"they are sitting on bad data and waiting for something better to come out"
Not so sure about your above statement Nome - when I asked BT recently if they got updates on the NCI Ovarian trial he basically said that Oncolytics and the PI himself (Dr. Cohn) are blinded until the data is published by thoses running the trial NCI/GOG in this case. I never asked him about the NCIC Colorectal trial but I assume it is the same for that trial - but not sure. Here is the exact exchange:
My Question to BT:
There was a question regarding what Open Label means vis a vis Oncolytics Biotech when a trial is being run by others. Specifically the Ovarian trial which is being run by Dr. Cohn GOG/NCI is randonized open label. Is Oncolytics privy to the ongoing data during the trial or must it wait until the GOC/NCI publishes the data?
Does Oncolytics get any periodic updates?
We (and the investigator) are unaware of the data. Neither of us get updates,
When they do the analysis, we will find out,
I think we'll have good results in more than one randomized trail in 2015 for various reasons previously mentioned on the board. But thinking and knowing for sure are two different things. I don't think anyone knows anything for sure. 2012???? - a lot of us have been waiting a lot longer than that.
Keep in mind as was previously posted BT has said they are waiting for 80% of the patients in the Ovarian Trial to progress before they get and publish the preliminary trial data - so we still wait now at 8.5 months since completion of enrollment. When asked if 80% progression would also be needed for the CRC trial before preliminary data reporting he responded only 50% progression would be needed for preliminary data reporting in the CRC trial. Enrollment for CRC completed Feb 18 2015 - 3 months ago. So we could very well see CRC preliminary results before Ovarian preliminary results. Both trials have PFS as primary endpoint and OS as secondary endpoint but time frames for each trial are different - for Ovarian it is up to 5 years and for colorectal it is up to 19 months. This is another reason why the colorectal trial can report earlier than the Ovarian trial.
Nome - you are correct in saying "MCR patients die of liver failure and we have seen what REO does to liver mets."
On the V2 board last November 8th I posted the below. People should be aware that there could be very good results from this trial:
Before you give up, go out and sell your Onc/Oncy shares - at least wait for the NCIC PH II randomized colorectal trial results - due within the next year. From the article and well worth keeping in mind (since reovirus clears to the liver and lungs and mets are likely ras activated and there is ample evidence in scans from PH I/II trials that liver mets are and have been shrunk and even eliminated in some patients):
"In the year 2014 colorectal cancers (CRCs) will be responsible for approximately 1.2 million new cancer diagnoses globally, and approximately half that number of deaths. In the United States CRC will be the third-most prevalent cancer diagnosed in both men and women. In the majority of these patients, distant metastaces to the liver and (less frequently) the lungs will be the proximate cause of death."
The article the above came from can be found by go'gling "Oncoselectivity in Oncolytic Viruses against Colorectal Cancer", downloading and reading the full article.
D2, Re HSV and GM-CSF - you could be wrong assuming Reo and GM-CSF will be only maginal like HV/GM-CSF. Remember Reo hitchikes on blood cells - not sure if HSV does the same as it is 2 to 4 times larger than the reovirus (70nm vrs 120 to 400 for HSV). GM-CSF creates more white blood cells (more blood cells for Reo to hitchike on maybe) and more immune system cells to identify and attack the type of cancer cells initially targeted and killed by reo. Also Reo/GM-CSF trial is a brain cancer trial because reo hitchiiking on blood crosses the blood brain barrier - not sure if HSV would do the same. Also the pre-clinical research on Reo/GM-CSF shows 100% survival for 60 days in what is I think a mouse model - see pg 20 of the Invsetors guide. So I think the NCI and the sponsor the Mayo Clinic are hoping for very good results. That would be amazing for Glioma sufferers. Depending on enrollment I think they will have an idea within a year or a year and a half if they are getting good results.
D2, I think we'll see a PH 1 checkpoint trial very soon.
Not a checkpoint inhibitor. Th below is a very simplistic explanation of both as I understand them - take it with a grain of salt.
GM-CSF Granulocyte macrophage colony-stimulating factor - stimulates the body to create more immune system cells that can identify, engulf and digest cellular debris, foreign substances, microbes, cancer cells etc.
From the new trial protocol - "Sargramostim (GM-CSF) may increase the production of blood cells and may promote the tumor cell killing effects of wild-type reovirus. Giving wild-type reovirus together with sargramostim may kill more tumor cells".
Checkpoint PD1 is a cell surface protein which when activated tampers down the immune system. Checkpoint inhibitors (anti-PD1 antibodies) prevent this tamping down and increase the immune system's ability to recognize and attack cancer cells. Checkpoints are activated in Reo infection and thus tone down the immune response. By using checkpoint inhibitors this toning down of the immune system is prevented enabling the immune system to better identify and attack the cancer cells.
They are using Reolysin - Oncy's product provided to them free of charge. Interesting to note about this trial is that the drugs are delivered intravenously - hence no surgery into the brain to deliver the medicines. Also this is the first Reo trial with direct NCI/Mayo Clinic collaboration although the Mayo Clinic has participated in other trials - namely melanoma, sarcoma and the Ph II Ovarian trial we are waiting for results. This is also the first trial with Reolysin in combination with a GM-CSF product (an immunostimulator).
Sargramostim - Sargramostim (marketed byGenzyme under the tradenameLeukine) is a recombinantgranulocyte macrophage colony-stimulating factor (GM-CSF) that functions as an immunostimulator.
Wild-Type Reovirus in Combination With Sargramostim in Treating Younger Patients With High-Grade Recurrent or Refractory Brain Tumors
A Mayo Clinic/National Cancer Institute collaborative trial
This phase I trial studies the side effects and the best dose of wild-type reovirus (viral therapy) when given with sargramostim in treating younger patients with high grade brain tumors that have come back (recurrent) or that have not responded to standard therapy (refractory). A virus, called wild-type reovirus, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells. Sargramostim may increase the production of blood cells and may promote the tumor cell killing effects of wild-type reovirus. Giving wild-type reovirus together with sargramostim may kill more tumor cells.
"This means no significant announcements before mid June."
Not true. The company is dependent on the NCI/GOG and NCIC to run the randomized trials. The data for the NCI Ovarian trial or the NCIC Colorectal trial can come at any time now. The company and PI do not now know when the data will be released by those running the trials and once the data is sent to them the company must release the data in a timely manner - good or bad. For all the company or PI know data on these two trials can be released tomorrow by NCI/GOG and/or NCIC. So your supposition that no significant announcements before mid June is incorrect. There may indeed be no significant news till mid June but no one can say that definitively.
As posted by moonthruclouds on the OncyV2 board:
Wayne Pisano a director of Oncolytics purchased 20,000 shares in the open market @.758 on May 12th.
From Oncolytics website:
Mr. Pisano has more than 30 years of experience as a pharmaceutical industry executive and was recognized in 2010 as Pharma Executive of the Year by the World Vaccine Congress. He is currently the president and CEO of VaxInnate a privately held biotech company. He joined Immunovaccine’s Board in October 2011 with a depth of experience across the spectrum of commercial operations, public immunization policies and pipeline development. Mr. Pisano is the former president and CEO of Sanofi Pasteur, one of the largest vaccine companies in the world. He is credited with driving Sanofi Pasteur’s leadership within the worldwide influenza market and capturing 50 percent of global sales. He also laid the foundation for the company’s global pediatric vaccines strategy. He joined Sanofi Pasteur in 1997, assuming increasing levels of responsibility. He was promoted to President and CEO in 2007, the position he successfully held until his retirement in 2011. During his tenure as CEO, Mr. Pisano bolstered the Sanofi Pasteur pipeline with the acquisitions of Acambis PLC, a bio-tech based in Boston in 2008 and Shantha Biotechnics, a highly regarded Indian vaccine company in 2010. Prior to joining Sanofi Pasteur, he spent 11 years with Novartis (formerly Sandoz). He has a bachelor’s degree in biology from St. John Fisher College, New York and an MBA from the University of Dayton, Ohio.
D2 - Don't know the answer to your question about neoadjuvant and OS but looked up a few neo-adjuvant trials on clinicaltrials.gov and where OS is specified it is usually associated with a time frame of a year or 2.
Nome - BT said in an email to me re the Ovarian trial "We (and the investigator) are unaware of the data. Neither of us get updates, When they do the analysis, we will find out." So the PI and Onc are in the same boat.
He did say in a previous email that when 80% progress they will get preliminary results. I am begnning to think we may get the colorectal results before Ovarian because in a followup email I asked Brad was it also 80% progression for CRC preliminary data and he said for CRC it is 50%.
Nice summary D2.
Nome - 8 months plus one week since completion of enrollment in Ovarian trial. Hope you are close in your PFS estimate for Ovarian. Brad did say at the Needham conference in April "I do not think anybody should expect us to be filing approval for a study even in Europe that doesn't incorporate overall survival as an endpoint". It would be nice if that first study is the randomized Ovarian with the OS modification as you suggest.
Here is the list of Orphan Drug designations for Reolysin:
Row Num Generic Name Designation Date Orphan Designation
1 Detailed Record for Productpelareorep 04-15-2015 Treatment of malignant glioma
2 Detailed Record for Productpelareorep 02-24-2015 Treatment of fallopian tube cancer
3 Detailed Record for Productpelareorep 02-24-2015 Treatment of primary peritoneal cancer
4 Detailed Record for Productpelareorep 05-04-2015 Treatment of gastric cancer
5 Detailed Record for Productpelareorep 02-10-2015 Treatment of ovarian cancer
6 Detailed Record for Productpelareorep 02-11-2015 Treatment of pancreatic cancer
"Jeez, you are talking about ULGX, which has been delisted by Nasdaq and relinquished to OTC trading. What a fitting example."
The point being made in that example was not about what eventually happened to that company but about the nasdaq granting the extension and how quickly it was granted - just a day after the original 6 month cure period ended.
Based on Urilogix's 180 day extension in 2011 it appears that we should know about Oncy's extension Tuesday or Wednesday provided the company has already written the letter - which they should have because they knew 8 or 9 days ago they wouldn't make the "10 days above $1" requirement by April 27th. I fully expect Oncy to get the extension.
Paraphrased from the article: On February 16 2011 Urologix received a letter from nasdaq that its request for a 180 day cure period had been granted until August 15,2011. Urologix was notified on August 19, 2010 that it did not meet the minimum bid price for continued listing and was provided until Feb 15, 2011 to achieve compliance.
Gogl "Urologix Announces Grant of 180-Day Extension to Regain Compliance With NASDAQ Minimum Bid Price Requirement" for the full article
Our data provide strong preclinical evidence to support the use of reovirus in combination with anti-CD20 immunotherapy for the treatment of CLL.
To see the wole research article
Gogl "leukemia oncolytic reovirus"
Another use for T3d/reovirus/reolysin/pelareorep. The Brits are doing so much new, free research on reovirus and it is all positive and encouraging for T3d. Every other week a new preclinical or clinical extract comes out. Below is an extract from a new release on reovirus research and chronic lymphocytic leukaemia (CLL) - the most common form of leukemia with a huge market.
The naturally occurring oncolytic virus (OV), reovirus, replicates in cancer cells causing direct cytotoxicity, and can activate innate and adaptive immune responses to facilitate tumour clearance. Reovirus is safe, well tolerated and currently in clinical testing for the treatment of multiple myeloma, in combination with dexamethasone/carfilzomib. Activation of natural killer (NK) cells has been observed after systemic delivery of reovirus to cancer patients; however, the ability of OV to potentiate NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) is unexplored. This study elucidates the potential of oncolytic reovirus for the treatment of chronic lymphocytic leukaemia (CLL), both as a direct cytotoxic agent and as an immunomodulator. We demonstrate that reovirus: (i) is directly cytotoxic against CLL, which requires replication-competent virus; (ii) phenotypically and functionally activates patient NK cells via a monocyte-derived interferon-α (IFNα)-dependent mechanism; and (iii) enhances ADCC-mediated killing of CLL in combination with anti-CD20 antibodies.