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Technology Stocks : SYNSORB (T.SYB)(SYBBF) CURE FOR CANCER? -- Ignore unavailable to you. Want to Upgrade?

To: Tupulak who wrote (84)	11/18/1999 10:35:00 PM
From: Tupulak	Respond to of 164

Nov. 18/99 SYNSORB Biotech Inc. Reports Third Quarter Results CALGARY, ALBERTA--SYNSORB Biotech Inc. ("SYNSORB") (TSE:SYB, NASDAQ: SYBB) today reported its consolidated results for the third quarter and nine month period ended September 30, 1999. Total consolidated loss for the quarter ended September 30, 1999 was $3.8M or $0.18 per share compared to $3.3M or $ 0.17 per share for the same quarter the previous year. Total consolidated loss for the first nine months of 1999 was $12.3M or $.55 per share compared to $9.5M or $.48 per share for the same period in 1998. The Company reported $0.1M in revenue for the third quarter of 1999 attributable to payments related to partnership agreements, compared to no reported revenue for the same period in 1998. This is expected, as SYNSORB's products are still under development. For the first three quarters of 1999, consolidated development expenses were $8.7M compared with $6.6M for the first three quarters of 1998. For the third quarter, consolidated development expenses were $3.1M compared with $2.3M during the same period in 1998. This increase is attributable to increased costs associated with the SYNSORB Pk(R) program in Argentina and the United States, as well as increases in process development costs and production of clinical trial materials. A major highlight of the clinical development program occurred during the quarter as SYNSORB announced exceptional results from an interim analysis of the Phase II trial for SYNSORB Cd(R). It was revealed that SYNSORB Cd(R) reduced the rate of recurrence of Clostridium difficile Associated Diarrhea (CDAD) by 80%, far better than the 50% reduction that is considered to be a significant clinical benefit and what would have been considered 'successful' according to the trial protocol. Because of this early success the Company has commenced planning for Phase III pivotal trials, expected to commence early in the second quarter of the new year. Recruitment into the Phase II trial has been discontinued since it has already met its clinical objectives, many months earlier than expected. "SYNSORB's third quarter of 1999 brought spectacular news in the development of SYNSORB Cd(R) and also saw continued progress with SYNSORB Pk(R),"- said David Cox, Ph.D., President and Chief Executive Officer of SYNSORB. "Not only did we announce outstanding clinical results for SYNSORB Cd(R), but we also finalized our first marketing and distribution agreement for Canada with Paladin Labs, Inc. The SYNSORB Cd(R) program clearly has taken a major step forward. SYNSORB Pk(R) is also making excellent progress in its clinical program: recruitment passed the 400 patient mark during the quarter and we were also delighted that the product was designated 'Fast Track' by the US FDA". Consolidated operating expenses for the third quarter of 1999 were $1.1M, compared with $1.0M for the same period in 1998. During the first nine months of 1999 and 1998, operating expenses were $3.1M. The Company's consolidated total expenses for the first nine months of 1999 were $13.4M compared with $10.0M for the corresponding period in 1998. In the third quarter of 1999 total expenses increased to $4.7M as compared with $3.4M during the same period in 1998. This increase is largely due to development costs as noted above as well as manufacturing and increased efforts in the Business Development area. On the corporate development front, SYNSORB's subsidiary, Oncolytics Biotech Inc. (ASE:ONC) concluded two private placements raising net proceeds of $1.9M, and subsequent to the quarter ending, concluded an Initial Public Offering of 4.0M common shares raising $3.4M. After these transactions, SYNSORB holds 6.75M shares in interest in Oncolytics Biotech Inc. (49.5% of the issued and outstanding shares) an asset of substantial value to SYB shareholders. This 'autonomy' approach to its subsidiary companies and pipeline projects is fully consistent with SYNSORB's strategy of full focus on the development of SYNSORB Pk(R) and SYNSORB Cd(R), with all other development projects being self-financed and independently managed. As at September 30, 1999 the Company's consolidated cash and investment balance was $13.2M as compared to $11.6M as at September 30, 1998. SYNSORB is a Canadian-based pharmaceutical company dedicated to drug development and manufacturing. The Company has two late-stage products, both of which are based on SYNSORB's proprietary carbohydrate chemistry platform technology. SYNSORB Pk(R) is in Phase III clinical trials, and is designed to prevent the progression to Hemolytic Uremic Syndrome (HUS) in children who have contracted verotoxigenic E. coli (VTEC) infections, including E. coli O157:H7. SYNSORB Cd(R) will commence Phase III trials in the first part of next year, and is designed to treat recurrent antibiotic-associated diarrhea (CDAD), a common hospital acquired infection. SYNSORB has built a cGMP-compliant manufacturing facility that has the capacity to meet or exceed the expected global demand for the Company's products. A pipeline of future products is accessible through subsidiary companies and SYNSORB's carbohybrid program. This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or expectations implied by these forward-looking statements. These factors include results of current or pending clinical trials, actions by the FDA/HPB and those factors detailed in the Company's registration statement on Form 20 F filed with the Securities and Exchange Commission. [QUARTERLY REPORT & CONTACT INFORMATION FOLLOW] /T/ SYNSORB Biotech Inc. Consolidated Interim Balance Sheets As at September 30 (000's) 1999 1998 ------------------ ASSETS Current assets Cash and term deposits $ 13,241 $ 11,574 Accounts receivable 202 482 Prepaid expenses 66 122 Advance to a director - 50 ---------------------- 13,509 12,228 Capital assets (note 1) 22,234 14,158 ---------------------- 35,743 26,386 ---------------------- ---------------------- LIABILITIES AND SHAREHOLDERS' EQUITY Current liabilities Accounts payable and accruals 1,436 1,770 Current portion of long-term debt 2,713 332 ---------------------- 4,149 2,102 Non-current liabilities Alberta Heritage Foundation 537 387 Long-term debt (less current portion) 8,876 5,905 ---------------------- 9,413 6,292 Minority Interest (note 2) 1,270 - Shareholders' equity Issued - 31,399,912 common shares 58,597 39,438 (1998 - 20,121,686) Deficit (37,686) (21,446) ---------------------- 20,911 17,992 ---------------------- $ 35,743 $ 26,386 ---------------------- ---------------------- NOTES 1. Acquisition of Oncolytics Biotech Inc. (OBI) Effective April 21, 1999, the Company acquired 100% of the issued and outstanding common shares of Oncolytics Biotech Inc. for total consideration of $2,500,000 comprised of $2,413,459 of SYNSORB common shares and cash of $86,541. Additional consideration, to a maximum of $4,000,000, is contingent upon completion of four specific pre-determined milestones. In addition, certain royalty payments are due based on various future revenues and arrangements. The amount by which SYNSORB's purchase price exceeded the underlying net book value of the assets and liabilities was $2,500,000. 2. Gain on dilution of investment in subsidiary During the third quarter OBI closed two private placements for net proceeds of $1,904,998. These two private placements reduced the Company's interest in OBI from 100% to 70.0% resulting in a gain of $603,000. 3. Subsequent event Subsequent to September 30, 1999, OBI filed a prospectus for the issuance of 4,000,000 common shares, converted the Special Warrants and Warrants to 2,899,997 common shares, and began trading on the Alberta Stock Exchange on November 8, 1999. The result of this Initial Public Offering was to reduce the Company's interest in OBI to 49.5%. SYNSORB Biotech Inc. Consolidated Interim Statements of Loss and Deficit For the nine months ending September 30 (000's) 1999 1998 --------------------- REVENUE Revenue $ 85 $ - OTHER INCOME Interest and other 391 520 EXPENSES Research and development 8,679 6,585 Operating 3,082 3,107 Amortization 500 327 Interest on long-term debt 1,101 - ------------------------ 13,362 10,019 ------------------------ Loss before the following 12,886 9,499 Gain on dilution of investment in subsidiary (note 2) (603) - ------------------------ 12,283 9,499 Minority interest (32) - ------------------------ Net loss for the period 12,251 9,499 Deficit, beginning of period 25,435 11,947 ------------------------ Deficit, end of period 37,686 21,446 ------------------------ ------------------------ Loss per common share $ 0.55 $ 0.48 ------------------------ ------------------------ SYNSORB Biotech Inc. Consolidated Interim Statements of Cash Flows For the nine months ending September 30 (000's) 1999 1998 --------------------- OPERATING ACTIVITIES Net loss for the period $ (12,251) $ (9,499) Add non-cash items Amortization 500 327 Gain on dilution of investment in subsidiary (note 2) (603) - Minority interest (32) - Change in non-cash working capital balances relating to operating activities 652 (232) ------------------------ (11,734) (9,404) ------------------------ INVESTING ACTIVITIES Purchase of capital assets (4,028) (10,444) Investment in subsidiary (note 1) (87) - Change in non-cash working capital balances relating to investing activities (559) 851 ------------------------ (4,674) (9,593) ------------------------ FINANCING ACTIVITIES Common shares issued on exercise of options and warrants 298 711 Common shares issued on private placements (note 2) 1,905 8,213 Net proceeds from share offering 16,448 - Repayment of long-term debt (1,476) - Proceeds from long-term debt 150 - ------------------------ 17,325 15,161 ------------------------ Increase (decrease) in cash and term deposits during the period 917 (3,836) Cash and term deposits, beginning of period 12,324 15,410 ------------------------ Cash and term deposits, end of period $ 13,241 $ 11,574 ------------------------ ------------------------ /T/ -30- FOR FURTHER INFORMATION PLEASE CONTACT: The Equicom Group Jason Hogan Investor Relations (416) 815-0700 ex 222 (416) 815-0080 (FAX) or SYNSORB Biotech Inc. Doug Ball, CA VP Finance and CFO (403) 283-5900 (403) 283-5907 (FAX) or SYNSORB Biotech Inc. Mr. Doug Froom VP Business Development (403) 283-5900 (403) 283-5907 (FAX) synsorb.com For product licensing inquiries

To: Tupulak who wrote (84)	3/29/2000 5:39:00 AM
From: SnowShredder	Read Replies (1) \| Respond to of 164

Some reovirus stuff...from the AACR 2000 abstracts...Best of Luck, Where'd He Go? BTW...a link to the Oncolytics thread... Subject 31728 >>>> Publishing ID: 2224 Reovirus as a Potential Anti-Breast Cancer Therapeutic Kara L Norman, Matt C Coffey, Kensuke Hirasawa, Douglas J Demetrick, James E Strong, Patrick W K Lee, Univ of Calgary, Calgary, AB, Canada; Oncolytics Biotech Inc, Calgary, AB, Canada. Previously we have shown that the human reovirus that is restricted to replicate in those cells with an activated ras pathway could be used as an effective oncolytic agent against human glioblastoma xenographs in a SCID mouse model. Here we present evidence that reovirus could potentially be used as an oncolytic agent against mammary tumors. Although ras mutations are infrequent in the etiology of breast cancer, aberrant Ras/MAPK signaling via upstream signal elements is common. We examined five breast cancer cell lines; MDA-MB-468, MCF7, MDA-MB-435, T47D, and SK-BR-3 as well as a cell line derived from normal breast tissue, HBL-100 for in vitro reovirus replication. All five of the tumor derived cell lines were infectable by reovirus while the HBL-100 was unable to effectively replicate the virus. To determine if the Ras pathway was indeed activated in these cell lines the level of MAPK phosphorylation was assessed in the presence and absence of serum. Those cell lines that were infectable exhibited constitutive MAPK phosphorylation even in the absence of mitogen indicating ras pathway activation. To determine if reovirus could be used as an oncolytic agent in vivo against breast tumors, SCID mice were implanted with MDA-MB-468 human tumor xenographs. Following the establishment of palpable tumors the mice were treated with a single injection of reovirus and tumor size was monitored for a four-week period. The single injection resulted in dramatic regression of the tumor size. Finally the ability of reovirus to act against primary breast cancer tumors was determined. >>>>>> Publishing ID: 2223 STUDY OF REOVIRUS-INDUCED CYTOPATHIC EFFECT (CPE), RAS AND DOUBLE-STRANDED RNA-ACTIVATED PROTEIN KINASE (PKR) IN HUMAN TUMOR CELL LINES. L-T Song, I Gelman, J F Holland, T Ohuma, Mount Sinai Sch of Medicine, New York, NY. Reovirus was reported to selectively kill tumor cells with an activated ras pathway (Science 282: 1332, 1998). We studied the relationship between reovirus-induced CPE and the ras and PKR protein levels in 8 human tumor cell lines. "Normal" NIH/3T3 and LLC-MK2 cell lines served as controls. Reovirus infection with MOI of 10 pfu/cell caused CPE on day 3 in all tumor cell lines and LLC-MK2, in decreasing order, (4+) MCF-7 breast cancer = U-87MGdEGFR glioblastoma subline expressing mutated EGFR = U-87MGwtEGFR > U-87MG glioblastoma = LLC-MK2 > HEp-2 laryngeal carcinoma > DND-1A melanoma = 2780 ovarian carcinoma = JAR choriocarcinoma (1+). Presence of viral RNA in the infected cells on day 4 detected by PAGE in combination with silver staining confirmed that CPE was the result of viral infection. The degree of CPE was correlated with the ras protein levels assayed with pan-ras antibody; in decreasing order, (3+) MCF-7 = U-87dEGFR = LLC-MK2 > U-87wtEGFR = U-87 = HEp-2 > DND-1A = 2780 = JAR (1+). Phosphorylated PKR protein levels measured by Western blot using 71/10 anti-PKR antibody did not correlate with the degree of CPE or Ras protein levels, however. NIH/3T3 cells had weakly positive ras protein and low PKR levels but absent CPE; no viral RNA was detected. These results confirm that ras levels are important for reovirus-induced CPE. Pre-infection PKR levels are not a determinant for CPE. The mechanism of reovirus resistance in NIH/3T3 cells was not explainable by Ras or PKR levels. >>>> Publishing ID: 4654 The Efficacy of Using Reovirus as a Treatment for Malignant Gliomas Mary E Wilcox, Zhong Shi, Barry N Rewcastle, Mathew Coffey, James E Strong, Patrick Wk Lee, Peter A Forsyth, Univ of Calgary, Calgary, AB, Canada. Background: Other potential viral therapies in gliomas have included herpes virus TK susceptible vectors and adenoviruses which selectively infect p53 deficient tumors. We have found that reovirus, a double stranded RNA virus, selectively infects ras-activated but not normal cells. Ras-activated cells dephosphorylate PKR and release a translational block (normally seen in normal cells) and viral protein synthesis subsequently ensues. Malignant gliomas are ideal candidate tumors because they commonly have ras-activation. We determined the effect of reovirus infection on the growth of malignant glioma cell lines: U87 and 9L both in subcutaneous flank models and intracerebrally. Results: 24 cell lines were tested in vitro for ras pathway activation and viral infection. A strong positive correlation was found for reovirus infection and MAPK actovation. In vivo (subcutaneous flank model) a striking inhibition of tumor growth, including complete tumor regression was seen (p=0.0001 ANOVA); only microscopic foci of residual tumor were found in most animals. Further, remote administration of reovirus infected and killed contra-lateral tumors (distant from injection site). Immunohistochemistry showed viral infection in both un-injected and injected tumors whereas it was absent from all other tissues. In immune competent animal models, antibodies to reovirus had no effect on the reproduction of previous results. In an intracerebral model, reovirus was found to dramatically reduce tumor burden. Further studies however are required to determine appropriate dosing regimen. Conclusions: Reovirus produced an inhibition and regression of glioma growth and warrants further investigation to be present in an intracerebral location. >>>>> Publishing ID: 777 Reovirus as a novel prostate cancer therapeutic Michael Nodwell, Chandini Thirukkumaran, Joanne Leuder, Sandra Nishikawa, Peter A Forsyth, Randall Johnston, Patrick Wk Lee, Don Gordon Morris, Univ of Calgary, Calgary, AB, Canada. Intro: Reovirus is a common isolate of human respiratory and gastro- intestinal tracts, that is not associated with significant human disease. We have recently reported that reovirus susceptibility parallels "ras" activation (or up/downstream elements) in a myriad of cell lines (Science 282,1332-1334, 1998). This study investigates reovirus as a potential prostate cancer therapeutic. Methods: The prostate carcinoma cell lines DU-145 and PC-3 were incubated with live and U.V. inactivated (control) reovirus (strain Dearing, serotype 3) at a multiplicity of infection of 40 for up to 72 hours. Apoptosis was measured via CPE, flow cytometry (annexin V abs), PARP cleavage products via western blotting and DNA laddering. Both cell lines were grown in SCID/NOD mice as a xenograft hind flank model by s.q. injection of 107 cells, letting the tumors grow to approx. 0.5 cm2 and then injecting reovirus (108 PFU) intralesionally. Results: Both DU-145 and PC-3 were found to be exquistly sensitive to reovirus with over 80% of the cells dead by 72 hrs. To confirm that apoptosis was a major mode of cell death, Annexin V staining increased to reach 48% and 47% of DU-145 and PC-3 cells, respectively over the same time period. Further, the caspase-dependent cleavage of poly(ADP-ribose) polymerase via western blots paralleled the annexin V results. After a single intratumoral injection of reovirus, both DU-145 (N=20) and PC-3 (N=12) tumor containing mice significantly regressed compared to U.V. inactivated reovirus controls which eventually needed to be euthanized. Conclusions: Unmanipulated reovirus is cytopathic to DU-145 and PC-3 prostate cancer cell lines in vitro and in vivo. CPE, flow cytometry and PARP caspase cleavage products confirm that apoptosis is the major mechanism of cell death.