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Nasdaq News Reports - Lung Cancer Data Release
http://nasdaqnewsreports.blogspot.ca/2013/02/oncolytics-biotech-rises-on-further.html
Thanks for posting this.
SATURDAY, 9 FEBRUARY 2013
Oncolytics Biotech Rises on Further Cancer Treatment Data
Feb. 9, 2013 - Oncolytics Biotech Inc. (ONC.TO, ONCY) rose over 20% to the $4.30's on Friday after news of their mid-stage trial of their experimental lung cancer drug showed that 95 percent of the patients experienced a reduction in the size of their tumors. Of the 20 patients, 19 of them experienced shrinkage of their tumors by a third on average. Additional data for the study can be found here.
The positive lung cancer treatment data builds upon the first endpoint Phase III Study data results for REOLYSIN® in the treatment for head and neck cancers announced in December, when we first alerted our readers of ONCY stock in the low $3's. The revenue potential from ONCY's drug is $900M per year and could reach as high as $3 billion if REOLYSIN® achieves success as a multi-purpose cancer drug and the news from the past three months indicates a strong likelihood of that happening, particularly at a time when the FDA has been generous with drug approvals. Byron Capital maintains a $9 target price on ONCY.
From the Reuters article:
"The drug, Reolysin, was used intravenously in combination with chemotherapy drugs carboplatin and paclitaxel. It was tested on patients suffering from metastatic or recurrent squamous cell carcinoma of the lung.
Squamous cell carcinomas account for about a fourth of all lung cancers, the company said in a statement.
"Based on these findings we intend to continue to look at Reolysin as a treatment for cancers of the lung and cancers that metastasize to the lung," Chief Executive Brad Thompson said.
The results further suggest that Reolysin may have potential use in pre-surgical settings, the company said."
In January the company announced Positive REOLSYIN® Clinical Trial Data for metastatic colorectal cancer. Many more clinical trials are ongoing for REOLSYIN across the US, Canada and the UK, allowing for plenty of opportunity for more positive data to be released.
A BioWorld article shows the potential for Oncolytics, as outlined by a quote from Douglas Miehm, an analyst for RBC Dominion Securities in his research report "support(s) a higher probability of success for final primary data points." With a quote such as this on record, expect analyst upgrades to the already very bullish targets for the stock.
Further quotes from the BioWorld article with respect to ONCY's results on the head and neck cancer study:
"The endpoint checked tumor changes between the pre-treatment and first post-treatment scans, typically at six weeks, and stabilization was described – more stringently than in other accepted criteria – as zero percent growth.
"It's not good enough to have some growth," Thompson said. "The surgeons involved want shrinkage, period."
Of the 105 total patients with evaluable metastatic tumors, 86 percent (n = 50) of those in the test arm of the study exhibited tumor stabilization or shrinkage, compared with 67 percent of patients (n = 55) in the control arm.
"To be candid, I think all of us here were modestly surprised that we saw the degree of differentiation, the amount of shrinkage that we did at six weeks," Thompson said. "Reolysin is a pretty gentle agent when it comes to tumor shrinkage."
One must ask upon all the positive data, how is ONCY at a mere $333M market cap? One answer is the foolish act of shorting on ONCY as the short interest has grown from 3M shares last year to 6.9M shares as of January 15th. As those shorts continue to lose on their position as the stock rises, one can only assume the high volume on Friday resulted in even greater shorting as they desperately try to keep the price down. The stock tanked from the $4.60's to the $4.30's on very light volume in the last hour of Friday afternoon trading, a clear sign of manipulation that didn't work very well the last time. On December 13 - the day ONCY released the data on the head and neck cancer trial - ONCY pulled back from a $3.85 high to a $3.03 close in a similar fashion near the end of the day. 11 of the next 12 trading sessions resulted in gains for the stock as it flew over $4. With only 76.7M shares outstanding, shorters of the stock are in great danger of experiencing a short squeeze, particularly after the recent run of positive data.
One driver for such a high short interest on the stock is the presumption that Oncolytics will run out of cash in 2013 and will need to do a dilutive equity financing. This Seeking Alpha article which very aptly describes the science behind ONCY's drug ends with commentary about the company's burn rate. ONCY had $22M in cash net of liabilities as of September 30, 2012. The burn rate for Q3 2012 was $9.3M so on the surface, the idea of the company running out of cash soon would appear correct. But one must dive into the detail of their expenses to understand the burn rate going forward. Of that $9.3M, $8.1M was for research and development activities. Reviewing the company's MD&A for the quarter reveals that $5.6M of that expense was for direct patient costs, an expense that occurs at the enrollment of the clinical trials undertaken for the quarter. As the enrollment period ended, we can reasonably expect for those costs to come down.
While the looming cash crunch appears overstated, at some point in time the company will need more funding. However one must understand the context. 5 million shares financed between $4-$5 brings in another $20-$25M for the company. That amount of dilution is only 6.5% for another year or more worth of cash. That's less than the short interest on the stock. Note that Oncolytics had no problems with financing exactly one year ago on February 8, 2012. That financing was for just over 5M shares for $21M in cash, and it had no negative impact on the stock price when reviewing the stock's price history on the days immediately following its announcement. Given how much ONCY has advanced its drug in the past year, it also has the option to finance by debt, acquire a partner or it could be a target of a hostile takeover.
The idea of shorting or being bearish on Oncolytics purely based on their need for financing is a poor investment decision. Being short or bearish on Oncolytics based on the data coming from the various REOLYSIN® cancer trials is absolutely ludicrous and not being long on ONCY is a clear missed opportunity. The extensive variety of treatments that REOLYSIN® is capable of within the cancer community with no side effects of note after all of these various trials will lead to the drug being approved by the FDA.
SD - Stable Disease
PD - Progressive Disease
MCR ? I think you mean MTR - Minor Tumor Response
The axis on the graph defines Event-Free Probability
oncoinvestor
Colorectal Cancer Patients, New Hope from a Cancer-Destroying Virus
http://www.newswise.com/articles/for-colorectal-cancer-patients-new-hope-from-a-cancer-destroying-virus
For Colorectal Cancer Patients, New Hope from a Cancer-Destroying Virus
Released: 1/28/2013 10:45 AM EST
Source Newsroom: Oncolytics Biotech
Newswise — What did Pope John Paul II, Ronald Reagan and Robin Gibb of the Bee Gees have in common? Each was diagnosed with colorectal cancer, the third most commonly diagnosed cancer in the world and the fourth most common cause of cancer death.
Now Calgary-based Oncolytics Biotech Inc. has reported interesting new findings at the American Society of Clinical Oncology’s 2013 Gastrointestinal Cancers Symposium (ASCO GI), held January 24-26 in San Francisco. The meeting attracted a diverse group of individuals involved in the prevention, detection and treatment of gastrointestinal cancers.
Oncolytics presented a poster reporting results from a phase 1 study in patients with colorectal cancer. In the study, REOLYSIN, a biologic agent developed by Oncolytics, was administered (along with a standard chemotherapy regimen called FOLFIRI, composed of folinic acid, fluorouracil and irinotecan) to 18 patients with colorectal cancer. The primary objectives were dose-limiting toxicity to determine maximum tolerated dose and pharmacokinetics; secondary endpoints were antitumor activity, response rate, progression-free and overall survival. The combination of REOLYSIN and FOLFIRI was found to be safe, well-tolerated and resulted in disease control in the majority of the patients. The researchers were encouraged by this activity and safety trial, and are planning advanced-phase studies.
The lead author of the study was Allyson Ocean, M.D., a medical oncologist and attending physician in gastrointestinal oncology, Solid Tumor Division, at New York Presbyterian Hospital/Weill Cornell Medical Center; assistant professor of medicine at the Weill Medical College of Cornell University; and medical oncologist at The Jay Monahan Center for Gastrointestinal Health.
The results will come as encouraging news to those who have been diagnosed with colorectal cancer, who face some stark statistics: According to the U.S. National Cancer Institute (a division of NIH), more than 140,000 Americans were diagnosed with this cancer in 2012, while nearly 52,000 died of it the same year. Globally, more than one million people get colorectal cancer annually, resulting in the deaths of about half a million.
Triggered by uncontrolled cell growth in the colon or rectum, colorectal cancer is often curable when confined to these areas, but the prognosis is much bleaker when it has spread, with management focusing on surgery, chemotherapy and radiation, with all of the attendant risks of these procedures. For example, while chemotherapy can shrink tumors, they often grow back and become resistant, or refractory to the treatment.
Oncolytics’ approach to treatment comes from an area called oncolytic virotherapeutics. Here, viruses are harnessed to infect, multiply within and subsequently lyse cancer cells; the virus targets tumors without affecting normal tissue. Oncolytics developed REOLYSIN from naturally occurring reovirus. The virus has demonstrated impressive results in clinical trials on its own, but particularly in combination with certain chemotherapeutics. In preclinical studies in a wide variety of cancer cell lines, investigators found that when used together, reovirus and chemotherapy resulted in more efficient and synergistic anti-cancer activity than when each agent was used on its own.
Many consider reovirus, from which REOLYSIN is derived, to be the most promising form of oncolytic virus. This virus preferentially replicates in cancer cells that feature a common mutation known as an “activated Ras pathway,” while sparing normal cells. This makes it intrinsically tumor selective without the need for any genetic manipulation.
Reovirus is a virus with no known associated disease. It replicates in the cytoplasm and therefore does not integrate into the cell’s DNA. Reovirus is found everywhere in nature and has been isolated from untreated sewage, river and stagnant waters. Exposure to reovirus is common in humans, with half of all children by the age of 12 having been exposed and up to 100 percent testing positive by adulthood.
Tumors bearing an activated Ras pathway cannot activate the antiviral response mediated by the host cellular protein, PKR. Studies have shown that reovirus actively replicates in transformed cell lines with an active Ras signaling pathway, eventually killing the host cell and freeing the viral progeny that go on to infect and kill more Ras-activated tumor cells. When normal cells are infected with reovirus, the immune system can neutralize the virus. Approximately one-third of human cancers have activating mutations in the Ras gene itself, and it is possible that more than two-thirds of cancer cells have an activated Ras signaling pathway because of activating mutations in genes upstream or downstream of Ras.
Future studies will provide an even clearer perspective on whether REOLYSIN offers an effective route toward a reliable and commercially viable complement to chemotherapy for oncologists and their colorectal cancer patients. There may be new hope on the horizon for these patients—a hope coming from within the human body itself.
3rd Intl Thoracic Oncology Congress Reolysin NSCLC
Sept 15, 2012 Dresden Germany
Presentation on Reolysin in NSCLC : Mode of action and clinical results
Glenwood Goss, MD,FCP(SA),FRCPC Professor and Director, Clinical and Translational Research The Ottawa Hospital Cancer Centre
University of Ottawa
3rd International Thoracic Oncology Congress Dresden Germany
Advances through Molecular Biology in Thoracic Cancer
http://www.itocd.com/fileadmin/presentations2012/120915_1030_Goss.pdf
Updated Investor Presentation Jan 7, 2013
http://oncolytics.s3.amazonaws.com/presentations/25/original.pdf?1353946216
Phase III pfs endpoint up next on H&N cancer
7 ongoing randomized clinical studies - most paid by NCI/NCIC
620 Patients treated to date 530 systemically
45 key US patents (325 worldwide) covering use of viruses to treat cancers
100 Liter manufacturing capacity scale - commercial manufacturing agreement in place with Sigma Aldridge
Landes Bioscience: Reovirus modulates autophagy during oncolysis of multiple myeloma
http://www.landesbioscience.com/journals/autophagy/article/22867/?show_full_text=true&
Autophagic Punctum
Reovirus modulates autophagy during oncolysis of multiple myeloma
Volume 9, Issue 3 March 2013
Keywords: apoptosis, autophagy, multiple myeloma, reovirus
Authors: Chandini M. Thirukkumaran, Zhong Qiao Shi, Joanne Luider, Karen Kopciuk, He Gao, Nizar Bahlis, Paola Neri, Mark Pho, Doug Stewart, Adnan Mansoor and Don G. Morris
Abstract:
Multiple myeloma (MM) is a clonal plasma cell malignancy that accounts for 10–15% of newly diagnosed hematological cancers. Although significant advances have been made in the treatment of MM the disease still remains incurable. The oncolytic potential of reovirus has previously been demonstrated by others and us and is currently in phase III clinical trials for solid tumors. In addition a phase I clinical trial has recently been initiated for MM. Despite the clinical activity, the mechanism(s) of cell death caused by reovirus in MM is yet not yet well elucidated. A comprehensive understanding of reovirus-mediated histology-specific cell death mechanisms is imperative if this therapeutic is to become a standard of care for patients. Previously we have shown that reovirus-mediated cell death of breast and prostate cancer is orchestrated via apoptosis. The present study demonstrates for the first time that in addition to inducing apoptosis reovirus also upregulates autophagy during oncolysis of MM.
Autophagic Punctum to:
CM Thirukkumaran, ZQ Shi, J Luider, K Kopciuk, H Gao, N Bahlis, et al. Reovirus as a viable therapeutic option for the treatment of multiple myeloma. Clin Cancer Res 2012; 18: 4962-72
PMID: 22761466 DOI: 10.1158/1078-0432.CCR-11-3085
Multiple myeloma is a clonal neoplasm of plasma cells that accounts for approximately 10% of all hematological malignancies. Despite the advent of novel therapeutics such as thalidomide, revlimid and bortezomib as well as improvements made in the understanding of MM biology, the disease remains incurable. Therefore the need for novel, more effective and better tolerated therapeutics for MM is required.
Oncolytic viruses are a group of therapeutics that demonstrates an extensive range of anticancer activity in both solid and hematological malignancies. Of these, reovirus, a ubiquitous, nonenveloped, double-stranded RNA virus has proven minimal pathogenicity in humans while exhibiting extensive oncolytic potential against a myriad of cancers such as breast, prostate, brain tumors, renal carcinoma and hematological malignancies in vitro, in vivo, ex vivo and in clinical trials as has been demonstrated by us and others. Currently, reovirus is undergoing phase III clinical trial testing for head and neck tumors and phase I clinical trials have been initiated for multiple myeloma. The viral sensitivity of a wide array of tumor histologies is likely mediated via multiple permissive oncogenic signaling pathways that allow reovirus to target malignancies while sparing normal cells.
Autophagy is a catabolic process involved in homeostatic turnover of proteins and intracellular organelles that is not well understood in cancer tumorigenesis, promotion and response to anticancer therapeutics. Autophagy may in fact act as a tumor suppressor in the setting of early tumorigenesis, and as a cancer potentiator in established cancers including mediation of therapeutic resistance. Thus, many investigators have suggested strategies that combine both autophagic inhibition with cytotoxic chemotherapy or targeted therapies for potential synergy. In contrast, several lines of evidence suggest that ER stress leads to autophagy, and recent studies have highlighted a prominent role between autophagic cell death induced by AKT-MTOR signaling triggered by ER stress. A recent study has demonstrated that reovirus infection of MM leads to ER stress-induced apoptosis. Therefore it is plausible to hypothesize that viral replication within MM, in addition to induction of apoptosis also promotes autophagic cell death initiated via a signaling mechanism of the ER stress pathway.
Recently we have shown the oncolytic potential of reovirus against several MM cell lines, ex vivo patient tumor, and demonstrated that reovirus could be used as a viable therapeutic for MM using a SCID/NOD murine model system. If reovirus therapy is to be optimized for patients it is imperative to understand sensitivity/resistant mechanisms of tumors. Previously we have shown that reovirus triggers apoptotic pathways in oncolyzing breast and prostate carcinomas. In the present study we demonstrate that in addition to inducing apoptosis, reovirus upregulates autophagy during oncolysis of MM, a novel finding that may link to synergy with other autophagy-directed strategies.
To examine the mechanisms of reovirus-induced cell death in MM, RPMI8226, NCI-H929 and U266 cells were treated with either no virus (NV), live virus (LV) or UV inactivated (dead) virus (DV) for 24, 48 or 72 h. Viable cell counts, DNA fragmentation and phosphatidylserine expression (annexin V binding), and active CASP3 were assessed via flow cytometry. Live reovirus treatment significantly enhances all apoptotic markers and dramatically reduces viable cell counts in MM cells in comparison to dead virus treatment. Caspase inhibition with Z-VAD-FMK-001 significantly reduces cell death in live reovirus treatments, but not in dead virus-treated MM cells, confirming reovirus-mediated apoptosis.
While apoptosis induction was prominent in reovirus-infected human myeloma cells, complete reovirus oncolysis could not be attributable to this process. We therefore hypothesized that autophagy may also be involved. RPMI 8226 cells were treated with NV, LV or DV for 0, 24 and 48 h. Cyto-ID Green Detection Reagent was utilized to identify vesicles colocalizing with LC3-II, a marker of autophagosomes and analyzed via flow cytometry. We observed that autophagy activity is similar in DV- and LV-treated RPMI 8226 cells at 0 h after virus infection. Autophagy induction is evident at 24 h in LV-treated cells demonstrating a 19% relative increase of median channel fluorescence (MCF) in comparison to NV treatment. This effect is more pronounced at 48 h leading to a 41% relative increase in median channel fluorescence. In contrast, the DV treatments showed only -4.0% and 5.3% relative changes in MCF in comparison to the uninfected controls. Autophagy was confirmed by treating RPMI 8226 cells with the autophagy inhibitor 3-methyladenine (3-MA), which downregulates this increase in autophagy caused by LV, resulting in a four-fold reduction by 48 h, suggesting that autophagy may contribute to cell death.
The novel finding that reovirus infection of MM leads to significant induction of autophagy prompts many critical questions that remain to be explored such as: (1) Is inhibition of autophagic pathways synergistic with reovirus for oncolysis? (2) What is the effect of MTOR inhibition in combination with reovirus on autophagic pathways? (3) Is this phenomenon unique to MM or similar with many different cancer histologies? (4) Are there activated cellular pathways such as RAS that are pivotal to this phenomenon? Interestingly, autophagy inhibitory drugs such as hydroxychoroquine are presently being tested in combination with cytotoxic chemotherapies and targeted agents. The rationale for these trials is that a majority of chemotherapeutics in vitro shows an increase in autophagy post-treatment, suggesting it acts as a prosurvival mechanism. Since autophagy is a dynamic process that could be histology specific and treatment specific it is intriguing to postulate that autophagy-inducing drugs such as verapamil or clonidine in conjunction with reovirus may in fact act synergistically in MM allowing better treatment options for patients. These avenues of research are worth exploration in the future.
Viral Treatments Halt Growth in Metastatic Tumors
News from Cancer Discovery Jan. 2013
Thanks kinaseman from V2:
January 3rd issue of Cancer Discovery - The journal of the AACR
Viral Treatments Halt Growth in Metastatic Tumors
Abstract
Preliminary results from a phase III clinical trial showed that a combination of the anticancer viral treatment Reolysin and chemotherapy was more effective at halting metastatic tumor growth than chemotherapy was alone.
A combination of anticancer viral treatment and chemotherapy was more effective at halting metastatic tumor growth than chemotherapy was alone, according to preliminary results from a phase III clinical trial in patients with head and neck cancers, announced by Oncolytics Biotech of Calgary, Alberta, Canada, in
December.
"To the best of our knowledge, this is the first successful double-blinded randomized data from a clinical study using an intravenously administered oncolytic virus," said Brad Thompson, PhD, chief executive officer of Oncolytics.
Known as Reolysin, the Oncolytics treatment is a reovirus similar to that which causes the common cold. Engineered reoviruses, such as the Oncolytics therapeutic, exploit the antiviral immunity defects that tend to accumulate in cancer cells. Moreover, Reolysin can only survive and replicate in cancer cells with an activated RAS pathway, said Matt Coffey, PhD, Oncolytics chief operating officer, who led early studies of reoviruses as potential anticancer agents.
Eventually, cancer cells become packed with so many viral particles that they burst and die, Coffey explained. But because normal cells lack activated RAS, they avoid a similar fate after viral treatment.
In the ongoing study, 167 patients with advanced head and neck cancers are receiving either carboplatin and paclitaxel followed by Reolysin, or the chemotherapy agents only. Reolysin doses amounting to an estimated 1 trillion viral particles were administered intravenously once a day for 5 consecutive
days.
The current results apply only to a subset of 105 patients with metastatic tumors in the liver, lungs, or lymph nodes. Six weeks after treatment, 86% of those patients treated with Reolysin had achieved metastatic tumor stabilization or shrinkage, compared with 67% of control patients who did not receive viral therapy. Side effects were limited to minor flu symptoms.
Results for the entire cohort, including patients who do not have metastatic disease, will be presented at a later date, Coffey said.
Oncolytics conducted the subset analysis after a preliminary assessment revealed that patients with metastatic illness had achieved more substantial improvements in progression-free survival (PFS) after Reolysin treatment than did patients whose primary tumors had not metastasized. Given those findings, a review panel at the U.S. Food and Drug Administration (FDA) recommended that Oncolytics evaluate Reolysin's effects specifically on metastasized tumors.
The difference in PFS between patients with or without metastatic illness makes sense, Coffey said, because metastatic tumors tend to have better circulation—and therefore better access to viral particles—than do their corresponding primary malignancies.
"Moreover, activated RAS drives the metastatic phenotype," Coffey said. "Because of that, metastatic tumors are particularly homogenous with respect to RAS activation and that makes them uniquely responsive to treatment."
More than a dozen clinical trials are under way for Reolysin. Positive preliminary results in phase II trials for non–small cell lung cancer and pancreatic cancer were reported in November at the 2012 Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland.
Although viral treatments for cancer have been studied for many years, none has been approved by the FDA. One other likely contender is Amgen's OncoVEX, which has been evaluated as a treatment for melanoma in a phase III trial whose results have not yet been announced.
Enjoy
Preclinical Evaluation of Oncolytic Reovirus in Targeted Therapeutics for High-Risk Pediatric Leukemia
https://ash.confex.com/ash/2012/webprogram/Paper54666.html
54th American Society of Hematology Annual Meeting
Atlanta, Georgia Dec 8-11, 2012
Poster Session on Pre-clinical data for Children's Leukemia
3571 Preclinical Evaluation of Oncolytic Reovirus in Targeted Therapeutics for High-Risk Pediatric Leukemia
Program: Oral and Poster Abstracts
Session: 614. Acute Lymphoblastic Leukemia - Therapy, excluding Transplantation: Poster III
Monday, December 10, 2012, 6:00 PM-8:00 PM
Hall B1-B2, Level 1, Building B (Georgia World Congress Center)
Matthew F. Clarkson1*, Aru Narendran, MD, PhD2 and Randal N. Johnston, PhD1*
1Biochemistry and Molecular Biology, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB, Canada
2Oncology & Pediatrics, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, AB, Canada
Purpose:
Leukemia is the most common malignancy in children. Improved treatment strategies in recent decades have yielded substantially enhanced outcomes for children with leukemia, reaching survival rates >80%. However, there remain significant issues with current treatment. Certain subgroups of patients who are resistant to or relapse from current treatments have a dismal prognosis. Furthermore, there are significant late effects of intensive treatments, including secondary cancers, neurocognitive defects, cardiotoxicity, obesity and infertility. For these reasons, novel treatment strategies are urgently needed for high-risk leukemia in children.
Reovirus type 3 Dearing is a wild-type double-stranded RNA virus that has shown great promise as a selective oncolytic agent by its ability to replicate in transformed cells but not in normal cells. Although a number of early phase clinical studies have been completed in patients with advanced, refractory solid tumors in adults, systematic evaluation of this agent in the treatment of refractory pediatric leukemia has not been reported. As an initial step towards developing an oncolytics based treatment approach, we report preclinical data with respect to the activity, target validation, target modulation and drug combinability of reovirus in childhood leukemia cells.
Experimental Design:
A panel of pediatric leukemia cell lines representing high-risk molecular features such as Bcr-Abl, MLL rearranged and mixed lineage was used (n =6). Expression of JAM-A, the cell surface receptor for reovirus, was assessed by flow cytometry. The Ras Activation Assay Kit (EMD Millipore) was used to assess activity of the RAS protein. Western Blots were used to assess the activation (phosphorylation) of the signaling partners downstream of RAS. Cells treated with reovirus, chemotherapy drugs, or both for distinct treatment schedules were assessed for cell viability by the CellTiter-Glo© Luminescent Cell Viability Assay (Promega), and cell death by apoptosis was confirmed by cleavage of PARP. Productive viral infection was assessed by measuring reoviral protein synthesis by Western Blots, and reoviral replication was assessed by virus plaque titration assay. Drug synergies were calculated according to the method of Chou and Talalay.
Results:
Target validation assays showed the expression of JAM-A, which facilitates effective viral entry into malignant cells, in five of six cell lines. These cell lines also demonstrated differential activation of RAS and downstream kinases, suggesting targeted susceptibility of these cells to reovirus oncolysis. To further test this, we infected cells with reovirus for 1-4 days and assessed cytopathic effects. Using phase contrast microscopy, we observed the virus treated cell lines to demonstrate morphological changes characteristic of cell death following infection. Cell viability assays were used to quantify this effect, and the mechanism of cell death was determined to be apoptotic as evidenced by caspase-dependent cleavage of PARP. Reovirus-induced cell death was correlated with viral protein production and replication. Next, we screened for the ability of reovirus to induce synergistic activity in a panel of conventional and novel targeted therapeutic agents. Our studies showed that, in contrast to the current antileukemic agents, the Bcl-2 inhibitor BH3 mimetic ABT-737 was able to significantly synergize with reovirus in all cell lines tested.
Conclusions:
In our in vitro studies, oncolytic reovirus as a single agent showed potent oncolytic activity against all pediatric leukemia cell lines tested that express the receptor for reovirus, regardless of the status of the RAS signaling pathway. Further, we found reovirus-induced oncolysis can be enhanced by combination with Bcl-2 inhibition but was unaltered or antagonized by the other drugs indicating a key relationship between the two pathways. As such, our data for the first time, show that pediatric leukemia cells carry the potential to be targeted by reovirus induced oncolysis and the identification of drug synergy and the biomarkers of target modulation provide the basis for further studies to develop this novel therapeutic approach for clinical studies in the near future.
Disclosures: No relevant conflicts of interest to declare.
Drs Harrington/Melcher - Expert Opinion Biological Therapy
Oncolytic reovirus type 3 (Dearing) as a novel therapy in head and neck cancer
http://www.ncbi.nlm.nih.gov/pubmed/23140488
Published 12/12/12
Expert Opin Biol Ther. 2012 Dec;12(12):1669-78. doi: 10.1517/14712598.2012.745507.
Kyula JN, Roulstone V, Karapanagiotou EM, Melcher AA, Harrington KJ.
Source
The Institute of Cancer Research, Targeted Therapy Team, Chester Beatty Laboratories , London , UK kevin.harrington@icr.ac.uk.
Abstract
Introduction: Locally advanced head and neck cancer carries a poor prognosis, even with standard combination (surgery, radiotherapy, chemotherapy) treatment regimens. There is a pressing need for novel therapies with activity against this tumour type. Oncolytic reovirus type 3 (Dearing) is preferentially cytotoxic in tumour cells with an activated Ras signalling pathway and represents a promising novel therapy with relevance in head and neck cancer. Areas covered: In this review, we discuss the pre-clinical and clinical data that have underpinned the translational development of oncolytic reovirus thus far. In particular, we describe the iterative nature of the research programme through initial studies testing single-agent reovirus therapy and on to subsequent work in which reovirus has been combined with either radiotherapy or cytotoxic chemotherapy. We will trace the process by which oncolytic reovirus has reached Phase III evaluation in combination with carboplatin/paclitaxel in patients with platin-refractory, relapsed/metastatic head and neck cancer.
Expert opinion: Reovirus is a self-amplifying, cancer-selective agent that offers huge potential advantages over standard chemotherapy, targeted small molecules or monoclonal antibodies. However, it is most likely that reovirus will show efficacy and be approved in combination with standard modalities (cytotoxic chemotherapy or radiotherapy) or other targeted agents, especially those that modulate signal transduction pathways. The next 5 years are critical for the development of oncolytic reovirus as an anti-cancer therapy and hinge on the ongoing Phase III trial in head and neck cancer and other Phase II programmes.
PMID: 23140488 [PubMed - in process]
AACR Molecular Cancer Research -Dr. Sanjay Goel Article
http://mcr.aacrjournals.org/content/10/12/1514.abstract
Reovirus: A Targeted Therapeutic—Progress And Potential
Radhashree Maitra1, Mohammad H. Ghalib1, and Sanjay Goel1,2
+ Author Affiliations
Authors' Affiliations: 1Montefiore Medical Center, 2Albert Einstein College of Medicine, Bronx, New York
Corresponding Author:
Sanjay Goel, Department of Medical Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, 1825 Eastchester Road, Bronx, NY 10461. Phone: 718-904-2488; Fax: 718-904-2830; E-mail: sgoel@montefiore.org
R. Maitra and M.H. Ghalib contributed equally to this work.
Abstract
Medical therapy of patients with malignancy requires a paradigm shift through development of new drugs with a good safety record and novel mechanisms of activity. While there is no dearth of such molecules, one particular agent, “reovirus” is promising by its ability to target cancer cells with aberrant signaling pathways. This double-stranded RNA virus has been therapeutically formulated and has rapidly progressed from preclinical validation of anticancer activity to a phase III registration study in platinum refractory metastatic squamous cell carcinoma of the head and neck. During this process, reovirus has shown safety both as a single agent when administered intratumorally and intravenously, as well as in combination therapy, with multiple chemotherapeutics such as gemcitabine, carboplatin/paclitaxel, and docetaxel; and similarly with radiation. The scientific rationale for its development as an anticancer agent stems from the fact that it preferentially replicates in and induces lyses of cells with an activated Kras pathway. As documented in many previous studies, the initial observation of greater tropism in Kras-compromised situation might certainly not be the sole and possibly not even the predominant reason for enhanced virulence. All the same, scientists have emphasized on Kras optimistically due to its high prevalence in various types of cancers. Incidence of Kras mutation has been found to be highest in pancreatic cancer (85%–90%) followed by colorectal (35–45%) and lung (25–30%). Reovirus, in fact has the potential not only as a therapy but also as a tool to unravel the aberrant cellular pathway leading to carcinogenicity. Mol Cancer Res; 10(12); 1514–25. ©2012 AACR.
Received March 15, 2012.
Revision received July 23, 2012.
Accepted September 20, 2012.
©2012 American Association for Cancer Research.
Oncolytics Biotech: What Is All The Excitement About?
Seeking Alpha Article at seekingalpha.com/article/1070591-oncolytics-biotech-what-is-all-the-excitement-about by C.R. Jackson
Author Disclosure: I am long ONCY, AMGN, YMI. (More...)
On December 13, 2012, Oncolytics Biotech Inc. (ONCY) jumped nearly 40% after the company announced initial positive top line data from a Phase 3 study of patients with head and neck cancers treated with Reolysin (Respiratory Enteric Orphan Virus) and two chemotherapy drugs, paclitaxel (Taxol) and carboplatin (Paraplatin).
Researchers found that patients on the Reolysin regimen were more likely to have stable or smaller tumors than patients who only took chemotherapy.
The study, known as REO 018, included 105 patients. Oncolytics researchers found that 86% of patients who were treated with Reolysin had stable or smaller tumors approximately six weeks after treatment, compared with 67% of patients treated with paclitaxel and carboplatin. Patients in the trial had tumors that had metastasized. They were not helped by previous platinum-based chemotherapy or taxane chemotherapy.
A second analysis showed Reolysin in combination with two types of chemotherapies was more effective in stabilizing or shrinking metastatic tumors than the two other chemotherapies alone.
"To the best of our knowledge, this is the first successful double-blinded randomized data from a clinical study using an intravenously-administered oncolytic virus," Brad Thompson, Ph.D, president and CEO of Oncolytics, stated.
Reolysin
Oncolytics has a pipeline that consists of one product that appears to be effective for a wide range of cancers. Reolysin is a proprietary variant of the reovirus, an acronym for "Respiratory Enteric Orphan Virus," which is widely found in the environment, as well as in the respiratory and bowel systems of humans and other mammals. According to Oncylytics, most people (70% to 100%) have been exposed to the reovirus. Most people have been exposed before they were 12 years-old. Infections are typically asymptomatic. In clinical trials, Reolysin has been shown to be well-tolerated, with patients exhibiting only mild, flu-like symptoms. Reolysin has been used alone, but has been found to be more effective in combination with chemotherapy and radiotherapy for various cancers.
Reolysin is based upon research conducted by Onclytics Chief Operating Officer, Matt Coffey, Ph.D. In 1998, while conducting graduate work at the University of Calgary, Coffey and other students found that a certain reovirus showed potential as a cancer therapeutic because it reproduced well in cancer cell lines, specifically in those cells that display an activated Ras pathway, a characteristic that could play a role in two-thirds of all human cancers. Reolysin can selectively kill tumor cells with activated Ras pathways.
Head and Neck Cancers
According to the National Cancer Institute at the National Institutes of Health, cancers that are collectively known as head and neck cancers usually begin in the squamous cells that line the mucosal surfaces inside the head and neck, such as areas inside the mouth, nose and throat. Cancers of the brain, the eye, the esophagus, and the thyroid gland, as well as those of the scalp, skin, muscles and bones of the head and neck, are not usually classified as head and neck cancers.
Head and neck cancers account for approximately 3% to 5% of all cancers in the United States. These cancers are nearly twice as common among men as they are among women. Head and neck cancers are also diagnosed more often among people over age 50 than they are among younger people.
The American Cancer Society estimates that more than 52,000 men and women in the United States will be diagnosed with head and neck cancers in 2012. In 2002, the World Health Organization (WHO) found that there were 600?,000 new cases of head and neck cancer and 300,?000 deaths each year worldwide, with the most common sites being the oral cavity (389,?000 cases a year), the larynx (160?,000), and the pharynx (65?,000).
Approximately 90% of all head and neck cancers are squamous cell carcinomas. These cancers are frequently aggressive in their biologic behavior, and patients with these types of cancer are at a higher risk of developing another cancer in the head and neck area. These cancers often spread to the lymph nodes of the neck.
Head and neck cancer is highly curable if detected early. If treated early, most of these cancers have a five-year survival nearing 90% with standard therapy that usually includes some form of surgery. Radiation therapy and chemotherapy are also used. Unfortunately, the average survival rate for head and neck cancer is low due to the lack of early detection and the inability of current therapies to achieve a sustained response when the disease is in an advanced state.
A significant amount of head and neck cancer therapy research has centered around the epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase receptor involved in the proliferation and survival of cancer cells. Almost all head and neck cancers, 90% to 95%, have high levels of EGFR expression. EGFR is the first molecular target against which monoclonal antibodies have been developed for cancer therapy. In March 2006, the US Food and Drug Administration (FDA) approved the first head and neck cancer treatment in 45 years-cetuximab, an anti-epidermal-growth-factor-receptor (EGFR) monoclonal antibody.
Bristol-Myers Squibb's (BMY) and Eli Lilly's (LLY) Erbitux (cetuximab) was approved by the FDA to be used in combination with radiation therapy to treat patients with squamous cell cancer of the head and neck that can not be removed by surgery. The FDA found cetuximab to be the first drug approved for head and neck cancer that has shown a survival benefit in this population. In November 2011, Erbitux was also approved for use as a monotherapy to treat patients whose head and neck cancer has spread (metastasized) despite the use of standard chemotherapy.
Other monoclonal antibodies like Amgen's (AMGN) Vectibix (panitumumab), and YMI Biosciences' (YMI) nimotuzumab may also prove to be effective head and neck cancer treatments.
In June 2011, Copenhagen, Denmark based Genmab (GEN.CO) announced that it was discontinuing research of another fully human EGFR monoclonal antibody, zalutumumab, a drug that was showing promising results treating squamous cell carcinoma of the head and neck because it was unable to find a partner to finance costly trials of the drug, which were necessary to achieve regulatory approval.
Conventional treatments have been found to be inadequate for the majority of advanced or recurrent head and neck cancer patients. The major limitations of current treatments are the lack of specificity for the tumor cell and unacceptable toxicity to the patient. As a result, research in therapeutics for advanced, chemotherapy-resistant or recurrent head and neck cancer patients has focused on new treatments that exploit biological differences between tumor and normal cells. These therapies include monoclonal antibodies, molecular inhibitors, gene therapy, photodynamic therapy and oncolytic virotherapy.
Oncolytic virotherapy utilize biotechnology to convert viruses into cancer-attacking agents by reprogramming viruses to kill cancerous cells without damaging normal cells.
Oncorine, also known as ONX-015 or H101 (Recombinant Human Adenovirus Type 5 Injection) is the first oncolytic viral therapy approved by any regulatory agency in the world. In November 2005, the Chinese State Food and Drug Administration (CFDA) approved H101, an oncolytic adenovirus, to be used in combination with chemotherapy as a treatment for patients with late-stage refractory nasopharyngeal cancer, a type of head and neck cancer.
H101 is a modified adenovirus, a type of common cold virus found in most people. By deleting an E1B-55kd segment in the virus, its ability to selectively replicate in and kill tumor cells results, while leaving normal cells unaffected. The SFDA approved H101 after a study group found a 27% increase in the number of patients taking H101 who had complete or partial tumor size reduction compared with the control group.
H101 is almost identical to ONYX-015, a virus Onyx Pharmaceuticals (ONXX) created in 1987 by genetically engineering an adenovirus. Although clinical trials found that ONYX-015 was generally safe and selective, some research concluded that the drug was not very effective. In 2000, Pfizer (PFE) suspended the ONYX-015 trial after acquiring Warner-Lambert, Onyx's development partner. Without funding, Onyx discontinued the ONYX-015 program. Shanghai Sunway Biotech Co., Ltd. acquired global rights for ONX-105. Onyx Therapeutics discontinued the therapeutic virus program in 2006. Few companies continue to work with adenovirus because the virus spreads very slowly and its capacity to express other genes is extremely limited.
In 2011, Amgen acquired BioVex Group, Inc. for $1 billion. BioVex was developing OncoVEX(GM-CSF), a novel oncolytic vaccine that showed promise as a new approach to treating melanoma and head and neck cancer. Several months after buying BioVex, Amgen announced that it was discontinuing OncoVEX research. During the company's second-quarter 2011 earnings call, Roger Perlmutter, Amgen's Executive Vice President of Research and Development announced that the company "decided not to proceed with the OncoVEX GM-CSF Phase 3 program in squamous cell carcinoma of the head and neck. Recent studies have demonstrated that head and neck cancers associated with prior human papillomavirus (HPV) infection behave very differently from tumors with other etiologies. These observations mandate that clinical trials ensure appropriate balance in the representation of subjects with prior papillomavirus infection. Since the changes in clinical trial design required are quite significant, we've elected to halt the current study and to initiate a redesign trial at a later time. Obviously, our approach to new indications for OncoVEX GM-CSF will take into account what we have learned through the conduct of our melanoma trial."
Other companies developing oncolytic viral therapies include GenVec Inc. (GNVC), Viralytics Ltd. (VLA.AX), and privately held companies Neotropix Inc., Crusade Laboratories Ltd., and Wellstat Biologic, Jennerex Therapeutics, Genelux and Oncos Therapeurics.
The research firm, GlobalData, estimated the global head and neck cancer market to be valued at $1.035 billion in 2009. The market is forecast to grow by 8.3% annually for the next seven years to reach $1.809 billion by 2016. This growth is primarily attributed to the high incidence rate, prevalence rate and diagnosis rate of the disease and the high prescription rates of the currently approved products, as well as the development of vaccines, gene therapy and biologics across different stages of clinical trials. GlobalData has concluded that the global head and neck cancer market is moderately served with the current product options and there is significant scope available to new entrants to capture value from underserved segments. The research firm contends that designing a product that can improve the five-year survival rate, reduce tumor size, prevent tumor recurrence and offer a high safety profile is one of key challenges for prospective entrants to this market and could provide a significant market share for any company.
GlobalData found that the global head and neck cancer market is becoming increasingly competitive. The unmet need in the head and neck cancer market is high and if a company wants to capture this unmet need, it will need to improve on the prevailing products' weaknesses and adverse effects.
According to the BioSeeker Group, 127 companies are developing 137 drugs targeting head and neck cancer.
Potential Treatment for a Wide Range of Cancers
Since Reolysin has shown activity in a broad range of cancers, Oncolytics has conducted clinical trials in multiple cancer indications with the objective of developing Reolysin as a human cancer therapeutic. Clinical trials are being conducted in the United States, the United Kingdom, Canada, and internationally.
In November 2012, Oncolytics announced expanded results from two Phase 2 trials , as well as preclinical research in Ras-activated pancreatic cancer.
The first trial, known as REO 16, evaluated 33 patients with non-small cell lung cancer with Kras or EGFR-activated tumors being treated with Reolysin administered intravenously in combination with paclitaxel and carboplatin. Of 30 evaluable patients, researchers found that 27 patients had stable disease or better for a 90% clinical benefit rate . Of the 27 patients, nine patients had partial response (30%) and 18 patients had stable disease (60%). Three patients had progressive disease as their best response.
The second trial, known as REO17, examined patients with advanced pancreatic cancer treated with intravenously administered Reolysin in combination with gemcitabine, also known as Gemzar, manufactured by Eli Lilly, as well as preclinical research in Ras-activated pancreatic cancer. Response evaluation among 25 evaluable patients showed 20 patients had stable disease or better (one patient had partial response, one patient had unconfirmed partial response, six patients had stable disease at six weeks, and 12 had stable disease at 12 or more weeks). Five patients had progressive disease as their best response. A number of patients remained in the study. Some patients were too early in their treatments to evaluate.
Reolysin has been studied in over 30 clinical trials including translational, Phase 1, Phase 2 (single arm and randomized), and Phase 3 studies in a broad range of cancer indications.
In addition to the Phase 3 trial examining the effectiveness of Reolysin in head and neck cancer, Oncolytics is conducting Phase 2 trials studying Reolysin in advanced or metastatic breast cancer, previously-treated advanced or metastatic non-small cell lung cancer, advanced or metastatic colorectal cancer, recurrent or metastatic castration resistant prostate cancer, metastatic pancreatic cancer, persistent or recurrent ovarian, fallopian tube or primary peritoneal cancer, squamous cell carcinoma lung cancer, metastatic melanoma, advanced pancreatic cancer, non-small cell lung cancer, advanced head and neck cancers, metastatic sarcomas, and advanced malignancies.
Phase 1/2 studies are investigating Reolysin in recurrent malignant gliomas, metastatic ovarian, and peritoneal and fallopian tube cancers.
Phase 1 studies are examining Reolysin in relapsed multiple myeloma, pediatric relapsed or refractory solid tumors, colorectal cancer, advanced malignancies, various metastatic tumors, and subcutaneous tumors.
The company has completed 15 clinical trials comprising four Phase 2 clinical trials, three Phase 1/2 trials, six Phase 1 trials, and two transitional studies.
The U.S. National Cancer Institute and the National Cancer Institute of Canada have made substantial investments by sponsoring clinical trials to research Reolysin.
In October 2003, Oncolytics announced that the U.S. National Cancer Institute (NCI) approved support for multiple clinical trials to evaluate the efficacy of Reolysin in a range of cancers. Since then, the NCI has sponsored clinical trials investigating Reolysin as a therapy for persistent or recurrent, ovarian, fallopian tube or primary peritoneal cancer, metastatic melanoma, metastatic ovarian, peritoneal and fallopian tube cancers, relapsed melanoma, pediatric relapsed or refractory solid tumors, and recurrent or metastatic pancreatic cancer.
The National Cancer Institute of Canada has sponsored and conducted clinical trials evaluating Reolysin as a treatment for castration resistant prostrate cancer, metastatic breast cancer, advanced or metastatic colorectal cancer, and advanced or metastatic non-small cell lung cancer.
Finances
As of September 30, 2012, Oncolytics had about $26 million in cash and cash equivalents. In 2011, the company had approximately $32.9 million in cash at the end of the third quarter. Total assets were $29.1 million in 2012, down from $36 million in for the same time period in 2011.
Total liabilities were $6.7 million in 2012, an increase from $6.5 million in 2011.
The company's expenses were $9.3 million for the third quarter of 2012, up substantially from $6.2 million spent during the same period in 2011. Oncolytics year-to-date expenses was $28.2 million, up from $17.4 million spent during the same time period in 2011.
Conclusion: Buy
Since Reolysin is a new and novel cancer treatment, there has been a considerable amount of skepticism about the drug's potential viability. However, Reolysin research has been conducted at some of the nation's finest hospitals, such as the Mayo Clinic. Reolysin research has been investigated by internationally respected oncologists, such as the University of Antwerp's Jan Vermorken, who was named editor-in-chief of the Annals of Oncology in December 2008. Both the U.S. and Canadian National Cancer Institutes have made substantial investments in Oncolytics by sponsoring costly clinical trials .
Oncolytics estimates that at least five million new patients a year will develop cancers with Ras involvement. Many of these patients may benefit from Reolysin therapy.
Oncolytics is burning cash fast. At current spending rates, the company will run out of money in 2013. Oncolytics must either cut expenses or raise additional funds by equity or debt financing, or obtain monies from in-licensing opportunities, corporate partnerships, research grants or other means to continue operating.
Despite all the promising clinical news, with a market cap of only $274.48M, Oncolytics is a micro-cap company. All investments involve risk, but investing in micro-cap companies is especially risky. These stocks are often extremely volatile, may be illiquid, and are subject to manipulation. The Security and Exchange Commission (SEC) has a significant amount of information about the dangers of investing in micro-cap companies and penny stocks. You can find it here.
Despite the risk, I think Oncolytics Biotech is a strong speculative buy.
Link to Press Release Positive Top Line REOLYSIN® Data for First Endpoint in Randomized Phase III Study in Head and Neck Cancers
www.oncolyticsbiotech.com/news_items/details?press_release_id=1916
CALGARY, Dec. 13, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics" or the "Company") (TSX: ONC) (NASDAQ: ONCY) today announced initial positive top line data from the first endpoint in its double-blinded randomized Phase III clinical study examining REOLYSIN in combination with carboplatin and paclitaxel in second-line patients with platinum-refractory, taxane-naïve head and neck cancers (REO 018).
The endpoint examines initial percentage tumour changes between the pre-treatment and first post-treatment scans (typically performed at six weeks post-first treatment) of all patients enrolled in the study. The analysis was designed to assess early differences in response between loco-regional tumours and metastatic tumours, as classified and observed by the investigators. This is the first, and to this point only, endpoint to be un-blinded for this study.
The first analysis compared the relative percentages of patients in the test and control arms with tumours that had either stabilized or exhibited shrinkage. For the purposes of this endpoint, the definition of tumour stabilization was restricted to zero percent growth only. Of the 105 total patients with evaluable metastatic tumours, 86 percent (n=50) of those in the test arm of the study exhibited tumour stabilization or shrinkage, compared with 67 percent of patients (n=55) in the control arm. This was statistically significant, with a p-value of 0.025.
The second analysis examined the magnitude of tumour response on a per patient basis using a comparison of percentage tumour shrinkage at six weeks in each patient with evaluable metastatic tumours. This analysis showed that REOLYSIN in combination with carboplatin and paclitaxel was statistically significantly better than carboplatin and paclitaxel alone at stabilizing or shrinking metastatic tumours, yielding a p-value of 0.03.
At the six week point, there is a numeric trend in favour of the test group towards differing activity between the test and control groups in patients with loco-regional tumours.
In an intragroup analysis of the test arm, an improvement in the percentage of patients' metastatic tumours over loco-regional tumours was noted (p=0.083) and an improvement of magnitude of response in metastatic tumours over loco-regional tumours was also noted (p=0.13). By contrast, in an intragroup analysis of the control arm, no statistical differences were noted between the responses of patients with evaluable metastatic tumours and patients with evaluable loco-regional tumours.
"To the best of our knowledge, this is the first successful double-blinded randomized data from a clinical study using an intravenously-administered oncolytic virus. We are delighted to have obtained statistically significant data for REOLYSIN in a randomized clinical setting," said Dr. Brad Thompson, President and CEO of Oncolytics. "We continue to await the data for the other endpoints of this study, to which all parties still remain blinded at this point."
Investor Presentation Updated Nov 26, 2012
http://oncolytics.s3.amazonaws.com/presentations/25/original.pdf?1353946216
BioWorld Coverage of positive PhIII Data Release
Front page news coverage in BioWorld
http://www.bioworld.com/
http://www.bioworld.com/content/wall-street-reolysin-value-oncolytics-soars-phase-iii-0
By Randy Osborne
Staff Writer
Stock buyers hardly cared that Oncolytics Biotech Inc.'s early Phase III results with Reolysin, its reovirus variant for head and neck cancer, lacked survival data and slipped on part of its endpoint – the rest was just too good.
Reolysin met statistical significance (p = 0.025) in patients with metastatic tumors, proving that, when combined with carboplatin and paclitaxel against platinum-refractory, taxane-naïve tumors, the drug did better at stabilizing or shrinking tumors: a secondary endpoint in the trial known as REO 018.
"The vast majority of patients [showed] shrinkage," said Oncolytics' president and CEO, Brad Thompson, during a conference call.
Outcomes were less convincing in those with loco-regional tumors, but at six weeks, the company said, a numeric trend favored "differing activity" in the group getting Reolysin.
The numbers, wrote analyst Douglas Miehm, of RBC Dominion Securities, in a research report, "support a higher probability of success for final primary data points."
Wall Street agreed in a big way, sending shares of Calgary, Alberta-based Oncolytics (NASDAQ:ONCY) up 40 percent, or 86 cents, to close Thursday at $3.03, after trading as high as $3.85.
The endpoint checked tumor changes between the pre-treatment and first post-treatment scans, typically at six weeks, and stabilization was described – more stringently than in other accepted criteria – as zero percent growth.
"It's not good enough to have some growth," Thompson said. "The surgeons involved want shrinkage, period."
Of the 105 total patients with evaluable metastatic tumors, 86 percent (n = 50) of those in the test arm of the study exhibited tumor stabilization or shrinkage, compared with 67 percent of patients (n = 55) in the control arm.
"To be candid, I think all of us here were modestly surprised that we saw the degree of differentiation, the amount of shrinkage that we did at six weeks," Thompson said. "Reolysin is a pretty gentle agent when it comes to tumor shrinkage."
Getting an accurate measure of shrinkage is difficult, he said. Scans may show that neutralized tumors retain their external dimensions, because of supporting strata. "If you don't kill it, too, then the tumors don't shrink very much," Thompson said, even though they contain only "necrotic goo."
Tumor profiles also may show what looks like enlargement, but is not. "In early studies, we actually lost patients, because doctors thought they progressed when they were having an inflammatory response around the edge of the tumor," which appeared as a ring on scans.
So, coming up with strong numbers in the endpoint was particularly unlikely, and the benefits are expected to continue beyond six weeks, Thompson said.
"It's just how Reolysin seems to work," he said. "I mean, we've seen partial responses develop six, seven, eight, nine months on continuous therapy before. It does sometimes take time" for the full effects of the drug to manifest.
In September, Oncolytics conducted an internal analysis of the blind, combined data for all 80 patients enrolled in the first stage of the Phase III study, with data showing a greater-than-expected median evolving progression-free survival (PFS) of the 80 patients, which comprised the combined control and test groups.
That's when a closer look found that patients for whom only metastatic disease was being measured were responding differently to treatment than patients who had local regional disease, with a statistically significantly greater median evolving PFS in the metastatic disease group.
Because of the difference in response, Oncolytics concluded that those two patient groups ought to be considered differently, and consulted with the FDA before deciding to expand enrollment in the first stage of the trial to include 160 patients, segregating between patients with local recurrent disease, with or without metastases.
That meant that the expanded first stage of the study became a separate supportive study to a planned registration study that took the place of the original second stage, resulting in a need for more time to analyze PFS from the expanded first stage.
And so the further endpoints became event-driven, rather than time-driven, Thompson said in the conference call. Asked when more complete data – on PFS, overall survival (OS) and objective response rate – will be available, he could only estimate.
"It's really when the PFS's stabilize, so that the remaining patients on study don't affect the median PFS, and the same with the OS endpoints," he said. "That window for PFS is between now and sometime in the first quarter of next year. Then, of course, we have to collect the data and get it out."
Tentative as they are, the results so far in hand "expand our universe rather markedly," Thompson said, adding that Oncolytics is exploring neoadjuvant use and "looking at metastatic disease as a separate indication. That's a rather new world," he said. "We'll take a little bit of time and energy to consider and ponder that."
The company has six more trials in metastatic cancers – breast, colorectal, lung, ovarian, pancreatic and prostate – and most should have all patients aboard next year.
Update on Phase III Study in Head and Neck Cancers
http://finance.yahoo.com/news/oncolytics-biotech-inc-provides-phase-110000516.html
CALGARY , Sept. 12, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics" or the "Company") (TSX:ONC, NASDAQ:ONCY) today provided an update on its Phase III trial of REOLYSIN in combination with carboplatin and paclitaxel for the treatment of head and neck cancers (REO 018).
The Company has conducted an internal analysis of the blinded combined clinical data for all 80 patients enrolled in the first stage of the study. The study remains blinded at this time. At the time of the analysis, 23 patients of the 80 had not yet progressed but were included for the purposes of analysis. The median evolving progression free survival (PFS) of the 80 patients, which comprises the combined control and test groups, was greater than expected, as was the best response rate. On further examination, it was observed that patients for whom only metastatic disease was being measured by clinicians, were responding differently to treatment than patients who had local regional head and neck disease. Patients in whom only metastatic disease was measured had a median evolving PFS of 120 days, which was statistically significantly greater than those patients with a noted local regional head and neck tumor. There was a statistically significant difference in PFS between these two groups (n=80, p=0.008, hazard ratio=0.536). Oncolytics therefore believes that, based on differential PFS, it has identified two distinct patient groups are being enrolled in this clinical study, patients with local recurrent disease, with or without metastases, and those with distal metastases. Each of these two groups contains patients from both the control and test arms of the study. Oncolytics believes that these two groups of patients must therefore be considered to be different for the purpose of both analysis and investigation.
The Company has consulted with its principal investigators and the independent statistician for the study, and, on September 10, 2012 , met with the U.S. Food and Drug Administration in Washington, D.C. Based on these discussions, the Company plans to expand enrollment in the first stage of the study to include 160 patients, all of whom have now been enrolled. Oncolytics intends to introduce an additional segregation to differentiate between patients with local recurrent disease, with or without metastases, and patients with distal metastases. Based on the analysis of the 160 patients, Oncolytics expects to generate randomized data from two discrete patient populations. The Company believes this will provide a sufficient number of patients to conduct a meaningful analysis of the two identified patient groups, as well as increased powering for the overall analysis. Oncolytics intends to treat this expanded first stage of the REO 018 clinical trial as a separate supportive study to a planned registration study that will be similar to, and take the place of, the original second stage of the REO 018 clinical trial. Enrollment in the first stage of the study is complete and no additional patients will be enrolled pending approval of a planned registration study. The Company intends to submit protocol amendments to regulators in the immediate near term to reflect these changes. It will require additional time to follow the expanded group of patients and allow the evolving PFS data to mature.
"Segregating and separately evaluating the two identified patient groups means we will be able to obtain our first randomized data in these two patient populations, including one with only metastatic disease," said Dr. Brad Thompson , President and CEO of Oncolytics. "All six of our randomized Phase II studies are examining indications with significant metastatic disease involvement. Patients with metastatic disease represent a large potential market."
Conference Call Details
Dr. Brad Thompson , President and CEO of Oncolytics, will host a conference call and webcast on Wednesday, September 12 th, 2012 at 6:00 a.m. MT (8:00 a.m. ET) to discuss in more depth the Company's Phase III study in head and neck cancers. To access the conference call by telephone, dial 1-647-427-7450 or 1-888-231-8191.
A live audio webcast will also be available at the following link: http://www.newswire.ca/en/webcast/detail/1034181/1121577 or through the Company's website at www.oncolyticsbiotech.com/presentations. Please connect at least 10 minutes prior to the webcast to ensure adequate time for any software download that may be needed. A replay of the webcast will be available at www.oncolyticsbiotech.com and will also be available by telephone through September 19 th, 2012. To access the telephone replay, dial 1-416-849-0833 or 1-855-859-2056 and enter reservation number 30393545 followed by the number sign. The Company also intends to post the prepared remarks from the call to its corporate website following the call.
iHub is much better than Yahoo ever was.
Hi RJC, Welcome back
Glad to welcome everyone here RJC. As you may know iHub has many advantages.... and is free to a point.
+Unlimited posting size
+Links
+Pictures
+No-multi Nics allowed
+Moderated
+Rules for posting
+Stickys
+Message Boxes
+The iHub informational page - Moderator controlled so if anybody has any suggestions of additions/changes to this Im always open to suggestions to this format or content.
Free accounts are pretty limited but functional. I subscribe. I had the Level 2 for a while and that was pretty good.
I have used this message board to document all the significant events occurring with Oncolytics being careful to use the first 8 words in the post to convey as much meaning as you can get since the message "title" in iHub is a limited number of characters/words. Hope to continue its use as a serious forum.
Also you have access to one of the best Biotech message boards out there... Biotech Values run by DewDiligence.
onco_investor
PH3 H&N Musings by Geneman on Biotech Values Board
Thanks for sharing your insight!
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=78735914
"ONCY At the end of 6 weeks, the CRO would have done a "data scrub" on all 80 patients. This would have covered off all of the demographics, the background clinical information and loose bits on the ITT patient group. The evaluation at 12 weeks should involve the collection of the interim clinical data, two blinded evaluations of the RECIST evaluations and delivery to the statistician(s). The statistician looks at the single (unblinded - all 80 patients) curve and compares these data to the data expected from a very well performing (upper percentile survival/progression) historical "control" group. From this statistical analysis comes the stats about clinical effect of Reolysin. The curve for all 80 patients would contain 40 "control" patients and 40 patients treated with Reolysin and, blinded, this 80 patient curve should look moderately better than a control curve. It is the job of the statistician to opine about the likelihood that unblinding the trial (80 patients) would produce a observable difference between treatment (40 patients) and control group (40 patients).
The language of the statistical analysis provided to the company is intentionally non-committal. For example, the company may hear many options......"there is an 80% chance that the data will resolve to (at least) a 6 week improvement in PFS"; "there is a 90% chance that the data will resolve to (at least) a 4 week improvement in PFS": "there is a 95% chance that the data will resolve to (at least) a 2 week improvement in PFS. In fact, the statistician would produce a pretty, curved dataset plotting an observable PFS difference vs. likelihood. There would be many iterations of the data provided to the company.......all before unblinding. The company looks at the data and decides about unblinding......or not. The CRO collects and scrubs the data; the stats person tortures the numbers and provides a "best guess" about the trends of the unblinded data; the company decides on the unblinding and subsequent statistical analysis.
The devil is in the SPA details. At what point is the company forced to unblind the trial? At what point will the company unblind the trial? We have heard 6 weeks, 12 weeks and, yet we are now past 18 weeks. To play the devil's advocate, if the stats person came to you after the 12 week scans and said that there is an 80% chance that the data are currently stat sig for a 6 week PFS difference (doubling of PFS), would you risk unblinding the trial? In a trial trending toward success, you are taking a 20% chance of negative stats (often spuriously negative) and a resultant futility decision that torpedoes the entire Ph III H+N program. What numbers convince you to unblind? How much risk to the entire Ph III program do you assume to see the data early?
As the data mature, so do the stats. At the 18 week scan, the statistician would have tighter confidence intervals and would be able to say that there is a 98% chance of a 6 week PFS improvement (maybe a 99.5% chance of a 4 week difference). Would you unblind now?? We do not know the constraints or flexibility built into the H+N SPA but this is the gist of the decision making process.
Once the company makes the decision to unblind, they will have to live with the results as they stand. They direct the CRO to break the blind; the unblinded data comes to the statistician and two curves are generated and compared. If the difference between the two curves is sufficient (ie: >70% likelihood of success with 400+ patients enrolled), the SPA allows for continuation of the trial. Anything less.....the trial is discontinued on the basis of futility.
I don't know how much flexibility the SPA allows for......no matter what, the survival data are rapidly maturing at this point. The PFS data determine the go vs. no-go decision but what happens if the raw survival data are ready to report? Not much interpretation on those numbers and, at this point, more than half of the ITT population has died. If the trial were unblinded today, there would be very, very strong survival data already. Survival trumps PFS but what would the FDA say if the PFS is weak but the right side of the survival curve is strong?
It is getting interesting.....the screws are turning tighter.
For most of the biotechs that I have followed over the years, delays in data release portends bad results. I hope that this trend does not hold true for the ONCY H+N data!! No matter what, the lifespan of this group of patients enforces the duration of the trial. In October (6 weeks from now), 6m survival stats are available on all 80 patients. Effectively, the statistical package would be complete. Not much ducking that milestone event!!
Dog days of August!!!
Cheers, Geneman"
Response from pcrutch
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=78736792
"From the company’s June 20th DMC safety review,
“The study design stipulates that the study will proceed to full enrollment in Stage 2 (ranging from 100 to 400 additional patients) provided that the DMC concludes that safety data in Stage 1 is acceptable for continuation to Stage 2, and an independent statistical analysis of Progression-Free Survival (PFS, a measure of efficacy) in Stage 1 predicts probability of success in Stage 2. The data collection for this analysis is currently being performed.
The safety analysis was performed on the 80 patients enrolled in Stage 1 of the study, once every patient had sufficient follow up after starting treatment on the study (six weeks). The statistical analysis will be performed once every patient has had sufficient follow up after starting treatment (12 weeks) to determine potential differences in PFS between the control and test arms of the study.”
ONCY does not plan to release OS data from this."
Part 2 Response from geneman
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=78737547
"ONCY Those press releases are very carefully crafted. Once the trial population reaches 12 weeks, the company will complete the analysis.....this does not say that they will complete the analysis at 12 weeks (or even on the 12 week data), it just says that they will do an analysis after that maturity date.
It is my understanding that Part 1 and Part 2 of the Ph III trial will be treated as separate trials within one. Obviously, the unblinding of the first 80 patients would compromise the rest of the statistical analysis through another 400 patients. I think the unblinding of Part 1 will lead to a survival analysis at 6m and 1y. Part 2 has started fresh at Patient 1 and will be completely blinded until enrolment is complete. There would be interval evaluations of progression free survival at landmark patient enrolment numbers (no or minimal statistical penalty). Additionally, more mature survival data would be evolving in parallel from Part 1 and could be publicly available. The Adaptive statistical package allows for the evolving clinical results of Part 1 to be used to understand/predict the performance of Part II.
How much data the company gives to us is a different story, I am afraid!! Often the provided information is limited and critical raw data is considered to be "secret". I am pretty sure that the defined survival numbers from Part 1 are partly to be used to define enrolment numbers for Part 2. This is the way I understand it, anyways.
Clarifying this would be a good topic for the question period after one of the company's conference calls.....there will be one coming up, no matter what.
Cheers, Geneman"
REO12 UK PH1 w/Cyclophosphamide Advanced Malignances Completes Enrollment
http://finance.yahoo.com/news/oncolytics-biotech-inc-completes-patient-110000929.html
CALGARY , Aug. 16, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics") (ONC.TO) (ONCY) today announced that it has completed patient enrollment in its U.K. Phase I clinical trial using intravenously-administered REOLYSIN in combination with cyclophosphamide in patients with advanced malignancies (REO 012).
"We are pleased to complete enrollment of this technical study examining cyclophosphamide's potential to modulate the immune system's response to REOLYSIN," said Dr. Matt Coffey , COO of Oncolytics. "Studies of this type help to advance our understanding of the interaction between the immune system and our product."
The primary objective of the open label, dose-escalating, non-randomized, 36-patient study is to determine the Minimum Effective Immunomodulatory Dose (MED) of cyclophosphamide necessary to obtain successful immune modulation. Secondary objectives of the trial include assessing the safety profile of the combination and gathering any evidence of antitumor activity.
Eligible patients include those who have been diagnosed with advanced or metastatic solid tumors, including pancreatic, lung and ovarian cancers that are refractory to standard therapy, or for which no standard curative therapy exists.
The principal investigators for the study are Dr. James Spicer of King's College, London , Dr. Johann de Bono and Dr. Kevin Harrington of the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research, London , and Professor Hardev Pandha of the Royal Surrey County Hospital NHS Trust, Surrey and Mount Alvernia Hospitals.
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including the Company's expectations related to the U.K. Phase I clinical trial with REOLYSIN in combination with cyclophosphamide , and the Company's belief as to the potential of REOLYSIN as a cancer therapeutic, involve known and unknown risks and uncertainties, which could cause the Company's actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of REOLYSIN as a cancer treatment, the tolerability of REOLYSIN outside a controlled test, the success and timely completion of clinical studies and trials, the Company's ability to successfully commercialize REOLYSIN, uncertainties related to the research and development of pharmaceuticals and uncertainties related to the regulatory process. Investors should consult the Company's quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake to update these forward-looking statements, except as required by applicable laws.
SOURCE: Oncolytics Biotech Inc.
REO22 PH1 Colorectal completes enrollment PH2 Started in Canada
http://finance.yahoo.com/news/oncolytics-biotech-inc-completes-patient-110000624.html
CALGARY, Aug. 16, 2012 /PRNewswire/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC, NASDAQ:ONCY) today announced that it has completed patient enrollment in its U.S. Phase I clinical trial using REOLYSIN in combination with FOLFIRI (Folinic Acid (leucovorin) with Fluorouracil (5-FU) and Irinotecan) in patients with oxaliplatin refractory, Kras mutant colorectal cancer (REO 022).
The trial is a 21-patient, single arm dose escalation study designed to determine a maximum tolerated dose and dose-limiting toxicities for the combination of REOLYSIN and FOLFIRI.
Eligible patients include those with histologically confirmed cancer of the colon or rectum with Kras mutation and measurable disease. They must have progressed on or within one hundred and ninety days after the last dose of an oxaliplatin regimen in the metastatic setting, or be intolerant to oxaliplatin.
The principal investigator for the study is Dr. Sanjay Goel of the Montefiore Medical Center at the Albert Einstein College of Medicine in New York.
"We are pleased to complete enrollment in this clinical study as we learn more about using REOLYSIN for the treatment of colorectal cancer," said Dr. Brad Thompson, President and CEO of Oncolytics. "Oncolytics continues to expand its colorectal cancer program and we recently announced entry into an agreement where the NCIC Clinical Trials Group would conduct an open-label, randomized, non-blinded, Phase II clinical study of REOLYSIN given in combination with FOLFOX-6 plus bevacizumab (Avastin) versus FOLFOX-6 plus bevacizumab alone."
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit:
Oncolytics Biotech Inc.
SAFC Case Study PharmaTech Article
Thanks botinsel for this
http://www.pharmtech.com/pharmtech/article/articleDetail.jsp?id=757458&sk=&date=&pageID=3
Case Studies in Pharmaceutical Project Management
Feb 1, 2012
By: Patricia Van Arnum
Pharmaceutical Technology
Volume 36, Issue 2, pp. s14-s22
Viral product manufacturing
Nick Johnson, marketing manager at SAFC
This case study in project management involved the partnership between SAFC and Oncolytics Biotech, a biotechnology company headquartered in Calgary, Canada, which has developed a novel cancer treatment, Reolysin, based on a modified wild-type reovirus expressed in suspension-adapted human embryonic kidney cells (HEK 293). In 2007, Oncolytics partnered with SAFC's Carlsbad, California, site as part of the commercialization process for Reolysin. After officially announcing SAFC as the contract manufacturer for the project in early 2011, Oncolytics announced in November 2011 that validation studies were underway. Now in Phase III clinical trials, SAFC and Oncolytics have worked as partners to manage this project from the initial phases of identifying how to make the technology work through to making the consistent batches required for licensure. The current goal is to obtain a successful regulatory approval for Reolysin.
Project challenges. The production of the modified reovirus presented a significant manufacturing challenge. Not only was it going to be the first time for this type of product to be made on such a large scale, it also involved transferring technology from a contract development organization (CDO) in Canada to the SAFC site in Carlsbad. At the beginning of the project, there were four partners in different locations, including Oncolytics, its CDO, SAFC, and SAFC Biosciences in St Louis, which developed the novel media used in the production process.
SAFC Carlsbad already was filling the bulk product for clinical trials out of a product that was being made at another CMO in the United Kingdom. As the product progressed into later-stage clinical trials, the production was ramped up and transferred to Carlsbad, at first on a 40-L scale, and up to the present 100-L batches. The technology transfer was a whole new ballgame in terms of scale and complexity and required a new project team to be formed. On the SAFC side, this included a director of operations plus senior managers in manufacturing, quality assurance, quality control, and project management. Business-development support was also brought in when new scopes of work and new contracts needed to be worked out and finalized.
Despite the disparate locations, the communication between the teams in the different sites worked well with routine weekly conference calls and many coordinating activities carried out electronically. Some face-to-face meetings were essential, including the manufacturing representative and project manager visiting the CDO to address process scale-up. A week also was spent with all partners, including the CDO, watching the process and filming it so that it could later be used for operator training in Carlsbad.
The whole process took quite some time with many technical challenges, leading to a stop–start of operations from late 2008 through to 2009. By the end of 2009, however, sufficient clinical material had been made to continue with the trials, so there was less urgency from that perspective. Once the 100-L scale was reached, one or two batches were made per year until the program was ready to initiate process validation batches. Now that the product has advanced to conformance batches, three to six batches will be made per year.
Tracking progress.From a production standpoint, Gantt charts (i.e. charts used to show the project's schedule) are used for all SAFC projects. They are mapped out further than just a single department and include everything that might affect the timeline from the vendor through to the customer. The anticipated timings were all shared with the customer as well as the troubleshooting of possible technology-transfer issues that the technical team mapped. The team was tasked to look through historical data from the previous partnership to identify where there were areas for improvement and to help resolve issues quickly with input from both the SAFC team and the CDO. Specifically, SAFC Biosciences also helped by developing a custom growth media that increased the viral productivity and eased the purification process.
When SAFC inherited the contract, it already contained the required specifications that were used as an ultimate metric for success. The new goal became making and purifying the product to the required level for a commercial launch. After a number of changes to the process on the CDO's side and a few creative manufacturing approaches from SAFC, these specifications were exceeded and brought the project to the current point. Oncolytics is now in a position where accessing materials for its clinical needs is no longer a constraint, and the project has advanced into process validation in anticipation of commercial launch.
Issue resolution. One issue the team faced was the presence of an impurity that prevented the product from meeting specifications. The teams were brought together, and all the possibilities that might have led to the impurity were considered. From there, action items were distributed to the teams for them to pursue, including the review of historical data. This approach was successful as by the time of the next team meeting, the problem had been pinpointed. By adapting the process for the next batch slightly, a solution was found allowing the product to met specifications and the issue was resolved.
A key factor in the overall project's success was the customer relationship. In addition to the customer having a very good project manager, the relationship was developed based on trust and a common goal. Another key factor was ensuring that we had the resources needed to move the project forward. When the program moved into the process-validation phase, a second project manager was added to increase bandwidth. The way all parties worked together allowed the manufacturing to enter into conformance batches within a relatively short period of time with only a limited number of clinical batches having been completed.
Clinical Trial Facts & Figures - CISCPR
A Very comprehensive collection of information about clinical trials and participation. Thanks to Taltell on the Yahoo board for finding this
http://www.ciscrp.org/professional/facts_pat.html
Public Attitudes and Perceptions -- Charts
General Information About Clinical Trials
-The Drug Development Process
-Cost of Research/Investment and the Economic Impact
-Physician Involvement
General Patient Recruitment Information
Global Data About Clinical Trials
Information About Participation and Clinical Trials by Ethnicity, Age and Gender
Information About Participation and Clinical Trials by Disease
Public Attitudes and Perceptions:
1. In a survey conducted by CISCRP on 1000 people in 2008,
17% say that they generally believe clinical research studies and trials are very safe
51% said that they believed them to be somewhat safe
11% said they did not believe them to be very safe
7% said they did not believe them to be safe at all
14% said they did not have any knowledge on the topic. (www.ciscrp.org)
2. In a 2006 survey conducted by CISCRP a thousand people were asked to choose which form of medical participation makes the greatest contribution to mankind, among the options were: giving blood, volunteering in a clinical trial, raising money for a charity by running a race and donating an organ, participating in a clinical trial finished last with nine percent of the votes. (www.ciscrp.org)
3. According to CenterWatch, 94% of people recognize the importance of participating in clinical research in order to assist in the advancement of medical science. Yet 75% of the general public state they have little to no knowledge about the clinical research enterprise and the participation process. (www.ciscrp.org)
4. More than half of respondents to a 2005 CISCRP survey on clinical trial registry users would have greater trust in clinical research information if the results were made available on a public website registry. (www.ciscrp.org)
5. In March of 2008, 57% of Americans say health-related research has helped them or someone close to them, but 90% purchased prescription drugs for themselves or family last year. (Research!America, 2008)
6. Seventy five percent of Americans think it is very important that the United States is a global leader in medical research. (Research!America, 2007)
7. Sixty nine percent of Americans are more likely to support a presidential candidate in favor of federal spending on medical, health and scientific research and 25 % say there are less likely to vote in that favor. (Research!America, 2007)
8. Seventy nine percent of Americans believe that it is very important that new medicines and health services are made available as soon as the FDA can adequately test their safety. (Research!America, Charlton Poll 2007)
9. Seventy one percent of Americans believe the information and research achieved through clinical trials is of great value. (Research!America, Charlton Poll 2007)
10. Fifty seven percent of Americans say they would be likely to participate in clinical research and 40% say they would not. (Research!America, Charlton Poll, 2007)
11. Recent polls show that positive public opinions persist in regards to the importance of clinical research. Out of 450 US households surveyed, the results showed that 63% believe that clinical trials contribute to the advancement of medicine and health care. (LJS Healthcare, 2007)
12. A 2007 Harris Interactive poll found that among 1,726 US adults, 27% of the public distrusts- 'somewhat' or 'very strongly'- the Food and Drug Administration. That same poll found that 31% of Americans believe that the FDA is effective at ensuring safety, down from 56% who did so in 2004. Nearly half of those polled said that they distrusted Capital Hill officials who govern regulatory oversight and drug development processes. (Harris Interactive, 2007)
13. Forty two percent of Americans distrust the pharmaceutical and biotechnology companies and 39% gave poor ratings to pharmaceutical and biotechnology companies for failing to serve companies in 2007. This percentage is significantly higher than the 19% who rated pharmaceutical and biotechnology companies poorly in 1997. (Harris Interactive, 2007)
14. In January of 2008, 44% of Americans said they viewed pharmaceutical and biotechnology companies unfavorably, 27% said that they do not trust them to provide reliable information about drug side effects and safety, and 45% said they do not trust the research sponsors to inform the public quickly when safety concerns about a drug are discovered. (Kaiser Foundation, 2008)
15. One in four respondents to a 2007 survey believed that their doctors would expose them to unnecessary risk in clinical trials. (Braunstein, Medicine, 2008)
16. A 2006 CISCRP survey conducted among 900 US adults found that the public's perception regarding why people choose to participate in clinical trials is because they are 'very sick without any other options' or they are 'looking to make money'. Sadly, also in this study, 34% of Americans said that they 'Do Not Admire' people who volunteer for clinical trials. (www.cicsrp.org)
17. A recent study showed that less than five percent of Americans know where to find information about relevant clinical trials. (Getz, Philadelphia Survey)
18. More than 70% of those who have participated in clinical trials] are likely to do so again. (Sun, "Sometimes Bumpy Road". 2008)
General Information About Clinical Trials:
The Drug Development Process:
1. The delays in patient recruitment for clinical trials account for an average of 4.6 months lost per trial. When calculated, this is an annual cumulative loss of 26 years, on average, for each company. (Beasely, "Recruiting". 2006)
2. Over the past five years the number of potential new drugs in development for 4,600 indications, has increased from 2,000 to 2,700. (PhRMA, 2008)
3. Between June 2007 and April 2008, 50 new medicines have been approved by the FDA in the United States. However, new drug applications and supplemental new drug applications for more than 200 drugs are still awaiting approval. (www.pharmalive.com)
4. It takes approximately 10 years of study in test tubes and laboratory mice to reach the point where a treatment may be tested for its safety and effectiveness in humans. (Getz, Informed Consent, 29)
5. A clinical trial is sometimes called a clinical research study or a research protocol, but a clinical trial primarily refers to the location where a study protocol is being tested. In other words, a single protocol involves multiple locations across a variety of cities, states and even countries where clinical trials are conducted. (Silverman, Star-Ledger, 2004)
6. Approximately one in 50 drugs that enter pre-clinical testing prove safe enough and effective enough to be tested in people. (Getz, The Gift of Participation, 59)
7. One in five drugs that enter clinical trials will prove safe and effective enough to receive FDA approval. Some of these drugs end up being most effective for patients with different diseases than those that they were originally created to treat. (Getz, The Gift of Participation, 60)
8. In 2006, 119 new remedies got the FDA's stamp of approval, including 29 "priority" drugs with a potential for significant advances over preexisting treatments. (Getz, The Gift of Participation, 60)
9. Even relatively small improvements to existing drugs, which represent over 40% of new drugs approved by the FDA each year, provide important health benefits to patients. (Getz, The Gift of Participation)
10. According to the FDA, approximately 70% of new medical treatments pass Phase I testing stage. (Ken Getz, Informed Consent, 34)
11. One-third of drugs that enter clinical testing ever successfully complete phase II and progress to larger-scale phase III studies. This stage provides hard, statistical facts about a drug. (Getz, The Gift of Participation, 26)
12. Phase III clinical trials involve extensive testing to assess safety, efficacy and dosage levels in a large group of patients facing a specific illness. The study drug is tested on as many as several thousand people over a period of two to five years. (Getz, The Gift of Participation, 26)
13. Therapies that have reached phase III have already passed toxicity testing and have proved to be at least somewhat effective. However, subjects in phase III trials still usually have no better than a 50% chance of getting the investigational treatment versus a placebo or standard therapy. (Getz, The Gift of Participation, 27)
14. The FDA review period usually lasts about one year for most New Drug Applications (NDAs). The FDA also has an expedited review process for priority drugs - usually lasting under six months. Priority drugs are those that represent a notable treatment benefit for critical and severe illnesses. Approximately 60% of all NDAs are approved by the FDA. (Ken Getz, The Gift of Participation, 28)
15. About 80% of drugs that enter Phase III will successfully complete this stage. (Ken Getz, Informed Consent, 36)
16. Currently more than 530 drugs - new chemical entities, new formulations, and new indications - are in Phase III trials in the United States and, new indications, and new formulations are in Phase II/III trials. (www.pharmalive.com)
17. More than 1,000 new chemical entities, new indications, and new formulations are being investigated in Phase II trials in the United States. (www.pharmalive.com)
18. There are more than 130 new chemical entities, new indications, and new formulations comprising Phase I/II trials in the United States and more than 840 new chemical entities, new indications, and new formulations are in Phase I trials in the United States. (www.pharmalive.com)
19. According to a recent report in Cutting Edge Information, clinical trials last 42% longer than expected in Phase I, 31% longer in Phase II, and 30% beyond planned deadlines in Phase III - all because of recruitment delays. (Beasely, "Recruiting". 2008)
20. Each day a drug is delayed from market, sponsors lose up to $8 million. (Beasely, "Recruiting". 2008)
21. In 2007 there were 174,000 adverse effects reported to the FDA by consumers and 121,000 reported to the FDA by physicians. (www.fda.gov)
22. New medicines generated 40% of the gain in life expectancy over the past 25 years. (U.S. Census, National Vital Statistics)
23. Fifty thousand to 60,000 of these trials are industry sponsored, while the remaining are government sponsored. (Institute of Medicine)
24. Six percent of clinical trials are completed on time, and 72% of trials run over schedule by more than one month. (www.fda.gov)
25. Eighty percent of total trials are delayed at least one month because of unfulfilled enrollment. (Lamberti, "State of Clinical Trials Industry", 292)
26. The average number of patients per new drug application (NDA) is declining; a typical NDA had data from 2,186 patients in 2007, less than half the level observed ten years ago (5,582). Changing clinical study design strategies and investigator difficulty recruiting and retaining study volunteers are contributing factors to this decline.
Cost of Research/Investment and the Economic Impact:
1. The average cost of clinical trials has risen to nearly 60% of total development costs, compared to just over 30% in the 1980s. (www.pfizer.com)
2. The cost of pediatric trials increased nearly eight fold from 2000 to 2006.
(www.pfizer.com)
3. Currently about six cents of each health dollar spent in the United States is spent on medical health and research; when Americans were polled in regards to this figure:
-55% said they would like to see it increased to at least seven cents or more
-14% believe five to six cents should be adequate
-4% voted for zero to four cents
-27% percent said they did not know (Research!America, Charlton Poll, 2007)
4. Fifty seven percent of Americans said that they were willing to pay one dollar more per week in taxes, if they were sure that this money would be spent on additional medical research. (Research!America, Charlton Poll, 2007)
5. The United States' pharmaceutical and biotechnology research companies put forth a record $58.8 billion in the year 2007 towards the research and development of new life changing medicines and vaccines. This is an increase of nearly $3 billion since 2006. (PhRMA, 2008)
6. Over the past seven years, America's pharmaceutical research companies have consistently invested 18% of their sales in research and development projects. (PhRMA, 2008)
7. As of 2007, due much in part to the rigid regulations of the FDA, the average cost for moving a new drug from the test tube to the market ranges from $500 to $800 million. (www.emedonline.com)
8. The average American spends around $5,000 a year on health care. Less than $20 of that amount is invested in research to prevent, treat and cure diseases and disabilities. (Research!America, Charlton Poll, 2007)
Physician Involvement:
1. Sixty percent of physicians surveyed by CenterWatch in 2006 said that they have referred patients to clinical trials. Those that had not referred patients into trials, explain that their number one hindrance to participation was the lack of information available about the treatments. (CenterWatch 2006)
2. The most common types of clinical trials that the doctors refer their patients to are cardiology, oncology and psychology. (MacDonald, "The Psychology", CenterWatch 2006)
3. The Top Five Reasons Doctors Don't Refer Patients Into Clinical Trials:
-31% Lack of information on treatments and new investigational drugs
-15% Trials are not appropriate for my particular practice
-13% Not enough time to learn about a particular trial
-10% Lack of access to information
-7% Fear of losing a patient (MacDonald, "The Psychology", CenterWatch 2006)
4. A crucial aspect of the clinical trial process is finding an appropriate trial for each patient. Within the past few years, several useful online resources were made available to healthcare professionals to help better direct their patients towards making an education decision regarding clinical trials. Some examples of available resources: www.patientnavigation.com, The American Cancer Society (ACS), NCI and AstraZeneca all offer patient navigation programs and 60 ACS navigation programs are in place, with plans for another 50 to begin over the next five years. ("Bringing Cures". 2007)
5. Industry data suggests that fewer than four percent of all U.S. physicians participate in clinical trials. (www.futurepharmaus.com)
6. Most adult cancer patients who participate in clinical trials say that a physician had a great deal of influence on their decision to participate. (Harris Interactive)
7. Even though most people do not rely on their physicians for information, 78% of the public say the physician is their most trusted source of information. (CenterWatch)
8. A new survey in May 2008, released by the Society for Women's Health Research indicates 94% of Americans have never been informed by their doctors of medical research studies in which they might participate. (Sun, "Sometimes Bumpy Road". 2008)
9. Seven percent of Americans say that their doctors have ever suggested that they participate in a clinical study. (Getz, Public Confidence)
General Patient Recruitment Information:
1. Less than 1/3 of people who come in for a screening end up completing a clinical trial. Some participants never pass the eligibility criteria. Others drop out...or get too busy. You have the right to quit a trial at any time, for any reason-or no reason at all. (Getz, The Gift of Participation, 40)
2. Out of all of the research sites in the United States, less than a 1/3 contain 70% of the valuable subjects. Therefore 70% of the research sites under-perform, and somewhere between 15%-20% never even enroll a single patient. (Pierre, "Recruitment and Retention". 2006)
3. Fifty percent of clinical research sites enroll one or no patients in their studies. (Pierre, "Recruitment and Retention". 2006)
4. In an analysis of 25,855 study volunteers in the United States 73.2% of participants completed Overall clinical trials (Phases I-IV), 75.4% completed Phase I clinical trials, 69.7% completed Phase II/III clinical trials and 93.8% completed Phase IV clinical trials. (CenterWatch, 2003)
5. Recent studies show that enrollment rates have dropped from 75% in 2000 to 59% in 2006 and retention rates have fallen from 69% to 48% during same period. (Getz, "Public Confidence")
6. Surveys have shown a trend toward poor volunteer retention in studies, because overall one out of every four stick with a study until its completion. Most participants dropout during phases II and III. (CenterWatch, 2005)
Global Data About Clinical Trials:
1. 26,145 unique investigators conducted FDA-regulated clinical trials world wide in 2007. (Getz, Zuckerman and Rochon, 'Landscape changes highlight growing challenges for clinical research sponsors' 2009)
2. Since 1990, the number of unique PIs has been growing 8.7% annually though year-to-year growth since 2001 has been far slower at 2.1%. (Getz, Zuckerman and Rochon, 'Landscape changes highlight growing challenges for clinical research sponsors' 2009)
3. The number of active investigators in the US has declined 3.5% annually since 2001 whereas active investigators outside the US has increased 13.5% each year during that same period. Annual growth in non-US based investigators is decelerating due to a number of factors including diminishing economic advantages and global regulatory constraints. (Getz, Zuckerman and Rochon, 'Landscape changes highlight growing challenges for clinical research sponsors' 2009)
4. Latin America, Eastern Europe and Asia have seen rapid growth in FDA-regulated clinical trials primarily for confirmatory, later stage studies. Steady growth in emerging regions is due to many factors including lower relative study conduct costs; harmonization of good clinical practice guidelines; well-positioned contract research organizations; and the availability of well trained professionals and treatment-naive patients. (Getz, Zuckerman and Rochon, 'Landscape changes highlight growing challenges for clinical research sponsors' 2009)
5.- 8.5% of active FDA-regulated investigators are based in Central and Eastern Europe, making it the largest non-Western region; the proportion of investigators based in Asia is now comparable to that from Latin America at 5.5% each. (Getz, Zuckerman and Rochon, 'Landscape changes highlight growing challenges for clinical research sponsors' 2009)
Information About Participation and Clinical Trials by Ethnicity, Age and Gender:
Volunteer Demographics:
1. In 2006, of the total number of people completing clinical trials, 775,000 people participated in government funded clinical trials, 880,000 participated in industry funded clinical trials (phases I-III) and 750,000 people participated in industry funded clinical trials (phase IV). (www.ciscrp.org)
2. About 2% of the United States population gets involved with clinical research trials each year. Among people who suffer from severe, chronic illnesses, only 6% participate. As a result, an increasing number of clinical trials are delayed because too few people...even knew they had the opportunity to get involved. (Getz, The Gift of Participation, 42)
3. Studies have shown that while 44% of people find out about studies through the media, 14% gain the information from their physicians. (Humphrey, Public Awareness)
4. An overwhelming majority of people (77%), say that they would consider getting involved in an appropriate clinical research study if asked; however, 10% of those eligible to participate in clinical trials do so in the United States. (www.ciscrp.org)
Minority
a. The involvement of minority physicians has been shown to have a positive impact on minorities in clinical trials. At this time, only about 7% of all physicians in the United States belong to a minority group and a very small percentage are actively involved in clinical research. Several medical societies and associations are now looking for ways to encourage minority physician involvement in clinical trials. (Getz, The Gift of Participation, 71)
b. Unexplained cancer-related health disparities remain among population subgroups. For example, Blacks and people with low socioeconomic status have the highest rates of both new cancers and cancer deaths. (http://progress.cancer.gov)
c. In a study conducted nationwide on 3,000 women who are HIV positive and 1,000 women who were at high risk for contracting the disease, 80% of these women were of a minority subgroup. (www.womenshealth.gov)
d. Certain minority populations are more likely to suffer from specific diseases, such as diabetes and hypertension, and respond to medications differently. In response, the government has made minority inclusion mandatory for trials that it sponsors. (Getz, The Gift of Participation, 68)
e. A survey conducted on 717 US adults in 2007 found high levels of public distrust in clinical research staff. The break down showed that this level of distrust was significantly higher in minority adults, as 73% said they were 'very likely' or 'likely' to be treated as guinea pigs without their consent, whereas 49% of whites responded this way. (Braunstein, "Race Medical Researcher". 2008)
Women
a. Many diseases disproportionately affect women; among them: breast cancer, Alzheimer's disease, rheumatoid arthritis, multiple sclerosis, osteoporosis, diabetes and depression. And there are a multitude of unanswered questions. (Getz, The Gift of Participation, 67)
b. A Federal Law passed in 1993 requires that the women be included in every clinical trial involving a disease that affects them and that the NIH make sure studies are designed to collect and analyze data on gender differences. (www.healthywomen.org)
c. From 1977 to 1993, the FDA forbade early-stage testing of most medications on women of childbearing potential for fear of causing birth defects. Now, women are recruited for trials even if they are of childbearing age, but are informed of any potential risks of untested medication on fertility- and pregnancy- related issues. (www.healthywomen.org)
d. Researchers are finding that men and women are different in ways that go far beyond their reproductive systems, hormones and bone structures. Diseases may evoke different symptoms in men and women, run a different paced course through the body and finally men and women may respond differently to the same treatment. Therefore, it is very important that both sexes are represented in trials and the FDA ensures it. (www.fda.gov)
e. The National Institute of Health offered a $50,000 grant in 2006 to be put towards research regarding women and gender differences in drug usage, abuse, prevention and treatment. (www.grants.gov)
f. Cardiovascular disease is the leading killer in the United States of both men and women, but it is still considered a man's disease. The discrepancy lies in the fact that women exhibit much different symptoms and the onset of these symptoms on average occurs 10 years later in life. Seventy percent of the cardiovascular clinical trials over the past 100 years have included women, without sex difference analysis. The FDA is currently pushing to increase the enrollment of women in these trials and to cater specifically to gender differences. (www.medicaldevicestoday.com)
g. Females are underrepresented in clinical trials. Nine percent of the female respondents in a survey of 2,000 American adults released concerning Sex Differences in Health Awareness Day had ever participated in medical research, and 93% said their doctor had never mentioned the opportunity to them. In addition, 25% of these 2,000 people were unaware that healthy individuals can participate in clinical trials. (Coles, "Doctors Lack Female Participants". 2008)
Seniors
a. While seniors make up two-thirds of patients with breast, colorectal, prostate, or lung cancer, they represent one third of clinical trial participants. (www.ciscrp.org)
b. More than 700 of the approximately 1,000 drugs now being evaluated in clinical trials are aimed at treating diseases or conditions associated with aging. (Baker, "Assessing the Risks". 2008)
c. A recent study, which reviewed the Medline database for randomized controlled trials, revealed that patients were excluded due to age in 72.1% of all trials, (60.1% in pediatric populations and 38.5% in elderly patients). (Fowler, "Eligibility Criteria". 2007)
d. 63% of people in the general population age 65 or older had cancer, only 25% of patients in that age group were represented in clinical trials. (Hutchins, New England Journal of Medicine, 1999)
Pediatric
e. In 2006, the FDA disclosed that there were 465 proposed pediatric study requests, 317 actual written requests and 118 exclusively granted. (www.fda.gov)
f. Including vaccines, the pediatric drug market reaches close to $20 billion worldwide. (Lamberti, State of the Clinical Trials Industry, 88)
g. An estimated 20-30% of drugs approved by the FDA are labeled for pediatric use. (FDA, From Test to Patient, 2006)
According to a chart generated by PhRMA in 2005, the majority of drugs in clinical trials for children are intended to treat cancer. (Getz, The Gift of Participation, 209)
h. For all childhood cancers combined, the five year relative survival has improved markedly over the past 30 years from less than 50% before the 1970s to nearly 80% today due to new and improved treatments. (American Cancer Society, 2007)
Information About Participation and Clinical Trials by Disease:
Cancer:
a. Finding a cure to cancer would be worth about $47 trillion to the U.S. Economy alone. (Wu, "Cure for Cancer". 2006)
b. Nearly nine million Americans have survived cancer and today in the United States, there about 400 new cancer therapies in preclinical and clinical development. (Colaizzi, "Most Cancer Patients". 2006)
c. While the majority of cancer clinical trial participants are highly satisfied with their experience, as few as one in ten cancer survivors report ever being made aware of trial opportunities during treatment, according to Cancer Clinical Trials Awareness and Attitudes in Cancer Survivors, a survey conducted by the Coalition of Cancer Cooperative Groups and Northwestern University. (Colaizzi, "Most Cancer Patients". 2006)
d. Less than five percent of cancer patients participate in clinical trials. If ten percent participated, studies could be completed in one year, instead of the three-five years that studies currently require. (National Cancer Institute)
e. Government agencies, such as the National Cancer Institute (NCI) and other parts of the National Institutes of Health (NIH), the Department of Defense, and the Department of Veterans Affairs, sponsor and conduct clinical trials. In addition, organizations or individuals, such as physicians, medical institutions, foundations, volunteer groups, and pharmaceutical companies, also sponsor clinical trials. NCI sponsors a large number of clinical trials and has a number of programs designed to make clinical trials widely available in the United States. (National Cancer Institute)
f. When informed about a clinical trial by their doctor, 40% of cancer patients either enrolled or tried to enroll. Of those people who met eligibility requirements and participated, 96% said they "were treated with dignity and respect" during the trial, and 91%, said they would recommend participation to a family member or friend with cancer. (Mundell, "Clinical Trials". 2006)
g. Clinical trial participants are credited with helping to develop treatments that now save the lives of 70% to 80% of the victims of childhood leukemia. (Reader's Digest) 8. In the past three decades, the cure rate for childhood cancer has improved from less than 10% to 75%, thanks to the medical advances made by clinical research. (www.CureSearch.org)
h. In June 2008, the United States House of Representatives passed the "Caroline Pryce Walker Conquer Childhood Cancer Act", which promises significantly increased federal investment into childhood cancer research. (www.CureSearch.org)
i. Overall four out of five children diagnosed with some form of pediatric cancer can be successfully treated. (www.ccrf.org)
Ninety seven percent of respondents who participated in cancer clinical trials reported they were treated with dignity and respect and received excellent or good quality care, while 76% of trial participants said they would recommend clinical trial participation to someone with cancer. (Taylor, "Misconceptions". 2001)
j. From 1996 through 2002, 75, 215 patients were enrolled in National Cancer Institute-sponsored cooperative group nonsurgical treatment trials for breast, lung, colorectal, or prostate cancers. Approximately 3.1% of trial participants were Hispanic, 85.6% were white, 9.2% were black, 1.9% were Asian/Pacific Islanders, and 0.3% were American Indians/Alaskan Natives. In addition, although cancer incidence was evenly divided among the 3 participating age groups (30-64, 65-74, 75 years), the representation of trial participants was heavily skewed toward the youngest age group (68.0% of trial participants were 30-64 years old).
Heart Disease:
a. Death rates from the nation's number one killer, heart disease, have been cut by more than 60% in the past 50 years. (Research!America)
b. On average, it takes five years to develop, from IND filing to NDA submission, cardiovascular therapies. (CenterWatch)
Trial volunteers are credited with helping to develop the treatments that have cut the male death rate from coronary heart disease by 50%. (Reader's Digest)
If you have suggestions for more facts and figures to add to this page, please contact info@ciscrp.org or 617-725-2750.
ONCY Q2 2012 Financial Results
http://finance.yahoo.com/news/oncolytics-biotech-inc-announces-second-110000978.html
CALGARY, Aug. 2, 2012 /PRNewswire/ - Oncolytics Biotech Inc. (TSX:ONC, NASDAQ:ONCY) ("Oncolytics" or the "Company") today announced its financial results and operational highlights for the quarter ended June 30, 2012.
"Early in the quarter, we announced that we had completed enrollment in the first, 80-patient stage of our Phase III trial in head and neck cancers," said Dr. Brad Thompson, President and CEO of Oncolytics. "We continued to make progress on this key clinical initiative during the quarter with our independent Data Monitoring Committee recommending the trial proceed based on a review of the safety data. We continue to await the results of an ongoing data review which will enable us to determine the next steps for the study."
Selected Highlights
Since March 31, 2012, the Company has made a number of significant announcements:
Clinical Trial Program
Completion of enrollment in the first, 80-patient stage of its Phase III clinical trial examining REOLYSIN® in combination with paclitaxel and carboplatin in patients with platinum-refractory head and neck cancers (REO 018);
Review by Company's independent Data Monitoring Committee (DMC) of the safety data for the first stage of the Company's Phase III trial in head and neck cancers and received a recommendation that enrollment continue in the study while awaiting the ongoing data review;
Entry into an agreement whereby the NCIC Clinical Trials Group (CTG) at Queen's University in Kingston, Ontario, will sponsor and conduct a randomized Phase II study of REOLYSIN in patients with advanced or metastatic colorectal cancer enrolling up to 100 patients;
Entry into an agreement whereby the NCIC CTG will sponsor and conduct a randomized Phase II study of REOLYSIN in patients with advanced or metastatic non-small cell lung cancer enrolling up to 150 patients;
Entry into an agreement whereby the NCIC CTG will sponsor and conduct a randomized Phase II study of REOLYSIN in patients with advanced or metastatic breast cancer enrolling up to 100 patients; and
Clinical Trial Results
Publication of a paper entitled "Cell Carriage, Delivery, and Selective Replication of an Oncolytic Virus in Tumor in Patients," in the June 13, 2012 issue of the journal Science Translational Medicine (Vol. 4 Issue 138 138ra77), covering findings from a U.K. translational clinical trial (REO 013) investigating intravenous administration of REOLYSIN in patients with metastatic colorectal cancer prior to surgical resection of liver metastases. The researchers found that intravenously-administered reovirus could specifically target and infect metastatic liver tumors in 90% of the patients, even though all patients treated had had a pre-existing immunity to the virus.
Updated AGM Investor Presentation Available
http://oncolytics.s3.amazonaws.com/presentations/33/original.pdf?1340230047
Link to the current investor presentation used at the recent AGM.
Randomized Phase II Breast Cancer Trial Announced NCIC
http://finance.yahoo.com/news/oncolytics-biotech-inc-enters-sponsorship-110000415.html
Oncolytics Biotech® Inc. Enters into Sponsorship Agreement with NCIC CTG for Randomized Phase II Study in Advanced and Metastatic Breast Cancers
CALGARY , June 21, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics") (ONC.TO) (ONCY) today announced that it has entered into an agreement whereby the NCIC Clinical Trials Group (NCIC CTG) at Queen's University in Kingston, Ontario, will sponsor and conduct a randomized Phase II study of REOLYSIN® in patients with advanced or metastatic breast cancer.
"We are excited to announce our fourth randomized study with the NCIC CTG," said Dr. Brad Thompson , President and CEO of Oncolytics. "This study will build upon pre-clinical research conducted with REOLYSIN in human breast cancer primary tumour samples."
The study will be an open-label, randomized, non-blinded, Phase II clinical study of REOLYSIN given in combination with paclitaxel versus paclitaxel alone. Approximately 50 response-evaluable patients will be enrolled in each arm, after a six- to nine-patient safety run-in.
About Breast Cancer
The Canadian Cancer Society estimates that 22,900 Canadians will be diagnosed with breast cancer and 5,155 Canadians are expected to die from the disease in 2012. The American Cancer Society estimates that 229,060 Americans will be diagnosed with breast cancer and 39,920 will die from the disease in 2012.
About the NCIC Clinical Trials Group at Queen's University
The NCIC Clinical Trials Group (NCIC CTG) is a cancer clinical trials cooperative group that conducts Phase I-III trials testing anti-cancer and supportive therapies across Canada and internationally. It is a national research program of the Canadian Cancer Society. The NCIC CTG's Central Office is located at Queen's University in Kingston, Ontario, Canada .
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN®, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
Phase III H&N Study Recommended to continue
http://finance.yahoo.com/news/oncolytics-announces-independent-data-monitoring-110000113.html
Oncolytics Announces Independent Data Monitoring Committee Recommends Continued Enrollment in Phase III Study of REOLYSIN® in Head and Neck Cancers Following Review of Safety Data
CALGARY , June 20, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics") (ONC.TO) NASDAQ: ONCY) announced today that the Company's independent Data Monitoring Committee (DMC) has reviewed the safety data for the first stage of its Phase III trial of REOLYSIN in combination with carboplatin and paclitaxel for the treatment of head and neck cancers (REO 018). Based on the review of the safety data the DMC has recommended that enrollment continue in the study.
"The safety data from the first stage of the Phase III study met our expectations and confirms the positive safety data from our other clinical studies using REOLYSIN," said Dr. Brad Thompson , President and CEO of Oncolytics. "We will now focus our time and attention on conducting the statistical analysis of the efficacy of the first stage's patient population, which is forthcoming."
The study design stipulates that the study will proceed to full enrollment in Stage 2 (ranging from 100 to 400 additional patients) provided that the DMC concludes that safety data in Stage 1 is acceptable for continuation to Stage 2, and an independent statistical analysis of Progression-Free Survival (PFS, a measure of efficacy) in Stage 1 predicts probability of success in Stage 2. The data collection for this analysis is currently being performed.
The safety analysis was performed on the 80 patients enrolled in Stage 1 of the study, once every patient had sufficient follow up after starting treatment on the study (six weeks). The statistical analysis will be performed once every patient has had sufficient follow up after starting treatment (12 weeks) to determine potential differences in PFS between the control and test arms of the study.
The study is a randomized, two-arm, double-blind, multi-centre, two-stage, adaptive Phase III trial assessing the intravenous administration of REOLYSIN with the chemotherapy combination of paclitaxel and carboplatin versus the chemotherapy alone in patients with metastatic or recurrent squamous cell carcinoma of the head and neck, or squamous cell cancer of the nasopharynx, who have progressed on or after prior platinum-based chemotherapy. On April 2, 2012 , the Company announced that enrollment in the non-adaptive, 80-patient first stage of the trial had been completed. Enrollment is currently underway in the adaptive second stage, which is designed to enroll between 100 and 400 patients. This adaptive trial design allows data evolution to determine if the probably of reaching a statically significant endpoint has been achieved. The trial is currently being conducted at more than 80 centres in 14 countries in North America and Europe , including the United States following an agreement with the U.S. Food and Drug Administration (FDA) under the Special Protocol Assessment (SPA) process with respect to the trial's design.
Oncolytics Patent on Lyophilized Viruses
Thanks wcz
Kind Code A1
Coffey; Matthew C. ; et al. June 7, 2012
LYOPHILIZED VIRAL FORMULATIONS
Abstract
Provided herein are lyophilized viral formulations useful for the stabilization and storage of viruses and methods of preparing these formulations. The lyophilized viral formulations described herein include a virus (e.g., a purified virus) and a non-viral composition including excipients. The formulations can be used, for example, to retain the infectivity or immunogenicity of viruses during periods of storage.
Inventors: Coffey; Matthew C.; (Calgary, CA) ; Serl; Sarah; (Calgary, CA) ; Pavliv; Leo; (Cary, NC)
Assignee: ONCOLYTICS BIOTECH INC.
Calgary
CA
Serial No.: 309901
Series Code: 13
Filed: December 2, 2011
Current U.S. Class: 424/215.1; 424/204.1; 424/93.6
Class at Publication: 424/215.1; 424/204.1; 424/93.6
International Class: A61K 35/76 20060101 A61K035/76; A61P 31/14 20060101 A61P031/14; A61P 37/04 20060101 A61P037/04; A61K 39/12 20060101 A61K039/12; A61K 39/15 20060101 A61K039/1
Randomized Phase II NSCLC Announcement Webcast
Partial Transcript
Thanks to RJC for transcribing this Webcast.
June 5, 2012 Conference Call "Randomized Phase II Conference Call"
Audio: http://podcast.newswire.ca/media/oncolytics20120605.mp3
PR: http://www.oncolyticsbiotech.com/news_items/details?press_release_id=1892
=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-
{1:40} Brad: This morning we announce that Oncolytics has entered into an agreement with the NCIC CTG to sponsor a randomized Phase II Study in second line NSLC. The study will enroll approximately 150 patients …
{2:30} To date, the single arm non-squamous NSCLC Study [REO-016] has demonstrated a Disease Control Rate (which is Stable Disease or better) of 89%, and the single arm Squamous Cell Carcinoma Study [REO-021] has demonstrated a Disease Control Rate of 82%. These are approximately twice the Clinical Benefit Rates [=Disease Control Rate] reported for paclitaxel treatment for similar stage NSCLC patients …
{3:25} Today's announcement brings the total sponsored studies in our clinical portfolio to 8, 5 of which are randomized Phase II Studies. Now that we have finished enrollment for the first stage of our Phase III H&N Clinical Trial, these additional randomized Studies will help us determine where to focus our future Phase III Clinical Trial program. …
{3:55} The 5, third party sponsored, randomized, Phase II Trials in our portfolio are expected to enroll approximately 520 patients. It would cost Oncolytics approximately 42 million dollars to conduct all 5 randomized Studies on a non-sponsored basis. However, with the sponsorship of the NCI and NCIC, our total contribution to these 5 Trials will total around 6 million dollars, some of which will be payable from resources that Oncolytics already has in hand.
{4:55} Question from Alan Ridgway – Paradigm: Brad, maybe just a little bit more detail on the design of the Trial. Is there a cross-over with patients on the control arm at all?
Brad: No, there is not. We felt in this particular Study that it was better to stick with pure PFS as the primary end point.
Alan: As far as the non-squamous running with pemetrexed, have you guys run any Studies with this before, and is there going to be a run-in of any kind going into this Trial"
Brad: There'll be a 6 to 9 patient run-in on the pemetrexed arm just to make sure that everything is ok with that particular drug combination. It is our first time using that combination. Pemetrexed is a simpler disease treatment regime here in Canada than it is in the United States, which is part of the reason we chose to run the Study here. The use of pemetrexed is really common in that particular stage, for that particular indication.
Alan: And do you guys believe that pemetrexed will give the same sort of benefits that carbo/tax does in the Trials that you've run to date?
Brad: Yes … based on the information that we have, it should run pretty much the same. The choice of second line is interesting because I would think that further Studies with the carbo/tax combination (which we're still contemplating) would back up into first line again. So I think you could potentially see having two separate lung programs, running one in first line and one in second line, but we're focusing on the second line first.
Alan: The Clinical Benefit Rates that you quoted in your prepared statement of 89% and 82% … how many patients have been enrolled in those two Trials now? What's the patient size that we're talking about for those two numbers?
Brad: That's still evolving. We're, I think, just a patient or two short of finishing the primary enrollment in the NSCLC Study in the States, and the squamous cell lung study is in behind that, so those numbers are around 60ish patients and that's still evolving upwards as we speak, so I think we're getting a pretty good handle on the magnitude of difference. If we were looking at going from 40- 50% to 50- 60% Stable Disease or better, I don't think I'd be visually impressed or enthused, but getting up into the 80's, the high 80's on those two separately is potentially significant.
Alan: And that's 60 patients combined; right? … about 30 patients in each?
Brad: Yes … that's about right.
{8:10} Question from Neil Maruoka – Canaccord Genuity: In regard to some of the previous Studies that you put out, you announced the non-small cell Study last year; if I recall, you haven't talked too much about the SCC [REO-021] Study, but has the data you have gleaned so far from the study … does that impact on the design of this Trial, and does it impact what lung cancer indication you might move into going forward?
Brad: I think it's a fairly complicated Study evolving … particularly looking at EGFR mutation, EGFR over-expression, and KRas mutation status, in these patient groups; and a further reason we're proceeding cautiously with this is because we're actually seeing some interesting patterns emerging that are a little surprising. For example, in the non-small cell lung study that we've already previously reported a little bit of the detail on, and you're seeing a very high correlation with Stable Disease or better with KRas, but you actually get a higher Response Rate based on some interesting differentiations ... with EGFR status, but a lower Clinical Benefit rate.
So you're seeing differences within the supposed all Ras pathway activated populations based on these different markers. I want to see that data mature to get some differentiation on that. Now, that one piece of data alone has influenced not just these Studies' design, but all our Studies' design going forward. We're having a much heavier emphasis on correlative work looking at those three particular elements. For example, our colorectal Study that we're about to initiate enrollment in has those correlative elements, the prostate Study has some of that, we're already doing that in some of our other Studies; and I think in the end, that's really going to be the key about where Reolysin is going to find its home as it were. So yes, those Studies have really heavily influenced not only the design of these Studies, but other Studies as well.
{10:30} Neil: any timing on when we can expect to see data from the lung or the squamous cell study?
Brad: I'm not sure on the defined date for the squamous cell Study. For the non-small cell lung Study, I expect to have enough data in a meeting sometime in the near future. We've a pretty mature data set and the investigator is basically just selecting a time that he would like to present it. The squamous cell is really turning into an interesting Study for a very different reason … out of all the minor tumor responses and partial responses that we've seen, we haven't to date, yet, seen any of the kind of weeping side-effect issues that other Studies have reported for similar responses. We're focusing very heavily on making sure we evaluate that particular component separately, so we'll just grind through that, and get it out when we get it out.
It is interesting that we're seeing very similar Stable Disease or better rates between these two patient populations, albeit in relatively low numbers, because you see quite different responses in other Studies when you actually compare squamous to non-squamous. Reo in combination appears to … consistently … whether you're talking radiation, or with taxanes, or with taxane combinations, or platinums … you get this very typical 80% to much higher than 80% Stable Disease or better rate, pretty much regardless of the primary indication. It's interesting. Dealing with that in randomized studies is what we're dealing with now, but it is interesting that you're actually starting to see this pattern, at least on the Clinical Benefit side, that kind of transcends the primary indication.
{12:40} Question from Philippa Flint – Bloom Burton: Can you just talk a little bit about your potential options for a strategy going forward. I expect data on the Head & Neck Study soon, but how do you look at the other indications in terms of when you get pancreatic data, the non-small cell, what are your options for next steps in terms of either positive or … regardless of the data from Head & Neck?
Brad: Thank you for asking that, because that's the critical question for company at this point and time. I don't have any idea what's going on with the data of Head & Neck … I mean, I'm as blinded as everybody else on the planet, in that analysis is just going on independent of anybody inside Oncolytics. So, when the data comes out, the data will come out, which (for people that know me, and know my curiosity about things), as you might imagine how that is affecting my psyche at the moment, but that's a completely different discussion.
You have to initiate two paths. Path A is the Head & Neck looks great, and we continue on and finish the Study, and we go down that path, and that's a good path. And on that path, you always have the question of what's next. We've tried to be as diligent as we can in moving Reolysin into other randomized indications where it makes sense scientifically, and now that we have 5 randomized Phase II Studies ongoing, I think that that's answered that question.
The flip side is that if the H&N Study, for some reason isn't as positive as we all hope, and it can … that happens in oncology, people pick different indications, and sometimes they pick the wrong one first, but the key for us has been to have the resources in-house to proceed on with this other randomized program, and we do. All these Studies that we've announced, because of the way we've structured the funding with the sponsorships, we already have the resources in-house to do these Studies regardless of what happens with the H&N program. So if you want to think of Plan B (if you want to call it that), Plan B is to carry on with randomized Studies that are rational from a scientific perspective to define Reolysin's home … to find the right home for it. So Plan A has you expanding use, and Plan B has you finding (in a randomized clinical setting) where the best place for Reolysin is, both being fully funded.
I think the first Phase II randomized data that's likely to come out will be the pancreatic Study in the States, which is carbo/tax vs carbo/tax/Reolysin, and that's an interesting Study in that we're not using Gemzar in first line patients.
But I think you can see a theme across all these clinical Studies that we're doing, is that there's a very heavy emphasis on metastatic disease, and that's the case there. Even primary pancreatic cancer which is all metastasized, or the primary colorectal Study which we'll be doing in Canada, virtually all the patients will metastasize. All the second line patients and further on, like the Ovarian Study are all metastasizing. You have this kind of theme of metastatic disease running through the whole program and I would think that the panc study will be the first Phase II Study to report out either on an interim or a final basis.
Philippa: And when would you expect that data?
Brad: We're just working through that right now. I don't have a specific date on that, and it's an evolving picture, and we're having discussions with the Investigator about when would be best to discuss the data. Again, there's a heavy emphasis on looking at the correlative bits, particularly the KRas in that indication. Again, there's a picture emerging, and it's really when we're comfortable with the picture … that is the time to talk about it.
< Close by Brad >
I'd just like to thank everybody for their time and attention this morning, and let everybody know that I would expect to see further evolution of this Phase II program, all these different randomized Studies, within these coming weeks and months. This is an exciting stage for the company to be in, to be actually spreading out in randomized Studies, to really definitively answer with respect to specific indications about whether Reolysin actually has the statistical evidence of being active in each one of these indications. It's been a long time coming, and we're delighted to actually be at this stage of development with the company.
So again, thank you, and hopefully we'll have another communication with you soon.
< end >
Transcribed by rjc
Webcast - Randomized Phase II Conference Call
http://www.newswire.ca/en/webcast/detail/986501/1062975
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN(R), its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit:
www.oncolyticsbiotech.com
BOA/ML Healthcare Conference
http://finance.yahoo.com/news/oncolytics-biotech-inc-present-bank-110000829.html
CALGARY, May 15, 2012 /PRNewswire/ - Dr. Brad Thompson, President and CEO of Oncolytics Biotech Inc. (TSX: ONC, NASDAQ: ONCY), will present a corporate overview of the Company at the Bank of America Merrill Lynch 2012 Health Care Conference on Tuesday, May 15th, 2012 at 8:40 a.m. PT.
The conference will take place from May 15th to 17th at the Encore at the Wynn in Las Vegas, NV.
The live audio link to the webcast presentation is available at:
http://www.veracast.com/webcasts/baml/healthcare2012/id78487700.cfm
, or on the company's website at http://www.oncolyticsbiotech.com/presentations. It is recommended that listeners log on 10 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
Randomized PhII Colon trial combo w/FOLFOX-6 plus Avastin will be the second trial sponsored and conducted by the NCIC Clinical Trials Group (CTG)
http://ih.advfn.com/p.php?pid=nmona&article=52266413&symbol=ONCY
This trial has been long in coming but another Phase II trial paid for by somebody else and hmmmmmm, who makes Avastin?
Key parts of this announcement in my mind are:
NCIC Clinical Trials Group (CTG) at Queen's University in Kingston, Ontario, will sponsor and conduct a randomized Phase II study of REOLYSIN® in patients with advanced or metastatic colorectal cancer.
Approximately 50 response evaluable patients will be enrolled in each arm, after a six to nine patient safety run in.
The NCIC Clinical Trials Group (NCIC CTG) is a cancer clinical trials cooperative group that conducts Phase I-III trials testing anti-cancer and supportive therapies across Canada and internationally. It is a national research program of the Canadian Cancer Society.
More than 60 member institutions, from major cancer centres to community hospitals, enroll patients in NCIC Clinical Trials Group studies.
Enrollment should be fast after the first 9 with 100 patients total planned and 60 centers enrolling.
Each indication Reolysin is tested in makes the potential steadily grow with each indication advanced into Phase II trials.
Yorkshire Post Article on PHII UK H&N Trial
This article is based on already published trial results
Leeds scientists find way to boost drugs used in cancer battle
Published on Monday 2 April 2012 06:00
CANCER specialists working in Leeds have found that a harmless human virus may be able to boost the effects of two standard chemotherapy drugs in some patients.
A new drug called RT3D, or Reolysin, is based on a virus that is found in the respiratory and gastrointestinal tracts of most adults without causing any symptoms.
RT3D has the ability to grow in and kill certain types of cancer cells, but does not grow in normal cells.
Previous trials injecting patients with the virus on its own showed limited effectiveness, but in clinical trials researchers found that RT3D appeared to magnify the effects of platin and taxane-based chemotherapy on tumour cells.
Dr Kevin Harrington and colleagues in Leeds started a clinical trial testing intravenous RT3D in combination with chemotherapy drugs carboplatin and paclitaxel in 31 patients with advanced cancers who had stopped responding to standard treatments.
An initial study was carried out in patients with a range of advanced cancers, which showed the drug combination was safe. Side-effects were found to be generally mild, and consistent with chemotherapy alone.
Patients with head and neck cancers were found to have the best responses, so a second study at the Royal Marsden Hospital, London, and St James’s Hospital, Leeds, was targeted at patients with these types of cancers.
Cancers shrank for about one third of the patients who could be evaluated, and disease stabilised for a further third.
For one patient, all signs of cancer disappeared.
Dr Harrington said: “We saw really very impressive response rates in these patients. These are patients whose cancers had grown despite a great deal of previous treatment, including platinum-based chemotherapy for many.
“Under those circumstances, we’d expect that the average response rate to chemotherapy alone might be as low as single- digit figures and the average survival would be somewhere between three and four months. In our Phase I/II study we show this had been prolonged to an average of seven months, albeit not in a randomised trial.
“We’ve now started recruiting patients with advanced head and neck cancer to a randomised Phase III trial, in which all patients will receive chemotherapy and half will receive Reolysin as well.
“We are extremely excited about this progress.”
The study also found the virus was not shed after treatment. This means people could be given the drug as outpatients as no risk was found that they could transmit the virus to others.
Head and neck cancers include tumours of the eye, nasal cavity, tongue, gums, lip, cheeks, voice box and oesophagus.
Dr. Thompson Needham Conference Transcript 4April2012
Neeedham Conference April 4th 2012
Webcast: http://wsw.com/webcast/needham51/oncy/
Thanks to inthno57 for the transcript from the Yahoo V2 group
[Brad:] Today I would like to talk about our product Reolysin, which is in clinical stage development and we would really like to draw people's attention to today and over the next couple of months, is our ongoing phase 3 study for second line head and neck cancer patients which has actually finished the first stage of a 2 stage study of the enrollment and we're expecting a preliminary data readout in the very near future and to also start bring people's attention to our other randomized studies that we're now enrolling in...we have a drug trialed ovarian study in the united states, an interesting first line study in pancreatic cancer where we're not using Gemcitabine, and one we just announced recently which is a recurrent castration resistant prostate cancer study in Canada that I'm waiting for Oncogenics who is 2 before me to finish enrolling in Canada so that I can start enrolling which should be in the next 6-8 weeks.(small planet)
1:49) I'd like to talk briefly about our ip portfolio and I'll talk very briefly about our manufacturing program which is moving parallel in pace with our phase 3 study. Outside of our randomized studies (which is the first 4 on the list of the slideshow) ongoing right now are a number of single arm studies which we're finishing up...we have 2 studies in small cell, we have adenocarcinoma lung study just finishing enrollment right now and a squamous cell lung study running in parallel with the same study design that is a little behind that and we'll actually be making a decision on which of these 2 studies to take into a randomized study this quarter....and so I think you should expect to see some form of announcement on Reolysin this quarter on which one will go into a randomized study.
2:41)..and talking about colorectal cancer similar thing in the works, either this week or next week finishing enrollment in the phase 1 for the colorectal and we'll be announcing a decision to go into a randomized phase 2 study on that sometime this quarter as well.....
3:00) What is Reolysin? It is somewhat different than most products you will encounter. It is based on a proprietary isolate of a very common environmental virus called the reovirus which is a double stranded RNA virus for those of you who are into that side of things....it's a fully replication competent virus and it's considered to be safe to humans or it was at least when we entered into clinical studies.
The natural infection cycle for Reo is oral-fecal so it's ingested, it replicates at very low levels in a sub cell population that lines your bowel and it's excreted in feces and then it contaminates your food and water supply which is far more regular than I should talk about before lunch and then you get the re-infection cycle....about half the children at age 5 have evidence of Reo infection and almost all adults. So it's a very common environmental virus.
Our clinical isolate is 11base pairs different than the wild type but it's functionally identical.
We went into our clinical program and just assumed that we would have to go back to the beginning because it's quite different than administering directly into different organs than systemically. So we've done a fairly extensive intravenous program, started out intratoumorally and ran 2 glio studies where we did direct injection into the brain....which is the most extreme safety challenge of all because if you see any signs of encephalitis you'll see it clinically and we did not of course which was reassuring.
4:40) The agent acts based on a differentiation between cells that have a constituous Ras pathway and cells that do not. The virus will enter every cell in your body, the most common binding site is sialic acid which is a sea of it covering every cell in your body....what happens inside the cell that differentiates this, in cells that do not have an activated Ras pathway...those cells will actually have an intact anti double stranded RNA anti-defense mechanism that's not immune, it's actually ancient lineage, it's conserved across all mammals so it's a very ancient event that is based upon the activity of a compound called PKR (protein kinase R) which actually binds the double stranded RNA in the cytoplasm and shuts down replication. So if you have a normal cell, Reo will go into the cell, un-coat, double stranded RNA is bound by PKR and that's the end of the story and that's an absolute on off switch.
In cells that have an activated Ras pathway, PKR is deactivated so the viral defense mechanism is gone and the cell is open to infection. So that's the basis for selectivity...Now that would be a curiosity at best if there wasn't disease states associated with Ras activation...the main side effect of Ras activation is uncontrolled cell growth which all cancer is and so you find a very high degree of Ras activation in oncology and in different indications. We think about 2/3 of solid tumours have a Ras pathway defect and over 90% of metastatic disease and varying levels in non solid tumours.
6:23) and so you have a nice marriage between a potential activity based on the selectivity and a disease state which has commercial interest which is for us....fortunately for us, most of this Ras activation is caused by two different mutations where over expressions EGFR, either a mutation over expression causes Ras pathway activation and mutation at the Ras protein itself which is mostly K-Ras also leads to that and those are now 2 commonly tested for various reasons...mutations and over expressions in oncology patients so it's already integrated into the standard of care mostly here in the united states, so it's a nice marriage between potential mechanism and an interesting indication.
Looking at this schematic, the virus enters all cells, the differentiation is not there, if it's a normal cell that the Ras pathway is not activated or a cancer cell that does not have a Ras pathway activation then nothing happens, the viral mechanisms are intact and in the cell that has an activated Ras pathway you get this replication cycle which leads you to an interesting fact or side product, that this drug if you want to think of it as a drug, actually replicates, so you get this large amplification of virus within tumours that it's actively growing in....
7:40) We've taken human samples from human tumours in patients and actually seen a many log amplification of virus within the tumours and actually most of the effect of the virus is due to the virus produced within the body, not the input virus which makes pharmacokinetics very awkward to do.
The selectivity is absolute, we've run actually 2 studies where we were looking at selectivity, an early T-2 prostate study and this particular slide which came from the new adjuvant study in patients with metastatic colorectal cancer which had metastasized to the liver. In this study we were treating patients with monotherapy Reo prior to surgical excision of the tumours and then looking at the histopathology and most people when they take a look at this slide think we were staining for tumour which is sort of correct, actually we're staining for replicating virus and with one exception in all of slides that we've every looked at absolutely centered all inside the tumour cell and tumour mass and you actually have dead and dying tumour butting up against healthy tissue, cell to cell contact without transfer of cellular death event into the healthy tissue. One exception is one apadocyte that we saw infected with Reo once and that`s just for disclosure purposes. It is very very selective.
9:03) With respect to looking at a potential market for Ras mediated cancers, a firm (not Needham) has given me an estimate that drug sales worldwide for oncology in 2011 was 77 billion dollars and when you relate that to the number of carcinomas that have ras-pathway incidence you come up with about 5 million patients in Western Europe and the united states and accessible markets in Asia that actively have a Ras pathway depending on incidence of cancer, it's a big potential market.
Our phase 3 study is looking at 2nd line head and neck cancer patients, head and neck is a little different, 2nd line can mean 3rd treatment,...first treatment is often radiation and or surgery which is actually curative in about half the cases...They then go on to first line treatment which refers to their first exposure to chemo...the most common first line therapy , increasingly with Erbitux involved is platinum 5fu. Occasionally people will substitute a taxane for the 5fu just because it's easier to administer although it doesn't actually give you any more benefit but it is easier on the patients and then they progress onto 2nd line about half those patients and those patients are very consistent which makes them a nice patient group. So our particular patient group is platinum refractory taxane naive patients in the 2nd line. The first country applied for was here in the U.S. under a spa and then we expanded it out internationally...we're now currently approved in 13 countries internationally and enrolling patients in 12 and currently have around 85 sites that are actually enrolling patients right now and on the way to 100.
10:55) it's a 2 arm study, double blinded, one to one weighting, so the control arm is carboplatin paclitaxel saline, there are getting blinded saline, and the test arm is carboplatin paclitaxel Reolysin and it's a 3 week cycle....after 8 cycles on the triplet, then the patients, if they are stable disease or better are eligible to go on maintenance therapy of Reolysin by itself or saline if that's the arm they're in.
The primary endpoint is over survival, the secondary endpoint and tracking endpoint which is important is progression free survival....there's certainly a lot of dialogue about whether PFS is predictive of OS in oncology....and it appears for some indications that it is very predictive and those are the ones that actually have a short time duration between progressing and death, and as a general rule of thumb, if that progression leads to death in 6 months or less, generally there's a good statistical correlation , if it's longer than 6 months, then it's a terrible statistical correlation, so one has to be careful when using PFS as a tracking endpoint, but certainly the differential in this patient population is about 10 weeks which falls comfortably in that 6 month time frame, so it's actually a very good tracking endpoint.
12:11) The study is structured as a pier (?), we run 80 patients in the first stage of the study which we announced last Friday that we had completed. We then do a statistical analysis to look for probability of success in the 2nd stage and that's based actually on looking at the relative PFS, the weighted PFS's of the population in the first stage which we're using as a surrogate for overall survival....based on that, you then decide whether to continue treating in the second stage or not. We have actually moved seamlessly into the 2nd stage already and we'll decide whether to continue that stage or not based on this predictive analysis which will be happening in the very near future. The second stage of the study is adaptive from 1 to 400 patients which will actually be largely sized by this predictive analysis...our best guestimate at the moment is around 200 patients in the 2nd stage which at our current rate of enrollment, we would be enrolled before the end of the year assuming we actually still treat patients in August in Europe or not which is always a big question in oncology.
13:22) One of the interesting things that come out of our phase 2's in head and neck was looking at some of the interesting oddball kind of things that are a positive... the first one I think was, that's why I show a scan of a metastatic lesion rather than a primary is that when you grade metastatic lesions on Reo and it doesn't really matter where the primary is, because if you look at lesions in the lung, liver, and lymph nodes , you get a true true response rate by RECIST somewhere between 40 and 50%, regardless of the drug combination, regardless of the study, and we see this in head and neck too and this is what the main cause of death is in head and neck is the metastatic lesions, so I think it's relevant ... and this is an example where you have a heavily pre-treated patient, which has actually seen everything pretty much with this nice dramatic response, and durable response. This is a post cycle 3 scan and the response was maintained through the entire duration of this particular study program and this is very typical when you see responses of Reo, there is aggressive, rapid and quick as I mentioned between a 40 and 50% true response rate in metastatic lesions and that is actually one of the reasons we are looking at metastatic head and neck cancer.
14:37) If you look at historical rates for this particular patient group, most studies give you response rates in the low single digits, and Vermorken who is the PI for the registration study for Erbitux in Europe and who is my PI in Europe estimates that for the control arm we should be looking at a 10% response rate to be conservative....In our phase 2 study in Europe we had a 42% response rate and actually if you merge our U.S. and European study, and look at the same patient group which is the taxane naive patients, the response rate is actually 50% which is gratifying when you're comparing it to historical....and everybody does this and it's not hugely relevant, if you plot your Kaplan Meir from single arm studies against historical, it's always vaguely reassuring, but the key thing for us is that we see a pretty long survival tail that is quite unusual especially for these head and neck patients and while we can't see the blinded study which arm the patients are in and again this, you start looking at your blinded data and try to imagine what it might look like, everybody does it, I don't know how useful it is, we're seeing a similar survival tail that you wouldn't expect to see but we'll see when we break the code if it pans out or not.
16:00) The other randomized studies that we are running are all phase 2's in different stages of enrollment....We're running a 110 patient drug trailed ovarian here in the United States in combination with paclitaxel, it's a one to one weighted arm and this is an odd merger sponsored by the NCI but we have a bunch of co- responsibilities underneath it which is not typical with an NCI study ... and it's being conducted by the gynecological oncology group. We anticipate full enrollment on this study late this year and so data will not be available on this until q2 or q3 of 2013....
We just announce a castration resistant prostate cancer study in Canada again a kinda fused one between us and the ncic in Canada and this will be an 80 patient exploratory study and this is based largely on a collection of very dramatic responses we saw in both patients in other studies and some special access patients that we had done in Canada....and again the combination with taxanes which you'll see very commonly with Reo is where we're looking at with this study ... enrollment should start later this quarter and we expect enrollment to be finished by the end of the year and my most fun and kind of interesting one that we focus on is pancreatic cancer....pancreatic cancer should be amenable to treatment by a lot of things and it's not and that's why it's been a question ... I think a lot of us who work on this think that it is more drug penetrability into the pancreatic head that's the issue rather than that the drugs work or not...I mean if you take Gemzar, it works great on tumours excised but not so great on tumours in vitro ... it's really getting the drug into it and so you see studies like taxane Gem combinations that try to do that because taxanes open up tumours quite nicely and we're the same....our thinking is that using an agent that helps the drug get into the tumour is a good thing, so we're actually running carboplatin paclitaxel in combination with Reo.
18:10) We're omitting Gemzar in that randomized study simply because I believe there's that increasing belief that you really have to beat Gemzar rather than matching Gemzar to have a chance of coming up with something new that will be approvable ... the primary endpoint in this particular study is PFS because we have a crossover arm so all the patients that fail on carbotax will then go onto carbotax Reolysin which will also give us valuable information on drug failed patients, again people are actually starting to talk about 2nd line pancreatic patients for the first time in my experience which is nice, it's actually nice to be developing a patient group that actually might live long enough to be 2nd line.
Again it's a odd one ... we're sponsoring some of the sites and the NCI is sponsoring some of the sites so it's an odd fusion and we expect to have data at least preliminary data on this study this year so we're quite looking forward to that.
19:05) We're also running a single arm Gem Reo study with the anticipation for a registration study, the fda will then buck up and decide that we have to have a Gemzar somewhere and so we want to have Gem Reo data prior to going into that discussion with the FDA ...
This is a partial response with Gem Reo in that single arm study and generally I show this because partial responses in panc studies are so rare but to also show that we actually get a nice response in the lymph node sitting on top of the pancreatic head and again, very characteristic of Reo is once a tumour is outside the primary, you have very high expectation of getting responses in the metastatic lesions.
This is a live agent, it's a virus so we continue to focus and talk about safety...We've now treated over 500 patients in our in house clinical program and the NCI is coming up on 200 patients in their program....most of which we treated intravenously and when you look at the monotherapy safety profile of Reo, it's very reproducible, it's basically pre-flu syndrome which causes a bit of an issue in blinding....if fever for example is predictive of clinical response, which it is in Reo, then you have to blind the fever which means we treat with ibuprofen in our phase 3 study to get rid of the fever. But the toxicities are basically clinically mild fever, mild joint and muscle pain and usually grade 1 or 2 fatigue.
When you look at the blood chemistry, it's just like you'd expect with an infection which is low grade neutropenia and lymphopenia which resolves quite quickly ... the only caution I would ever have to date about using Reo is when dosed with high dose Gem....the Gem doses that we use here in the United States are not an issue....the Gem doses in the U.K. are about 20-25% higher and then you start to see grade 3 and grade 4 neutropenia and lymphopenia ....I mean, Gem causes that at high doses and you push it a little further with Reo and those can be an issue and that's my only caution to date using this drug and the nice thing about these is that the symptoms only usually last less than 6 hours, they usually express on day 2 or day 3 of a 5 day cycle and that's it....so we're getting quite comfortable with the safety profile.
21:30) With respect to intellectual property, we were very aggressive very early and we actually have almost 300 patents issued worldwide now and another couple hundred filed worldwide after that...we do have composition of matter claims which expire in 2028 which is interesting for a virus that was discovered in 1958 or 1959, but pharmaceutical use, combination therapy and all manufacturing steps which were quite unique so I think we've done as good a job as one can be expected of this and of course we're now starting to see challenges and we've actually had a couple of challenges from our big Pharma colleagues which we've actually defended successfully, so we'll see in the end how it works out....we're comfortable to date with our IP portfolio and of course 10 years of work condensed to 2 data points on a slide....biologics are notorious for looking interesting in the clinic and not looking so interesting when you try to reduce the manufacturing in practice for filing and so we became a bit obsessive about this early on and we're actually have a very efficient process, very cost effective...now a manufacturing facility that fills half this room can produce 100 thousand dosages a week, iv standard dosages a week, we're just finishing off actually our last conformance run for the product dossier for our hopefully rolling BLA and we have a commercial manufacturing agreement with Sigma Aldrich with a facility that they purchased for our use in Carlsbatton California... and so the conformity runs will actually be stockpilable for launch so hopefully this is not going to be Oncolytics Achilles heel .. it's certainly something we paid a lot of attention to.
23:20) I skipped a bit about the labeling
Trade both on Toronto and NASDAQ ... approx 76 million shares and fully diluted about 85 million shares and with the cash we have on hand, we're fully funded for all our programs until the end of 2013...so out past the endpoint of our phase 3 study and out past the endpoints of the randomized phase 2 studies that we are currently running...
Summary ... phase 3 for head and neck stage one data rollouts happening very soon and a stage rollout for a predictive probability of success in stage 2 and then we'll get the PFS and OS data later this year and then the other randomized studies moving forward that you can expect to hear about in the next quarters and years.
The END
Q&A
Question 1 about whether you would see the same with wild Reo infection? (I skipped some of this) basically Reo doesn't cross the bowel barrier and that's the real issue and the dosage is low....It comes down to delivery and dosage....A wild infection you might ingest 100 viral particles, well below the therapeutic dosage in a human...we're administering 3x10 to the 10th daily of infectious and 3x 10 to the 12th total particles, so the route matters and the dosage matters a lot and for us it's just the numbers game, I mean you have about 10 the the 15th cells in your body and I'm putting 10 to the 12th particles in and I'm trying to get some of the tumour infected and then the infection will take over....
26:00) skipped a bit of talk about gastroenterology...etc..
Question 2 about people being naturally infected by 5 years old----basically people coming into the clinics have very low titers of neutralizing antibodies against the virus... and early on we thought that neutralizing antibodies might be a real problem but you put Reo in intravenously and you get a robust immune response and how does that affect things and honestly we spent a lot of time and energy and a lot of other companies have spent energy focusing on that and we found it was a complete red herring in the vernacular ....the virus actually binds to red blood cells which makes them almost instantly invisible to the immune system and the red blood cells when they're delivering oxygen to a tumour are also hitchhiking the virus and we just actually recently just found this out...here we are in the middle of a phase 3 study and we actually figured out how the virus gets to tumours, but those are the kind of surprises that you find, but the immunes system doesn't seem to be an issue at least from a therapeutic perspective, the virus fortunately is fairly benign so it clears out very quickly if you don't get an infection in a tumour...most of it's a filtration of the liver and lungs, it's a mechanical filtration so the body doesn't have time to mount an immune response and the virus is gone....it's an odd virus....
27:50)...Question 3) do we get resistance to Reo and why do patients and why do patients die....it's been a bug bear in the whole industry as you know, I mean you take a patient, get a complete response and they still die on schedule or almost on schedule and you scratch your head and go why ... We seem to have 3 distinct patient groups, there's about a quarter of the patients generally, that the tumours just grow like you're not even treating them, they just keep going ... about another 25, 30,35%, depending upon which study you're looking at, you get stabilization ... and as soon as you quit treating....BOOM...the tumours just explode again...
We did a metastatic sarcoma study a few years ago using Reo as a monotherapy and we had patients out on study between 2 and 3 years, quite a few of them and of course they start taking themselves off therapy, they thought they were fine and everyone of them as soon as they came off therapy within weeks was dying and were all dead within 8 weeks.... and one guy was just a month short of 3 years of therapy, I mean he comes in for a couple of days, comes home and he's fine , goes off therapy and you have that patient group...and you have the other patient group, the 40 odd percent that have aggressive fast robust responses that maintain for a long time and it seems like there's 3 groups, we're taking biopsies as often as prudent in the phase 3 to hopefully correlate backwards to find out...it would be nice to screen out non responders or screen in responders....my guess is that head and neck doesn't have much k-ras, but there will be strong correlation with some EGFR sub type mutation, because there is differences in the different EGFR's and in the other studies where we're looking more at k- ras, there seems to be a virtual absolute correlation with K-Ras and response....I mean, I can say it pretty confidently now that if you have a K-Ras mutation driven disease, I can almost guarantee you a stable disease or better on Reo....it doesn't matter what it is...panc...non small cell lung, colorectal, it's interesting to date...it's not statistical yet, but it's getting there....so why patients progress, we don't know...and I wish we did know...we don't seem to get immunity getting back to the original part of your question to Reo, I mean if there's a mechanism of action it doesn't lead to resistant populations of tumours, if it has a Ras pathway it will kill it, if you don't , it won't....
30:40) question 4) will Oncolytics wait for a broader based label or launch statistically on head and neck?
If we get the results we hope to get in the phase 3 we will launch specifically on head and neck and then broaden the label out on subsequent studies...
Question 5) ... Are you looking to sell out or partner?
We set ourselves up to partner originally....the question was whether we should partner or not....the standard however running joke at Oncolytics is that people are always wanting to see the next stage, so I'm sure some of my big Pharma colleagues will wait to see first quarter sales now before they get interested....but my expectation is that we'll still partner prior to actual first sales...of course recently in the last 18 months to 2 years we're seeing an increasingly and large different types of partnerships which is M&A which is normal for the rest of the universe, just not for biotech and it's becoming more normalized....when you look at the private company acquisitions by our big Pharma colleagues, they have been much more aggressive than I think people realize on the public side just because it's invisible...I mean Pfizer...look at how many companies Pfizer has bought over the last 5 years, it's a pretty remarkable path but private most of them, so that etiquette is just as likely today as partnering honestly...
32:25),...question on accrual rates
I'll comment on the accrual rates..I'm never happy with the accrual rates in the clinical studies and if I can find a biotech oncology CEO who says I am delighted with my accrual rates, I'd love to meet them ... at the moment however, I am delighted with my accrual rates on my head and neck study...I was not early on ... it's interesting, we based our accrual rates for our phase 3 study on historical accrual rates, not forecasted but historical accrual rates at the sites that we're running other head and neck studies, primarily falling out of the Erbitux head and neck studies ... so we thought we were rock solid going in and we found our accrual rates were actually less than half than anticipated, now you scratch your head and go away and you find that individual sites quite often broaden enrollment criteria beyond what the company thinks they're enrolling in, that's the accrual rate which of course that's disastrous for clinical studies, so once we found that out we said, we'll our guys are sticking to the enrollment criteria, that's good, so the way to combat that is to have more sites....so we had planned actually to have 40 sites entering the 2nd stage of the study and you'll notice I mentioned a number greater than 40, more than twice than 40, heading to 2 ½ times 40 and so we're actually at our peak enrollment rate that we had anticipated for for the second stage now and so I'm happy now....whether I'll be happy later is another issue...The one study that I'll have to say the accrual rate befuddles me is our squamous cell lung study. This is common with other squamous cell studies that I talk to people about too....I mean squamous cell is what, 25-30% of non small cell lung cancers....horrible outcomes, nothing works, nobody's working on it so you would expect that all of us would have no trouble at all recruiting patients....quite the opposite. Again, our response to that is to add more sites and so that's a commonality, so there are some areas that you just don't know why ... and another one that`s working better than expected is pancreatic cancer ... easy peasy...I hate to use that expression, but panc studies are really easy to enroll into ... I think we all know why, but it's indication specific....
End of Webcast
Needham Conference Highlights
Thanks to several on the Yahoo private board (matdu in particular) for posting highlights of this conference. There were several very interesting comments by CEO Brad Thompson of Oncolytics Biotech.
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Some have posted a few of the highlights on the public board, I am trying to add a few that I think are important to the list:
- More than 500 pts treated so far, with the NCI enrollment approaching 200.
- H&N phase III stage A data read-out should be coming in the near future.
- Some time this quarter, they should be able to come up with a decision on the NSCLC or squamous lung trial to see which one to take into a randomized study.
- Squamous lung trial enrollment is slower than expected, while the panc trials are enrolling faster than thought. Highly indication dependent.
- This quarter: should be able to decide whether to advance the colon trial into a randomized trial.
- H&N phase III : currently registered 13 countries with 12 enrolling. Total centers is 85, going to reach 100. Enrolling rate is expected to reach peak level about now. If they need to enroll 200 more patients in stage b, could accomplish that by the end of the year.
- H&N: PFS is generally a good indicator for OS if the time frame is less than 6 months. It should serve as a good tracking end point for the H&N trial.
- The NCI ovarian trial should complete enrollment by the end of the year, with data coming in Q2 or Q3 next year.
- Prostate trial should complete enrollment by the end of the year.
- Only safety concern with reolysin combo trial is with gemzar, especially with the higher (25%) European dosage.
- Has obtained composition of matter patents for reolysin that expire in 2028. Big pharmas have couple patent challenges but were defended successully by ONCY. My question is were those challenges for reolysin or for other viruses like herpes and vaccinia. It would be even more interesting if these were for non-reo viruses because it could mean that ONCY might have claims on the use of these other viruses for cancer treatment. That could further enhance the value of the company.
- A question on partnership: Bt said he still expects some kind of partnership before launch, but he did mention all these other M&A schemes done in other industries are becoming common in the biotech/pharma field.
- There are 11 bps differences between what ONCY uses in the trials compared to the wt strain.
- Reo appears to evade the immune system by attaching to red
blood cells
- In regards to manufacturing Brad said they can currently put out 100,000 doses per week (in a facility that was specifically build for them). He mentioned that the virus they are producing in these ongoing trial/confirmation runs would be usable for commercial release.
Needham Healthcare Conference Presentation April 4
CALGARY , April 4, 2012 /CNW/ - Dr. Brad Thompson , President and CEO of Oncolytics Biotech Inc. (TSX: ONC.TO - News) (NASDAQ: ONCY - News), will present a corporate overview of the Company at the 11th Annual Needham Healthcare Conference on Wednesday, April 4 th, 2012 at 11:20 a.m. ET . The conference will take place on April 3 rd and 4th at the New York Palace Hotel in New York, NY.
A live audio link to the webcast presentation is available at: http://wsw.com/webcast/needham51/oncy/ or on the company's website at www.oncolyticsbiotech.com. It is recommended that listeners log on 15 minutes in advance of the presentation to register and download any necessary software.
An audio replay will be accessible approximately one hour following the presentation on the Oncolytics website.
Enrollment completed First Stage -Phase III Head&Neck
http://finance.yahoo.com/news/oncolytics-biotech-inc-completes-enrollment-110000297.html
CALGARY , April 2, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC, NASDAQ:ONCY) announced today that it has completed enrollment in the first, 80 patient stage of its Phase III clinical trial examining REOLYSIN® in combination with paclitaxel and carboplatin in patients with platinum-refractory head and neck cancers (REO 018).
"This is an important milestone for this study," said Dr. Brad Thompson , President and CEO of Oncolytics. "A data analysis that will involve examining evolving progression free survival will now be performed on this patient group to determine the probability of success in the second stage of the study."
The randomized, two-arm, double-blind, multi-centre, two-stage, adaptive Phase III trial will assess the intravenous administration of REOLYSIN with the chemotherapy combination of paclitaxel and carboplatin versus the chemotherapy alone in patients with metastatic or recurrent squamous cell carcinoma of the head and neck, or squamous cell cancer of the nasopharynx, who have progressed on or after prior platinum-based chemotherapy. All patients will receive treatment every three weeks (21 day cycles) with paclitaxel and carboplatin and will also receive, on a blinded basis, either intravenous placebo or intravenous REOLYSIN. All dosing takes place in the first five days of each cycle, with all patients receiving standard intravenous doses of paclitaxel and carboplatin on day one only, and on days one through five, either intravenous placebo or intravenous REOLYSIN at a dose of 3x1010 TCID50. Patients may continue to receive the trial combination therapy for up to eight, 21-day cycles and, thereafter, blinded placebo or blinded REOLYSIN until the patient has progressive disease or meets other criteria for removal from the trial.
The primary endpoint for the trial is overall survival (OS). Secondary endpoints include progression free survival (PFS), objective response rate (complete response (CR) + partial response (PR)) and duration of response, and safety and tolerability of REOLYSIN when administered in combination with paclitaxel and carboplatin. The first stage of the trial is non-adaptive, and was designed to enroll 80 patients. The second stage is adaptive, and is designed to enroll between 100 and 400 patients with the most probable statistical enrollment being 195 patients in this stage. This adaptive trial design allows data evaluation to determine if the probability of reaching a statistically significant endpoint has been achieved.
The trial is currently being conducted in more than 80 centres in 12 countries in North America and Europe , including the U.S. following an agreement with the U.S. Food and Drug Administration (FDA) under the Special Protocol Assessment (SPA) process with respect to the trial's design.
Investor Presentation Updated - 80th Patient Milestone Reached
March 31, 2012
http://oncolytics.s3.amazonaws.com/presentations/25/original.pdf?1331049058
Harrington Video from Institute of Cancer Research Publication
http://www.icr.ac.uk/press/press_archive/press_releases_2012/22642.shtml
Trials show promise of human virus to treat head and neck cancer patients
Sunday 1 April 2012
A naturally-occurring harmless human virus may be able to boost the effects of two standard chemotherapy drugs in some cancer patients, according to early stage trial data published today in Clinical Cancer Research.
RT3D, trade name Reolysin, is a new drug developed by Oncolytics Biotech Inc with preclinical and clinical studies conducted at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital. It is based on a virus (reovirus type 3 Dearing) that is found in almost all adults’ respiratory and gastrointestinal tracts without causing any symptoms.
RT3D has the ability to grow in and kill certain types of cancer cells, but does not grow in normal cells.
Previous trials injecting patients with the virus on its own showed limited effectiveness, but the team found that RT3D appeared to magnify the effects of platin and taxane-based chemotherapy on tumour cells.
Dr Kevin Harrington Video
Dr Kevin Harrington talks about how a human virus may be able to boost the effects of two standard chemotherapy drugs
Dr Kevin Harrington and colleagues in Leeds therefore started a clinical trial testing intravenous RT3D in combination with chemotherapeutics carboplatin and paclitaxel in 31 patients with advanced cancers who had stopped responding to standard treatments.
An initial Phase I study was carried out in patients with a range of advanced cancers, which showed the drug combination was safe. Side-effects were found to be generally mild, and consistent with chemotherapy alone.
Patients with head and neck cancers were found to have the best responses, so a Phase II expansion study at The Royal Marsden Hospital, London, and St James’s Hospital, Leeds, was therefore targeted to patients with these types of cancers.
Cancers shrank for about one third of the patients who could be evaluated, and disease stabilised for a further third. For one patient, all signs of their cancer disappeared.
“We saw really very impressive response rates in these patients. These are patients whose cancers had grown despite a great deal of previous treatment, including platinum-based chemotherapy for many,” Dr Harrington, Leader of the ICR’s Targeted Therapy Team and Consultant Oncologist at The Royal Marsden, said. “Under those circumstances, we’d expect that the average response rate to chemotherapy alone might be as low as single digits figures and the average survival would be somewhere between three to four months. In our Phase I/II study we show this had been prolonged to an average of seven months, albeit not in a randomised trial.”
“Based on the results of this study we’ve now started recruiting patients with advanced head and neck cancer to a randomised Phase III trial, in which all patients will receive chemotherapy and half will receive Reolysin as well. We are extremely excited about this progress.”
The study also found the virus was not shed after treatment. This means people could be given the drug as outpatients as no risk was found that they could transmit the virus to others.
Head and neck cancers include tumours of the eye, nasal cavity, tongue, gums, lip, cheeks, voice box and oesophagus. Around 650,000 people are diagnosed with squamous cell cancer of the head and neck each year worldwide, and around 350,000 die from the disease annually.
- ENDS -
Media Contact: Jane Bunce on 0207 153 5106 or after hours 077217 47900 or Tatjana Trpoksa on 0207 153 5312 or after hours 07780689891
Notes to editors:
Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies with first author Eleni M. Karapanagiotou from the ICR and The Royal Marsden publishes in the print edition of Clinical Cancer Research on April 1.
The Phase III trial is recruiting patients with head and neck cancer who have already been treated with platinum but not taxane. More details at: http://clinicaltrials.gov/ct2/show/NCT01166542
The Institute of Cancer Research (ICR) is one of the world’s most influential cancer research institutes.
Scientists and clinicians at the ICR are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR’s mission is to make the discoveries that defeat cancer. For more information visit www.icr.ac.uk
The Royal Marsden NHS Foundation Trust
The Royal Marsden opened its doors in 1851 as the world’s first hospital dedicated to cancer diagnosis, treatment, research and education.
Today, together with its academic partner, The Institute of Cancer Research (ICR), it is the largest and most comprehensive cancer centre in Europe treating over 44,000 patients every year. It is a centre of excellence with an international reputation for groundbreaking research and pioneering the very latest in cancer treatments and technologies. The Royal Marsden also provides community services in the London boroughs of Sutton and Merton and in June 2010, along with the ICR, the Trust launched a new academic partnership with Mount Vernon Cancer Centre in Middlesex.
Since 2004, the hospital’s charity, The Royal Marsden Cancer Charity, has helped raise over £50 million to build theatres, diagnostic centres, and drug development units. Prince William became President of The Royal Marsden in 2007, following a long royal connection with the hospital.
Reovirus Research being presented at 2012 AACR
http://www.oncolytics.com/news_items/details?press_release_id=1830
03/29/2012 07:00:00
Oncolytics Biotech® Inc. Announces Reovirus Research to be Presented at AACR Annual Meeting
CALGARY, March 29, 2012 /CNW/ - Oncolytics Biotech Inc. ("Oncolytics") (TSX:ONC) (NASDAQ:ONCY) announced today that abstracts of preclinical research on reovirus (REOLYSIN®) are available on the American Association for Cancer Research (AACR) website at www.aacr.org. The research is scheduled to be presented at the 2012 AACR Annual Meeting in Chicago, IL, which takes place from March 31 to April 4, 2012.
"We are delighted to see that the research community has been embracing preclinical research utilizing reovirus," said Dr. Matt Coffey, Chief Operating Officer of Oncolytics. "This research helps us to continue to refine our understanding of REOLYSIN's mechanism of action, its suitability for combination with other treatment modalities and its potential for application to a growing range of potential cancer indications."
The first abstract, entitled "Reovirus (REOLYSIN) as a potential therapy for malignant peripheral nerve sheath tumors," covers preclinical work malignant in peripheral nerve sheath tumors (MPNST), a rare form of soft tissue sarcoma. The results show that MPNST-derived cell lines including sporadic MPNST without active Ras were efficiently transduced, promoted virus replication and were killed by the oncolytic reovirus. The poster is scheduled to be presented on Monday, April 2, 2012.
The second abstract, entitled "REOLYSIN: A novel reovirus-based agent that induces endoplasmic reticular stress in RAS-activated pancreatic cancer," covers preclinical work done to better understand the mechanisms associated with the synergies in this co-treatment approach. The results demonstrate that the abnormal protein accumulation induced by REOLYSIN and bortezomib promotes heightened ER stress and apoptosis in pancreatic cancer cells. The poster is scheduled to be presented on Monday, April 2, 2012.
The third abstract, entitled "Oncolytic reovirus synergizes with bortezomib and dexamethasone in overcoming therapy resistance of multiple myeloma," covers preclinical work done in therapy resistant multiple myeloma (MM) cell lines. The investigators noted that highly synergistic cytotoxicity was observed with reovirus and bortezomib in both reovirus and drug resistant cell lines OPM2 and KMS-11 at all drug combination ratios. Dexamethasone and reovirus treatment induced synergy in OPM2 cells. The poster is scheduled to be presented on Tuesday, April 3, 2012.
The fourth abstract, entitled "Serum regulates reovirus-mediated cytopathy in K-Ras activated colorectal cancer and intestinal epithelial cell lines," covers the use of isogenic human-derived colorectal cancer cell lines that differ only by the presence of mutant Kras and normal rat intestinal epithelial cells (IEC) with inducible Kras to evaluate whether the presence of oncogenic Kras alters the sensitivity of colon cancer cells to reovirus. The investigators demonstrated that the activity of reovirus was observed in all cell lines studied. Reduction in cell variability was greater in Kras-mutant HCT116 compared to WT Hke3 cells. Consistently, induction of Kras in IEC cells increased the potency of reovirus. The poster is scheduled to be presented on Tuesday, April 3, 2012.
The fifth abstract, entitled "Mammalian orthoreovirus downregulates HIF-1a in hypoxic prostate tumor cells via RACK1-mediated proteasomal degradation and translational inhibition," was added as a late-breaking abstract. The poster is scheduled to be presented on Tuesday April 3, 2012.
About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Oncolytics' clinical program includes a variety of human trials including a Phase III trial in head and neck cancers using REOLYSIN, its proprietary formulation of the human reovirus. For further information about Oncolytics, please visit: www.oncolyticsbiotech.com.
2011 Year End Results Announced
http://finance.yahoo.com/news/oncolytics-biotech-inc-announces-2011-110000413.html
CALGARY , March 15, 2012 /CNW/ - Oncolytics Biotech Inc. (TSX:ONC, NASDAQ:ONCY) ("Oncolytics" or the "Company") today announced its financial results and operational highlights for the year ended December 31, 2011 .
"In the last year we made substantial progress as we announced positive clinical trial results and started clinical trials in additional cancer indications while maintaining the strength of our balance sheet," said Dr. Brad Thompson , President and CEO of Oncolytics. "Our primary focus in the near term remains completing enrollment in the first stage of our Phase III study in head and neck cancers with the support of an increasing number of enrolling centres in Europe and North America ."
Selected Highlights
Since January 1, 2011 , the Company has made a number of significant announcements:
Clinical Trial Results
Presented interim data from a Phase II clinical trial using intravenous administration of REOLYSIN® in combination with gemcitabine (Gemzar®) in patients with advanced pancreatic cancer (REO 017) indicating that the clinical study had successfully reached its primary endpoint, and that the drug combination was active. Eight patients of 13 evaluable patients in the study had stable disease (SD) for 12 weeks or longer, for a clinical benefit rate (complete response (CR) + partial response (PR) + SD) of 62%. An additional patient had an unconfirmed PR of less than six weeks. Seventeen evaluable patients with pancreatic cancer were expected to be treated in the first stage and if three or more patients received clinical benefit, the study would then proceed to the next stage. This endpoint was met after six evaluable patients were enrolled;
Presented positive results from a Phase II clinical trial (REO 015) using intravenous administration of REOLYSIN in combination with paclitaxel and carboplatin in patients with advanced head and neck cancers at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Of the 13 patients evaluable for response, four had PRs, for an objective response rate of 31%. Six patients had SD or better for 12 weeks or longer for a disease control rate (SD or better) of 46%. Two of the four patients with PRs and both patients with SD had received prior treatment with taxanes;
The presentation of interim preliminary results from a Phase II clinical trial using intravenous administration of REOLYSIN in combination with paclitaxel and carboplatin in patients with non-small cell lung cancer (NSCLC) with Kras or EGFR-activated tumours at the International Association for the Study of Lung Cancer World Conference on Lung Cancer. As of the presentation date, response evaluation in 21 patients showed six PR (28.6%), 13 SD (61.9%) and two progressive disease (PD) (9.5%), translating into a clinical benefit rate (complete response (CR) + PR + SD) of 90.5% and a response rate (CR + PR) of 28.6%;
Interim data from a U.K. translational clinical trial (REO 013) investigating intravenous administration of REOLYSIN in patients with metastatic colorectal cancer prior to surgical resection of liver metastases. On initial histological analysis of the 10 treated patients, there was evidence of selective delivery of virus to tumour versus normal liver and viral replication in the majority (seven) of patients;
Ongoing Clinical Program
Entry into an agreement whereby the NCIC Clinical Trials Group (CTG) at Queen's University in Kingston, Ontario, will sponsor and conduct a randomized Phase II study of REOLYSIN in patients with recurrent or metastatic castration resistant prostate cancer enrolling up to 80 patients;
Agreement with the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the National Institutes of Health, to sponsor a Phase I study of REOLYSIN alone in patients with relapsed multiple myeloma;
The opening of enrollment in a U.S. Phase 1 study of REOLYSIN in combination with FOLFIRI (Folinic Acid (leucovorin) + Fluorouracil (5-FU) + Irinotecan) in patients with oxaliplatin refractory/intolerant Kras mutant colorectal cancer (REO 022);
Start of enrollment in a 2-Arm randomized Phase II study of carboplatin, paclitaxel plus REOLYSIN versus carboplatin and paclitaxel alone in the first line treatment of patients with recurrent or metastatic pancreatic cancer sponsored by the NCI;
Completion of enrollment in a U.S. Phase II clinical trial using intravenous administration of REOLYSIN in combination with paclitaxel and carboplatin in patients with advanced head and neck cancers (REO 015);
Manufacturing
SAFC®, a Division of Sigma-Aldrich Corporation, commenced validation activities designed to demonstrate the manufacturing process for the commercial production of REOLYSIN is robust and reproducible;
A commercial supply agreement with SAFC for the commercial manufacture of REOLYSIN. Under the terms of the agreement, SAFC will perform process validation of the product, will continue to supply clinical requirements and will supply commercial material upon approval of the product;
Preclinical Program
The posting of a study in the online version of Molecular Therapy, a publication of The American Society of Gene and Cell Therapy, investigating the timing of chemotherapy delivery that optimizes the efficacy of systemic REOLYSIN. The paper, authored by Kottke et al., was entitled "Precise Scheduling of Chemotherapy Primes VEGF-producing Tumors for Successful Systemic Oncolytic Virotherapy." It describes when best to administer taxanes with reovirus to optimize viral delivery to the tumor mass. The researchers demonstrated that this drug combination yielded superior results to either treatment alone. They were able to reproducibly cure nearly half of the treated animals by employing this optimized schedule of paclitaxel/REOLYSIN;
Financial
Closed bought deal financing, that had been increased to $18.5 million from $15 million , for gross proceeds of $21.3 million following the full exercise of the over-allotment option by the syndicate of underwriters;
Pursuant to the acceleration of the expiry date of those warrants issued on November 23, 2009 , the Company received proceeds of approximately US$6.8 million resulting from the exercise of 1,943,000 warrants;
The exercise of 1,322,750 warrants, issued in connection with the financing that closed on November 8, 2010 , providing the Company with proceeds of approximately $8.2 million ;
Corporate
The appointment of Gerard Kennealey, MD as Senior Vice President of Clinical Development and Chief Medical Officer (CMO). Dr. Kennealey most recently held the position of Vice President of Scientific Affairs at Cephalon Inc.; and
The appointment of George M. Gill, MD as Senior Vice President of Regulatory Affairs and Chief Safety Officer. Dr. Gill has been an officer of Oncolytics since 2002.
Current Investor Presentation Link Feb 2012
http://oncolytics.s3.amazonaws.com/presentations/25/original.pdf?1330043644
Also the ONCY wesbite has been updated.
Noting the text on the Careers page ...
http://www.oncolyticsbiotech.com/careers
Technology Changing Life™
Oncolytics is a growing biotechnology company focused on the development of oncolytic viruses as potential cancer therapeutics. Our goal is ambitious: to improve quality of life for as many patients as possible. To that end, we look for talented, driven and results-oriented individuals with diverse backgrounds and experiences. We strive to foster a collegial work environment with career development opportunities for every member of our team.
This page will be updated with the details of open positions as they become available. Should you wish to have your information kept on file, please send your curriculum vitae to careers@oncolyticsbiotech.com.