RE: "What did and did not happen"??? - probAs you'll see bilo consistently chose to ignore pre-clinical trial results. I personally think the pre-clinical trial results are important in validating the science, providing new IP, and they are the necessary groundwork preceeding human clinical trials. So I chose not to omit them.
Imo, they actually further serve to prove my point – they have done “all” this preliminary work, yet it has not translated to what I would call successful development of their clinical trial program. I’m not a viral oncologist, but I think I have enough of a basic understanding to realize that the purpose of pre-clinical work is to ensure that clinical trials are worth the while of going through all the work & expense of setting up in the first place AND ensuring they are properly planned & conducted so they produce statistically significant results on a timely basis.
Based on the limited enrolment, time taken and limited actual results to date of the following list of ALL their clinical trials, imo, Onc has failed to properly plan & conduct their trials. – perhaps that is due to poor or insufficient pre-clinical work and/or the actual clinical trial design and/or execution, but ultimately it reflects poor management, squandering of very limited financial & human resources which ultimately hurts shareholder value.
18 patient Phase I safety trial – Site Locations - Calgary
March 22, 2000 approval obtained,
June 2000 – enrolment initiated
Nov 29, 2001 – 18 patient enrolment completed
Dec. 13, 2001 - interim results released.
Mar. 21, 2002 – final “summary” results released
In the Dec 13, 2001 release, management stated “Oncolytics is now in a position to initiate multiple follow up trials of REOLYSIN® to better determine its efficacy and safety profile. The first of these studies, a T2 prostate cancer trial, is expected to initiate enrollment in January of 2002.”
Note BT at that time was looking out only at 1 month into the future, yet the prostate trial wasn’t initiated until April 16, 2002 – more than 3 months beyond the 1 month horizon he stated at the time. Did he already have an inkling of Pfizer’s impending withdrawal (to be announced in January, 2002) and thus decided to create a positive diversion for shareholders in anticipation?
Further the Dec interim results release stated “Detailed final results of this study
are expected to be presented next year at an international cancer conference, and
will include final safety, efficacy, and immune data on all the patients.”
Final “summary” results were released by onc on Mar 21, 2002 – however, they failed to disclose any detail.
These types of inconsistencies have been a pattern with onc management since the beginning.
6 patient Phase II T2 Prostate Trial Site Locations - Calgary
Oct. 11, 2001 – approval obtained
Apr. 16, 2002 – enrolment initiated
Mar. 31, 2003 – interim results on the first 6 patients released
Feb. 27, 2004 - final (same as interim) results on the same 6 patients released
the Oct 11 news release informing of trial approval included the following
description
“The trial is expected to enroll(sic) a total of 45 patients in three or more clinical
sites across Canada.”
We all know now there were a total of 6 patients treated in one site – namely
Calgary.
The Mar. 31, 2003 release said the folowing
Dr. Don Morris of the Alberta Cancer Board and the University of Calgary
presented results from an interim assessment of the first six completed patients of
a clinical study to evaluate the efficacy and safety of REOLYSIN® for the
treatment of T2 prostate cancer. The preliminary data showed clear
histopathological evidence of apoptotic tumour cell death, one measure of viral
activity, in four of the six patients. In a fifth patient, the PSA level dropped by
53% and the prostate gland shrank by 67% from just prior to treatment to the time
of surgical removal. There was no evidence of viral activity in the sixth patient. In
all six patients, there was no histopathological evidence of any viral effect on
healthy prostatic tissue.
The “final” results released 11 months later revealed no new material information not surprisingly since no additional patients were treated after release of interim
results 11 months earlier). Worse, no explanation was given as to why they
waited a year to release “final” results, unless you take BT’s infamous “there is nothing material happening at the company” remark at face value.
Was the delay in issuing final results due to enrolment problems due to protocol design (that several including myself questioned before the trial started) or was it perhaps money being tight and they didn’t think they had enough to carry out everything on their plate but wanted to make it look like they were doing so? (Oh yea, they were spending millions on manufacturing, when they only need 1 liter of pure virus to satisfy up to 1,000 trial patients) – proboscis, you suggest management was exercising good foresight regarding spending millions to set up a 2nd supplier. I suggest it is all too similar to SYNSORB (with BT & Doug Ball at the helm) wasting $20M of shareholder money on building a cGMP plant to manufacture drugs that were only in Ph II and eventually dropped due to enrolment problems.
if the prostate results were actually that good so they could “reduce” the planned enrolment and proceed quickly to the next (systemic) trial, 2 years isn’t exactly my expectation of “quick”. the share price obviously hasn’t reflected those “good” interim results either since they were originally released almost 2 years ago. But we should simply take BT at his Feb 27, 2004 word that the Ph II EFFICACY results were necessary for getting approval for a PH I (Safety) UK Systemic Trial, and not question the inconsistency as to why "final" completion of a very limited PH II trial is necessary before starting a PH I trial, like you apparently do?
40 patient Ph I/II Cdn Glio Trial Site Locations - Calgary
Jan. 24, 2002 – application filed with Health Canada (2 wks after Pfizer pulled out)
Apr. 11, 2002 – approval obtained
Jul. 3, 2002 – enrolment initiated
Dec. 23, 2002 – trial halted after 6 patients – independent data safety monitoring
board recommends changes be made to enhance the measurement of the safety
and efficacy of REOLYSIN® in the intended patient population in future studies. The physician investigators have also made observations during the care of the six patients that may lead to protocol changes. “
So a data safety monitoring board suggests changes to measurement of safety, yet onc emphasizes positive safety results – and choses not to clarify or explain the inconsistency between proclaiming positive safety results and HALTING THE TRIAL AFTER 6 PATIENTS TO IMPROVE MEASUREMENT OF SAFETY!!!!!
Of course when you have an apparent army of believers to promulgate the faith
on message boards, ready & willing to read between the lines and present their
interpretation & explanation for you, why worry about any inconsistencies in your
press releases?
May 7, 2003 – glio Ph I trial resumes – suggested changes to protocol made &
approved – but no explanation as to what they were & why they were necessary –
but its SAFE – JUST READ BETWEEN THE LINES & TRUST US!
Jan. 24, 2005 – no further official interim update. Nothing on whether they are still
doing Ph I enrolment or have moved on to Ph II, nothing on how the enhanced
safety & efficacy protocol changes have changed or effected results from the first
6 patients, nothing. At the rate of 6 patients in 6 months (from Jul to Dec 2002),
with UP TO 40 patients total, we can apparently expect the last enrollee sometime
in late in 2006. perhaps we can expect them to release interim results on the first 6
patients as final results a year from now, just like they did with the prostate trial??
Ph I/II US Glio Trial
Mar 8, 2002 – application filed with FDA
Proboscis, your comment that “it's widely understood that the FDA will be very
cautious with Oncolytic viruses and they'll be looking for a lot of reassurances before
proceeding.” Either conveniently ignores FDA approval of ph I & II oncolytic virus trials
by ONYX, or an acknowledgement that onc management isn’t up to the task.
Jan. 24, 2002 – management (consistent with its handling of most if not all the
other inconsistencies between promises and performance) has never issued an
official release offering any type of explanation for the reasons for the delay, or anything attempting an update on the current status. Is the delay perhaps due to
the safety issues identified in the Cdn trial? Apparently such legitimate
shareholder questions are not considered worthy of an official update issued by management.
.
40 patient UK Ph I Systemic Trial Site - Royal Marsden UK
Feb. 11, 2004 – commencement of project per UK National Research Register
Feb. 27, 2004 – Announcement of receipt of Approval
May 26, 2004 – enrolment initiated
No interim updates so far.
No clinical trial collaborations with NIH since Oct 2003 announcment.
As for your other points.
RE: Patents
For you to conclude that 13 patents represents a “very good job with multi-layered IP protection” is imo, presumptuous.
Given BT’s published comment about filing patents and that in the world of biotech, “days mean something” in protecting their IP, (in direct reference to the pace of discovery and the number of competitors), I hardly view that as a ringing management endorsement of the protection ONC’s untested patents provide, particularly given the length of time it is taking them to proceed with clinical trials.
The patents will mean little if it is going to take onc as long as it has to date to execute clinical trials to prove reolysin may actually have commercial value. Remember, patents have a LIMITED life and the longer clinical trials take the less value all those wonderful patents have. Perhaps the market is discounting their value based on the slowness & smallness of trials to date & the questions such slowness & smallness raise about management competence & ability?
RE Pfizer – your comment that “The decision was a reflection of Pfiser's overall corporate strategy, not the particular merits of REOLYSIN” ignores the optics and is also presumptuous imo. I don’t think you had access to Pfizer’s internal decision making process re: whether development of reovirus and/or onc’s patents held sufficient value or whether onc management (& shares) were ultimately worth entrusting that development to. onc share price since has so far at least born out pfizer's reasoning for their decision.
In many of your other comments, as I tried to point out previously, you focus too much on the science and attribute its apparent revolutionary cancer killing properties to onc management performance, rather than look at what tangible results management has actually produced to date in terms of advancing reolysin in clinical trials.
IMO, the advancement of reolysin in clinical trials is the single most important matter for cancer sufferers & onc shareholders alike and should be the most important to onc management though that doesn’t appear to be the case to me. Promising trial results provide the underlying commercial value to onc’s patents and ultimately to onc shareholders. Management should be selecting the most effective (which would also happen to be the quickest) route to partnership & ultimate commercialization of reolysin, namely glio, pancreatic & other cancers featuring a high proportion of RAS activation. Yet after 5+ years, I still don’t see the necessary sharpened focus nor the commitment/competence from management despite all their unkept promises & misleading expectations they helped to create. The continue to manage onc as their own private company with little to no transparency or accountability to shareholders (at least to ones who choose to think for themselves).
The Ph I/II Cdn glio trial is about to enter its 3rd year, yet no official update has been given in almost 2 years on its status, while the PH I/II US glio trial application continues to apparently sit with the FDA approaching completion of its 3rd year, without any explanation from management on what is (or isn’t) going on.
Despite the NIH collobaration being announced in 2003, onc has yet to commence a clincial trial in the United States to date - i'm sure if anyone had posted that "bash" in 2000, they would have been run off of stockhouse, yet here we sit in 2005, and there is no update from management on when shareholders can expect a US clinical trial. (meanwhile management compensation comparison to nasdaq companies rather than on actual management performance is used to justify excessive compensation, and supported by management apologists)
That simply is not acceptable to me and shouldn’t be acceptable to any shareholder imo, yet countless posts are made not only defending management, but commending and otherwise praising them on the terrific job they are doing. It is apparent to me from the share price that the market is not overly impressed with the very slow (despite the small enrolments) & limited results to date either.
the problem with onc management hasn't been so much as what did happen (though there are enough examples of that - tth acquistion & subsequent sale, ph I glio trial protocol design & subsequent delay despite all that pre-clinical work, etc.) the problem with onc management has largely been of what hasn't happened in over 5 years of waiting. and their failure to communicate coherently, clearly & consistently with shareholders compounds their performance failures to the point where they need to be held to account by shareholders.