ArGen-X BV raised €27.5 million (US$37.1 million) in a Series B round to move its first two programs into clinical development.

The company, based in Rotterdam, the Netherlands, has developed a proprietary antibody platform, called SIMPLE, which exploits the variable regions of the conventional antibody repertoire found in camelids, such as llamas and camels. This is distinct from the heavy-chain-only antibody repertoire, also found in camelids, which Ghent, Belgium-based Ablynx NV is exploiting.

Conventional camelid V-domains are indistinguishable from those found in human antibodies. They are fused with human antibody backbones – the Fc domains of the antibodies are not human-like – to form what are essentially fully human antibodies.

ArGen-X, which raised €12.5 million in Series A funding, is positioning the technology as an unencumbered platform that can generate high-affinity antibodies against difficult targets. 'With the A money, we generated very strongly validated datasets underpinning the claims,' CEO and co-founder Tim Van Hauwermeiren told BioWorld Today. 'The value proposition we've built is superiority in the V-region space.'

ArGen-X developed antibodies against 10 targets in house, while also collaborating with Indianapolis-based Eli Lilly and Co.

'Within six months of signing the deal on what Lilly thought was an impossible target, we cracked it and overdelivered,' Van Hauwermeiren said. 'You will see us doing a few more deals in the next quarters.'

The platform's claimed superiority derives in part from the antibody diversity it can access. Active immunization of just three or four outbred llamas with an antigen of interest is sufficient to generate far greater antibody diversity than can be achieved with hundreds of in-bred transgenic mice, Van Hauwermeiren said. 'If you do that in transgenic mice you typically find more of the same.'

The company also claims greater ease of manufacturing.

'In general, it's becoming clearer and clearer now that in-vivo-generated antibodies have lower attrition compared to synthetic or in-vitro-derived antibodies,' he said.

The company has partnered with Princeton, N.J.-based BioWa Inc. to gain access to its Potelligent technology. That involves the use of a special line of CHO cells that lack the FUT8 gene, which encodes alpha-(1,6)-fucosyltransferase. The resulting antibodies are fucose-free and exhibit enhanced antibody-dependent cellular cytotoxicity.

ArGen-X plans to submit its first investigational new drug application in early 2013. It concerns ARGX-110, which targets an undisclosed cell surface receptor.

'It's a novel B- and T-cell target,' Van Hauwermeiren said. 'There is very limited competition.' The molecule has potential in several oncology and inflammation indications.

Behind that is ARGX-111, an antibody targeting the receptor tyrosine kinase c-Met (mesenchymal-epithelial transition factor), which is slated to enter the clinic several quarters later. Also known as hepatocyte growth factor receptor, c-Met is overexpressed in many tumors.

Several small-molecule kinase inhibitors targeting the c-Met signal pathway are in development. XL-184, which South San Francisco-based Exelixis Inc. and Bristol-Myers Squibb. Co., of New York, are co-developing, is in Phase III trials. So, too, is tivantinib (ARQ-197), which Woburn, Mass.-based Arqule, Inc., is developing with Tokyo-based Daiichi Sankyo Co. Ltd. and Asian licensee Kyowa Hakko Kirin Co. Ltd., of Tokyo.

So far, antibody development efforts have been less successful, however.

'Think of it as EGFR,' Van Hauwermeiren noted, referring to epidermal growth factor receptor. 'It's the holy grail in cancer antibody discovery. Many people have tried [to target it] and failed.'

Dimerization of the receptor – which can be triggered by antibody binding – can cause unwanted signaling.

'It's very important where you hit the target. You want to avoid activating it, but you still want to completely block it,' Van Hauwermeiren said.

Genentech Inc., a member of the Roche Group, addressed that problem by developing a monovalent, single chain antibody fragment, ornartuzumab (MetMab), which is undergoing a Phase III study in combination with the EGFR inhibitor erlotinib (Tarceva) in patients with metastatic non-small-cell lung cancer. 'We know the molecule can be improved,' Van Hauwermeiren said.

The company aims to find a partner for a third preclinical antibody, ARGX-109, which targets interleukin-6 (IL-6), a multifunctional cytokine that plays an important role in immune regulation. The company is positioning the molecule as a therapeutic for ovarian cancer, an indication that New Brunswick, N.J.-based Johnson & Johnson Co. has explored with another anti-IL-6 antibody siltuximab (CNTO 328).

Several other firms are developing anti-IL-6 antibodies for rheumatoid arthritis, notably Regeneron Pharmaceuticals Inc., of Tarrytown, N.Y., and Paris-based Sanofi Group, which are in Phase III studies with sarilumab, and Alder Biopharmaceuticals, Inc., of Bothell, Wash., and New York-based Bristol-Myers Squibb Co., which are in Phase II studies with ALD-518.

'It's a very competitive space, and therefore we will partner the program,' Van Hauwermeiren said.

The company is now funded until well into 2015, he said, even without any new deals between now and then. Securing U.S. investment was a priority for the company in this round, and it landed one of the biggest, New York-based OrbiMed Advisors LLC, which co-led the deal with Paris-based Seventure Partners.

Existing shareholders Forbion Capital Partners, Credit Agricole Private Equity, Life Sciences Partners, BioGeneration Ventures, the Erasmus Biomedical Fund, Thuja Capital and Vlaams Instituut voor Biotechnologie (Flanders Institute for Biotechnology) also participated.

In other financing news:

• BiOasis Technologies Inc., of Vancouver, British Columbia, closed a private placement of about 2.6 million units at 45 cents per unit for gross proceeds of $1.2 million. Each unit contains a common share and a warrant to purchase a common share at a price of 60 cents per share, exercisable until Nov. 30, 2012, or 70 cents per share until Nov. 30, 2013. Proceeds will be used to increase working capital for the company.

• Investors will purchase $15 million of securities in Celsion Corp., of Lawrenceville, N.J., in a private placement expected to close on or about Dec. 6. The company will sell about 6.5 million shares of common stock at $2.3125 per share, plus warrants to purchase about 3.2 million shares of common stock at an exercise price of $2.36 per share. The warrants will have a term of five years. Net proceeds of $13.9 million will fund the Phase III (HEAT) trial of ThermoDox.

• Inovio Pharmaceuticals Inc., of Blue Bell, Pa., priced an underwritten public offering of about 6.7 million shares of common stock and warrants to purchase 5.1 million shares by five institutional investors. Each unit of one share of common stock plus a warrant to purchase 0.75 shares of common stock is priced at $0.5195 per unit. The warrants have a term of five years, and an exercise price of 65 cents per share. Net proceeds of $3.2 million will be used to fund clinical trials and research and development of synthetic vaccines for cancer and infectious diseases.

• Novelos Therapeutics Inc., of Madison, Wisc., priced an underwritten public offering of 9.8 million units of stock for gross proceeds of $5.9 million. Each unit comprises one share of common stock and a warrant to purchase one share of common stock and is priced at 60 cents. Warrants bear an exercise price of 60 cents per share with a five-year term. The underwriter has a 45-day option to purchase an additional 15 percent of the units.

• Synergy Pharmaceuticals Inc., of New York, priced an underwritten public offering of about 1.9 million units of stock at $8 per unit. Each unit contains two shares of common stock and a warrant to purchase one share. Warrants will have an exercise price of $5.50, with a term of five years. The units will trade on the NASDAQ under the symbol SGYPU. Gross proceeds of approximately $15 million will support a Phase II/III trial of plecanatide and a Phase I trial of SP-333. Additionally, Synergy has effected a 1-for-2 reverse stock split, and Synergy's common stock will trade on the Nasdaq under the symbol SGYPD, and will cease trading on the OTCQB.