June 1, 2005 (Vol. 25, No. 11)

State Commitment and Established Pharma Boost Biotech Industry

BIO’s annual conference, which will be held in Philadelphia later this month, highlights the fact that Southeastern Pennsylvania represents a significant focus of biotech and pharmaceutical activity. Indeed, recent developments reinforce the area’s prominence as a center of drug development and manufacturing expertise.

Pennsylvania Governor Edward G. Rendell announced last month that URL/Mutual will create at least 325 jobs by the end of 2006 and retain 441 existing jobs in Philadelphia. The pharmaceutical manufacturing company, which has already created 113 jobs, is expanding operations at its new Dungan Road facility. The company is also planning improvements at its existing Orthodox Street location.

That news was quickly followed by the opening of Shire Pharmaceuticals’ new, U.S. corporate headquarters in Wayne, PA. Shire is in the process of creating 400 jobs within the next three years at the Chester County facility.

“Shire joins 80 percent of the world’s largest pharmaceutical companies that currently maintain a presence in the region that provides them with premier medical schools and academic health centers, an extensive talent pool, a strong venture capital presence, and exceptional patent productivity,” noted Governor Rendell at the opening ceremonies at the facility.

In addition to having a long-term and entrenched life sciences infrastructure, a number of major developments have helped establish the Greater Philadelphia region as a pharmaceutical and biotech center of excellence.

For example, when Pennsylvania received its share of the Tobacco Settlement Fund in 2001, the state made a strategic commitment to promote the life science industry. In 2002, BioAdvance (www.bioadvance. com), also known as the Biotechnology Greenhouse of Southeastern Pennsylvania, was established to administer $20 million of seed capital to support life science entrepreneurs who are commercializing technologies and growing businesses.

“We plant the seedlings, nurture them, and they grow,” says Gary Kurtzman, M.D., COO at BioAdvance in Philadelphia. BioAdvance also invests in basic research and venture capital funds. “The model creates a lot of energy and momentum,”says Barbara Schilberg, managing director and CEO of BioAdvance.

BioAdvance coordinates several initiatives, such as the Greater Philadelphia Bioinformatic Alliance (GPBA), a consortium of informatic specialists from nine local universities, including the University of Pennsylvania, Drexel, and Temple.

GPBA’s mission is to work with life science companies to answer basic research questions and other issues facing the life science industry, such as deciphering genomes or predicting patient responses to drugs. The goal is not to form new bioinformatic companies, “but I anticipate there will be spinoffs,” says Dr. Kurtzman.

In 1963, Philadelphia opened the first urban research park, the Science Center Port of Technology, located between the University of Pennsylvania and Drexel University. The park offers 30,000 square feet of incubator space, laboratories, and offices to support life science startups.

Life Science Industry

The state’s life science industry employs 84,000 people, and eight of the top 10 pharmaceutical companies operate facilities in the Philadelphia region. While “the technology sector overall is regrouping after the dot.com bust, the life science sector shows employment and earnings growth,” says Richard Overmoyer, deputy secretary of the Technology Investment Office at the Department of Community and Economic Development in Harrisburg.

Among the 200 members of Pennsylvania BIO (www.pennsylvaniabio.com), about 80% are based in the Philadelphia region, and 120 are emerging biotechnology, biopharmaceutical, or medical device companies.

Philadelphia holds a unique advantage over Boston, San Francisco, and San Diego because of the expertise housed in the region’s large pharmaceutical companies (e.g., Merck, GlaxoSmithKline, and Wyeth) to manufacture and commercialize products.

“You can do basic research anywhere,” says Schilberg. But the local knowledge of clinical trials, manufacturing, and sales “makes us a potential international powerhouse,” she adds. The concentration of pharmaceutical companies also inspired some special training programs, like the dual master’s degree in biotechnology and business administration offered by the University of Pennsylvania.

Started five years ago, “our program is one of the largest in the nation with 130 students enrolled,” says Scott Diamond, Ph.D., program director. Students can specialize in tracts, such as pharmaceutical manufacturing, drug discovery, or biomolecular engineering.

The density of pharmaceutical companies around Philadelphia traces back to the Philadelphia College of Pharmacy (now the University of the Sciences).

“All the heads of the old pharmaceutical companies graduated from the College of Pharmacy, and the large companies sprung up around Philadelphia,” according to Fritz Bittenbender, president of Pennsylvania BIO in Malvern. The pharmaceutical companies, in turn, spawned the biotechnology industry.

Among the first biotechnoloy firms was the monoclonal antibody company Centocor (www.centocor.com) founded in 1979. Headquartered in Malvern, Centocor employs 3,000 people worldwide and develops such novel products as Remicade.

Now owned by Johnson & Johnson, the current focus is on biotherapeutics for immune-mediated inflammatory diseases (IMID). “Centocor is the IMID company for Johnson & Johnson,” says Michael Parks, director of public relations at Centocor.

First approved as a treatment for rheumatoid arthritis, Remicade now has approval for nine indications spread across four disease states. “It’s a fantastic example of a product that broadly treats inflammatory conditions,” explains Parks.

Emerging and Growing Firms

Neuronyx (www.neuronyx.com) in Malvern was founded in 1999 by Hubert Schoemaker, Ph.D., who also co-founded Centocor. Neuronyx, a development-stage biopharmaceutical company, plans to develop therapies based on adult bone marrow-derived stem cells.

“The cells are a bone marrow population that we produce with 99.99% purity through optimization of culture conditions,” says Stephen Webster, president and CEO of Neuronyx. Using special procedures for growth, Neuronyx generates 2 x 1019 cells from a single bone marrow aspirate in four passages. “That’s billions of therapeutic doses,” says Webster.

The stem cells show efficacy in animal models to repair tissue damage caused by heart attacks, stroke, and spinal cord injuries. The stem cells are recruited to areas of injury and secrete progenerative cytokines and anti-inflammatory factors that promote tissue repair.

At Protez Pharmaceuticals (www.protezpharm.com) in Malvern, researchers are developing small molecule compounds to improve antibiotics. One category of small molecules are potentiators, which when given in combination with current antibiotics make them more potent, although potentiators alone are inactive.

Many existing antibiotics slow the growth of bacteria, then rely on the immune system to clear an infection. “Potentiators kill bugs and eradicate the infection,”says Christopher Chapman, president and CEO. This benefits people with compromised immune systems. In addition, bacteria treated with potentiators are less likely to become drug resistant.

Other types of small molecules are stand-alone compounds that target biofilm infections. Biofilm bacteria slow their growth, and “we’re screening for compounds active against this slow growth phase,” says Chapman.

Although still in the lead optimization and preclinical validation stages, Protez plans to test its new potentiators against community-acquired infections like pneumonia, whereas the biofilm compounds will be used to treat urinary tract infections and endocarditis.

In the fall of 2004, Acuity Pharmaceuticals (www.acuitypharma.com) in Philadelphia became the first company to administer a small interfering RNA therapeutic to humans in the U.S. The company’s lead product, Cand5, is in Phase I trials in patients with age-related macular degeneration (AMD).

Cand5 uses RNA interference (RNAi) technology to turn off genes that produce the growth factor VEGF. “VEGF causes unwanted blood vessels at the back of the eye that are central to blindness in wet AMD,” says Dale Pfost, Ph.D., president and CEO of Acuity.

The RNAi technology was discovered in the laboratory of Sam Reich, Ph.D., at the University of Pennsylvania. The goal of Acuity is to create a variety of RNAi technologies to treat other ophthalmic disorders, such as diabetic retinopathy.

Nanoacoustic Sensing

Biosensus is pioneering the use of miniaturized nanoacoustic sensing technology licensed from Drexel University to monitor blood coagulation. The prototype device “interrogates individual blood cells at the molecular level and the interactions of cells in blood,” says Yasha Kresh, Ph.D., chief biomedical officer of Biosensus and a professor of Cardiovascular Medicine at Drexel.

Dr. Kresh co-founded the company with two other Drexel researchers, biomedical engineer Ryszard Lec, Ph.D., and mechanical engineer David Wooten, Ph.D. The prototype blood monitor, which was inspired by personal glucose monitors, uses a finger prick drop of blood. “People who take blood thinning drugs, including aspirin, to prevent coagulation do not know if they’re taking too little or too much,” says Dr. Kresh.

The new monitor will improve dosage recommendations and compliance. The technology also can be adapted to detect other endpoints, including anthrax in public places. “You make the surface of the detector specific for what you want to detect, then it gives nanoacoustic signatures that tell you something is there,” says Dr. Kresh.

John McElroy, Ph.D., founder, president, and CSO at Jerin Discovery (www.jerindiscovery. com) in Philadelphia, is resurrecting an off-patent, neuropsychiatric drug and repurposing it as an obesity treatment. “If you increase the dosage, it fights obesity,” says Dr. McElroy of the undisclosed drug.

All existing obesity drugs work by suppressing appetite, blocking absorption, or speeding metabolism. In contrast, Jerin’s compound directly eliminates fat tissue through a novel mechanism. In animal studies, the compound causes a 14% decrease in body weight, including a 30% loss of body fat. Dr. McElroy foresees the compound being used in combination with other obesity drugs and lifestyle changes.

Utilizing Academic Labs

Yaupon Therapeutics(www.yaupontherapeutics.com) seeks out small molecule drugs developed in academic laboratories, “which are untapped repositories for drug candidates,” says Robert Alonso, president and CEO of the Radnor-based company.

Yaupon is an American Indian name for tree leaves, and two of the company’s four lead candidates are derived from plants. The lead candidate, Lobeline, obtained from the leaves of lobelia plants, treats metamphetamine addiction by modulating dopamine in the central nervous system to prevent the dopaminergic high induced by metamphetamine. Lobeline is moving into a multidosing Phase Ib trial.

Another plant product, nornicotine, comes from tobacco plants and is in preclinical evaluation as a treatment for smoking cessation. The company also will begin Phase II/III trials of Clearazide, a topical drug for cutaneous T-cell lymphoma with Orphan Drug Status.

Han Cao, Ph.D., founder of BioNanomatrix (www.bionanomatrix. com), in Philadelphia, knows first hand that necessity is the mother of invention. As a molecular biologist working with embryonic stem cells, he needed to accumulate samples for two months in order to perform microarray experiments.

“I wanted a technology to look at single cells,” says Dr. Cao. So he joined a nanotechnology group at Princeton University to learn about nanomaterials used in the semiconductor industry. He designed a nanoarray with parallel channels to look at large populations of molecules at the resolution of a single molecule.

“You can look at hundreds to thousands of molecules in parallel simultaneously, yet every molecule is in its own channel,” he says. Dr. Cao foresees nanoarrays enabling researchers to look at a stream of genomic DNA in its native state with all the biological information intact.

In contrast, all current methods, like Northern blots, require that samples be broken up, then reassembled, and provide indirect data. BioNanomatrix plans to provide instruments, nanochips, and consumables to help clinical researchers zoom in on parts of chromosomes related to diseases.

“The world of protein therapeutics is exploding,” says David King, CEO of BioRexis Pharmaceutical (www.biorexis.com) in King of Prussia. However, many biophamaceuticals have short half-lifes and are expensive to manufacture.

“We have a technology to solve these problems,” says King. The proprietary platform fuses transferrin to protein and peptide therapeutics, thereby extending their half-life from minutes or hours to weeks. Consequently, patients may require just a weekly injection rather than daily injections.

“Transferrin is the second most abundant protein in blood that carries iron,” says Rick Jones, M.D., director of business development at Biorexis. Transferrin not only protects the attached peptides, but also is “very bioavailable and reaches all the cells in the body,” says Dr. Jones.

In addition, Biorexis manufactures its transferrin fusion proteins in yeast. The yeast process can be scaled up to produce large quantities of biotherapeutics, so “our cost of goods is much less than other biopharmaceuticals,” says Dr. Jones.

Biorexis will file its first IND in the summer of 2005 to evaluate its formulation for glucagon-like peptide 1 (GLP-1) for type 2 diabetes.

In May 2005, the FDA approved Byetta (exenatide), the first commercial product based on GLP-1, made by Amylin Pharmaceuticals and Eli Lilly & Co.

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