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This is what we have been waiting for. Absolutely awesome. Can't wait.
Ok, no tweets today. And . . . GO!
As I've said several times, the more manipulation we have here accompanied by large accumulation by the big boys, the more violent the reversal will be. If you look at the last several major pps increases (dec, feb, march, etc.), each time the increase becomes more and more violent. That is why I believe that the next increase will be the most furious. The real question going forward is how to play the upcoming swings at higher levels that will most assuredly occur.
Look at the Deerfield filings in feb. They divided the shares between several entities so as not to violate. Baker Bros does the same thing. Sometimes the group, sometimes the individual, sometimes both. Sneaky fellows.
To accumulate more shares. Let's say you are baker brothers (personally I don't think it is) and you purchase a bunch of shares at .71 but really want more shares than that. You don't want your name attached to the stock to potentially drive the stock price up. You want the price to sag for you to have an opportunity to buy more v
Awesome post tremors!!!! I'm glad you are excited again.
That's good advice. Try oncosec.com. This site offers a great amount of information about ONCS. Good luck.
Ya, I don't know when is the minimum results a company had to have to apply for something like that.
Why would they have applied already? Don't they have to wait for phase 2 results?
No, that's not what he meant. What he meant is that like INO, which has more indications than oncs, it is important to get more in the pipeline to increase pps value which would result in a higher buyout/partnerships etc. That doesn't mean they won't partner with pd-1 for phase 2b.
Of course he is right. Punit is trying to develop a company that is broad on its applicability which will make all shareholders happy.
Jbeam77: I don't have pm. Contact me at jackpetersonattorney.com
By the way, I spoke to pazzo1212 thus morning and he is a good guy. His statements were really taken out of context. He is a larger share investor who is involved in the brokerage industry. There is no doubt why punit wanted to meet with him. He told me what punit told him and nothing was out of the ordinary. Just enthusiasm from a CEO who is excited about his product.
Actually, I'd like to hear what you have to say. I'll try to tower you and connect.
Keep posting here. Anyone you takes the time to meet Punit and verify their investment is a valuable contributor.
We, as investors, can take people's statement with a grain of salt. We are all responsible for our own investment.
My summary of your post is simply that Punit is a good guy, oncs is going places and he is excited about where the company is going. Sounds good to me.
Never seen it
Below is a list of all the oncology trials that Ferrone's research center is involved in:
http://www.massgeneral.org/cancer/SearchTrials.aspx?condition=%3C%3C+ALL+%3E%3E
There are two studies involving MK-3475 and one phase 2 study involving Nivolumab (Bristol's PD-1)
Very interesting.
Below is Dr. Ferrone's most recent article. About melanoma and BRAF resistance.
http://www.ncbi.nlm.nih.gov/pubmed/24732172
More info on Dr. Ferrone:
Soldano Ferrone, MD, PhD
Dr. Soldano FerroneSoldano Ferrone, MD, PhD, is a translational tumor immunologist who earned his MD and PhD degrees from the Medical School of the University of Milan Italy in 1964 and 1971, respectively. He received his clinical training in oncology at the Medical School of the University of Milan as well. In 1971 he moved to the Scripps Clinic and Research Foundation in La Jolla, California, where he held a tenured faculty position until 1981 when he moved to Columbia University in New York. During the following years he held senior administrative faculty positions at New York Medical College, Roswell Park Cancer Institute, and the University of Pittsburgh Cancer Institute. He moved to Massachusetts General Hospital in November of 2012.
His research program is focused on tumor immunology with special emphasis on the development and application of novel combinatorial antibody-based immunotherapeutic strategies for the treatment of malignant diseases. The design of these strategies is guided by the realization that effective immunotherapeutic strategies have to eradicate not only differentiated cancer cells, but also cancer initiating cells and have to counteract the multiple escape mechanisms used by tumor cells to avoid destruction. For the last 40 years, Dr. Ferrone’s research program has been supported by grants from the NIH, American Cancer Society, DOD and various foundations. Dr. Ferrone has co-authored more than 900 papers and has edited 18 books.
Here at the MGH, Dr. Ferrone has established the Monoclonal Antibody & Immunotherapy Laboratory. In collaboration with clinician scientists such as Drs. Joseph Schwab and Cristina Ferrone, he will continue to investigate the role of immunological events in the pathogenesis and clinical course of malignant diseases and use this information to develop novel immunotherapeutic strategies for the treatment of malignant disease. The information derived from studies in the laboratory and in animal models will be translated to a clinical setting, taking advantage of the expertise and infrastructure at the MGH that facilitates the development of translation research. We look forward to working with Dr. Ferrone!
http://www.orthojournalhms.org/corners/mgh/newFaculty_mgh.html
I totally agree that the details don't need to be perfect for a partnership to occur. Every big pharma with a pd-1 should be dying to share the "problem" that ONCS has.
This is taken from the 2014 strategic update issued in January. Sometimes we as investors are impatient but it looks like things are really on schedule:
Metastatic melanoma Phase 2 study (OMS-I100)
Complete enrollment in study being led by the University of California San Francisco (UCSF), University of Washington and other U.S. cancer centers
Evaluate dose-intensified treatment schedules
Report interim and final analysis of clinical data
Initiate Phase 2b metastatic melanoma study
Merkel cell carcinoma Phase 2 study (OMS-I110)
Complete enrollment in study being led by the University of Washington and UCSF
Report clinical data
Expand Phase 2 cutaneous T-cell lymphoma study to a multi-institution trial to enhance enrollment and leverage additional expertise in CTCL
Initiate additional Phase 1 study in new solid tumor indication
There are 7 now and for $295 you can see the list. lame.
I wrote IR about a webcast or anything in the form of a transcript from today and haven't heard anything from them. Has anybody gotten a response on that question?
Even better: promote TVgit to moderator and partnership the next day.
Ya, you blew it on that one. You even knew his favorite drink. You could have least gotten a disguise and have stocked him. Gees Zoridan !!!
That assumes no news. Oncs will not go 3 months without news.
Couldn't agree more.
If you can't beat them, promote them.
No, as a partner, not a competitor. It puts BMS neck and neck with Merck in my opinion.
This is the WSJ article:
http://online.wsj.com/articles/bristol-myerss-nivolumbab-shows-favorable-comparison-1403646918?mod=yahoo_hs
If someone has access to this article, please cut and paste it into a post.
Thanks.
Nice.
Did you get yours?
What does level 2 show right now?
Touché.
No to scare anyone, but if I was an MM, today would be the day I would do a bear raid. If they do, buy buy buy guys or at least hold on to your shares.
No kidding.
I thought you would like that. Did you listen to the webcast from Merck I posted last week. It was even better.
Below is the transcript that was sent to me my investor relations at Bristol-Meyers. It is from their Goldman Sach presentation. Very interesting. Enjoy.
C O R P O R A T E P A R T I C I P A N T S
Michael Giordano Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
C O N F E R E N C E C A L L P A R T I C I P A N T S
Jami Rubin Goldman Sachs - Analyst
P R E S E N T A T I O N
Jami Rubin - Goldman Sachs - Analyst
Good day, everybody. I am very pleased to have Michael Giordano from Bristol-Myers, Senior Vice President, who is currently Head of Developmentfor Oncology and Immunoscience, and is responsible for leading development of the immuno-oncology portfolio. So really, we could not be more fortunate to have you right here at this time, coming right off of ASCO and the continued development of your program which we continue to believe is very, very exciting.
But let's start right in with ASCO. Michael, unlike last year which I would describe as a Bristol-Myers lovefest, this year has been a Bristol-Myers
bashfest with investors walking away from ASCO asking more questions, concerns about competition, concerns about your combinations. So I
really want to use this session to review the take-ways, but more importantly to address investor concerns, for you to respond to those.
But before we go there, will you please share with us what you learned? What surprised you? What were your big take-aways this year from your
perspective?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Thanks, Jami. It's nice to be here. As I was reflecting upon ASCO on the short plane ride home, I think there were maybe three things that come to
mind. First, the role of immuno-oncology at the entire conference was dramatically increased. We've been at ASCO for 5 years with immuno-oncology
milestones, but the shear voice, if you like, on immuno-oncology was dramatically increased.
Two, the amount of BMS data was actually increased from what we have presented previously at congresses and it may not have seemed that way
because other companies are also presenting their data. The strategy that we have been articulating for, I think, three or four years was being
validated by the data being presented. One, the importance of durability of response, two, realization that these medicines can have long-term
survival, and three the combinations offer the best opportunity for patients to achieve long-term survival. So that was my BMS take-away.
The take-away from some other companies is that they are validating our approach. And two, they're validating signals and other tumor types
which I'm delighted that we can use that information to then drive our own programs. Or, in the case of bladder, or in the case of head and neck,
validate our Phase 3 program. So I think we learned a few things from the competition. Those are a couple of my take-aways.
With regard to tumors, if I could just talk a little bit about that, melanoma data in combination I thought was -- and I've said this -- unprecedented
with regard to the performance of 1 and 2-year survival on the combination of YERVOY and nivolumab.
Two, the renal data, including the monotherapy data, the randomized Phase 2 and the combination data, I was quite honestly surprised that there
wasn't more deep dive into the value of that. Why? Because the way (inaudible), the survival data from the monotherapy study which has not really
been seen with TKIs. Granted it's a Phase 1B study, but the issue with TKIs that are used to treat renal cell cancer is that none have demonstrated
overall survival advantage. And in this instance, we're seeing survival which exceeds what's been seen with TKIs.
Two, the tolerability of the combination of YERVOY plus nivo at the 3 milligram nivo, 1 milligram of YERVOY, was extremely good in my view, and
is better than TKIs monotherapy, and better than TKIs plus nivolumab. That did not seem to come through. I think folks focused on lung cancer,
and we can get into some details about that because I'm sure that that's of interest, and I have some insights that we'd like to share.
Jami Rubin - Goldman Sachs - Analyst
Okay. Just before we get into that just, Michael, just given how fast this market is changing and it really is. Just in the last 3 years, it's incredible how
fast things are moving. What gives you confidence your Company can still maintain its lead with the best assets? And while I don't think anyone
disputes that Bristol is clearly the front runner, and the early pioneer in immuno-oncology, is there risk that your competitors might learn from
your mistakes leading to potentially better designed trials, better biomarkers? Just as an example, we haven't really seen (immunitis) in their studies
likely as a result of learning from your earlier trials.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
I think it's clear that the competition has learned from some of the BMS successes. I don't think we've had too many missteps. Successes with regard
to the treatment algorithm that we have implemented in all of our I-O programs which has been extremely successful with YERVOY. If you go to
some sites, you'll see the BMS posters of our algorithm being used by other companies which is to monitor for safety issues and to intervene early
and we've found this to be extremely successful, YERVOY in combination.
Yes, the competition can learn from the way we design our studies, however, I think that the competitive advantage is really on the depth and
breadth of what we have -- depth of pipeline by clinical assets, and the breadth of the program for nivolumab of 7,000 patients which is on top of
10,000 patients that we've enrolled in clinical trials from YERVOY. So we take that data, integrate it, and use it to stay ahead of the competition, so
to speak, with regard to how we design our studies. I am sure that any one of the companies who are competitors will design a program in one
tumor type or another and be able to successfully compete. But in the aggregate, I think that it's going to be quite difficult.
Jami Rubin - Goldman Sachs - Analyst
And then I think also, just in terms of timelines, I think clearly investors were very surprised that Merck's product surpassed you in melanoma given
they started 4 years behind you. And so my question is, and I know many investors share this, are you doing everything you can to accelerate the
filing timelines? And just how do you think about balancing survival data which is, I think, what you believe is clearly the most important, I would
agree, but with just getting your drug out there quickly with overall response rates which is clearly what your competitors are doing?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Both are very important. Speed to patient and demonstration of overall survival. We learned with YERVOY that in Europe and in the US, the need
to characterize survival is critical for access and critical for demonstrating that the innovation is better than the older drug. So we will remain focused
on the characterization of survival throughout all of our programs.
However, in the melanoma program -- that's five studies, three of which have the possibility of demonstrating survival. However, as I've said before,
every one of the Phase 3 programs incorporates the opportunity to do an analysis on the basis of a shorter term endpoint, typically durable response
rates, and we have that opportunity in a very (inaudible) study, which is a post-YERVOY survival study, in the 069 study which is a study of the
combination of YERVOY plus nivolumab which can mature this year, and in the definitive study of mono versus combination 067. So every one of
our programs in melanoma and in lung incorporates the possibility of making the choice to analyze the response rate, or have built into it already
an interim analysis of looking at response rates to get faster to patients while maintaining an ability to demonstrate survival.
I believe that the window will close with regard to a PD-1 being able to demonstrate a survival advantage in melanoma. The window will close this
year and Bristol-Myers will probably be the only company based upon the studies that are designed that can demonstrate that. I think that in
conjunction with a soon-to-market strategy is going to be a winner.
Jami Rubin - Goldman Sachs - Analyst
Will you have that opportunity in melanoma this year?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
I'm not going to speculate on when we'll have the opportunity. I will tell you that the 037 which has a survival endpoint does offer the opportunity
for a potential earlier analysis based upon response rates that we could look at sooner than the survival outcomes.
Jami Rubin - Goldman Sachs - Analyst
And the 069, does that --?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
The 069 study which is the combination of nivolumab plus YERVOY also has the potential to be significantly supportive of the study we presented
at ASCO. And if those data mature this year or early next year, provide an opportunity to really characterize in a well-controlled study, the performance
of the combination which I think clinicians and potential regulators will find very important.
Jami Rubin - Goldman Sachs - Analyst
Okay, so let's move to the lung story. First point of concern is the combo lung study and investors continue to question the rationale in taking the
combo nivo-YERVOY into Phase 3 given the low response rates and the high toxicity. So what can you tell us to give us confidence that the planned
move into Phase 3 is not just a plan to please investors, but based on really good scientific rationale to move this into Phase 3?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
So several points. One, many of you know that I learned much of my drug development from Elliot Segal and Brian Daniels, two really brilliant drug
developers. And part of their teaching was that in drug development, information evolved over time, and that you need to use that information
evolved over time to make informed risk-based decisions. The data that we presented at ASCO represented the data from an ongoing cohort of
the 3-1 and 1-3 dosing regimens in nivo and ipilimumab in combination. And it's fair to say that that combination resulted in about a third of
patients not being able to tolerate the regimen and prematurely coming off-study. When a third of the patients come off study for tolerability
issues, they don't have the opportunity to benefit from the combination, so that automatically, of course, reduces what you can achieve in a response
rate.
We have learned, however, from those cohorts how patients that stay on-study perform, and what have we learned? We learned that their responses,
irrespective of PD-L1 status, critical, because it may provide an opportunity for the PD-L1 negative patients to finally have a therapeutic option
that may be real in the first-line setting. So we'll use that learning to design Phase 3.
Last, we have an additional ongoing cohort of 1 plus 1 milligram which has not yet fully matured but which will mature before we make the dosing
decision for Phase 3. So if you take into consideration what we learned from 1-3-3-1, what we will learn from 1 and 1, what we will learn from the
Pharmaco kinetic and (Pharma) dynamic data that we have generated over the course of during this experiment, and if you take the fact that
combination in multiple tumor types works despite PD-L1 status, that gives you an awful lot of data upon which to design a Phase 3 program -- a
Phase 3 study. And there is the opportunity to be creative on how the Phase 3 study is designed. So I would not be narrow in thinking that it's going
to necessarily be a simplistic head-to-head comparison.
Jami Rubin - Goldman Sachs - Analyst
Will there be data -- I mean, will we see data this year that provides a better understanding as to why there is potential -- will we see data at some
point that, I see why you're moving into Phase 3. Will that happen?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
I'm not sure, to be totally frank. I'm not sure when the 1-1 milligram data will be mature enough to present at a congress. Certainly by next year it
will. I don't know if it will make it on time for any of the lung congresses this year.
Jami Rubin - Goldman Sachs - Analyst
So you will have that data in-house in order to make --
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
We will have those data assessed and in-house in order to make a dosing decision for the Phase 3 this year.
Jami Rubin - Goldman Sachs - Analyst
Is there anything you can -- you said a third of the patients dropped out because of tolerability issues. Are those just -- is there anything you can
do in terms of algorithms in managing their toxicities to improve the ability to stay on the combination?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Yes. I think -- again, that was the first combination experiment. We learned from it and the investigators learned from it how to intervene early on
the basis of potential side effects. Remember, these are lung cancer patients. They automatically have potentially more debilitative status than
potentially melanoma patients. They're older. And despite that, I think with implementation of an algorithm, and the right dosing regimen, we can
do a very well-designed Phase 3 study. I'm not going to pre-suppose the outcome of that Phase 3 study. I'm going to say that it will be a Phase 3
study that is based upon good drug development principles. If I knew the result of the Phase 3 study, we wouldn't do it. But I believe there will be
sufficient data, applying good drug development principles, to design a Phase 3 study that satisfies the needs of the patients, and the need of
bringing the medicine to first-line lung cancer patients, (inaudible) I mean, combinations, in particular, the PD-L1 negative population.
I don't know what else is being offered for them. You guys may know more than I do but I think that they're currently a population of between 50%
and 60% of patients in lung cancer for which there isn't an otherwise clear path.
Jami Rubin - Goldman Sachs - Analyst
So on to the Phase 3 trial in second-line lung which reports later this year.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
This is my fourth conversation in about four hours.
Jami Rubin - Goldman Sachs - Analyst
While I am asking you, you can drink your water. So this is another trial that investors are really nervous about. And investors are nervous about
the trial design and the implications of PD-L1 status. So let's break it apart and I want you to respond to those concerns. First, can you address the
trial design? And I think part of the issue too is that it's a small study. There are 300 patients. And we did see a very large study at ASCO, a Lilly trial
in ramucirumab which enrolled 1,100 patients, and they just barely showed a survival benefit. So I think that is one of several issues that investors
are worried about.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Okay. We do work backwards. So the larger the study, the smaller difference you're able to detect. And the less clinically-relevant potentially that
difference is. And so you can all be the judge of whether the 1.9 months, I think it was, is a relevant innovation to what's available.
The second-line Phase 3 study that we're talking about has as an endpoint overall survival using a hazard ratio. That is the best way of demonstrating
a survival advantage for an I-O agent, which they have a Kaplan-Meier curve which has a different shape from chemotherapy. We powered that
study on the basis of a survival endpoint, and based upon a mix of PD-L1 positive and negative that we were anticipating from testing of multiple
tumor samples, we have not yet completed -- well, we talked about the frequency of the PD-L1 population in that study, but I can tell you that it
is not in any way worrisome and it's not 25%, it's higher than that. So it is has a sufficient number of PD-L1-positive patients to potentially enrich
the endpoint which is survival. It's not response rate.
Then let me comment also on what contributes to overall survival in a nivolumab study or in most I-O studies. We know from multiple analyses
that two things contribute to survival advantage. The first are the responders. It's wonderful to get a complete response. They will contribute about
typically one-third of the survival advantage -- I'm sorry, two-thirds of the survival advantage. Then there are the stable disease patients who
contribute about one-third of the survival advantage. So when you take the mix of responders that may be enriched by PD-L1 status, and when
you take the contribution of the stable disease patients, we use that information to constantly pressure-test our assumptions. And we have done
that recently and I'm feeling as if the study is correctly designed with a hazard ratio and with the PD-L1 mix to demonstrate what it's meant to
demonstrate.
Jami Rubin - Goldman Sachs - Analyst
What can you learn, though, from the -- I might be mixing up my CheckMate studies -- 003. I believe, the long-term 2-year survival we saw with
nivolumab of I think 45%, what did that inform you at all about this trial?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Interesting guess. That's what we call the survival effect or the tail of the curve. The tail of the curve contributes a greater amount to the hazard
ratio than the beginning of the curve. So we've learned that waiting the right amount of time to do the analysis is critical in order to incorporate
the survival advantages achieved through the tail. That is precisely what we did in YERVOY. We waited long enough for a sufficient number of
events so that the flat part of the curve, which in YERVOY goes out to 10 years, can contribute to the hazard ratio. So doing the analysis at the right
time is important. Waiting for the right number of events will be critical. 017 is an event-driven study. When we've talked about when we would
analyze it, it's been an estimate on the basis of events. If, for whatever reason, events stop happening, then we come and talk to you about when
we would analyze that. That would be a good thing for patients. So the tail of the curve is incorporated into the statistics of that study to help
optimize when and how to do the analysis.
Jami Rubin - Goldman Sachs - Analyst
And what is the sort of best estimate in terms of timing?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
We believe we'll be able to do the interim analysis of that 017 study this year in November or December based upon the event rate.
Jami Rubin - Goldman Sachs - Analyst
And you need to complete that in order to -- you need to have seen that and analyze that in order to complete the third-line squamous study?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
What we have agreed with -- what we have proposed and agreed with the FDA after having started the rolling submission with the 063 third-line
heavily pre-treated squamous population is to provide them with additional information before the dossier is completed, so before the filing is
completed. We haven't talked about what combination of -- or whether it's additional data from 063 or data from a different study. We've not been
specific about that.
Jami Rubin - Goldman Sachs - Analyst
Okay. But you did say that data would be available in October?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Yes.
Jami Rubin - Goldman Sachs - Analyst
I'm just going to jump here. We can talk about some of the other tumor types. But another issue coming out of ASCO is that there's a perception
that Bristol has a biomarker problem, in part focused on the lack of consistency. So as an example of lack of consistency, at the World One Conference,
after you presented lung data that demonstrated PD-L1-negative responded to therapy, although less than PD-L1 positives, that there was a
response. And then when we saw your first-line trial, the data stated that only PD-L1-positive patients responded. So I think that's probably why
people are worried about your ability to select the right patients for these trials. Can you comment on this?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Yes. So let's remember that this is an immuno-histochemistry test and not a (BUF) like test which you get in the easy plus or negative. And there
are various contributions to the quality of the results. 003 which is our first study done with a not yet the final biomarker assay that we will bring
forward for commercialization. The results of that study were based upon scavenging available tissue samples from roughly half of the patients.
And also the results of that study were a Phase 1 exploratory study in which we did not have IRC or confirmed responses. So the results of that
study and correlated biomarkers, I think, is an outlier with regard to the quality of the information that was generated. All of the
contemporaneously-generated data since that time, since we learned how to use the validated assay has been extremely consistent meaning the
frequency with which we're observing positives has been assessed over 26 tumor samples, and it is highly validated and consistent.
The consistency of the enrichment of response, meaning how more frequent are responders in the population are positives versus negatives, has
consistently been between two and three-fold across all tumor types -- melanoma, renal and lung. That gives me -- and by the way, that's been
consistent across all PD-1s and PD-L1s that exist. Two to three-fold enrichment response rates. So I see an extreme amount of consistency with
regard to the frequency of picking up positives, and extreme consistency in all the contemporaneously executed studies on enrichment. That is
what gives me confidence in the assay.
The approach we took -- the data we presented on 012, so the 50% response rate, the positive, zero response for negatives was based upon 20
patients. That cohort has been expanded and continues to demonstrate a nice enrichment, but also continues to demonstrate the consistency
that I have explained for all the other tumor types.
Jami Rubin - Goldman Sachs - Analyst
One thing that I didn't understand is despite no response rate in the first-line PD-L1 negative patients, their 1-year overall survival was so relatively
high. Can you explain that?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
It's an important nuance that gets back to what I was describing earlier which is that responders and stable disease contribute to survival. That is
a consistently observed fact -- a fact now from every I-O study we've done. Therefore, PD-L1 positivity contributes probably incrementally to survival,
but as many have said, both other company development leaders and other thought leaders, the PD-L1-negative patients do respond and they
have stable disease and contribute potentially to the value proposition of a study, or of clinical practice. And I think that's what we're seeing in that
particular study.
The correlation between PD-L1 status and survival has only begun to be understood. You've not seen at ASCO or elsewhere a great deal of data
with regard to strong correlations. And that's something we will see with time.
Jami Rubin - Goldman Sachs - Analyst
Does the FDA understand that?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
They do.
Jami Rubin - Goldman Sachs - Analyst
Okay.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Smart people.
Jami Rubin - Goldman Sachs - Analyst
So moving on to the melanoma data which we thought was very impressive, you showed a 1-year survival of 94% and a 2-year overall survival of
88% I think in one of the new cohorts. Yet again, the investor focus was mainly on the toxicity profile. And again, if you could comment on that,
and if memory serves me right, about 65% or 60% of patients had grade three, four toxicity.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
63%, I think.
Jami Rubin - Goldman Sachs - Analyst
Okay. 63%. Has that changed from last year? And maybe if you could just help to put that into context, because clearly that is yet -- that is something
that people are really focused on.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Let's think a little bit deeply about how the study is executed and then how the drug will be used in practice. So the first 11 weeks, patients get a
combination of ipilimumab and nivolumab. After that, at 11 weeks, they get 3 milligrams of nivolumab until progression, which many of the patients
did not progress. When you observe 88% of patients alive at 2 years, it means that although some patients may have experienced side effects
within the first 11 weeks, they are deriving substantial benefit.
B, melanoma treaters have become extremely familiar with managing side effects associated with I-O agents and particularly YERVOY. So in that
11-week period, I feel competent that oncologists will be able to A, monitor, and B, manage any potential side effects that are seen from the
combination and patients will go on to the 3 milligram, what I might call, longer-term therapy. So I think the value which is being provided by 88%
of patients alive at 2 years, 94% at 1 year versus perhaps 69% with a monotherapy, that's 20 to 25 patients who would otherwise not be alive. And
as some have said, you can't salvage a dead patient. So I think you need to look at the totality of how the study is done and how the drug will
actually be given.
The treatment algorithms work really well. And so there will be an aspect of education, and the algorithms are nothing more than monitor for side
effects, withhold the dose if the side effects get to a certain point, and treat with corticosteriods. That is far simpler than many of the algorithms
that physicians need to use with other more traditional chemotherapies. So I feel good about it.
I'm not surprised at others who overly focus on this if monotherapy were their initial approach, but others also who have monotherapy as initial
approach are studying the combination.
Jami Rubin - Goldman Sachs - Analyst
I mean, I guess, as you just said, there's some perspective for me. We did see Merck data, single-agent data in melanoma that did look better than
nivo as a single-agent in melanoma. And maybe you can explain why. But they showed a very high 1-year survival rate. And so A, what were the
differences between the two trial designs? And why wouldn't you just use Merck's single agent which has, I think, 12% of patients experienced
grade four or five toxicity versus your combination 50%, 60% experiencing grade four or five toxicity? And the differences in survival, yes, yours
was higher but that's dramatically higher, so just when you think about balancing the tolerability profile with the survival benefit.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
So when I take the two monotherapy experiments, I think the one-year survival rates observed are both in the 60s. Nivolumab is 63% in our
monotherapy study, and Merck is 69% across a variety of doses. So I think those are within a similar range. I think the safety profile of monotherapy
is also quite similar with regard to the frequency of grade three, four. Maybe nivolumab has slightly fewer grade three, four events than the Merck
compound. So I think in essence, the performance in monotherapy of those compounds is quite similar. Why would I -- if I were a patient or a
physician want to ask for therapy that gave me the most likely opportunity to achieve long-term survival? It would be based upon the Kaplan-Meier
curve that we're seeing for the combination in which there is a difference in my view between 94% and 69%. I think there's a difference.
Jami Rubin - Goldman Sachs - Analyst
Just segwaying a bit to the adjuvant melanoma data which was also, I think, very positive with YERVOY. I think the issue there though was that it's
not clear what you're going to do with it. And when do you think you'll be able to provide us with your filing plans? Or is the plan to just move that
-- move nivolumab into an adjuvant setting and put your capital behind that instead of YERVOY?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
So I think all of those, probably. One, the demonstration of YERVOY being effective in the adjuvant setting is a very important event. One, it
demonstrates that an immuno-therapy can be effective when there's no microscopic tumor. And so in the post-surgical setting, the use of an
immuno-therapy as adjuvant as a checkpoint inhibitor has never previously been demonstrated. So that's critical for YERVOY, and critical for the
field of immuno-oncology. The fact that relapse-free survival was improved is clinically relevant to many melanoma experts, and is an acceptable
endpoint to the FDA. We will take those data, therefore, to the FDA to discuss their views of the data, and then based upon that discussion, decide
on the registrational path forward.
Jami Rubin - Goldman Sachs - Analyst
Are you optimistic you'll be able to file with that study?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
I'm optimistic that that study is a fileable study.
Jami Rubin - Goldman Sachs - Analyst
Have you had that meeting yet with the FDA?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
We have not yet had the meeting. We will. We've shared the data with the FDA, and we'll have a more formal discussion with them as soon as it
can be scheduled.
The promise of a checkpoint inhibitor, YERVOY and adjuvant, redoubles our enthusiasm about investing in an adjuvant study for melanoma which
we have said we will do, and in renal cell cancer which we have said we will do.
Jami Rubin - Goldman Sachs - Analyst
Why not lung? I think Astra Zeneca is starting their trial in lung.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
We'll continue to explore adjuvant lung. I think as I understand it, the 3B population post-reception is an interesting population which is a relatively
small opportunity. We will look at whether that's a place we want to invest as well.
Jami Rubin - Goldman Sachs - Analyst
And we don't have much time, but I just want you to briefly comment on other assets in immuno-oncology. There are other potential combinations
that you are exploring. What are you most excited about? And when are we going to see them?
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
I expect the data on anti-(inaudible) LAG3 and anti-CD137 to potentially be available towards the end of next year. Those studies are now rapidly
enrolling in combinations with either YERVOY or with nivolumab. And we will collect those data. We are aware of those data in real-time because
they're Phase 1 studies, and we anticipate not being public with those until the end of next year.
Jami Rubin - Goldman Sachs - Analyst
The end of 2015.
Michael Giordano - Bristol-Myers Squibb Company - SVP, Head of Development, Oncology and Immunoscience
Yes. I am enthusiastic about each of them for different reasons. LAG3 because it works on T-cell exhaustion which may be quite useful as adjuvant
to PD-1. And (inaudible) because of its impact on (inaudible) system, and anti-CD137 because of the direct immune enhancing effect. So I'm excited
about all three of those.
I'm also excited -- I just want to make sure I mention this -- about the breakthrough designation in Hodgkins Disease and the proof of principle
that PD-1s, either nivolumab or others, appear to have activity in ovarian cancer and bladder cancer, and head and neck. That means that there
are well more than half a dozen tumor types where this paradigm has been demonstrated to work, but gives me an enormous amount of enthusiasm
about its potential across the broad spectrum of tumors which is what we are currently doing, 17 tumor types and counting.
Jami Rubin - Goldman Sachs - Analyst
Great. With that, thank you very much. We've actually run out of time.