Ablynx technology rivals GSK's mini-antibodies

By Mike Nagle

- Last updated on GMT

Related tags Antibody

Belgian biopharma Ablynx has announced its lead miniature antibody
has shown good interim results in a first-in-man trial, leaving it
one step ahead of GlaxoSmithKline (GSK).

The two companies are both developing miniature antibodies - officially called nanobodies and domain antibodies (dAbs) by Ablynx and GSK respectively - but whereas the pharma giant is yet to test any of its drugs in clinical trials, Ablynx yesterday announced positive interim results for its first Phase I trial. GSK is in the race through its recent acquisition of Domantis, and in May, a Domantis licensee called Peptech did begin a clinical trial using mini-antibodies. PN0621 targets tumour necrosis factor (TNF) to treat auto-immune inflammatory diseases such as rheumatoid arthritis. At the time, Peptech claimed this was the first time a domain-derived antibody had been given to humans but it has now emerged that Ablynx had already started a Phase I trial in the first quarter of this year - some two to four months before Peptech. That arguably leaves Ablynx slightly ahead in the race to get this class of drug to market, although the research is still at a very early stage. It won't be until either company enters pivotal Phase III trials that the likely winner will emerge. Ablynx's front running drug in the mini-antibody race is the blood-clot busting ALX-0081. It targets von Willebrand Factor (vWF) to reduce the risk of thrombosis in patients with acute coronary syndrome. Although the final Phase I results are not expected until the end of September, Ablynx said there were no serious side effects or dose limiting toxicity and the drug appeared to be highly potent. "We are very encouraged by the positive results of our first Nanobody in clinical development which is believed to be the first ever single domain antibody human trial," said Dr Edwin Moses, Ablynx CEO. Why is smaller better? ​ Compounds that retain the specificity and effectiveness of traditional antibodies yet are much smaller hold a number of advantages, normally reserved for small molecule drugs. They can be administered in a variety of ways: injected, orally, in sprays or creams, as opposed to full size antibodies, which can only be delivered by injection. They can also address therapeutic needs beyond the reach of antibodies, for example targeting epitopes such as receptor clefts, enzyme active sites and viral canyon sites, according to Ablynx. They can also enter the central nervous system more easily and so treat a number of diseases that bigger molecules cannot. According to Domantis, another advantage can been seen in diseases where more than one antibody could be used; it is possible to stitch together two or more antibody domains in one product, which could then do the job of multiple traditional antibodies. As well as these clinical benefits, both types of mini-antibodies are also cheaper to manufacture. How do Ablynx and Domantis drugs differ?​ Ablynx's mini-antibodies were oringially developed following the discovery that camels and llamas (camelidae) possess fully functional antibodies that lack light chains. These heavy-chain antibodies contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Importantly, the cloned and isolated VHH domain is a perfectly stable polypeptide harbouring the full antigen-binding capacity of the original heavy-chain antibody. These heavy chain VHH domains form the basis of Ablynx's drugs. By comparison, Domantis' molecules consist of either the heavy or light chains of human antibodies, but again only the variable regions. As such, the company believes its drugs are superior as they are not derived from animals. Ablynx claims that because the nanobodies are derived from naturally-occurring heavy-chain antibodies, they are extremely stable; whether they are more stable than Domantis' products is unclear. This isn't the first time Ablynx and Domantis have gone head-to-head, although last time it wasn't in the clinic, it was in the Opposition Division of the European Patent Office. Back in 2005, Domantis challenged Ablynx's patents relating to mini-antibodies. The result was a major amendment of the main claim in the patent and a significant narrowing of the scope of 34 of the 41 other claims, according to Domantis, although Ablynx also heralded the court's decision as a success, saying the division had upheld the key composition of the patents. Lucrative market​ No matter who wins the race, both could eventually enter a highly lucrative market. According to figures from La Merie, global antibody sales stood at a massive $22bn (€16bn) in 2006, making it by far the highest-selling class of biopharmaceutical and over a third of the $63.83bn total. With the many advantages domain antibodies have over traditional antibodies, it is conceivable they could snatch a significant share of that market over time. As GSK's £230m (€340m) acquisition shows, the technology is already attracting big pharma's interest - and money. Ablynx have signed collaboration deals with Genencor - now part of Danisco, Proctor and Gamble, Wyeth and Boehringer Ingelheim. These last two deals alone were worth nearly half a billion dollars.

Related topics Preclinical Research

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