The research for CroFab, a treatment for crotalid snakebites, might stretch back to Vanderbilt University in Nashville, Tennessee, but integrated biopharmaceutical concern Protherics, which developed its science into a viable product in the 1990s, now bases its headquarters in London. The reason is simple: its London Stock Exchange listing.

“It makes sense to have your headquarters where your investor base is,” says Saul Komisar, president of Protherics Inc (USA) in Brentwood, Tennessee.

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The company maintains its US headquarters outside of Nashville because of its legacy with Vanderbilt University. It is there that Andrew Heath, one of Protherics’ original investors and now Protherics CEO, conducted research and built up the team.

Dr Heath holds an MD and PhD from Sweden’s Gothenburg University. After a career in research and clinical medicine at Vanderbilt University, he began working in private industry for such companies as Glaxo Wellcome, AstraZeneca and AeroGen in Europe and the US. In 1988, he became CEO of Therapeutic Antibodies, a predecessor company to Protherics. He continued as CEO upon the incorporation of Protherics in 1999 following the merger of Therapeutic Antibodies and Proteus International.

“It was only a few years later when we relocated our headquarters to London,” says Mr Komisar. Protherics’ British roots exemplify how international biotechnology has become.

“The original science for the antibody side of our business came out of St Bartholomew Hospital in London,” says Mr Komisar. “Most of our research is done in London. Our investor base understands this research.” As Protherics shifted from individual investors in the US to a different investor pool in the UK, its ownership became more London-based. “It got to the point when we decided to go public,” says Mr Komisar.

Business focus

Protherics’ primary manufacturing site for antibodies is in Wales, where it employs about 100 people. “We received some grants from the [former] Welsh Development Agency to set up that site in the beginning,” says Mr Komisar. “We went to Wales primarily because one of the company’s founders had roots in Wales and there is a good talent pool.”

In the US, Protherics maintains facilities in West Valley City outside of Salt Lake City, Utah – the result of its recent acquisition of MacroMed, a private drug development and manufacturing company there. It also has a production site in Australia. It employs about 260 people across its operations in Europe, North America and Australasia.

Protherics has evolved into a leading biopharmaceutical company focused on developing, manufacturing and marketing critical care and cancer products for use in emergency rooms and intensive care units, particularly for the treatment of medical emergencies. “We are well beyond the feed money phase,” Mr Komisar says.

Product licences

The company has developed two US Federal Drug Administration (FDA)- approved products in house: CroFab and DigiFab. The US market potential for CroFab is estimated to be $80m. The current global market size for DigiFab is estimated at $30m-$35m. Both products are sold in the US: DigiFab is distributed by Protheric’s marketing partner Fougera in Melville, NY, and Beacon Pharmaceuticals in Tunbridge Wells, Kent. The product is distributed in Germany and the Nordic countries by Protherics itself.

Protherics has also developed ViperaTAb, which is sold in Europe on a named-patient basis, and its anti-sepsis product CytoFab, which is being prepared for its next clinical study this year. That study will be conducted by Protherics’ licensing partner, AstraZeneca.

“AstraZeneca is responsible for the clinical and commercial development of the product on a worldwide basis,” says Mr Komisar. “This relationship partners the product with a company that is very good at clinical studies since they have more resources than we do. It gives the product a much better chance of success.”

Protherics works with other partners in addition to AstraZeneca, although AstraZeneca is the largest. “We also have situations where we work in the reverse. We license the product,” says Mr Komisar. Typical of the biopharmaceutical world, companies partner with those that offer a greater depth of experience, marketing expertise and resources. “The goal is to be creative,” he says. “We look for partners who have capabilities beyond our own.”

Today Protherics is less concerned with early stage R&D as it is with product development. “We work with universities on clinical trials,” says Mr Komisar. “But we are more into the D than the R of the business.” In that regard, there is no secret recipe. “Every company makes different decisions on how to grow,” he says. “Much depends on the products, a company’s financial situation, and where its growth is coming from or going to be. That will dictate how you go about capitalising your company or opportunity.”

Market expansion

That said, last year was one of transformation for Protherics. In December, the company announced three deals to expand the development pipeline of its core products and franchises. To fund the transactions, it proposed to offer a £38.2m ($74.8m) equity fundraising effort by selling ordinary shares of stock.

The stock sale is critical. The transactions comprise two strategic in-licensing deals with two companies, Glenveigh Pharmaceuticals of North Carolina’s Research Triangle and Advanced in Vitro Cell Technologies SL (Advancell) based in Barcelona, and the acquisition of another, MacroMed of Utah.

The in-licensing agreement with Glenveigh Pharmaceuticals expands Protherics’ critical care portfolio. “This could move DigiFab from being a niche market product into a blockbuster in what could be a $5bn market,” says Dr Heath. DigiFab offers a potential application in the treatment of pre-eclampsia, a life-threatening complication of pregnancy.

The in-licensing and co-development agreement with Advancell involves Acadesine, a treatment for B-cell chronic lymphocytic leukemia.

The $25m acquisition of MacroMed significantly expands Protherics’ cancer pipeline of drugs, gives it a US manufacturing base and provides access to MacroMed’s lead product OncoGel, which is used in treating oesophageal and brain cancers.

Protherics’ management believes that OncoGel and Acadesine will leverage the sales and marketing infrastructure of Voraxaze, a recombinant enzyme for oncology treatment, and thereby position Protherics to become a world-leading biopharmaceutical company. Protherics submitted the marketing application for Voraxaze in the EU in 2005 and the US last year. This January, the FDA granted it ‘fast-track designation’. That dramatically decreases the time needed to gain full approval.

EU and US market launches for Voraxaze and other products used to treat and manage cancer patients are being planned for 2008. This includes development programmes for OncoGel, Acadesine and Prolarix.

Patent protection

Protherics is encouraged by the progress made with the phase one study of Prolarix, which treats liver cancer and other solid tumours. A patent protecting its co-factor technology has been granted in the UK, US and Hong Kong, and is under examination in other territories. It intends to develop Prolarix in the US and the EU, and sign a licensing partner for Asia. Target markets are estimated to be worth more than $1bn.

“Our plan is to use revenues from our marketed products and licensing income to help fund the development of a robust and high-value pipeline of products,” says Dr Heath.

Like many biopharmaceutical companies, Protherics seeks to use industry collaborations and mergers and acquisitions to achieve its goals where critical mass is needed to achieve long-term growth.