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PRIMA BIOMED DISCUSSES CAN-003 ABSTRACT PRESENTED AT ASCO TRANSCRIPT
Adam Holdsworth, ProActive Group
Scott Hazelwood, Continual Capital Group
Michael Rosenberg, Hudson Capital
Prima BioMed (ASX:PRR,
3rd June 11:00am AEST
Good day ladies and gentlemen and
welcome to the Prima BioMed Limited conference call to discuss the abstract presented at ASCO on new interim overall survival and final progression free survival data for the company s CAN003 trial. My name is Travis and I will be your
moderator today. I would now like to turn the conference over to Mr. Adam Holdsworth, Prima investor relations representative. Mr. Holdsworth please proceed.
Adam Holdsworth - ProActive:
Hello everyone and thank
you for joining us today for the Prima BioMed ASCO conference call. With me is Dr. Heidi Gray, the lead investigator of Prima s CAN003 trial and presenting author of the CAN003 data at ASCO and Dr. Brad Monk, chair of Prima s
clinical advisory board. Before I begin I d like to remind you that during this call we will be making forward looking statements that are subject to risks and uncertainties that may cause actual results to differ from the results discussed in
the forward looking statements. Reference to these risks and uncertainties are disclosed in detail in our public announcements to the ASX and our disclosure filings, with the US Securities and Exchange Commission. I will now turn the call over to
Thank you Adam, it s really a pleasure to be speaking today to you. The results of CAN003 which I just presented on Saturday at the ASCO meeting and was
very well received. So ovarian cancer is really an ideal cancer to target for immunotherapy as a maintenance strategy. Most ovarian cancer patients, even at advanced stages will achieve a first clinical remission following surgery and standard
chemotherapy. And patients will then be in some degree of a remission for 12 to 24 months in which time they ll experience a clinical relapse or first remission. Patients will then, usually many will go on to develop a next remission following
chemotherapy and/or surgery and so there s these blocks of time that we have tried to look at in maintenance strategies to help improve these and reduce these recurrence rates. So the purpose of CAN003 was really to perform a randomised phase
two trial openly while looking at the CVac dendritic cell vaccine versus standard of care which was observation at the time and patients who are in their first or second clinical remission. And to look at the safety and efficacy of this response.
So the primary objectives were safety and progression free survival and the secondary objectives were overall survival and then looking at markers of
immunologic response, both humeral and cellular. So this slide shows you the study design. Patients had to be within 12 weeks of obtaining their first clinical response, so they had to be 12 weeks after finishing their chemotherapy. The first seven
patients in the trial were not randomised, they all received CVac and this was really because the manufacturing had changed from Australia to the United States and we needed a safety lead in to make sure that this was appropriate. After that point
patients were then randomised to either receive maintenance CVac or the control arm, which was observational standard of care. And this was a one to one ratio. Patients who are in the maintenance CVac arm received a total of 10 doses of vaccine,
they got a dose every four weeks for seven doses and then three doses every eight weeks and this was over 56 weeks.
Follow up then for patients were for
progression free survival were both using GCIG criteria CA125 if they had an elevated CA125 previously as a marker and recist. And those were done every 12 weeks with visits, CA125s and imaging. So this slide shows you a demographics between the two
arms. The CVac you can see in the middle column and then the standard of care observation arm. Of course well balanced; there were 29 patients in the CVac arm and 27 patients in the observation arm and looking at basic characteristics between the
two groups, about two thirds of the patients in both groups were in their first clinical remission and then a third were in their second clinical remission. And these were stratified for randomisation, so of course we expected them to be equal. Most
patients had stage three disease and were serous cell type which is the most common for ovarian cancer and other demographics such as optimal site of reduction, which can be prognostic and age were also matched. The P Values aren t shown, but
they were not statistically significant between the two groups.
This slide shows the serious adverse events that happened on the trial. None of these
were related to the administration of CVac, there were nine in total. Most of the events were related to prior therapy, either surgery, having a bowel obstruction or progression of disease. There was one death on the trial in a patient in the
standard of care observation arm. Again that was unrelated to the vaccine or the trial. So this is really where the crux of the data is. So again our primary objective was looking at progression free survival. So of the 56 patients total split into
arms, the blue line is the CVac arm and the yellow is the standard of care observation arm. And you can see that the median progression free survival for the CVac arm was about 12.9 arms and the
median progression free survival for the standard of care arm was 8.6 months. Now this was not statistically significant, but you can see there is some signal there that was more intriguing.
So we decided to look at the data a little bit differently as this was a very heterogeneous group of patients, both in their first and second clinical
remission. So we re going to look at the next slide, which really breaks down the groups a little bit further. And so if we look again on the left hand side, those are the patients in their first clinical remission and then on the right hand
side are patients in their second clinical remission. So if you see the Kaplan Meyer survival curves here, patients in their first remission. You ll see that again there is no difference seen between patients who received the CVac versus
observation. However when we look at the patients who are in their second clinical remission, this is where we really see an amazing response. Patients in the CVac arm, the median progression free survival has not yet been reached, it s over 13
months. And the patients in the standard of care arm, their median progression free survival is about five months. And this is of course is statistically significant with the hazard ratio of .32.
We ve looked preliminarily at an interim analysis of overall survival and the data is not yet mature, which is pretty typical for overall survival for
this group, because there hasn t been enough deaths which is a good thing. Again looking at the two groups into their remission, so first remission group on the left hand side, second remission group on the right hand side. Again in the first
remission group, neither group has reached their median overall survival yet, so really can t say anything about that group. In the second remission group however we ve actually reached the median overall survival for the standard of care
observation arm and that s 26 months. In the CVac treated group, those patients have not yet met their median overall survival and this is also statistically significant and really shows that there s likely to be a signal in the overall
So really in summary again we have multiple goals for this trial, first was it feasible? So yes it was able to manufacture and distribute
multi-nationally the CVac drug, it was very safe as expected with most immunotherapeutics, well tolerated, minimal toxicities, really just mostly injection site reactions and of that nature. I didn t show the data, but this also has been
presented before that we were able to demonstrate that we showed that the patients who received the CVac vaccine were able to produce a mucin 1 specific T cell response; again I didn t show that data today. And then really importantly is that
we did see a significant progression free survival improvement in patients in their second clinical remission. This seems to be translating to an improvement in overall survival in second remission, however the data are not yet mature to
definitively say this.
So I think that these results are incredibly exciting; I was very pleased to be able to present them at ASCO and they ve been
very well received in the media and with others that I ve been speaking with. I m going to conclude my remarks and actually turn this over to Dr. Monk who is going to maybe expand a little bit on what his thoughts are where CVac might
sit in the ovarian cancer maintenance treatment arena.
So thank you very much and Dr. Gray let me just be one of many to congratulate you. The American Society of Clinical Oncology as you know is the largest
oncology meeting around the world, there were almost 30,000 attendees and this was one of the most highlighted presentations. So congratulations to you, your investigators, your patients who most importantly who appear to be receiving considerable
clinical benefits from this intervention and obviously to Prima BioMed for their commitment to ovarian cancer. My point to make here is that ovarian cancer is ideally suited to study immunotherapy. Probably heard a lot in the literature about
melanoma, renal cell cancer, maybe even lung cancer, but if there was ever a cancer where immune intervention would work, it s ovarian cancer. And why do I say that? So when we look at ovarian cancer under the microscope, we can see right
within the tumour, the immune cells, the lymphocytes, the white blood cells who are trying to attack this cancer. So the more that those white blood cells are within the tumour that we see under the microscope, the better the prognosis. The problem
is that those white blood cells do not recognise the tumour very well.
So the point of CVac is to take those white blood cells outside of the patient to
reprogram them if you will, to expose them to the mucin 1 antigen, the antigen which is present on almost all ovarian cancer cells to teach them if you will to recognise what they re there to fight, but yet not fighting very well. And so
that s what was so remarkable is that this was yes able to be done, but that the theory was really proven, proven that you could delay these cancers from coming back, which would ultimately be a third time. And to what level of magnitude? Well
really we don t know, because the patients that got the intervention of CVac are doing so well, we can give you a minimum boundary. The minimum boundary is 13 months compared to five months. But the difference in progression free survival is
probably even better and we have a statistical function that can compare that and that s called the hazard ratio. And the hazard ratio of that end point within the second remission group was .32. What does that mean?
That means that at any given time 68% of the patients are doing better. That the risk of recurrence is 68% less in those that receive CVac versus those that
received the observation. The observation, there s no question the standard of care is unacceptable, because as shown in this trial, the average time to recurrence is about five months. And once the cancer comes back the patients become
symptomatic and ultimately die. And as you ve seen, progression free survival is not enough; we need to help these patients live longer, which is the ultimate goal. And again that was confirmed in a very preliminary observation, but again
preliminary because the patients treated with CVac are not dying, which is remarkable. So at least 25 months of survival and I think again thank you to Prima BioMed for trying to do a more definitive trial, a definitive trial which we call CAN004B,
again B meaning it s the second remission cohort.
Now this time with over 200 patients. So if this can hold up I think ultimately this will be
practise changing and ultimately I think lead to a different way that we look at ovarian cancer. So it s exciting, congratulations Dr. Gray and time to move forward and get to the next phase two study, the more definitive trial done, thank
Thank you. At this time if you wish to register a question please press *1 on your phone and wait for your name to be announced. If you wish to cancel your
request please press *2.
Scott Hazelwood, Continual Capital Group:
First of all thank you very much and this is very compelling and intriguing data and I appreciate the presentation. Can you give us your thoughts on why
progression free survival looked better in the second remission versus the first?
Go ahead, we re both eager to jump on that, because that s really important, go ahead.
I did get this question quite a bit; again
we had to think about this in its context. I think there s really two things to focus on. One is that patients in their first clinical remission are a very heterogeneous group, 80% of patients will have achieved this after first line
chemotherapy surgery and their prognostic outcome can be varied. A lot of patients might recur in six months, maybe it ll be two and a half years. So this study was small in numbers, so to be able to detect a difference when you have a wide
heterogeneous group is going to probably be small. So what I m saying is there might still be or there may be patients in the CR1 group who would benefit, but you would need a much larger study. Secondly patients in the CR2, so if you re
able to achieve a second clinical remission, no detectable cancer after a first recurrence, that s actually a smaller group of patients. And statistically they have a better prognosis, much better outcome. They will tend to live longer
obviously than patients who aren t able to achieve that. And so maybe there is something about those patients that they are able to respond to say an immunotherapeutic signal, that places them at a better advantage for responding to some of
these maintenance strategies. So that s the best I can do to kind of think through why we saw that difference. Brad did you have any other thoughts?
Yeah so Scott remember what I said, I said
that the patients that have tumour infiltrating lymphocytes have the best prognosis ok. And then what Dr. Gray said is the patients who have a second are also the patients that have a good prognosis. So really what you re doing is
you re using the biology of the tumour to sterilise the trial, in other words to sanitise the trial, to enrich the population to those women who have an ovarian cancer with what I call an immunophenotype. These are individuals whose immune
system is working, but not working well enough. And that s I think where I see that works. So there s a group of patients where the immune system probably is not involved in helping these women live longer and better, but in the second
remission group, again the better prognosis group, the patients who have tumour infiltrating lymphocytes, patients whose immune system can recognise the tumour, but not fight it efficiently, those are the patients that you can boost if you will. And
in the CAN004B we re going to look at that and we re going to look at infiltrating lymphocytes and some of those translational signs and point really to prove that hypothesis. But this is no surprise to me that the second remission group
did better, again because those are the patients where immunology is really playing a role in their longevity.
Scott Hazelwood, Continual Capital Group:
Thank you, can I ask one follow up question and I ll drop off? Why have so few products demonstrated overall survival advantage in ovarian cancer?
So overall survival is difficult to show when
post progression survival is long. Let me say it in another way. So if we triple or double progression free survival, but the patient goes on to live two or three years, it s very, very difficult. So you have to have a magnitude of difference
in the PFS that is great, not just improving it by 50%, but improving it by two or three times ok. And you have to have a group of patients that are not going to live a long time, so that s another important reason why I am, as a drug
developer, in a clinical trial excited here, because in this group quite honestly where the survival is not nearly as long as front line, we actually had a chance to show an overall survival benefit. And that s why the end point of the follow
up trial is overall survival. Do you see what I m saying? So in the beginning, because patients live four or five years, you ll never show a survival benefit, but in this group of patients where they re living two to three years, your
chance of translating progression free survival and overall survival will be more likely. And if you look at let s say other trials in some of the anti angiogenesis medications, they ve mostly been studied in first and second line. So this
is a very rational clinical trial development program, not only to show clinical benefit, but have a direct strategy to registration. Because bringing this drug to market is really the only way that will help patients.
Michael Rosenberg, Hudson Capital: