Some of my background DD on Oncolytics (some might be a little dated):
============
Company Info
============
Oncolytics Biotech
Trades on TSE (T.ONC) and Nasdaq smallcap (ONCY)
President: Dr. Brad Thompson
CFO: Doug Ball
VP Product Development: Dr. Matt Coffey
Senior VP, Clinical and Regulatory Affairs: Dr. George Gill
Less than 30 million common shares issued and outstanding
Well funded with over 3 years of cash
============
Lead Product
============
REOLYSIN - A potential cancer therapeutic based on the naturally occurring reovirus. REO is an acronym for respiratory enteric orphan. Orphan due to the fact that there is no known disease caused by the reovirus. 70-100% of all adult populations have been infected with the reovirus without knowing it. The oncolytic properties of the reovirus were discovered in 1998 by Dr. Patrick Lee at the University of Calgary.
===========
Preclinical
===========
Glioblastoma:
- glioma tumours U251N and U87lacZ implanted intracerebrally in mice
- median survival of untreated mice, 42 and 48 days
- 67% and 82% of treated animals still alive at conclusion of experiment at day 90
- complete tumour regression found in 20 of 23 of animals treated with live virus
- also tested on established glioma cell lines and surgical specimens
- widespread cell killing seen in 19 of 24 cell lines
- all primary surgical glioma specimens (9 of 9) were infected and killed
- human glioma tumour cells killed within 48 hour period (both cell lines and ex vivo glioma specimens)
- dramatic survival benefits for nude mice following intracerebral inoculation
- caused tumour regression in the presence of pre-existing anti-reovirus antibodies in immunocompetent Fischer rats
- killed tumour remote from the site of administration in immunocompetent host
- proceeding to clinical trial in patients with malignant gliomas
Medulloblastoma:
- majority of cell lines (7 of 11) were susceptible to reovirus oncolysis
- in all MB cell lines tested, Ras activity was shown to correlate with susceptibility to reovirus infection
- median survival of live virus-treated mice was 160 days, compared to 70 days control
- these data suggest that reovirus may be a novel and potentially effective therapeutic against human medulloblastoma
Breast:
- widespread cell killing was seen in all five established breast cancer cell lines and in one surgical specimen
- no cell killing observed in two cell lines established from normal breast tissue
- in mammary fat pad of SCID/NOD mice, a single injection of reovirus caused a continuous regression of the tumour during a thirty-day observation period
- independent tumours established in both flanks of the mice, a single injection of the reovirus into only one tumour resulted in complete regression of both the injected and non-injected tumours over thirty-two days
Colon:
- efficiently infected 5/5 human colon cancer cell lines (Caco-2, DLD-1, HCT-116, HT-29, and SW48)
- did not infect normal colon cell line (CCD-18Co)
- in mice model with tumour implanted in hind flank, both intratumoural and i.v. administration of reovirus resulted in significant regression
Ovarian:
- efficiently infected 4/4 human ovarian cancer cell lines (MDAH2774, PA-1, SKOV3, and SW626)
- did not infect normal ovarian cell line (NOV-31)
- in mice model with tumour implanted in hind flank, both intratumoural and i.v. administration of reovirus resulted in significant regression
- significantly greater survival benefits for reovirus treated mice
- reovirus infected ex vivo primary human ovarian surgical samples
Non-Hodgkin's Lymphomas:
- cell lines sensitive to reovirus: Raji, NC-37, UJ937 and CA46
- cell lines unaffected by reovirus: Daudi, ST486, Ramos, and A20
- ex vivo samples responded in similar ratio
- reovirus caused significant regression of in vivo Raji tumour
- reovirus may be effectivce against some types of human NHL
Prostate:
- prostate cell lines (PC-3, Ln-CaP, DU-145) were infected with reovirus
- cells were harvested at 0, 24, 48, 72, 96 and 168h post infection
- virus treatment caused significant disruption of cells as early as 24h
- the observed cytopathic/apoptotic effects of reovirus were not evident in controls
Pancreatic:
- from Matt Coffey's thesis, pancreatic cell lines Capan-1, MIAPaCa-2, PANC-1, AsPC-1, and Hs766T were infectible while BxPC-3 was not (it is known to have wild type Ras) the others have mutations in codon 12 so are expected to be infectible
Lewis lung:
- in a Lewis lung carcinoma mouse model, they [Dr. Lee, et al] demonstrated that IV treatment with REOLYSIN also resulted in a significant reduction in tumour volume
Superficial Bladder:
- reovirus demonstrated better efficacy than current treatments with fewer adverse outcomes
- survival data in days: control=54, BCG(5x10^5)=73, BCG(5x10^6)=52, BCG(5x10^7)=64, BCG(5x10^5)&IL-2=81, reo(5x10^5)=96, reo(5x10^6,5x10^7)=more than 100
- significant toxicity with BCG and some animals died tumour free from obstructive uropathy
- these findings not observed in reovirus treated groups (only adverse outcome was bladder calculi)
Autologous Purging of Breast, Lymphoma, and Myeloma cells:
- stem cell rescue with high-dose ablative therapy in autologous bone marrow and peripheral blood transplantation is extensively used for treatment of many solid and hematopoetic cancers
- breast cancer (HTB 133, HTB 132, MCF7 and SKBR3), lymphoma (U937) and myeloma (RPMI 8226) cell lines were used in the purging experiments
- cell viability decreased significantly with virus treatment in all cell lines and these effects corresponded with an increase in apoptotic markers
- results indicate the ex vivo use of an oncolytic virus as an attractive purging strategy for autologous stem cell transplants
Quote from Patrick Lee J.C.I. paper:
"So far, more than 80% of human tumor cell lines of various origins have proved to be infectible"
=============
Phase I trial
=============
Description:
- 18 terminal cancer patients (12-14 weeks to live) who have failed all other therapies
- Primary endpoint: Safety - no serious adverse effects, no dose-limiting toxicity found
- Secondary endpoint: Tumour Response - tumours regressed (transitory or lasting) between 32 and 100% in 11 of 18 patients (61%)
- Secondary endpoint: Remote Tumour Response - every remote tumour measured (more than 8) in eight patients showed evidence of tumour regression
Of note:
- patient with complete tumour regression did not show up for final evaluation, therefore not included in results
- patients not pre-screened for RAS activation; percent of patients that had tumour regression consistent with expected RAS activated cancer in a random tumour population (although small sample size not statistically significant)
- results consistent with safety and efficacy observed in animal models
=======================
Phase II prostate trial
=======================
The preliminary data showed clear histopathological evidence of apoptotic tumour cell death, one measure of viral activity, in four of the six patients. In a fifth patient, the PSA level dropped by 53% and the prostate gland shrank by 67% from just prior to treatment to the time of surgical removal. There was no evidence of viral activity in the sixth patient. In all six patients, there was no histopathological evidence of any viral effect on healthy prostatic tissue.
===================
Phase I/II glio trial
===================
"Five of the six treated patients remain alive and on study with duration after treatment ranging between 10 and 25 weeks." 2002
3 patients alive after 13, 14, 15 months
-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-
Disclaimer: I own shares of Oncolytics Biotech. Other
than being a shareholder, I'm not compensated or affiliated
with the company in any way.
Please let me know via PM of any errors contained within.
©2003, PullDaTrigger.
This summary may be freely reposted or emailed "in its entirety",
including this section.
E&OE
-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=-=- |
