'Miniature antibodies' are set to enter clinical trials for the first time ever, potentially paving the way for more effective antibody therapies that are also cheaper to manufacture.
Peptech has announced that its lead drug candidate, PN0621, has started a Phase I clinical trial. The study will access the safety of the drug in 30 healthy volunteers, and is expected to last up to four months. PN0621 targets tumour necrosis factor (TNF) to treat auto-immune inflammatory diseases such as rheumatoid arthritis. Therapeutic antibodies are nothing new to the world of drug development. However, they are large proteins that are unable to reach certain parts of the body. Not only that, but it is well documented that patients can develop resistance to one antibody, yet respond to another.
Domain antibodies (dAbs), however, are much smaller - around a tenth of the size of conventional antibodies. This is because the bulk of the antibody is missing - they only consist of the variable regions of either the heavy or light chains of human antibodies. As such, they are the smallest antibody-like protein capable of strongly and selectively interacting with target molecules. This gives them several advantages over normal antibodies. Which is the most important depends on the indication. In the case of immune system drugs, their small size could enable them to enter the central nervous system more easily.
Alternatively, if current therapies are all administered by injections, the dAb could, instead, be given orally, by inhalation or even through a cream. Another advantage can been seen in diseases where more than one antibody could be used - it is possible to stich together two or more antibody domains in one product, which could then do the job of multiple traditional antibodies. All of these benefits can be achieved without losing the highly selective nature of antibodies. As well as these potential clinical benefits, the mini-antibodies also carry a financial plus in that they are cheaper to manufacture.
"We intend to demonstrate key differentiators against existing anti-TNF treatments, namely improved efficacy, reduced toxicity, points of convenience (eg home administration) and cost of goods," said Peptech. There are currently three marketed anti-TNF drugs: Centocor Pharmaceuticals' (Johnson & Johnson's) Remicade (infliximab) for Crohn's Disease and rheumatoid arthritis; Abbott's Humira (adalimumab) for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Crohn's. Finally, Amgen and Wyeth's Enbrel (etanercept) approved for use against arthritis, spondylitis and psoriasis.
Together, these drugs had combined global sales of $10.8bn (€8bn) in 2006, with a projected market value of greater than $20bn in 2012, according to Peptech. The Australian firm also said that the number of diseases that could potentially be treated with anti-TNF drugs is increasing to include, asthma, atherosclerosis and atopic dermatitis. "To date, PN0621 has shown an excellent pre-clinical safety profile and advantages in cost of manufacture compared to full-sized, conventional antibodies. Peptech is now looking forward to gaining the first data from humans as PN0621 progresses through this necessary step towards commercialisation," said Peptech CEO, Dr John Chiplin.
The idea for these mini-antibodies came from UK firm Domantis. Founded by Sir Gregory Winter and Ian Tomlinson, the biotech owns technology for producing dAbs. Since its inception, Domantis has attracted numerous high-profile investors, including Novo Nordisk. Indeed, Peptech themselves owned over 30 per cent of Domantis. More recently, as reported by DrugResearcher.com last December , GlaxoSmithKline (GSK) has now agreed to acquire Domantis for £230m (€340m). Under a research collaboration agreement signed in 2001, Peptech commissioned Domantis to develop dAbs against four targets nominated by Domantis. The first resulted target was TNF and the second was an anticancer target called P2X7, which is a ligand gated ion channel. The last two targets were described to DrugResearcher.com by Chiplin as "open slots". He explained that GSK has said it will honour the original agreement and the two companies are currently in talks about how to proceeed.
Just over two weeks ago, Peptech also announced it was to merge with Evogenix, another Australian biotech that specialises in antibodies. The new name for the company is yet to be decided, but Peptech shareholders will hold around 70 per cent of the merged entity. "Peptech have really pushed this product through the development process and it is the first domain antibody-based product to enter into the clinic," said Sir Gregory, Domantis co-founder.
"It marks a significant milestone in the translation of research to commercial application of this new class of therapeutics."