Using nanoparticles for effective drug delivery

While there are many effective in- haled drugs on the market, the exist- ing techniques for pulmonary delivery result in much of the drug being de- posited at the back of the throat where it can potentially enter the systemic circulation. In most products, only 15 to 30% of the drug actually reaches the lung, with just 20% of that reaching the deep lung.

To resolve this drug delivery chal- lenge, Cory Berkland and George Lau- rence co-founded Savara Inc. in March 2007. The company is developing respi- ratory therapeutics using its proprietary NanoCluster dry powder aerosol drug de- livery platform, which is based on Berk- land’s research.

Berkland designed and developed the NanoCluster technology at the Uni- versity of Kansas to improve the aero- sol properties of drugs delivered into the lung. The NanoCluster technology has potential for local or systemic de- livery of a wide variety of drugs, in- cluding poorly soluble and highly soluble drugs, small molecules, pep- tides and biological therapeutics. The NanoCluster manufacturing process can create microparticles to specific sizes and incorporate two or more dif- ferent therapeutics to make a combina- tion product.

“We typically create nanoparticles and assemble these into low-density microparticles that can be delivered using an oral or nasal inhaler,” explains Berkland. “The technology allows us to create defined particle sizes, which ‘fly’ in different ways—for example, larger particles are deposited in the upper airways and smaller particles travel further, into the deep lung.”

The NanoCluster technology can be used for life cycle management and line extensions, increasing the patent life of existing marketed drugs. It also has potential for improving the ef- ficiency of delivery of drugs, thereby increasing the therapeutic efficacy or reducing the required dose of drugs to reduce side effects. Due to the powder performance, the microparticles can be delivered using older off-patent dry powder inhaler devices, which would reduce the cost of entry to market.

Savara’s business operations are based at the Austin Technology Incu- bator (ATI) in Texas, where it moved in late 2008, and its labs and tech- nical operations remain at KU, from which it obtained exclusive rights to the NanoCluster technology. The com- pany applied for the first NanoCluster patent in 2005, and expects approval during 2009.

Savara regards Nektar Thera- peutics Inc.’s pulmonary assets (now owned by Novartis AG) and Alkermes Inc. as its nearest rivals. “While our competitors generally use spray drying to produce the particles and excipients to provide the ‘flight’ properties, we are able to do this simply using our nanoparticle technol- ogy, without the need for non-active ingredients, which increases the drug loading,” says Rob Neville, Savara’s executive chairman.

“A key differentiator between us and our competitors is our ability to manu- facture fine particles of one to three microns, leading to improved aerosol performance,” explains Berkland. “We are not aware of anyone else tailoring mi- croparticle size using nanoparticle build- ing blocks as we do. Improvements in aerosol efficiency and elimination of un- wanted excipients will allow us to deliver at least two to three times more drug to the lung than our competitors.”

Savara’s business model is based on out-licensing, and the company has a number of agreements ongoing, with further discussions under way with a number of top-10 pharmaceutical companies as potential partners.

Potential partners pay Savara for a feasibility study with the partner’s drug and Savara’s technology. If the study is successful, the partner has the option to license the technology. Savara can provide pharmaceutical companies with preclinical- and clini- cal-scale batches of material. “We allow the industry to drive the development of our technology, based on the formulation issues presented by our clients,” explains Neville.

He says that Savara’s NanoCluster technology is broadly applicable across a number of therapeutic areas. The company has successfully formulated products for asthma, COPD and pul- monary infections, cancer diagnosis and treatment, tuberculosis and hy- pertension. Savara is in the process of publishing some of its preclinical data that demonstrate effective deposition in the peripheral lung.

In July 2008, Savara closed a seed round providing $1 million, and in June 2009, the company received an $833,000 first tranche of its Series A funding. The second tranche will close in the second half of 2009, providing a total of $1.4 million, and involves most of the company’s existing inves- tors. Savara has earmarked the Series A funding for expansion of the Nano- Cluster platform into new areas, such as combining it with nebulizers, or propellant-based inhalers.

“As we out-license the technology, and receive fees from service agree- ments, we do not need to seek as much funding as a typical drug development company would,” says Neville. “We also have some grant applications under- way and should be able to run for two years without seeking any additional money. We feel that this financial strength is an achievement for a young company.”

Rob Neville has been with Savara since the beginning, and he saw the op- portunities presented by Berkland and Lau- rence, and by the NanoCluster technol- ogy. “Not only did this present financial potential, but I also saw an opportunity to have an impact on marginalized peo- ple—people without a voice, such as those in South Africa, where I was born, for exam- ple. We are currently working with lead- ing researchers and organizations to cre- ate pulmonary based tuberculosis and vac- cine treatments,” says Neville. “I had a real desire to see my ideas translated into products that could better lives,” adds Berkland.

Neville was previously the founder and CEO of a software company, Evity Inc., which was acquired by BMC Soft- ware Inc. in 2000. He also founded the management consulting company Clockwise Consulting, which has part- nerships with a number of Texas bio- tech companies. Neville was a finalist for the Ernst & Young Entrepreneur of the Year award.

Over the next 12 to 24 months, Sa- vara hopes to see some of its partner products move into clinical trials. “I think the major challenge that we face is skepticism from the phar- maceutical industry. They see the performance as too good to be true for such a simple and integratable particle engineering con- cept,” says Berkland. “We need people to appreciate the clinical benefits of this

unique approach.” Despite the current economic climate, Savara is still expanding. “We took on three new people in June 2009, taking our staff up to five full-time people and 10 part-time people. We would expect to have recruited another three or four people by mid-2010,” says Neville.

Like all start-ups, Sa- vara will face the trials of the economic slowdown, but it appears to be rid- ing it. “We seem to have done well. Our reach must exceed our grasp,” says Neville.

http://www.savarapharma.com/Documents/SavaraInc_StartUpProfile.pdf

—Suzanne elvidge

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