Evolving strategy

Hilary Ayshford met Christopher Searcy to hear how Nektar Therapeutics moved into the acquisition market to increase the range of technologies it can offer its clients

Just as drugs are constantly evolving to treat an ever-widening range of conditions more effectively, so the pharmaceutical manufacturing sector is changing to develop new technologies to enable these advances to take place.

While some companies are taking the approach of specialising in one or two particular market niches, others have gone on the acquisition trail to expand their offering to encompass a number of complementary technologies. Nektar Therapeutics is among the latter.

expanding horizons

Founded in 1990 as Inhale Therapeutics, the company concentrated during its first 10 years on the non-invasive delivery of peptides and proteins through the pulmonary route. But after building up a successful range of products and customers, it then started looking for ways to grow. Traditionally, drug delivery companies seeking to expand have become integrated pharmaceutical manufacturers, to market their own products rather than being at the whim of the customer, says Dr Christopher J. Searcy, vice president of corporate development.

But Inhale Therapeutics, as it was then, decided instead to concentrate on what it was good at - drug delivery - and to grow by broadening its technology platform.

It therefore looked around for companies that led their fields with technologies that could be applied across a wide range of molecules. The first that came to mind was Bradford Particle Design (bpd), a leader in the use of supercritical fluids technology for pharmaceutical applications, with which Inhale had a long-standing relationship; and the second was US-based Shearwater Polymers. And since the activities of the enlarged company were a lot wider than pulmonary delivery of drugs - bpd's technology is oral delivery of small molecule crystalline products, and Shearwater is focused on less invasive delivery of peptides and proteins by PEGylation - a name change was called for, and Nektar Therapeutics was born, along with a strategy to take the company forward.

'We looked at drug delivery from drug discovery through to commercialisation, and we decided that the best way to accelerate our growth is to take the mature technologies that we have and use them to create differentiated products,' said Searcy.

Rather than just licensing the technology to partners, Nektar aims to complement the technology licensing with a proprietary programme by applying the technology to molecules that are either off-patent or coming off patent to address an unmet medical need. But working with existing molecules means that for the strategy to be successful Nektar needs to have a technological edge.

'We have three really solid, broad-based technologies,' Searcy emphasised. 'If we had one technology platform and it was applicable to only two or three molecules, our only choice to grow would be to take a molecule all the way through to approval. But our three technologies and their ability to differentiate products gives us a great opportunity.

'We think we can take 10-15 products into Phase I or Phase II for the same cost as taking one product right through to market and at much lower risk for a relatively high commercial return.' Once a product reaches Phase II, Nektar would look for the right pharmaceutical partner to take it the rest of the way and commercialise it.

The three technologies allow the company to cover a broad base of therapeutic areas. The pulmonary delivery technology, originally developed by Inhale, is particularly suitable for rapid onset drugs for conditions that require the speed of an injection but the convenience of oral administration. Its other main application is for certain lung infections that are currently being treated systemically with oral antibiotics. With an oral antibiotic only 5-10% of the active ingredient reaches the lung, so targeting the lung directly is a very effective method of delivery and one that has not be been exploited to any significant extent, Searcy claimed.

The bpd technology can also be used to speed up absorption of active ingredients for oral delivery. For example, it allows particles to be made with higher surface areas or to co-formulate them with excipients to speed up the rate of absorption. It can also be used to improve the taste-masking in oral suspensions or chewable tablets, and to reduce the size of large tablets by improving the bioavailability of the active ingredient.

product technologies

Shearwater's PEGylation technology is used primarily to reduce the frequency of administration of peptides and proteins, for example changing them from daily to weekly or from weekly to monthly. But what the technologies have in common is the ability to produce differentiated products. They are also complementary, said Searcy.

Nektar believes that there are a number of instances where different product concepts can be created by using the different technology platforms, or by combining two or more of the technologies to make a product that could not be achieved using one of the technologies alone.

For example, it may be desirable to deliver a drug locally to the lung to treat an infection, but because it is a small molecule it passes rapidly through the lung and into the bloodstream and would therefore have to be administered several times a day. But using PEGylation, it may be possible to make the active ingredient remain in the lung for a much longer period before it is eliminated.

There are currently 19 products in Nektar's pipeline, of which six are approved and on the market, all of which use PEGylation technology. There are a further three products in Phase III, of which one is pulmonary and two are PEGylations. All four products in Phase II use PEGylation technology and of the six products in Phase I, three are pulmonary and three are PEGylations.

Among the Phase III products are inhaled insulin, which is being developed and marketed by Pfizer as Exubera, and Maxygen, a breakthrough injectable PEGylation product to treat macular degeneration that is being developed by US company Eyetech.

The third Phase III product is CDP870, an antibody fragment against TNF developed by Celltech in the UK and licensed to Pfizer.

'The problem with antibody fragments is that because they are smaller than whole antibodies they are cleared a lot faster, so Celltech and Nektar have collaborated to PEGylate these fragments, so that CDP870 can now be administered once a month just like a whole antibody,' Searcy explained.

Ultimately, Nektar believes that the bpd technology is the broadest of the three, and for this reason the company is committed to investing in scaling up during 2003. 'Two thirds of all drugs being developed are small molecules and one third are peptides and proteins,' Searcy said. 'Bradford sits primarily in the small molecule space.

'We want to make sure we do two things: continue to invest so that we not only develop next generation technology but also document the applications of that technology towards creating products. That is critical to Nektar Therapeutics' strategy.'

The second part of the strategy is adding more technology to the toolbox, although the weak economic climate means that there are no imminent acquisitions on the cards.

'We see a lot of people exiting the drug delivery space and becoming fully integrated pharmaceutical companies where they end up competing with their technology partners in certain therapeutic areas,' Searcy said. 'So while everybody is leaving the space, we think it's a great place to stay. But if you are going to stay you have to make sure that you have good technology. If you have good technology and good execution, we think it can be a very good business.

'The products we are developing are all viewed as very strong products in the pipelines in some of the top pharmaceutical companies in the world. That tells me that our strategy is working because our technology is being applied to products that are going to make a big difference in patients' lives in terms of better therapies.'