November 1, 2005 (Vol. 25, No. 19)

A Plethora of Spin-offs Make Up the Thriving Industry in B.C. and Alberta

The biotechnology industry in Canada’s two western provinces dates back at least 20 years. In British Columbia “it’s been going strong for the last 15 years,” says Karimah Es Sabar, executive director of BC Biotech (www.bcbiotech.ca) in Vancouver, a trade organization that represents about 200 life science companies.

About 70% of the companies are involved in biopharmaceutical research, while the rest have diverse interests in marine biotechnology, forestry, and even the wine industry. Nearly half the companies are spinoffs of the University of British Columbia (UBC) in Vancouver, which ranks ninth among Canadian institutions for generating technology patents. “Of the five most profitable biotechnology companies in Canada, three are in British Columbia,” says Es Sabar.

QLT PhotoTherapeutics (www.qltinc.com), one of the oldest UBC spinoffs, employs 400 people and specializes in the development of drugs that enhance photodynamic therapy. QLT’s drug Visudyne, approved in 1999 and marketed by Novartis, was the first approved therapy for wet age-related macular degeneration.

Vancouver’s Angiotech Pharmaceuticals (www.angiotech. com) teamed with Boston Scientific to develop the Taxus stent launched in 2004. The Taxus stent was one of the most successful medical products ever, netting more then $1.4 billion in sales in the first year. Aspreva Pharmaceutical (www. apreva. com) in Victoria makes CellCept, an immunosuppressant approved in 1995 to prevent organ rejection.

Regional Attractions

Established scientific institutions like UBC and the British Columbia Cancer Agency attract life science companies to British Columbia. Others come to conduct clinical trials on the region’s diverse ethnic population. “Clinical trials cost 35% less to run than in the U.S.,” says Es Sabar.

The provincial government strongly promotes biotechnology and offers tax incentives, while partnering forums, such as BioPartnering North America, create access to capital. Several Discovery Parks provide incubator space and room for companies to expand. The quality of life and low cost of housing relative to California draws others to British Columbia. “We’re now seen as a serious cluster for biotechnology,” says Es Sabar.

Founded in 1993 as a spinoff of the University of British Columbia, Migenix (www. migenix.com) in Vancouver develops therapies for infectious and degenerative diseases. In collaboration with Cadence Pharmaceuticals (San Diego), Migenix started a Phase III trial in the U.S. of its lead compound CPI-226 to prevent catheter-related infections.

“Bacteria and fungi on the skin migrate to the catheter insertion site, colonize the plastic sheath, creep down the catheter, and can break off and cause bloodstream infections,” says Jonathan Burke, director of industrial relations at Migenix. CPI-226 is a cationic antimicrobial peptide with broad-spectrum activity against bacteria and fungi.

A previous Phase III trial of 1,250 catherized patients showed that CPI-226 reduces bacteria and fungi on the skin and prevents the colonization of catheters. Another candidate, MX-3253, is being tested as a monotherapy for hepatitis C in Phase II studies, and later MX-3253 will be combined with ribavirin and peg-interferon, the standard therapy for hepatitis C. “We have a diversified pipeline of infectious disease agents,” says Burke.

Protiva Bio (www.protivabio. com) in Burnaby created the SNALP technology (stable nucleic acid lipid particles) to deliver siRNA and other nucleic acid molecules. SNALPs consist of a lipid bilayer of cationic and fusogenic lipids to enable cellular uptake and endosomal release of siRNA. A coating of polyethylene glycol shields and stabilizes the particles.

“We’re unique in Canada because no one else is in the siRNA space,” says Ian MacLachlan, Ph.D., CSO. The company’s goal is to develop siRNA therapeutics for cancer, infectious diseases, and metabolic conditions, which will “knock down the expression of endogenous or viral transcipts,” says Dr. MacLachlan.

Vancouver’s Forbes Medi-Tech (www.forbesmedi.com) recently started a Phase II clinical trial in the U.S. of its cholesterol-lowering drug FMVP4. The new drug is derived from a natural plant sterol and inhibits the absorption of cholesterol. Only one other marketed drug, Zetia (Merck), falls into this class of cholesterol-lowering drugs, also known as transport inhibitors.

“It’s a tremendous marketing opportunity,” says Darren Seed, manager of industrial relations, since Zetia earned $1 billion during its first year of sales. Forbes Medi-Tech also manufactures an over-the-counter product called Reducol, which makers of dietary supplements use as an ingredient to lower cholesterol.

Cardiome Pharma (www.cardiome.com) in Vancouver developed a novel first-in-class drug, RSD1235, for the treatment of atrial fibrillation (AF), a type of heart arrhythmia. When RSD1235 was given intravenously to 237 patients with acute AF, 52% regained normal heart rhythms, compared to 4% given a placebo, according to the results of a Phase III trial.

An oral form is being tested to prevent AF in susceptible patients. RSD1235 specifically blocks select potassium channels in the upper heart or atrium and does not affect potassium channels or conductivity in the ventricles. This specific action reduces side effects and, according to the company, makes it safer than current therapies, which disturb rhythms throughout the heart.

Researchers at Cardiome “built the drug from scratch using rational drug design to make it better and safer,” says Alan Ezrin, Ph.D., CSO.

Founded in 1999, Perceptronix Medical (www.perceptronix.com) is a spin-off of the British Columbia Cancer Agency. The company’s scientists discover new tools to detect and diagnose cancer. The lead product, the ClearSign Test, is a non-invasive test for lung cancer that screens sputum. Like the PAP test for cervical cancer, the ClearSign Test “is not definitive, but suggests further investigation,” says David Garner, Ph.D., president and CEO of Perceptronix.

The test detects early shifts in DNA within populations of cells related to lung cancer. Prospective clinical trials show that it detects the major types of lung cancer. The company plans to market the ClearSign Test in Canada and Europe early in 2006.

Perceptronix also is developing automated, quantitative systems for pathology (ClearPath) and cytology (ClearCyte) procedures, in which cell morphology and tissue architecture are measured and compared to a database of reference images.

Alberta Life Sciences

The 100 life science companies in Alberta are “small, nascent, and growing,” says Ryan Radke, vp of programs and operations at BioAlberta (www. bioalberta.com) in Edmonton. In the past year, they added 500 jobs, the health biotech sector grew from 40 to 61 firms, agricultural biotech grew from 8 to 19 firms, and environmental biotech grew from 2 to 7 firms.

Alberta companies focus on medical applications and biopharmaceuticals and cluster around either the University of Alberta in Edmonton or the University of Calgary. “It’s an extremely exciting industry that has grown in the last five years,” says Radke.

The Alberta Research Council located in the Edmonton Research Park performs contract biotechnology services, and the park provides laboratory facilities for young and growing companies.

Biomira (www.biomira.com), Alberta’s oldest biotech firm, celebrated its 20th anniversary in 2005. Founded as a spinoff of immunology research at the University of Alberta, the staff of 120 focuses on the development of innovative therapeutic vaccines for cancer. The company’s lead product, BLP25, targets non-small cell lung cancer. In collaboration with Merck (Darmstadt, Germany), Biomira is evaluating BLP25 in Phase IIb trials.

Edmonton-based Isotechnika (www.isotechnika.com) discovers and develops novel immunosuppressive drugs that are safer than cyclosporin. “Our main focus is to prevent organ transplant rejection,” says Randall Yatscoff, Ph.D., president and COO. A clinical biochemist at the University of Alberta, Dr. Yatscoff co-founded the company in 1993.

The lead compound, ISA247, inhibits enzymes that are required for T-cell activation, similar to the action of cyclosporin, which has sales of $2 billion yearly. According to Isotechnika, ISA247 is more potent and less toxic.

“Few other drugs in this class are being developed,” says Dr. Yatscoff. Isotechnika received clearance from the FDA to start a Phase IIb trial in the U.S. in the last quarter of 2005. ISA247 is also being evaluated in Phase III trials of psoriasis that include 450 patients at 32 sites treated for 24 weeks. The 12-week results show that ISA247 is effective, safe, and well-tolerated.

When David Cox joined Altachem Pharma (www. altachempharm.com) as president and CEO in February, he repositioned the company and narrowed its focus to discover treatments for cancer based on its light or sound wave-based SonoLight platform.

The lead compound, known as ACP-SL017, will soon enter Phase I trials as a treatment for actinic keratosis. The kinase inhibitor is applied as a topical gel, then activated by a laser. Once activated, “the drug destroys any tissue into which it has been absorbed,” says Cox.

The precancerous skin condition actinic keratosis has the potential to progress to more serious skin cancers if left untreated. Altachem Pharma in Edmonton has other drugs in its pipeline, which require activation by SonoLight platform.

Based on his research at the University of Calgary, Patrick Lee, Ph.D., founded Oncolytics Biotech (www.oncolyticsbiotech. com) in 1998. His team discovered that the benign reovirus (respiratory enteric orphan virus) selectively kills cancer cells that contain the Ras signaling pathway that controls cell growth.

About two-thirds of human tumors have the Ras pathway, including those of the breast, bladder, prostate, pancreas, and brain. Mouse models containing human cancers show that the reovirus-based treatment, called Reolysin, successfully destroys tumors. Phase I trials of Reolysin are enrolling patients with different types of tumors to evaluate the therapy alone and in combination with radiation therapy.

John Wallace, Ph.D., a pharmacologist at the University of Calgary, founded Antibe Therapeutics (www.antibe-therapeutics.com) in 2004 to improve the performance of existing drugs. His team starts with a known drug, identifies its weaknesses, and then optimizes them with a rapid development program. “It’s an alternative approach that gets drugs into clinical testing in less than a year,” says Dr. Wallace, CSO.

The company’s first compound, ATB-249, is a derivative of mesalamine (5-amino salicylic acid), a first-line therapy for irritable bowel disease (IBD). But compared to mesalamine, ATB-429 better suppresses the production of key pro-inflammatory cytokines involved in IBD, including tumor necrosis factor and interleukin-12. “By modifying the structure of existing drugs, we can significantly improve their potency and safety,” Dr. Wallace says. ATB-429 will start clinical trials early in 2006.

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