Big drugmakers think small with nanomedicine deals

* Nanomedicine promises greater precision and monitoring

* Pfizer, Amgen, AstraZeneca among firms placing bets

* Early-stage research but scientists see momentum building

By Ben Hirschler

LONDON, May 3 (Reuters) - Is nanomedicine the next bigthing? A growing number of top drug companies seem to think so.

The ability to encapsulate potent drugs in tiny particlesmeasuring billionths of a metre in diameter is opening up newoptions for super-accurate drug delivery, increasing precisionhits at the site of disease with, hopefully, fewer side effects.

Three deals struck this year by privately held BindTherapeutics, together worth nearly $1 billion if experimentsare successful, highlight a new interest in using such tinycarriers to deliver drug payloads to specific locations in thebody.

U.S.-based Bind is one of several biotechnology firms thatare luring large pharmaceutical makers with a range of smartdrug nanotechnologies, notably against cancer.

And nanomedicine is also being put to work in diagnosis,with tiny particles used to improve imaging in scanners, as wellas rapidly detecting some serious infections.

In future, researchers hope to combine both treatment anddiagnostics in a new approach dubbed "theranostics" that wouldallow doctors to monitor patients via their medicines.

After much hype but limited clinical success, scientists inthe nanotechnology field finally see a turning point.

"We have been hearing about the promise of nanomedicine fora long time, but it is now really starting to move," said DanPeer, who runs a nanomedicine laboratory at Tel Aviv University.

"There is a new level of confidence in this approach amongthe big pharmaceutical companies ... We will see more and moreproducts in clinical testing over the next few years and I thinkthat is very exciting."

Nanoparticles made of polymers, gold and even graphene - anewly-discovered form of carbon - are now in various stages ofdevelopment. In cancer alone, 117 drugs are being assessed usingnanoparticle formulations, though most have yet to be tried onpatients, according to Thomson Reuters Pharma data.

Other potential applications include treatments forinflammatory disorders, heart and brain diseases, and pain.

COLLATERAL DAMAGE

Companies are increasingly focused on better drug targetingto increase efficacy and lessen the collateral damage caused by medicinal "carpet bombing" - a particular problem in cancer,where toxic compounds are needed to kill tumours.

The work on drug-carrying nanoparticles parallels advancesin using so-called "armed antibodies" to deliver drugs direct tocancer cells - an approach championed by Roche.

The Swiss group won U.S. approval in February for Kadcyla,its first such antibody-drug conjugate, which treats breastcancer with fewer side effects like hair loss.

"All these developments have prompted companies to look atnew avenues because the older ways of using drugs haven't workedso well," said Robert Langer, a pioneer of nanomedicine who runsthe world's largest biomedical engineering laboratory at theMassachusetts Institute of Technology.

Having worked on drug delivery since the 1970s, Langer hasseen plenty of ups and downs.

The world's first nanomedicine was actually approved back in1995 when U.S. regulators gave a green light to Doxil fortreating Kaposi's sarcoma, a cancer often associated with AIDS.

Doxil - a hollow fatty ball known as a liposome with acancer-killing drug inside it - was a breakthrough. Yet fewother nanomedicines have followed.

Recent scientific advances have changed the game, however.Bind's nanoparticles, for example, are programmed to reach theright spot using targeting molecules that recognise specificproteins linked to disease on the surface of cells.

They also have a stealth covering that shields them from theimmune system, in order to minimise adverse reactions.

Since January, Amgen, Pfizer andAstraZeneca have all signed up to use Bind's technology,which comes from work originally carried out in Langer's lab.

And Bind is not the only game in town. Another approach,using tiny particles of gold as drug carriers, is being exploredin a deal that AstraZeneca signed in December with CytImmune.

"Anything you can do to improve targeting of tumours ratherthan normal tissue - whether that is through an armed antibodyor nanoparticle approach - increases the chance of success,"said Susan Galbraith, who leads AstraZeneca's oncology research.

PARALLEL APPROACHES

The work remains early stage and Peer of Tel Aviv Universitysays all the novel carriers will have to be studied closely forpotential toxicity. However, experience with liposomes is goodand versions of gold nanoparticles have also been used safelyfor many years to treat rheumatoid arthritis.

Injecting patients with gold may sound like a pricey optionbut with thousands of nanoparticles fitting into the width of ahuman hair, the amount of metal used is tiny. Gold, unlike someother metals, is not toxic and has been used in various medicaltreatments for many years without harmful effects.

Bind CEO Scott Minick also thinks his polymer technologywill have cost advantages over expensive antibody drugs.

Further out, Kostas Kostarelos, professor of nanomedicine atUniversity College London, has high hopes for graphene - aone-atom-thick form of carbon. His team is currently workingwith graphene nanomaterials in pre-clinical experiments.

"We will see parallel development of different materials,each offering something different therapeutically," he said.

Other venture-backed nanomedicine firms include CeruleanPharma, whose technology has made a highly potent cancer drugtolerable but which recently had disappointing results in aclinical study, and two companies looking at new vaccines.

Selecta Biosciences has a deal on food allergy vaccines withSanofi, while Liquidia Technologies is allied withGlaxoSmithKline on vaccines and inhaled products.

MIT's Langer is convinced more Big Pharma companies willthink small in future.

"You can be sure others will jump on the bandwagon sooner orlater. That doesn't mean they might not jump off for a littlebit too - but they will jump back on. These technologies arehere to stay," he said.