February 1, 2005 (Vol. 25, No. 3)

Presentations from the Genesis 2004 Conference

London’s proximity to world-class universities providing high quality research and a thriving community of financial experts makes it an ideal place for biotech companies to locate, stated Jo Valentine, CEO of the business campaign group, London First, at the recent “Genesis 2004” biotech conference in London. “London could soon become a major European biotech cluster.”

John Brown, Ph.D., vp, central R&D, GlaxoSmithKline (Stevenage, U.K.), also believes that London has a lot to offer biotechs in terms of clinical expertise. Dr. Brown stated, “If government can exert enough influence, London could become a global center for translational medicine. With its network of good teaching hospitals, London could provide specialist clinical research facilities such as coordinated cancer networks.

“With the way patients are tracked from birth to death through the U.K.’s National Health Service, the patient information available could provide biotechs looking to perform early-stage trials with an effective method of selecting candidates. Additionally, since the U.K. has implemented the new EU clinical trials directive appropriately, it is a now a good center for Phase I trials.”

Interesting Technology

To show what types of biotech firms are starting up and settling in London, six emerging companies developing either platform technologies or therapeutics were featured as “ones to watch.” Keith Powell, Ph.D., CEO of Domainex, presented a method for making soluble domains of insoluble or difficult to express proteins using a random cloning technique and specific expression vectors.

“We have expressed fragments of a difficult-to-generate human phosphoinositide 3-kinase 85 kD protein. We have been able to go from a 96-well plate to a 5-L fermentor to produce soluble proteins with ease. This shows the protocol is applicable to studying any protein for structure-based drug discovery.”

Martin Stocks, Ph.D., founder, director, and CSO of Iclectus, contests that although making soluble proteins is vital, delivery of gene- and protein-based drugs is also an important issue that has yet to be solved.

Dr. Stocks commented, “We have developed technology to generate functional intracellular antibodies, which we call intrabodies. These can deliver viral or plasmid vectors, as well as protein-based drugs, in some situations, more effectively than RNAi. Intrabodies could be used to produce the next generation of antibody therapeutics and have potential applications in the treatment of cancer, immune-mediated diseases, and viral infections.”

Novel Therapeutics

Companies that presented at the conference are producing potential drugs to combat infectious diseases and other conditions such as cancer and obesity. IC-Vec’s research director of biochemistry, Michael Keller, Ph.D., explained how his company is producing siRNA therapies to treat liver diseases.

According to Dr. Keller, using the siFECTplus cationic liposome delivery vectors developed at IC-Vec, siRNA is delivered so that it downregulates a reporter gene in the liver of Balb/C mice. Using this combination of vector and siRNA technology, a proof-of-principle study is now underway to determine if hepatitis B virus can be treated in mice.

To treat life-threatening infections caused by MRSA and Streptococcus pneumonia, ImmunoPrime, a spin-out from Arrow Therapeutics, uses a technique known as transposon-mediated differential hybridization to identify the bacterial proteins essential for survival in the hostile environments of the human body.

Professor Ian Charles, Ph.D., CEO of ImmunoPrime, states, “We are trying to find a pathogen’s weak spots and disrupt them to cripple the bacteria. When we have identified the key proteins associated with survival, we are either going to produce monoclonal antibodies to them or use them to generate vaccines.

“This offers a fast track to the clinic as it can take as little as seven years to get monoclonal therapies to market, significantly quicker than the average for getting an NCE licensed.”

The firm impressed the London Biotech Network, London First’s networking group, and was chosen from 40 London-based biotech companies presenting at the meeting to receive the 2004 Bio-Innovation Award for the most innovative technology.

In contrast to IC-Vec and ImmunoPrime, Spear Therapeutics is developing a set of pro-drugs to treat a variety of cancers. Keith Powell, Ph.D., CEO of Spear, explained, “CYP1B1 is a cytochrome p450 that is over-expressed in a range of cancer cells but not normal tissues. Therefore, by generating pro-drugs activated by CYP1B1 we can target and localize the cytotoxic effects of the drug without the side effects often associated with conventional chemotherapy.”

Dr. Powell showed in preclinical studies that Spear’s two lead pro-drugs, DMU212 and DMU 949, have significant cytotoxic effects on breast tumor cells and no effect on normal breast tissue.

Dr. Powell stated, “We hope to begin a Phase I study of DMU212 early in 2006 for multiple clinical targets because this pro-drug has the potential to work in any tumor expressing CYP1B1.”

Preventing Obesity

For preventing obesity, Dr. John Burt, CEO of Thiakis, discussed how his company is using two peptide hormone based drugs, PYY 3-36 and oxyntomodulin, which act on the hypothalamus to suppress appetite. Dr. Burt presented data showing that when oxyntomodulin was given in a subcutaneous injection to 14 overweight subjects they lost an average of 2.3 kg in 28 days. Whereas, a control group of 12 overweight people given saline intravenously lost less than 0.5 kg in the same period.

“Clinically, obesity is a global epidemic affecting 300 million adults. Diseases related to this condition kill 1,000 people in the U.K. every week, yet there is no safe and effective medicine to treat it, which is why we are developing these types of drugs,” Dr. Burt concluded.

It would seem with all the talent and innovation shown by companies at the “Genesis 2004 Conference,” London could become a major European biotech hub.

However, in his review of the year, Mike Ward, director of Critical I Ltd. (Oxford, U.K.), a company that provides strategic business consultancy to the biotech industry, pointed out, “As companies become more mature in Europe they find it increasingly difficult to obtain VC funding.

“For example, only 15% of European biotechs established for more than 11 years are able to raise funds, yet U.S. biotechs do not have this problem as they are adequately funded at each stage of their life cycle. VCs in Europe should stop seeding so many companies but instead invest in slightly larger companies where there is plenty of IP already built in.”

Liquidity was cited by many at the “Genesis Conference” as the biggest issue facing European biotechs. It is perhaps only this that could delay some of the featured companies and other promising start-ups in London from getting their follow-on funding and thus prevent London from achieving its ambition of becoming a major biotech center.

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