Full Press Release Details
INVESTOR UPDATE by PRIMA BIOMED EDITION 12 JULY 2014
Message from the CEO
Welcome to the second issue of the Prima BioMed Investor update for 2014. It gives me great pleasure to be addressing Prima BioMed shareholders for the first time as Chief
First of all and before going into the operational details I would like to thank all our Shareholders for their considerable loyalty and support
and reassure you that the whole Prima team is fully committed to bringing CVacTM to market.
It is therefore most encouraging that the past three months have
delivered a series of very positive announcements related to our clinical development program and regulatory milestones in the US for CVac. These achievements are the culmination of a lot of hard work by the Prima team. I would especially like to
acknowledge the significant contribution of Matthew Lehman as CEO in building the Company to where it is today. Matt will continue to consult with the Prima team on the clinical development program.
I am grateful to the Board for putting their faith in me to lead Prima into the future. I am firmly committed to successfully executing Prima s clinical trial program for
CVac, while also assessing other market opportunities that may arise.
Most recently we announced that the United States Patent and Trademark Office (USPTO) has granted Prima a patent for CVac, along with a patent term adjustment of almost four years.
This takes patent expiry in the US out until August 2022, providing Prima with essential protection over its commercial development. This was the final patent in the Prima portfolio to be granted.
This news followed the United States Food and Drug Administration (FDA) grant of Fast Track status for CVac s clinical development program in May. There is a clear unmet
medical need in ovarian cancer and the potential application of CVac as a maintenance therapy for this disease.
Fast Track status means we will have higher levels
of engagement with the FDA through the clinical development program and faster review timelines, which could significantly shorten the approval time after completion of our clinical trials.
I would also like to take this opportunity to acknowledge and address shareholder concerns about a fall in the Company s share price after a perceived clinical trial failure
of CVac late last year. Our recent presentations of data at the American Society of Clinical Oncology (ASCO) conference in May revealed very promising CVac data which we explain in some detail in this newsletter. We are very excited about this data
and hope that this will go some way towards helping our investors understand why, more than ever, we believe CVac is a very promising therapy.
Our focus remains on
getting CVac through the clinical trial program successfully to meet the clear unmet medical need. To that end, our new CAN-004B clinical trial of second remission ovarian cancer patients will greatly assist in bringing CVac to market as quickly as
possible. As outlined in more detail in Professor Frazer s Q&A section, we have decided to focus on second remission patients because this group demonstrated an earlier clinical benefit during the CAN-003 trial. As the disease progresses,
the remission window shortens and we are able to achieve statistically meaningful data, more readily than with first remission patients.
In late April we announced
that enrolment for the CAN-004B clinical trial for second remission patients had commenced. By way of a progress update, we have increased the number of clinical sites across Europe and these are in the process of being initiated to allow enrolment
of patients into the trial. This is a rigorous and time consuming process which requires all clinicians to be properly vetted and trained.
The increasing political
instability in the Ukraine has caused some disruption to Prima s clinical trial enrolment as we are no longer able to ship CVac to our site in Donetsk. Prima will continue to monitor the situation closely to assess whether withdrawals from its
other Ukrainian clinical trial sites is necessary. We will provide a further update once the impact of any further site closures has been fully assessed.
As mentioned briefly earlier, the most important event that took place during the quarter was the presentation at ASCO by Dr. Heidi Gray, the Lead
Investigator on Prima s CAN-003 clinical trial, at the end of May.
Message from the CEO Marc Voigt
Understanding the CAN-003 data presented at ASCO
Q&A with Professor Ian Frazer
The addressable market for CVac
A patient s journey with CVac
[continued from p.1]
Message from the CEO
Dr. Gray presented extremely positive final progression free survival
(PFS) data and a very strong indication in overall survival (OS) interim data for CVac treatment in second remission ovarian cancer patients.
encouraging and fully supports the launch of Prima s new CAN-004B clinical trial, which has a very robust clinical trial design. Should the CAN-004B results demonstrate trends similar to CAN-003 in a larger population, it would be a major step
towards securing approval for CVac in this target patient population.
Clearly, this process will still take some time given the nature of these trials, but the
Directors of Prima, along with its clinical and scientific advisory board members, share my optimism that the Company has a clearly defined development plan for CVac supported by strong data and which has every chance of success. Along with the rest
of the Prima team, my priority is to bring this treatment to market at the earliest opportunity for the benefit of advanced stage ovarian cancer patients around the world.
As reported in our Appendix 4C for the quarter and financial year ended 30
June 2014, Prima has $23.20 million in cash and term deposits. Prima benefits from up to 7.9 million funding grant from the Saxony Development Bank in Germany to carry out its CVac program in Europe.
This is one of the fundamental reasons for the Company focusing its operations in Europe, where we are also able to achieve greater efficiencies both in our clinical trials and in
the manufacturing of CVac. During the year we also benefited from a R&D tax refund from the Australian Federal Government of $1.6 million.
management of the company s cash outflows remains a high priority for Prima.
In addition to successfully delivering the development program for CVac, part of my role is to assess future growth opportunities for Prima. The licensing agreement we reached with
the Neopharm Group earlier this year is a small example of the kind of commercial opportunities that are available to Prima and is symbolic of the kind of interest we receive from other industry players. As a Board and management team we will assess
any opportunities that arise and only enter into agreements which we consider to be value accretive for shareholders.
Finally, an important part of my role will be
to market the Company to a broad spectrum of industry participants as well as other key stakeholders including investors. This is an area to which I will be dedicating considerable time and effort and I look forward to updating Prima s many
shareholders, both in Australia and internationally, on its future achievements.
Marc Voigt | Chief Executive Officer
Understanding the CAN-003 data presented at ASCO
On 31 May 2014, Dr. Heidi Gray presented the
final progression free survival (PFS) and interim overall survival (OS) results for the CAN-003 trial of patients in first and second remission ovarian cancer.
ASCO is one of the largest annual oncology conferences attended by industry professionals in the world. This year there were 34,750 registered attendees. Out of
5,530 abstracts submitted for ASCO this year from numerous applicants around the world, only 210 were selected for oral presentation at the ASCO Annual Conference. Hence, it was a real privilege to have the data from our CVac CAN-003 trial presented
at this highly prestigious oncology industry event.
The purpose of this section of the newsletter is to assist our readers in understanding the significance of
Dr. Gray s presentation showed that there were multiple accomplishments of the CAN-003 trial.
One goal was to evaluate the ability to manufacture CVac outside Australia. This was successfully completed with the transfer of manufacturing to the USA. The trial also confirmed
that CVac is very safe and well tolerated with minimal side effects. The results showed that the drug appears to be working as expected: patients who received the CVac treatment were able to produce an immune response that was cellular (driven by T
cells) and very targeted or specific to the cancer type (mucin 1).
Most importantly, Dr. Gray s presentation revealed that the CAN-003 data was generating a
very positive PFS and OS signal in second remission patients.
PFS is a measure of the length of time during or after the treatment of a cancer, that patients
continue to live without disease progression (i.e, are in remission). It is used to measure the efficacy of a new treatment compared with patients receiving standard of care or a placebo control. OS on the other hand, is a measure of the percentage
of patients in a treatment group who are still alive for a certain period of
time after diagnosis or commencement
of treatment. It is important to look at OS in a treatment arm relative to that of the standard of care.
When examining the clinical impact in the PFS period,
while there was not a significant difference between the treated and standard of care patients in the first remission group, those patients in second remission showed a clinical benefit of greater than 8 months. Similarly, when looking at the
patients OS, although this is still an early analysis, the data shows a similar trend to that of PFS. Possible reasons for the differences observed between the first and second remission groups are discussed in the Q&A section with
Professor Fazer but it is important to understand that it doesn t mean CVac will not benefit first remission patients.
One of the primary conclusions from
CAN-003 was that a larger clinical trial focused on second remission patients was justified, leading to a trial redesign and enrolment into the enlarged CAN-004B clinical trial commencing in April 2014.
A more detailed look at the CAN-003 data
The final PFS and OS data from CAN-003 was presented
at ASCO in the form of Kaplan-Meier curves. A Kaplan Meier (KM) curve is a widely used graphical presentation that compares the proportion of patients that are either disease free (for PFS) or surviving (for OS) for each treatment arm. For CAN-003,
the treatment arms were either receiving CVac (blue line) or standard of care (in this case observation; yellow line). The steepness of the curves demonstrates the efficacy of the treatment being investigated. The shallower the survival curves, the
more effective the treatment because patients either are in remission longer or surviving longer. If the KM curves have similar patterns, it suggests that there is only a small amount of difference between the arms of the study. No differences
between the two different arms of the studies are measured if the curves meet.
Looking at PFS data in Figure 1, for patients in the first remission group, there is
little difference in PFS seen between patients who received CVac versus observation (the blue and yellow curves are close together). Possible reasons for this are discussed in the Q&A section with Professor Ian Frazer. However, encouragingly in
the second remission graph there is a separation of the blue and yellow curves, indicating a significant difference between the control and treatment groups.
Looking more closely at the second remission graph, patients in the CVac arm have a median PFS that has not yet been reached after more than 13 months (because the
trial finished and no more data can be collected) while median PFS for the observation group is about 5 months. From the difference in PFS between the two arms it can be concluded that the CVac treatment resulted in at least 8 months of benefit for
patients in the second remission group.
Statistical analysis of the data calculated a hazard ratio of 0.32 for the PFS of second remission patients. A hazard ratio
(HR) is a way of calculating the relative risk of experienc-
Figure 1 Final PFS analysis for first and second remission patients
First Remission HR1.18
Hazard ratio 1.18 (95% CI:0.51, 2.71)
P=0.69 by log-rank test (2-sided)
OSC: median PFS 18.20 months