Neowater: Not Science Fiction, Just Good Science

Neowater, the nanotechnological innovation from Do-Coop Technologies, may strike some as "magical" in the way it sails past many R&D problems thought to be unsolvable. However, Do-Coop CEO Eran Gabbai says Neowater is simply a logical extension of the unique properties found within water itself.

Arthur C. Clarke, one of the most prolific science-fiction writers of the twentieth century, once observed: "Any sufficiently advanced technology is indistinguishable from magic." Neowater technology has acquired this kind of science-fiction mystique, due to its seemingly effortless ability to cross barriers that have cost the pharma industry some $80 billion a year in dead-end R&D.

Neowater does indeed solve some stubborn problems, such as poor efficacy, bioavailability issues and high levels of toxicity that plague new drug development. But its unique ability is derived from the unique character of one of the most abundant – and least understood – elements on our planet: water.

The Extraordinary Habits of Water
There are odd things about natural water that scientists have observed for generations without understanding their mechanisms. For example:

• Why does radiation in water take so long to decay?
• Why does hot water freeze faster than cooled water?
• Why does water boil through a "hot spot" mechanism, instead of heating evenly?
• Why do gas bubbles rising through water wobble on their way to the surface?

Even more mystifying is intracellular water, which makes up 70 percent of living organisms but has different physical and chemical properties compared to natural ("bulk") water. Our bodies take in natural water at a fast rate every day, and yet by the time it appears in our cellular environment, it's quite another kind of water. Among its other peculiarities, intracellular water can deal with both hydrophobic and hydrophilic compounds at the molecular level, effortlessly sorting and handling them in a natural process that can only be envied by modern technology.

Perhaps because the peculiar behavior of water is so familiar, most pharmaceutical researchers have never considered the possibility that the oddities of natural water might hold the keys to the mystery of intracellular water. Instead, pharma R&D has related to both kinds of water as obstacles that hamper new pharma compounds, many of which are hydrophobic.

As a result, the standard course of drug development has included the use of a delivery vehicle other than water, usually a DMSO liquid system, to carry the hoped-for wonder drug in pre-clinical trials. Any necessary water is reduced to an inert state, as bulk or lab water; and intracellular water (regarded as just more water) is not taken into the equation at all.

Standard Pharma R&D: A Reality Check
The futility of this approach becomes apparent every time the drug testing moves to the clinical phase, where the highly toxic DMSO must be replaced by some other delivery vehicle. Whatever promising data was achieved with the DMSO system can become meaningless as the new vehicle carries the drug through in vivo testing. The drug development process often ends up back at Square One with efficacy failure or other unexpected results.

The wide prevalence of this approach might be considered the flipside of the popular definition of "insanity" which is traditionally attributed to renowned physicist Albert Einstein: "doing the same thing over and over again, and expecting different results." In this case, pharma researchers do the opposite: they keep changing the delivery vehicle in radical ways, and yet they expect the same data results.

The pharma industry's answer to this routine collision with reality is to follow the "insanity" method in earnest, through high-throughput screening.

High-throughput screening does not start with reality, by taking into account the properties of the disease being targeted, and the intracellular water environment in which the disease is to be confronted. Instead, the method starts with a wish – converting the company's entire IP library into a list of possible drug candidates for a match with a specific receptor. The same trial is made over and over, indiscriminately, in the hopes that one will prove to be a "hit".

This series of "shots in the dark" can number into the millions for each study – a hugely expensive and time-consuming process. And yet, in spite of the severe drain on R&D resources with little to show for it, pharma leaders regard high-throughput screening as the industry standard.

All this "insanity" became necessary because of two related assumptions that are out of touch with reality: (1) that a drug candidate and receptor should meet in an environment other than the cellular one in which the disease occurs; and (2) that pre-clinical trials can depend on a vehicle hostile to cellular function in order to predict efficacy in living cells.

These fictions in turn can be traced back to one basic mistake: failure to grasp the unique activity of water – natural water in general, and intracellular water in particular (one of most important elements in the in vivo environment, yet the least understood).

What might happen if researchers were to view the glass of water as half-full rather than half-empty? Instead of fighting water as an enemy in drug delivery, what if we were able to harness the unique properties of natural water to make it more like intracellular water? Could this new "water" become an ally in drug delivery, or even a drug delivery vehicle itself? 

Do-Coop researchers chose to seek answers to these questions, and we harnessed the power of nanotechnology to turn water from a barrier into an ally in drug development. The result, a liquid that mimics the intracellular water found in the human body, was logically dubbed "Neowater".

Moving Pharma Science from Fiction to Reality
It was the Nobel-Prizewinning physicist Richard Feynman who first introduced the concept of nanotechnology to the scientific world. He also declared that a successful technology must first and foremost relate honestly to reality, because "Nature cannot be fooled." 

For decades, the pharma industry hasn't taken Dr. Feynman's advice to heart. Pre-clinical delivery systems have tried to "fool Nature" and have only succeeded in fooling the researchers. If the delivery vehicle changes between the pre-clinical and clinical stages, how could the data not change as well? 

In a nanotech application that honors the Feynman Rule, Neowater has succeeded in shifting the physical and chemical properties of natural water, making it close to intracellular water. This allows R&D to deal more honestly with Nature by allowing the use of a single vehicle for the entire drug development process.

And since Neowater is already compatible with the intracellular environment where a drug candidate and a receptor are destined to interact, Neowater eliminates the need for high concentrations of co-solvents and surfactants - other attempts to "fool Nature" which cause a lack of predictability in efficacy testing.

The Mystery of Neowater Explained
This is an impressive achievement, but it's no slight-of-hand magic trick. The Neowater transformation is built on the reality of water itself, with the changes taking place at the molecular level.

Neowater is composed of two hydrogens and one oxygen – 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, efficacy and stability.

The result is nontoxic, inert, and similar in properties to intracellular water. It is also remarkably stable at STP, because Neowater does not try to fool Nature, but rather works with it.

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 a revolutionary proprietary process.

Good Science Means Good Business
As everyone knows, pharma R&D is facing a financial crisis due to shrinking pipelines, and just like Nature, the Bottom Line cannot be fooled by promises of a magical solution. The value proposition of Neowater for the pharma and biotech industries is phenomenal and yet realistic.

The Neowater vehicle facilitates the delivery of drugs 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. This opens the way for new and extended IP, based on extended therapeutic windows.

With Neowater as the consistent aqueous vehicle, companies can streamline their drug development process, moving from in vitro development to in vivo delivery, and from early laboratory experiments to late-stage studies in humans, more quickly, more cost-effectively, and with fewer unpleasant surprises.

Do-Coop Technologies' production of Neowater is GMP compliant, and a DMF file was submitted to the FDA (DMF no. 20503). In addition, Do-Coop is currently in the process of having Neowater being certified as GRAS (Generally Recognized as Safe) by the FDA.

Neowater's DMF file presents non-toxic studies which will allow pharmaceutical companies to integrate Neowater with their drug products as part of the standard drug development and FDA registration processes, without the need for a separate Neowater toxicity control. This is one more reason Neowater customers are able to bring their products to market more quickly.

The introduction of Neowater into pharma applications and formulations also improves their therapeutic activity: better hydration and overall in vivo bioavailability, as well as greater control in treatments requiring sustained release formulas.

For biotech applications, Neowater-based media become reliable allies to enhance the growth, secretion, clonability and long-term stability of products.

As for the business future of pharma R&D, Neowater restores the potential for blockbuster drugs, which will provide resources to fuel additional R&D.

Besides the opportunity to transform pharmaceutical and biotech research from a losing "game of chance" to a realistically lucrative industry, Neowater can open and/or widen the therapeutic window, giving pharma companies the chance to redeem earlier drug development concepts, which failed and were shelved because of efficacy and toxicity issues. This not only recovers lost R&D investments from the past; it can also unlock new therapeutic substances for the future, which will improve the quality of life for millions.

If there is any "magic" in Neowater, it is embodied in these new open doors. Other than that, Neowater is just good science that can be translated into good business.

Neowater® is a proprietary water-based nanotechnology substance produced only by Do-Coop Technologies Ltd., a private intellectual property company based in Israel.

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. Our business model is receipt of royalties and milestone payments only.

E: business@docoop.com
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