Like a bridge over troubled waters: Neowater closes R&D gaps for the pharma and biotech industry

Bringing a new drug to market is one of the riskiest ventures in the business world. Ms. Ayelet Dilion-Mashiah, VP Business Development at Do-Coop Technologies, explains how Neowater is propelling pharma and biotech development past some of the field's most frustrating obstacles to full market viability.

In the competitive world of new drug development, it's sink or swim for everyone, even the global leaders. R&D investments can reach $500 million or more, just to launch one promising concept. Then it happens.... The very first stages ran well, it appears the data is forecasting fair weather ahead, the coveted harbor is in sight – and suddenly the venture hits a submerged obstacle in the following stages. The clinical or even preclinical trials go wrong, the R&D project flounders and sinks.

Besides the disappointment and drop in morale, the company has to cope with irretrievable financial losses.

The usual culprit in these shipwreck stories is not the heroic research team and their painstaking work, but rather the "water barrier". In many cases, conventional aqueous and non-aqueous delivery systems are suited to the in vitro paradigm, but they fail to predict the unique molecular behavior of biological organisms, which are fuelled by intracellular water (a very different kind of water from that used in the lab).

This essential difference in water structure plays havoc in unexpected in vivo responses, which stubbornly refuse to follow the rosy in vitro predictions. Hydrophobic conflict, breakdown in the stability of compounds and other setbacks eventually force the project off-line, adding it to a growing number of failures.

Even if it were possible to turn back the clock and try again, many pharma and biotech firms would be unsure how to avoid repeating the same mistakes all over again. The "water barrier" is a fact of biological life; it's not going to just go away. Is there a delivery system that can cross this obstacle and provide smooth sailing in all stages of R&D?

Putting first things first
Until recently, the early-stage focus in drug development was on toxicity, and the question of efficacy was put off to the later stages of the drug trials. This old order was discovered to be an expensive mistake.

The impact on the disease entity (and the dosage required for that impact) is the bottom line for any drug; leaving it until the late stages of Phase III has caused the failure of many potential products, with the inevitable financial fallout. As a result, efficacy has finally become an integral part of early-stage drug development.

However, the good intentions are too often sabotaged by the use of different vehicles at different stages of the research process. This can lead to unpredictable dose responses in human subjects, a catastrophic outcome for late-stage trials. Ironically, this is precisely what the change in priorities was meant to rectify.

An early-stage focus on locating the optimal delivery system, one that can be used both in vitro and in vivo with consistent data results, is clearly both fiscally responsible and experimentally smart.

The love/hate relationship of compounds, cells and water
Getting hydrophobic and hydrophilic properties to live together on the same delivery platform has been a big issue for R&D. When new hydrophobic compounds are introduced to the field, the process becomes problematic. The search is on for a single, comprehensive solution for all the water-based issues in drug delivery.

DMSO has long been the vehicle of choice for solubilizing hydrophobic and hydrophilic compounds in early stages. However, the use of DMSO just for its solubility has led to naive assumptions about the jump from good in vitro results to the prediction of in vivo bioavailability and efficacy in humans.

The DMSO solution, as we all know, cannot be used in humans. An alternative for sufficient delivery via aqueous fluids demands that the compounds be initially hydrophilic, and this becomes a problem with hydrophobic compounds.

Internalizing this lesson resulted in a great deal of attention being focused on using lipids to deliver drugs, such as liposomal vesicles and other micelle delivery systems. The problem with these systems is that they are not inert, and the other materials they contain for the upload and release of the payload drug can cause complications.

The only sure way to avoid these pitfalls is to find a single medium that is ideal for both solubility and delivery, friendly to both hydrophobic and hydrophilic compounds, ensuring that it can both be delivered to the desired site and extracted to reach the targeted points on the cells. But the answer also has to be safe, inert, naturally stable and – last but certainly not least – cost-effective.

A tall order. Nevertheless, these challenges are met in a generic delivery system that opens the way for timely medical breakthroughs and healthy profits.

Bridging the water gap with Neowater
Do-Coop Technologies Ltd, a private IP company based in Israel, has reconciled these issues and conquered the water barrier at the molecular level. The company's production method for its water-based nanotechnology is appropriately named Neowater®.

Neowater is distinguished from regular water by a clear shift in physical and chemical properties, and a proprietary structure that is remarkably stable under standard conditions (STP). Moreover, Neowater closely resembles the water that naturally occurs in biological organisms, which can deal with both hydrophobic and hydrophilic compounds.

The unique organization of the water molecules is derived from interaction with water, suspended nanoparticles and carbon dioxide, resulting in improved solubility, dispersion of drugs, enhanced stability and bioavilability of drugs and biomolecules. Because it provides higher stability to proteins, enzymes and cell cultures, Neowater enhances biological in vitro and in vivo reactions. The non-toxic drug delivery platform can carry a wide range of biotech and pharma concepts past the water barrier for reliable testing at every stage in product development.

The compatibility of Neowater with the natural biological environment reduces the need to introduce stabilizers, detergents, organic solvents, or other chemicals commonly used in drug formulation and development.

How Neowater dissolves the differences
Nature uses the unique properties of structured water to enable a supporting environment for biological and chemical activities. Do-Coop Technologies has harnessed those same unique properties, enhancing them by adding inert nanoparticles in a proprietary process.

A form of water that is structured similarly to intracellular water, Neowater is composed of two hydrogen atoms and one oxygen atom – the same basic chemistry as “bulk” water. The main difference is that water molecules in Neowater are organized in clusters and therefore feature different properties when compared to “bulk” water. Neowater's key feature is the clusters' very large surface area, which is achieved by introducing nanoparticles to the water via a proprietary process.

Neowater's post-production composition is distinct from regular water in that the CO2 concentration is 10- to 100-fold higher, and the enlarged surface area, due to the nanoparticles, provides structure in the liquid phase. These characteristics result in an enhanced ability to disperse both hydrophobic and hydrophilic compounds while at the same time heightening bioavailability and stability.

The Neowater vehicle facilitates the delivery of drugs by leveraging this surface effect, making it unlike any other delivery system. However, because Neowater is a naturally generic solution, it provides an optimal vehicle structure for many drug compounds with only minimal customization.

When results become predictable, so does ROI
The shift toward examining both toxicity and efficacy during the first stage of drug development came about in order to avoid the lack of predictability in later stages. The use of standardized aqua-vehicle systems is a logical part of the wish-list as well.

With Neowater, companies can now streamline the drug development process, moving from in vitro development to in vivo delivery, and from early laboratory experiments to late-stage studies in humans, with the same vehicle. No more changes after in vitro results are in, and no more variable reliability that can result in late-stage failure – with the loss of significant capital.

The introduction of Neowater into pharma applications and formulations reaps other rewards as well: better hydration and overall in vivo bioavailability, as well as greater control in treatments requiring sustained release formulas. Neowater-based media become reliable allies to enhance the growth, secretion and clonability of biotech applications, and to increase the long-term stability of products.

And that's not all.

Neowater's non-toxic certification (FDA DMF#20503) saves additional time and costs. The FDA allows pharmaceutical companies to integrate Neowater with their drug products as part of the standard drug development and registration processes, without the need for a separate Neowater toxicity control. Neowater customers who start clinical studies for their compounds formulated with Neowater are able to enjoy faster, smoother progression from in vitro to in vivo implementation.

Do-Coop has also obtained ISO 9001:2000 and ISO 14001:2004 qualifications for its Israel facility, and is currently in the final stage of achieving cGMP compliance for its new Neowater production plant in Israel. Ensuring the quality of the delivery system at global standards is just one more plus that we pass onto our customers.

The value of Neowater to the life science industry is eventually expressed in new IP with enhanced pipelines – and the process now requires less capital and time investment than ever before.

A new wave of business opportunities
Neowater gives the pharma and healthcare industries a uniquely stable water-based environment that is closer than ever to the water that supports life itself. This has far-reaching implications for applied research, and for business potential.

Many novel therapeutic substances could improve our quality of life, if it were not for the drawbacks of the water barrier. Bridging this gap increases the chance that more of these promising concepts will no longer sink, but swim.

Neowater® is a proprietary substance produced only by Do-Coop Technologies Ltd. We are committed to licensing our technology to leaders in the life science industry, through a development stage with potential partners followed by technology transfer.

In keeping with that goal, a recent collaboration partnership with Champions Biotechnology was formalized, which has allowed that company to advance its novel oncology compound into Biomerk Tumorgraft™ testing.
 
Champions Biotech is engaged in the development of advanced preclinical platforms and tumor-specific data to enhance the value of oncology drugs. The company has established a collaboration agreement with Do-Coop Technologies Ltd. for the development of a more soluble form of SG410, its Benzoylphenylurea (BPU) sulfur analog compound. SG410, an in-licensed compound, is the first agent in Champions’ drug development pipeline.

Using Neowater, Do-Coop has been able to improve the solubility and activity of SG410. As a result, SG410 has demonstrated promising activity against prostate and pancreatic cancer in both in vitro and in vivo models. Champions Biotech expects to have early Biomerk Tumorgraft results for SG410 by the end of 2009 (within the next six months).

Under the terms of the agreement, Do-Coop will receive development milestones and royalties based on the clinical success of the compound.

Ayelet Dilion-Mashiah is the VP of Business Development and CFO of Do-Coop Technologies Ltd.