TransDermal Technologies, Inc. has developed innovative pharmaceutical solutions and products through the application of a new and unique drug delivery technology called the Transdermal Delivery System (TDS®). This drug delivery breakthrough is a programmed liquid vehicle which is modified for each drug. The system is applied directly to the skin as a liquid or semi-solid, not requiring a patch or other appliance. The medicine is delivered rapidly and in sufficient doses to accomplish a therapeutic outcome at a fraction of an equivalent oral dose. TDS® has not yet encountered an upper bound for size of molecule it can deliver in solution in the system across the skin, the largest to date being a hydrophilic peptide of 1725 Daltons. With TDS®, the medicine traverses the intact skin without a needle or significant irritation. Doses are typically compounded into one milliliter (cc) of the TDS® and measured with a metered spray pump or a unit dose package. This system enables significant clinical and cost advantages versus alternative drug delivery modalities and has a broad array of applications and business opportunities. The technology is patented with no prior art cited (U.S. Patent 6,444,234 and U.S. Patent 6,787,152) and pre-filing review by the patent office has not disclosed any companies pursuing similar technology. Division claims will further expand protection of the technology.

TransDermal Technologies' MISSION is to improve health care by:

Making existing medicines and treatments more effective, safer, and easier to use

Making medicines useful that were previously too dangerous or difficult to administer

Creating new medicines and treatments

TTI is pursuing its Mission by:

- Creating research and product development capabilities and resources. This is being done through a core internal research and development group combined with alliances with medical research institutions and clinical research organizations. The company has begun, and is expanding a four-year collaboration with the The WIlliam Harvey Institute at St. Bartholomew's and the Royal London School of Medicine and their work has proven the ability of the system to deliver a therapeutic dose of several medicines at a fraction of its oral or IV dose and achieve a therapeutic outcome across the skin. Several kinetic studies have been completed successfully on molecules including Cystamine, Morphine, Testosterone, Ibuprofen, Acetaminophen, Hydroxyzine, Acyclovir, alpha Melanocyte Stimulating Hormone and Diazepam and results are pending on several others. A Phase IIa Human trial on Lidocaine, two others on a Testosterone and one on a Diazepam application have been completed and results are awaited on one other. Additional human trials are scheduled to begin in 2008.

- Licensing and contract product formulation with pharmaceutical and consumer product companies leveraging TDS® to develop new classes of products and extend the patents of existing products. Plans, contracts and/or tests are under way for a variety of TDS® applications for a number of international pharmaceutical companies.

- Expansion of TTI's over-the-counter product business. Continuing as a profitable business with research and development funded by on-going business operations. TTI's business base is the production and sale of several OTC products including Penetran® and Penetran®+Plus and several private label arrangements.

- Establishing a positive evaluation with regulatory agencies.  TTI has completed 5 human trials under the oversight and auspices of the British MHRA.  In March, 2008, TTI met with the Center for Drug Evaluation and Research at the U.S. F.D.A. to discuss the clincial development of a particular TDS product and it was agreed that the company could submit a phase III IND application, whihc it plans to do as soon as possible and probably by 4th quarter 2008.  This same application will be submitted to ethics review and scrutiny by the MHRA to reconcile any additional requirements into the protocols and marketing approval will be sought simultaneously in the EU.

Technology Breakthrough

The TDS® delivery system capability to provide optimum bioavailability depends on a number of factors which can be tailored and exploited to maximize the potential for therapeutic and market success. The optimized TDS® delivery system:

- Protects the medicament from environmental effects.

- Protects the medicament from degradative enzymes and gastric acid found in the stomach or small intestines.

- Reduces dose size and frequency and minimizes side effects, and

- Reduces first pass hepatic elimination enabling smaller doses.

- Makes feasible the delivery of medicaments which are not deliverable with conventional methods such as unstable protein therapies or localized dosing of highly toxic chemotherapeutic agents.

The TDS® delivery system also:

- Dissolves or emulsifies a therapeutic dose of the medicine down to single molecule level in a carrier which remains liquid long enough to penetrate the skin,

- Remains stable as formulated and does not complex with other substances and/or minimizes premature processing by, and binding in the skin

- Does not damage the skin with repeated use.

- Releases the medicament appropriately and does not alter the drug or leave as residuals compounds which might be sensitizing.

The TDS® successfully penetrates the skin because:

- All elements used do not form chemical bonds with the medicine, leaving it free to seek appropriate receptors once released.

- All elements of the system are at least neutral as a foreign agent, do neither harm nor ill, and preferably are nutritive or otherwise useful as a part of physiology.

- It creates a transient modification of the elements in the delivery system which might trigger the body's defense mechanisms.

- It changes conditions in the structure of the skin allowing for movement of medicines of various sizes through the skin.

- It minimizes or offsets any damage done by the process.

Safety Testing and Clinical Results

The TDS® has undergone the following testing and clinical trials to date:

In Vitro System Toxicity and Irritation - The standard system has been evaluated as non-toxic and non-irritating in microbiological testing on a human skin model.

In Vitro Dermal Permeation - Skin permeation study is complete on systemic and local versions of Morphine Sulphate TDS®. Pilot data showed that even without rubbing in, system performed as well as patch delivery for localized application and twice as well as patch delivery for the systemic application.

In Vivo Animal Kinetics and Therapeutic Outcome - Cystamine, a compound with tumor shrinking, anti-angiogenesis and anti-inflammatory characteristics has been delivered. Conclusions: (1) TDS® can deliver a medicament through the epidermis to the viable skin (2) TDS® delivers a therapeutic dose and (3) TDS® accomplishes a therapeutic outcome with a heretofore sub-effective dose.

In Vivo Rat Kinetics - Delivery trials for Testosterone, a hormone of 288 Daltons Mol. Wt. administered to 6 rats with measurement of therapeutic blood levels are complete. Data gathered showed a mean increase of from 199 ng/dL to 943 ng/dL (therapeutic) reached in 30 minutes, and 1,062 in 60 and outer bound range of over 2,000.

In Vivo Rat Kinetics - Delivery trials are complete for Morphine Sulphate, a drug of 668.77 Daltons Mol. Wt. administered to 6 rats with measurement of therapeutic blood levels. Data gathered showed a mean increase of from 0 ng/dL to 171 ng/dL reached in 60 minutes, and 246 in 180 minutes and outer bound range of over 1,000. Drug was bioavailable as evidenced by the presence of Morphine-3-glucoronide, the metabolite. Morphine Sulphate has been considered undeliverable transdermally before now.

Therapeutic Outcome - Efficacy trials for Quaternium 27, an analgesic of 975 Daltons Mol. Wt., administered to 100 patients double blind versus placebo are complete. 70% of Patients completing the protocol were evaluated as having reduction in pain and symptoms secondary to inflammation, including reduced swelling and improved range of motion and strength.

In Vivo Rat Kinetics - Delivery trials are complete for Acyclovir, a drug of 225 Daltons Mol. Wt. administered to 5 rats with measurement of therapeutic blood levels. Data gathered showed a mean increase of from 0 ng/dL to 100 ng/dL reached in 30 minutes, and 189 in 60 minutes and 368 in 120 minutes and outer bound range of over 500.

In Vivo Rat Kinetics - Delivery Pilot, GLP Kinetics and Therapeutic outcome trials are complete for Ibuprofen HCL, a drug of 206.28 Daltons Mol. Wt. administered to rats with measurement of therapeutic blood levels and reduction in plueral edema. Data gathered showed a significant increases and maintenance of levels for over 6 hours. Drug was demonstrated bioavailable as evidenced by significant reduction of fluid edema and cell count versus a control of no treatment.

In Vivo Rat Kinetics - Delivery Pilot, GLP Kinetics and Therapeutic outcome trials are complete for Hydroxyzine, a drug of 375 Daltons Mol. Wt. administered to rats with measurement of therapeutic blood levels in 30 minutes.

In Vivo Human Kinetics and Therapeutic Outcome Phase II b trial for an anesthetic molecule TDS® in two formulations are complete. 100 patients each completed two trials. Anesthesia was accomplished in 5 minutes and blood levels detected.

In Vivo Human Kinetics and Therapeutic Outcome Pilot and Phase IIa trial for Testosterone TDS® are complete. TDS® formulation was compared against AndroGel®, a commercially available Testosterone preparation. Trial was performed in 12 healthy volunteers. The TDS® formulation was deemed bio-equivalent to the AndroGel, actually maintaining higher levels for the first 12 hours and maintaining 85% of the AUC over 24 hours with a single I mL dose at 50 mg micronized Testosterone per mL.

A Pilot trial of a TDS formulation for Diazepam was completed in 2007.  Diazepam has never been successfully delivered across intac skin before.  While, as expected,  the results were not bio-eqivalent to the comparator product, the system achieved therapeutic levels by the first draw at 30 minutes post dose versus the comparator which required over two hours before reaching therapeutic levels.   

For further information, please contact Kenneth B. Kirby at  561-429-6429, Fax: 561-653-1751 or info@transdermaltechnologies.com

Opportunities for New Developments

A substantial amount of the development time and expenditure in bringing a new drug molecule to market is centered in making the transition from being effective on a tissue sample in a Petrie dish to being effective in human dosing. The process for evaluating how a medicine will be absorbed and accounting for the various chemical and enzyme environments and challenges is a pains-taking and often lengthy task. A delivery system like the TDS® which bypasses the need for these steps in development of a molecule for Investigational New Drug (IND) status should prove to be a considerable help in drug development. Such a system may also enable other steps in the identification and development of new drug compounds by being able to apply the system at the animal model stage, accelerating the time line for trialing new compounds through multiple rounds of chemical modifications and biological testing.

Opportunities for Known Compounds

According to Reuters Business Insight, over $33 Billion a year in market pharmaceutical revenues will be extinguished from corporate financial statements as patents for molecules expire over the next five years. Companies are forced to compete increasingly in the generic market as the pipeline for new products trickles and / or they must make massive investments in genomic technology which will lead to smaller market-size drugs. This reality fuels the current trend of mergers, acquisitions and strategic alliances as companies seek distinct and sustainable competitive advantage. The TDS® will enable companies to maintain their franchise over proprietary technology by allowing them to market under "use" patents based on out technology, and achieve re-introduction of their drugs with only abbreviated new drug filings, just as if the drug were a generic, with only bio-availability and therapeutic levels at issue - safety and efficacy having been long established and accepted in the original NDA or monograph of the medicament.

TheTransDermal Team

TransDermal Technologies is a profitable, operating company with more than fifteen years of sales to its credit. To date R&D expenditures have been funded from revenue. We have an established team, experienced business and financial managers, and the accomplishment of our business plan will not require a significant ramp-up of infrastructure or business fundamentals learning curve. Details on specific potential applications of the system, preclinical and clinical data developed so far are available from the Company.

For further information, please contact Kenneth B. Kirby at 561-429-6429 ext. 105, Fax: 561-653-1751 or info@transdermaltechnologies.com

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