At BIO 2006

Biotechnology companies converging in Chicago for BIO 2006 last month reported steady progress in moving drug candidates based on novel technologies closer to market. Acknowledging the promise of significant new drugs by the end of the decade, speakers, including Secretary of the Department of Health & Human Services Michael O. Leavitt and former president Bill Clinton, laid out challenges ahead and spoke of the need to accelerate biotechnology via innovative partnerships and collaboration.

Leavitt, the keynote speaker, said tomorrow's researchers will have increased access to real-time data, including detailed health and genetic histories. He warned, however, that generating such a database opens up the potential for misuse of highly personal information. Leavitt called on researchers to address the privacy issues associated with collecting genetic data while developing the data as a tool for patient-centered care. "It will not be the technology or science that limits us," Leavitt said. "It will be the sociology that limits us."

A new era in drug development requires an overhaul of the regulatory process, he said, a movement that has started with the Food & Drug Administration's Critical Path Initiative. Other efforts include the National Institutes of Health's Roadmap for Medical Research, designed to identify and close gaps in biomedical research, and the NIH Genes & Environment Initiative, meant to help understand the root of common diseases.

Taken in sum, these private- and public-sector efforts will help transform "the painstaking plodding of trial and error that defines drug discovery" into a "six-month sprint," Leavitt said.

Former president Clinton pointed to the global efforts that led to the decoding of the human genome as the kind of cooperative problem-solving that the biotech sector needs to bring to health care, energy, and agriculture. The threat of international disease pandemics and the explosion of obesity and type 2 diabetes in the U.S. are among the frontline challenges, he said.

Clinton emphasized the growing role of the private sector in meeting these challenges, adding that governments need to respect the role of science. "I think that we should be driven in America by science, evidence, and argument, not by assertion and fear," he said.

While many of the biotech companies in attendance at BIO are still in a latent period prior to their first commercial successes, there was evidence that the sector is gaining momentum. "Some trends that have been predicted are actually happening," Matthew Hudes, manager of Deloitte's U.S. biotech practice, told C&EN. "We are seeing, for example, that the discovery side of biotechnology and the commercialization side of big pharma are a combination that really works now. A large part of the pharma pipeline is based on discovery from the biotechnology sector."

Several companies with novel drug delivery platforms highlighted their progress in getting drugs from the lab to patients. Seattle Genetics' antibody drug conjugate (ADC) technology, which uses a peptide to link cytotoxic molecules to an antibody, has evolved to a point where viable products are poised to enter the clinic, said Chief Executive Officer Clay B. Siegall. ADC technology draws on the specificity of an antibody to carry a cytotoxic compound, which is indiscriminate in the type of dividing cells it kills, directly to its target inside the cell.

The hope is that the delivery method will significantly cut down on the systemic toxicity associated with chemotherapy. "By using a drug conjugate, the overall amount of cytotoxic used is one-thirtieth to one-sixtieth the amount you would use if you administered it on its own," Siegall said.

The company has filed an Investigational New Drug Application for its first ADC candidate, SGN35, and expects to initiate a Phase I trial for hematologic malignancies later this year.

Nektar Therapeutics highlighted the next stage for PEGylation technology, which involves adding a polyethylene glycol (PEG) polymer chain to a drug molecule to enhance its bioavailability.

Early PEGylation technology was based on fixing single-chain, low-molecular-weight PEGs to a drug. Half-life improved, but problems included unstable drug linkages, nonselective attachments, and lower drug activity, explained Hoyoung Huh, Nektar's senior vice president for business development and marketing. The next generation of the technology introduced multichain, branched PEGs, which were more stable and site-specific in the body.

Nektar claims to have refined the technology even further with the introduction of modular or "dialable" PEGs. The approach enables the company to better control bioavailability and release profiles.

The company is also developing two proprietary PEGylation products, one for oncology and the other a central nervous system drug. Huh expects one drug to enter the clinic later this year.

Other firms emphasized efforts to expedite the commercialization of research and intellectual property. Jerusalem-based BioLineRx, for example, was formed in 2003 by Israeli life sciences companies to in-license and develop early-stage compounds discovered by independent researchers, universities, and small biotech companies in Israel. Investors include Teva Pharmaceutical Industries, the generics drugmaker, and Hadasit, a drug development and commercialization division of Hadassah Medical Organization.

Kinneret Savitsky, manager of preclinical development, said BioLineRx's strategy is to put dedicated teams on projects in early discovery with an emphasis on managing attrition. Basic development is handled at a new laboratory in Jerusalem, according to Savitsky. Projects are then passed along to contract research organizations (CROs) in 11 countries.

Yuri Shoshan, vice president for corporate development, said BioLineRx's project management strategy is geared toward efficiency and cutting the time needed to move candidates into and through the clinic. CROs are a key component. "We are very effective at identifying and choosing the right research partner" for specific drug candidates, Shoshan said. "We've spent three years building a database on expertise, so there are no repeat experiments. No reinventing the wheel."

The company hopes to have three candidates in clinical trials by the end of the year: BL 1020, a treatment for schizophrenia; BL 1040, a polymer gel injection that provides support for damaged tissue; and BL 2040, a metabolic syndrome treatment.

Arena Pharmaceuticals, formed in 1997, is looking toward a New Drug Application in 2009 for its lead drug candidate, APD356, an obesity treatment entering in Phase III clinical trials. Phase II results showed patients lost an average of 8 lb over 12 weeks without diet or exercise, according to CEO Jack Lief.

Arena has a pipeline of internally discovered, small-molecule drug candidates that target G-protein-coupled receptors (GCPRs), a class of receptors that mediate cell-to-cell communications in humans. The company has four candidates in clinical trials, including a diabetes drug being developed in partnership with Johnson & Johnson's Ortho-McNeil division and a cholesterol therapy being developed in partnership with Merck; both are currently in Phase I trials. Arena also has an insomnia treatment entering Phase II trials as well as a thrombosis treatment entering the clinic.

Invitrogen, a biopharma research services company, has identified GCPRs as the next big thing in cell-based assays for drug discovery. "Because G proteins are available on the cell surface, they are ideal drug targets," said Rob Bennett, vice president for life sciences R&D. "After kinases, it's clear that GCPRs are the most desirable target class."

Invitrogen has several cell-based assays that employ its promiscuous G-protein technology—a cell line expressing G-15 protein, which allows researchers to investigate multiple GCPRs in the same cell.

Bennett said Invitrogen is developing methods to express G proteins in vitro, which is a challenge because the proteins are located on cell membranes and need to react with other proteins. "Currently, cell-based assays are still the best way to go," he said.

Regardless of the technology they are based on, Robert J. Wills, vice president of alliance management at J&J, said partnerships, such as Ortho-McNeil's with Arena, are becoming more complex in structure and are being formed in earlier stages of drug development. He sees the need for a "breakthrough" that will cut the time it takes to deliver new drugs by reducing the formulaic and random nature of compound screening, development, and testing. "Our hit rate is the same as it was 50 years ago, and that has to change," Wills said.

The most likely catalyst for change, he said, is genomics-based research into disease mechanisms and pathways. As a new research paradigm emerges, Wills said, biotech firms "good at the nuances of science" will play an active role in early development, but they will still look to major pharmaceutical companies as partners in late-stage development and commercialization. "If there is a breakthrough, you will still need big pharma," he said.