jim Birchenough
Lehman Brothers - Analyst
* Sapna Srivstava
ThinkEquity Partners - Analyst
* William Flattery
Deerfield Partners - Analyst
* Larry Rifkin
Cumberland Associates - Analyst
* Chris Tanaka
ITRRS - Analyst
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Presentation
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Operator [1]
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Good morning, my name is Tony, and I'll be your conference facilitator today.
At this time, I would like to welcome everyone to the Regeneron Pharmaceutical
Phase II results of IL-1 Trap. All lines have been placed on mute to prevent any
background noise. After the speaker's remarks, there will be a
question-and-answer period. (OPERATOR INSTRUCTIONS) I would now like to turn the
call over to Mr. Charles Poole. Please go ahead sir.
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Charles Poole, Regeneron - Vice President, Investor Relations [2]
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Thank you, Tony. Good morning. This morning Regeneron issued a press release in
which we announced the results of our Phase II program for the IL-1 Trap. We
wanted to meet with you today to recap the major points of that release and give
you the opportunity to ask us any questions that you may have. During this
conference call, we will be discussing historical information that includes
forward-looking statements about Regeneron and its product, programs, finances
and business -- all of which involve a number of risks and uncertainties such as
risks associated with preclinical and clinical development of medicines and
biologics, determination by regulatory and administrative government
authorities, competitive factors, technological development, the availability
and cost of capital, the cost of the developing, producing and selling products
potential for any collaboration agreements to be canceled or to terminate
without any product distress and other material risks. A more complete
description of these risk
s can be found in Regeneron's filings with the United States Securities and
Exchange Commission, including our form 10-K for the year ended December 31st,
2002 and the form 10-Q for the quarter ended June 30, 2003. The Regeneron does
not undertake any obligations to update publicly any forward-looking statements,
whether as a result of new information, future events or otherwise unless
required by law.
Here with us today to discuss the IL-1 Trap results are President, Leonard
Schleifer, Chief Scientific Officer, George Yancopoulos, and Chief Financial
Officer, Murray Goldberg, and we have some members of our clinical development
team. For opening remarks, I'm going to turn the mike over to Dr. Schleifer,
Regeneron's President and Chief Executive Officer. Len.
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Leonard Schleifer, Regeneron - President, CEO [3]
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Thank you, Charles, and good morning. Thank you very much everybody for joining
us this morning to discuss the results of our Phase II of our IL-1 Trap in
rheumatoid arthritis. I would like to just begin by reviewing the study and its
results a little bit and try to put it in some context and then deal with
questions that you may have. I hope you can follow along on the slides.
The first slide outlines briefly the type of study that we did. It was a Phase
II study that had approximately 200 patients. They were randomly assigned to
receive either placebo 25 milligrams, 50 milligrams or 100 milligrams of the
IL-1 Trap by once a week self-injection for 12 weeks. And then after 12 weeks,
there was a off-drug follow-up period. Key eligibility criteria for the study
was that the patients had have failed at least one DMARD. They had to be on a
stable dose of the DMARD if they were taking that prior to receiving study
drugs, and possibly 2/3rds of the patients were on concomitant DMARDS. And no
concomitant CNF (ph) antagonist or anikendro (ph) was permitted.
Let's first look at the results of the safety that we saw in the study. And the
IL-1 Trap was generally well-tolerated compared with placebo. There were no
drug-related serious adverse events. And there was minimal inatrudicity (ph)
with less than 5 percent of the IL-1 Trap-treated patients developing
antibodies. And there was no dose response to that and no detectable effective
antibodies on safety or efficacy in the few patients who we could detect within.
And this seems to be rather good evidence thus far that the safety of the
product was what we had hoped for going into the study.
If you take a look at the old view of the key efficacy data from the study, I
think what you can see -- and a lot of this is detailed in the press release and
on this slide -- you can see across the board for a variety of end-points. It
looks like the 100 milligrams-dose group was clearly biologically, biochemically
and clinically active. The primary end-point of the study ACR-20 had an effect
size of 46 percent of patients achieving that treated with 100 milligrams dose
group and only about 30 percent of people treated with that in the placebo group
-- the P there was .11. If you look at the sustained ACR-20, you saw a P value
of about .03. If you looked at ACR-N, you saw a P value of .02. For those of you
not familiar ACR-N is the continuous variable of how people did, whereas ACR-20
is really a discontinuous variable -- it puts people in various buckets. The
ACR-N obviously has more power because of that, and we did see an effect of .02
P value with about a quarter of the subjects -- excuse me, with abou
t an average ACR score of about 25 percent in the treated versus about around
half that in the placebo group.
In the most objective measure of the study, we saw in a clear evidence of
effect on the C-reactive protein. The P value there was .004, and that -- the
low P. value reflects the precision with which one can measure C-reactive
protein -- because it's a laboratory test, it's well-standardized and you can
see even a dose response evidence in that study. As you compare across the dose
groups, C-reactive protein was a +.07 placebo, -.68 in the 25, -1.0 in the 50,
-1.4 in the 100 milligram dose group. If you look at patients who were on
background D-modular -- on background methotrexate -- you saw a very consistent
result, as well, where you had effect sizes of around 50 percent for the treated
patients in the 100 milligram dose group and around a 1/3rd -- 30 to 33 percent
-- for the patients either on Diamox (or back on methotrexate. About 2/3rds of
the patients were on background treatment. You can find the exact numbers in
your press release.
So I think over all, the data from the efficacy side of the study showed a
consistent effect. It showed that drug was active. You saw that in C-reactive
protein. It was active in clinical measures. And even in these small dose groups
of about 50 patients, we were able to see P values of .11. If you had the same
effect size and nearly had twice as many patients -- or the number of patients
you might have in the Phase III -- these P values would have been substantially
lower. And I think everybody would understand that it is just driven by the size
of the study.
If you take -- a lot of discussion has been made on how do these results fit in
compared to other biologics using the treatment of rheumatoid arthritis. And a
lot of people try to make a lot of comparisons, and I think that this is a
dangerous game. The way these studies were done in the early days was that
patients, for example, in the first studies of the anti-TNF drugs were flared --
that is they were taken off all their DMARDS. They were allowed to have a flair
after a washout period and then treated. So you got one sort of effect. In other
cases, they were done different patient populations. And I think it's very
dangerous to compare drugs between studies if they are not head-to-head. So
really for the purposes of context, we have tabulated straight from the PDR and
the part of labels what other drugs have done -- at least in a similar
population of ours as those on background DMARDS. And you can see the results
for Kineret, for amro-rheumdanhumilia (ph), both for the ACR 20's, 50's and 70's
to the bes
t we can raise at the time period if they were available for these drugs. And I
think if you put -- if you want to make comparisons, I think it should be done
for the context only. At the end of the day, how we would compare one drug to
another could only be determined in a head-to-head study.
Finally, if you go to the last slide -- we would say that the conclusions of
this study is the drug clearly had evidence of activity in both clinical and
laboratory measures. We had no evidence that a maximal effect was achieved. In
fact, it looks like the dose response were only at the low end of the dose
response based on the clinical measures. And we don't -- we shouldn't have them
saturated even based on C-reactive protein so there is the potential to seeing
better effects at higher doses.
There's been no significant safety issues observed in the study -- with no
drug-related serious adverse events, no indivigisity (ph) problems. We have only
had the data on vendors (ph) for a very short time. Both Regeneron and Novartis
have seen the data, but we have not had a chance to sit down together -- which
we will do very rapidly to tell you what the next clinical trial will be. We got
to -- you have got to give us a chance to do that. And as soon as we do, we will
get you that information. And we do want to call your attention to the fact that
we do plan to study other indications and particularly at seeing a lack
indivigisity (ph) in the good safety profile and evidence for biological
activity. So, at that point, Charles, I would be happy to turn that over to the
audience for questions.
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Charles Poole, Regeneron - Vice President, Investor Relations [4]
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Thank you, Len. Tony, would you remind the audience how they can queue up for
questions? And we will take questions.
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Operator [5]
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[OPERATOR INSTRUCTIONS]
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Questions and Answers
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Operator [1]
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Michael King, Banc of America Securities
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Michael King, Banc of America Securities - Analyst [2]
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Good morning, and thanks for taking my questions. I actually had a couple of
quick questions, Len, if you don't mind. Can you tell us how often ACR-N was
measured?
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Leonard Schleifer, Regeneron - President, CEO [3]
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Sure, Merdad (indiscernible) was the clinical investigator internally
(indiscernible) Regeneron response with this study. Merdad, can you handle that?
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Merdad Parsey, Regeneron - Director of Immunology [4]
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Yes, this is Merdad. All the HCR (indiscernible) were measured at every study
visit which were, in general, every week or every other week during the 12 week
period.
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Michael King, Banc of America Securities - Analyst [5]
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Okay, so you have between 6 and 12 measurements in that score?
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Merdad Parsey, Regeneron - Director of Immunology [6]
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That's right. I think there are 9 total measurements.
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Michael King, Banc of America Securities - Analyst [7]
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9 measurements. Okay. Can you give us any color on sort of what that trend
looks like -- does it improve with time? Does it stay constant? Does it kind of
wander around -- do we know?
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Merdad Parsey, Regeneron - Director of Immunology [8]
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I think, for example, compared to placebo, we know that it comes up faster if
you just look at the time whence -- the medium time when someone who is going to
get an ACR-20, gets one -- it happens in about a month versus about two months
or longer in patients on placebo versus patients on drugs. That is to say, the
patients get it a lot faster. I think that -- if you were to look at the over
time, you do see these measurements -- the (indiscernible) is still going up in
the 100 milligrams dose group, as would be expected. And the placebo is starting
to flatten out.
And there is noise, by the way, and that's what -- and I think what you're
getting at is what is the effect of the noise here. When you look at the
sustained ACR 20 score -- just as an example, Mike, and I think that's in there.
We saw a T of .03, and almost a tripling or from about 12.5 percent to 30
percent in terms of the people having a sustained ACR 20. So, I think what
you're getting at, maybe, is the question is -- is what is this sort of noise in
the data. By definition, 50 patient studies in an ACR-type score are going to be
noisy. I think that the effect size -- if it's stays the same -- which we had
twice as many patients -- you would have a P value of -- that would about .02.
You can do (indiscernible) squared (ph), it's pretty straight forward. And so,
remember, P values are driven both by effect size and obviously by the sample
size. These are relatively small sample size.
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Michael King, Banc of America Securities - Analyst [9]
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Okay. Can you talk about what were your anticipated --- speaking of that --
what your anticipated effect size was? And do you have a -- when you said that
if the study were twice as large, you could have had a statistically significant
P value but I guess I would ask the question of what -- how big did the study
need to be to hit that -- let's say, it was at 70 or 75, and you had that kind
of benefit in that number of patients -- I don't know if you have thought about
that?
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Leonard Schleifer, Regeneron - President, CEO [10]
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I haven't plotted exactly like but I know we have just run (indiscernible) with
the same effect size with twice as many patients, and you get P value of
somewhere around .02. And I think we can go through that. It's really
straightforward statistics. When we did this study, obviously we were somewhat
constrained by the fact that this was a Regeneron-conducted study with a
relatively small number of patients because of the drug availability and just
ability to recruit study patients and get all this done. I think all those
problems are behind us with Novartis as our partner, and we would be
anticipating doing larger studies in the future.
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Michael King, Banc of America Securities - Analyst [11]
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What was your effect size that you were anticipating -- can you say?
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Leonard Schleifer, Regeneron - President, CEO [12]
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I don't think we had set a specific P value.
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Michael King, Banc of America Securities - Analyst [13]
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No, the specific effect size. What was your assumption going into Phase II on
the effect size -- to get the powered-up, to show the effect you wanted?
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Leonard Schleifer, Regeneron - President, CEO [14]
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I don't know the answer to that. I will have to get back to you but I think
what you're asking was the power to get a .05 based on what effect size, Mike?
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Michael King, Banc of America Securities - Analyst [15]
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Correct.
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Leonard Schleifer, Regeneron - President, CEO [16]
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I don't have the answer to that.
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Michael King, Banc of America Securities - Analyst [17]
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Okay, and I will just ask one quick one, and then get back into the queue. It
sounds like -- from your opening comments -- that you will likely do another --
at least one more Phase II study. Is that a reasonable assumption?
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Leonard Schleifer, Regeneron - President, CEO [18]
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No, I don't want anybody to walk away with any conclusions on what the next
study is. I think that everything is on the table, whether it's another Phase 2
or 2-3 or 2-B or 3-A or 3 or what have you. I think all that has to be
considered by the partners, and let them sit down together and talk to the
experts and make some decisions. See what they think about if we reproduced the
100 milligrams dose group, is that enough? What would we be satisfied with? If
it looks like we can get into the higher dose, how do we figure that out? These
are just questions we're going to have to work out with our partner. And we have
not made any decisions. When we do, we will let you know. But everything, I
think is on the table at this point.
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Michael King, Banc of America Securities - Analyst [19]
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Okay, thanks.
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Operator [20]
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Raymond Myers (ph), Princeton Institutional.
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Raymond Myers, Princeton Institutional - Analyst [21]
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My questions from is for Merdad. Merdad, can you characterize the efficacy of
the highest dose -- the 100 milligrams IL-1 Trap -- in patients who had failed
to achieve or maintain the ACR 20 on the TNF-alpha (inhibitors or also,
specifically, on Kineret?
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Merdad Parsey, Regeneron - Director of Immunology [22]
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Do you mean people who had been on those in the past?
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Raymond Myers, Princeton Institutional - Analyst [23]
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Correct, people who had been on those in the past, and who we assumed have
failed and that's why they have joined this study.
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Merdad Parsey, Regeneron - Director of Immunology [24]
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In turns out that, although -- as you probably know -- we had allowed patients
who had failed those treatments in the past to be enrolled in this study, the
numbers were actually relatively small. I think it is safe to say that what we
saw in the patients who had a history of being on those agents for the past was
similar to what we saw in the patients who had not had that history in the past.
The major caveat being we don't know why they stopped taking those medicines in
the past.
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Raymond Myers, Princeton Institutional - Analyst [25]
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So, there was some effect. I mean, if the results were dissimilar, there was
some effect on the patients who failed or discontinued TMF-alpha in the past?
Leonard Schleifer I think what Merdad is saying, is if you look at that group,
it is a small subgroup. I think it's only about one-third of the patients or
less. (Multiple Speakers) Yes, less. So, you saw a small fraction, and
therefore, you saw a similar proportion. But you really can't tell because one
patient more or less is the difference between 10 or 15 percent if you only had
a 1/3rd or so of the patients or a quarter. I don't think we can reach any
definitive conclusions about that at this point in.
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Raymond Myers, Princeton Institutional - Analyst [26]
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But you did see some activity?
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Leonard Schleifer, Regeneron - President, CEO [27]
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Yes, but, once again, these are small numbers, and so I think -- I just don't
think we can say anything definite at this point.
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Raymond Myers, Princeton Institutional - Analyst [28]
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Okay. It's encouraging, though, that we have seen something though.
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Leonard Schleifer, Regeneron - President, CEO [29]
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Yes.
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Operator [30]
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(OPERATOR INSTRUCTIONS) Jim Birchenough, Lehman Brothers.
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Jim Birchenough, Lehman Brothers - Analyst [31]
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Hi, Len. A quick question just on the selection of the doses for this Phase II.
What was it in Phase I that made you select the 100 milligrams as your top dose
-- did we reach an MTD in Phase I? And where might we go if we are on the early
part of the dose response curve? How far can we go up in dose based on what you
have seen in Phase I?
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Leonard Schleifer, Regeneron - President, CEO [32]
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I don't think we have any evidence that we've reached the MTD. So I think we've
made substantial progress in the -- really, truly remarkable progress in terms
of the production side of this. So I think we can go significantly higher. I
just don't know what the appropriate -- how high we should go. We're going to
have to discuss this with Novartis and figure this out.
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Jim Birchenough, Lehman Brothers - Analyst [33]
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Can I ask, how far have you dosed-up in Phase I, so we might have a sense of
where you could go?
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Leonard Schleifer, Regeneron - President, CEO [34]
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Yes, I think we have dosed to 100 in Phase I, and we dosed obviously to 100 in
this study without any evidence. And we've got toxicology studies that cover
substantially higher doses. So I think we can go higher. We just have to figure
out what the right strategy is.
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Jim Birchenough, Lehman Brothers - Analyst [35]
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And then, just in terms of this Phase 2, will we see 10-week follow-up data at
some point? And will you follow these patients out to get ACR 20 with 50 and 70
scores at six months and a year?
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Leonard Schleifer, Regeneron - President, CEO [36]
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Yes, remember, they are off drug at the end of 12 weeks. And we can already
tell we will present this data, and I think what you should look for is to see
some of these effects go away overtime -- further evidence, we will present that
at a clinical conference.
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Jim Birchenough, Lehman Brothers - Analyst [37]
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Is there any expectation of data at the upcoming ACR meeting?
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Leonard Schleifer, Regeneron - President, CEO [38]
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No, I don't think so. We didn't get the results in time to get included in
that.
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Jim Birchenough, Lehman Brothers - Analyst [39]
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Okay, great. Thanks for taking my call. |
