Nerium Bio Technology, Inc.

Denise E. Dunn*, Dong Ning He*, Peiying Yang**, Mary Johansen**, Robert A. Newman** and Donald C. Lo*

* Center for Drug Discovery and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, USA

** Department of Experimental Therapeutics, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA

Article represents a new area of research with Nerium oleander extract, neurodegenerative disease at Duke University.

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Nerium™ International, LLC of Addison, TX and Nerium SkinCare™, Inc., a subsidiary of Nerium Biotechnology, Inc. ®, of San Antonio, TX are pleased to announce their exclusive licensing partnership. This partnership was designed with the purpose of building a global brand through the development and distribution of breakthrough products in the anti-aging skincare market.

"First Of Its Kind" Topical/Dermal Product – NeriumAD - Age-Defying Treatment …. is LAUNCHED.
Press Release

Natural Technology, Inc. (Naturtech) initiates the first commercial production run of NeriumAD for exclusive distribution by Nerium International, LLC.

Nerium SkinCare’s initial topical/dermal formulation NeriumAD is provided for by Don Smothers, President, CEO of Natural Technology Incorporated (Naturtech) a GMP manufacturing facility. Mr. Smothers has more than 40 years experience in the formulation, development, and manufacturing of consumer products and also has more than 30 years of experience with Aloe Vera research, Aloe Vera industry affiliations, and Aloe Vera based consumer products.

Nerium SkinCare’s NeriumAD formulation includes utilization of Naturtech’s proprietary naturally grown Aloe Vera processing technology, known as "cold processed, whole leaf aloe vera" as the extraction media with the patent-pending Extraction process NBio-PL²™ and the resulting Nerium extract NAE-8™ which has been clinically tested for safety and efficacy.

Today Naturtech provides for formulation and manufacturing of enhanced skin care products as Nerium SkinCare moves forward with its topical cosmetic and OTC healthcare consumer products.

Clinical trial for Nerium AD is completed. NeriumAD Final Report – Larry K. Fan, M.D.

Haby Henary, M.D.
University of Texas M. D. Anderson Cancer Center "Final results of a first-in-human phase I trial of PBI-05204, an inhibitor of AKT, FGF-2, NF-Kb, and p70S6K in advanced cancer patients." (Abstract 3023), Session, Developmental Therapeutics - Experimental Therapeutics

The Annual Meeting of the American Society of Clinical Oncology (ASCO) was held at McCormick Place June 3-7, 2011, in Chicago, Illinois. The ASCO meeting is the premier educational and scientific event in the oncology community, highlighting the most advanced treatments, products, and services in cancer care.

More than 30,000 cancer specialists from around the world gathered at the 2011 ASCO Annual Meeting to discuss the latest innovations in research, quality, practice and technology in cancer. This meeting is the platform for the release of thousands of scientific abstracts -- highly anticipated research news for many people, including patients, caregivers, and the general public. News announced during the meeting includes the latest findings from cancer clinical trials, including new drug studies that could change current standards of care.

Clinical research for NeriumAD product safety, efficacy, and dermal application was initiated with ST&T Research (Science, Toxicology & Technology). ST&T Research is comprised of a group of prominent scientist, including M.D. and Ph.D. pharmacologists/toxicologist and research product development oriented physicians, scientist, and regulatory compliance specialists which include a legal team specializing in US FDA/FTC/Customs regulations. ST&T Research provides product development, product compliance, regulatory compliance, clinical testing, and information and data for safety and efficacy.

Dr. Robert A. Newman as scientific advisor to Nerium SkinCare assisted by providing safety data from previous research, studies, and experience from the FDA safety trial at the University of Texas M. D. Anderson Cancer Center (MDACC). In addition, Dr, Newman provided the analytical method for determination of oleandrin (CG) in blood plasma and MDACC provided for blood analysis.

Background: Anti-aging skin creams are abundant in today’s cosmetic marketplace. Newer ingredients that may provide additional efficacy are sought to improve existing products. This study investigates the safety and efficacy of two such ingredients, a soluble Nerium oleander extract (NAE-8) and proprietary protein blend (collagen, elastin & glycosaminoglycans)

Study Methods: Thirty-five (35) subjects were enrolled in a single-site, open-label Pilot Study to evaluate the safety and efficacy of NAE-8 in reducing aged skin related wrinkles and sun damage. The composition described in this study is a topical skin cream, which was a formulated Nerium extract suspended in a base cream “carrier” to facilitate application.

Subjects were instructed to apply the study product to the face for four (4) consecutive weeks. Subject evaluations were conducted at the initial visit and at the end of weeks 1, 2 and 4.

Primary outcomes included an objective evaluation of changes in the appearance of “aging and sun damaged” skin of the face using an advanced R&D fluorescence spectroscopy skin analyzer (Moritex BTBP Clarity Pro system, San Jose, CA), as well as the subject’s perception of changes in the appearance of their “aged and sun-damaged” face in terms of wrinkling, discoloration, complexion, and tone as reported by questionnaire administered at the end of weeks 2 and 4.

Secondary outcomes included an assessment of safety to determine if the active ingredient was absorbed systemically and subjective input from subjects regarding skin irritation.

The antiviral research of Nerium Biotechnology, Inc. has focused on the human immunodeficiency virus (HIV). Review of Dr. Jagannadha Sastry’s preliminary HIV research at M. D. Anderson has been very positive and has been duplicated. His research has been conducted utilizing various Nerium extracts (Aqueous, NAE-8, etc.), oleandrin, other cardiac glycosides and additional compounds. This research continues to move forward and is currently centered on publication of research results to date, potential new IP and the initiation of a new animal trial, utilizing a monkey animal model [simian immunodeficiency virus (SIV), the Monkey-HIV equivalent].

The trial design has been approved and initiated. Successful completion of this animal trial will hopefully allow Nerium to proceed to a FDA Human HIV Trial at M DACC, in Houston, Texas with assistance from Quintiles, an international clinical research and consulting organization.

New product formulation: Nerium SkinCare, Inc. is dedicated to offering solutions that are based on proven science and actual customer use experience. Products offered to the consumer will be founded on continuing research at leading medical institutions using the latest scientific methods and technology. All products will be nature based and scientifically developed.

New Technology The foundation of each product will be derived by utilizing the unique patent-pending extraction process NBio-PL² for its skin care products. This extraction technology incorporates pure liquid Aloe Vera (cold processed) as the media to extract the Nerium oleander plant components in a way that preserves the beneficial properties of both plants, without any additional solvents. This natural extraction technology combines the unique beneficial properties of the Nerium oleander plant and the known beneficial properties of Aloe Vera plant. This process provides the core ingredient NAE-8™ extract for product development.

Initial Product Development, Nerium AD
In collaboration with Nerium International, LLC, Nerium SkinCare has identified the anti-aging market as the initial target market for product development and has formulated its initial product for market launch, NeriumAD™ an age –defying treatment (Night Cream). Exclusive distribution of NeriumAD™ is provided for in a licensing partnership agreement with Nerium International, LLC. Anti-aging skin creams are abundant in today's cosmetic marketplace. New ingredients that may provide additional efficacy are sought to improve existing products. The NeriumAD™ formulation is specifically designed for this market and provides two (2) such ingredients, NAE-8™ extract and a proprietary protein blend (collagen & elastin & glycosaminoglycans) which are unique to this market. Prior to product launch, Nerium SkinCare will now move forward with clinical testing on NeriumAD for product safety, efficacy and clinical application with ST&T Research.

Nerium Biotechnology, Inc. announced a new clinical study is in process for Anvirzel™. The integrative Medicine Program at M. D. Anderson has initiated a request to research Anvirzel™ as a complementary/adjuvant therapy (FDA Phase 1 Study of Anvirzel™ utilizing chemotherapy and Anvirzel™ administered by sublingual application). This research is funded by the National Cancer Institute (NCI) through the Clinical Community Oncology Program (CCOP). Preparation for this trial is currently in process (IND application, IRB approval, Protocols, Investigator’s Brochure, etc.) with a projected start date of fourth quarter 2011.

Presentation
Robert Newman, Ph.D. and Peiying Yang, Ph.D.
Department of Experimental Therapeutics and General Oncology
The University of Texas, M.D. Anderson Cancer Center
The Scientific Program Committee of the Society of Integrative Oncology (SIO) extended an invitation for an oral presentation by Dr. Robert Newman to the attendees of their annual meeting. The meeting was held on November 11-13, 2010 in New York, New York at the New York Academy of Medicine. Dr. Newman presented on Nerium oleander extract (oleandrin), titled “Cellular location and expression of the Na, K-ATPase a-3 subunit is associated with relative anti-proliferative activity of oleandrin”.

2010 SIO Presentation (Anvirzel™, PBI-05204)

After serious due diligence on distribution options, Nerium SkinCare, Inc. has determined the Direct Sales / Relationship Marketing channel would be the best option to build a global skin care brand. Lengthy discussions with industry leader Jeff Olson has led to an exclusive licensing partnership for skin care product development/distribution between Nerium SkinCare, Inc. and Nerium International, LLC.

This collaboration provides Nerium SkinCare the opportunity to develop for the consumer an ever expanding pipeline of natural botanical and specially formulated Nerium extract-based skin care products. Nerium International provides the opportunity to build and develop a world class marketing company to attract and train Independent Brand Partners to engage in building a national and global sales organization.

Nerium SkinCare, Inc., a subsidiary of Nerium Biotechnology, Inc. was established to provide for the commercialization and distribution of all skin care/topical applications of Nerium Biotechnology’s botanical extracts. Nerium SkinCare provides for product development, product compliance, regulatory compliance, clinical testing for safety and efficacy, manufacturing, and marketing to the consumer the “first of its kind” natural skincare products for topical use. Nerium SkinCare’s products are founded on the technology, core science, and continuing research of Nerium Biotechnology, Inc.

Nerium SkinCare is charged with harnessing what has been learned over the last ten (10) plus years regarding the safety and healing effects of the Nerium oleander plant and its application to the skin care market. By utilizing Nerium Biotechnology’s patent-pending technology, the knowledge gained through research, and core science on the Nerium oleander plant, Nerium SkinCare will have the opportunity to develop for the consumer an ever expanding pipeline of natural botanical and specially formulated Nerium extract-based skin care products.

Nerium Biotechnology, Inc. (Nerium) was granted approval by the U.S. Securities Exchange Commission on August 28, 2010. The approval process was very extensive and demanding. Today Nerium is very fortunate to have accomplished registration with both the U.S. Securities Exchange Commission and the Ontario Securities Exchange as a public reporting company. The next step is to move to a listing with the Canadian, Toronto Stock Exchange or the USA, Nasdaq Exchange. The listing application is currently being held for a future date pending favorable market conditions and the determination for the appropriate time for listing.

Participation was limited to the company’s shareholders and family. The opportunity was extended to participate in on-going specialized product clinical research and experience Nerium Biotechnology’s new skin care products first-hand prior to market launch. In so doing, they would help gain market experience; provide additional product safety data, and product use feedback. This group is limited in size and only this group will be offered additional new products to sample.

The data collected with this consumer research will assist with evaluation of product formulation/re-formulation. . In addition to providing determination/identification of product to move forward with to market and time to explore distribution options.

From historical/anecdotal use, continuing cancer and antiviral research with Nerium oleander extracts, Nerium Biotechnology, Inc. (Nerium) has identified the potential for Nerium extracts use in topical skincare applications.

The formulation and limited commercial production of 2 new skin care products was initiated at Natural Technology, Inc. (Naturtech) to provide for additional research and testing.

Products include:
NeriumDerm™ - an amazing and potent skin soothing and repair cream for topical applications. It is designed to enhance skin health and is a dramatic relief cream for aged, blemished, sun-damaged skin, and a variety of common skin conditions. The product is formulated to soothe, moisturize, nourish, and help repair. For best results, apply the cream at least one a day, or as needed. Longer duration of application is associated with better results.

Nerium CS™ - a natural lip repair and cold sore relief serum for topical application. In addition to the NAE-8™ extract, this product has been further enhanced with L-Lysine, Olive Leaf Extract and Clove Flower Oil known compounds used for this condition. It is designed to enhance lip health and is a dramatic relief serum for cold sores and sun-damaged chapped lips. The product is formulated to relieve, soothe, moisturize, nourish, and help repair. We recommend early application to cold sores before any visible symptoms appear (often called the “Tingle Stage”) and continued use through the final stage (the " Healing Stage"). The longer duration of application is associated with better results. Continued use may extend time between additional breakouts.

The Scientific Program Committee of the Society of Integrative Oncology (SIO) extended an invitation for an oral presentation by Dr. Robert Newman to the attendees of their annual meeting as the Best of SIO. The meeting was held on November 12-13, 2009 in New York, New York at the New York Academy of Medicine. Dr. Newman presented on Nerium oleander extract (oleandrin), titled "Development and Evaluation of a Cardiac Glycoside Extract (PBI-05204) as a Novel Anticancer Agent".

SIO Presentation

On October 13, 2009, Nerium Biotechnology, Inc. filed the new Nerium oleander-based extraction process to the US Patent and Trademark Office and PCT Patent Office (International). This extraction process incorporates pure liquid Aloe Vera to extract the unique Nerium oleander plant components in a way that preserves the unique and beneficial properties of both plants, without any additional solvents. This natural extraction process combines the unique beneficial properties of the Nerium Extract and the known beneficial properties of Aloe Vera. Nerium, if successful with this patent, will have an additional patented process for Nerium oleander extraction and its cytotoxic component oleandrin.

Yang, P.; Newman, R. A., et al., Oleandrin-mediated Inhibition of Human Tumor Cell Proliferation: Importance of Na, K-ATPase a Subunits as Drug Targets, Molecular Cancer Therapeutics, August 1, 2009 8, 2319 Article featured on publication cover. Read the Publication

Market research has been initiated at the University of California at Berkeley. The Berkeley Marketing Department through its International Diploma Program is conducting market research on behalf of Nerium. International students in this marketing program are currently conducting and compiling marketing research on Nerium’s dermal products (market size, competition, product positioning, product name, purchase intention, product promotion, consumer behavior, etc.). We await final report for our review and consideration in the future marketing plans of our dermal products.

Phoenix Biotechnology, Inc. was invited to present at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida. Attendees included 30,000 physicians, healthcare professionals and companies from 120 plus countries. At this meeting several hundred scientists and healthcare companies are allowed a poster presentation for discussion, although precious few are allowed to actually present to attendees. Phoenix’s presentation on May 29, 2009 to attendees was on Nerium oleander extract (oleandrin), titled PBI-05204, an inhibitor of Akt, FGF-2, NF-kb and p70S6K.

Presentation

Poster

Nerium has contracted with PharmaForm, LLC, in Austin, Texas. PharmaForm is the same company Phoenix Biotechnology, Inc. contracted with for product development, formulation and validation method of their product PBI-05402. This Phoenix formulation is currently in FDA Trials at the M.D. Anderson Cancer Center, in Houston, Texas.

PharmaForm is assisting Nerium in developing the validation method for its new dermal formulations and the new sublingual administration formulation of Anvirzel. PharmaForm will assist with the further development of a new administration route for Nerium extracts (pill, capsule, etc.) and is also performing product stabilization studies on the dermal and sublingual formulations.

An additional pilot study has been initiated with Science, Toxicology & Technology (STT) on Nerium Biotechnology’s dermal formulation for cold sores (Herpes Virus, HSV-1). The enhanced cold sore formulation for this study will include additional antiviral compounds in the formulation.

Nerium Biotechnology, Inc. has ongoing antiviral cold sore research with the Herpes Simplex Virus (HSV-1). This research is being conducted in the laboratory of Dr. Gus Kousoulas, Director of Biotechnology and Molecular Medicine at Louisisana State University (LSU) in Baton Rouge, Louisiana.

HSV-1 can spread from cell-to-cell avoiding the extracellular environment. This mode of transmission is particularly important in cold sores where the virus spread from cell-to-cell often producing fused cells that allow the virus to be transmitted from one-cell-to-another adjacent cell. In Dr. Kousoulas's lab the effect of Nerium Extract on viral spread was tested using plaque and plaque-size reduction assays. Results indicated more than a 99% inhibition in plaque size. Overall results and conclusions indicate the Nerium Extract possess limited direct anti-viral activity. However indirectly, they appear to produce drastic inhibition of virus spread in cell culture at relatively low concentrations. Nerium's antiviral research is moving forward to the next appropriate step.

In December 2008 Nerium signed a sponsored research agreement with Louisiana State University (LSU). The focus of this antiviral research is the Herpes Virus, HSV-1. This research will provide data for future antiviral FDA Trials.

Nerium was granted approval by the Ontario Securities Exchange on November 26, 2008. The approval process was very extensive and demanding due to the current economic conditions; the downturn was at its peak during this application period. Nerium was very fortunate to have accomplished this goal. The next step is to move to a listing with the Canadian, Toronto Stock Exchange or the USA, Nasdaq Exchange. The listing application is currently being held pending the appropriate time and dependent upon stabilization of capital markets.

In July 2008, Science Toxicology and Technology, LLC (ST&T) provided a patentability opinion on a new method of extracting materials from Nerium oleander for medicinal use. The conclusion, after the review of the references cited, was that in their opinion the new extraction process used to extract glycosides and other compounds from Nerium-derived plant material is novel and unobvious. Nerium has provided a description of the invention and ST&T has moved forward with the Plant Extraction Method and Compositions paperwork and filed a provisional patent October 14, 2008. Nerium, if successful with this patent, will have an additional patented process for an Nerium oleander extraction and its cytotoxic component oleandrin.

As of August 2008, two additional pilot studies have been initiated. In these studies the cream is applied to a larger surface area on each patient. One study relates to sunburn and the other to acne. In addition we are testing the Nerium dermal creams against well-known products already in the market place.

In July 2008 Nerium signed its own Sponsored Research Agreement directly with M. D. Anderson Cancer Center. The anti-viral research focus has been on a specific target and preliminary research has been very promising, although Nerium is unable to share details at this time. Upon completion, the next step will be the animal model testing and then human clinical trials.

After development of a basic Nerium oleander-based cream, Nerium has initiated animal and human pilot studies during the month of July 2008 with Science Toxicology and Technology, LLC. The initial human pilot is on age/liver spots and actinic keratosis. Nerium’s focus remains safety and efficacy with this new dermal application.

In April 2008 Nerium Biotechnology, Inc. signed a research and testing agreement (the first in a series) with Science Toxicology and Technology, LLC (ST&T). Nerium discussions with ST&T provided for a model to bring our dermal formulations to market. Initial product targets would be cosmetic (Neutraceutical) versus a drug. This initial research includes an animal model to confirm safety and a series of human studies on various skin diseases, skin cancer and sun-damaged skin. The agreement also provides for initial patent research and processing for our new Nerium oleander extraction process NBio-PL2.
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The dermal market is a multi-billion dollar market and presents an opportunity for Nerium to bring new dermal oleander-based products to market in the USA. Nerium hopes to develop a line of oleander-based dermal products for sun-damaged skin, several specific skin diseases, and skin cancer. In April 2008 Nerium Biotechnology, Inc. signed formulation and manufacturing agreements with Affiliated Consultants (formulation) and Natural Technology, Inc. (manufacturing). These negotiations included an additional new oleander extraction process which provides the opportunity for Nerium to obtain additional intellectual property.
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AMERICAN ASSOCIATION FOR CANCER RESEARCH (AARC)
ANNUAL MEETING 2008
April 12-16, 2008

Dr. Robert A. Newman
The University of Texas MD Anderson Cancer Center
Pharmaceutical Development Center

Abstract Poster Presentation:
OLENADRIN-MEDIATED INHIBITION OF HUMAN TUMOR CELL PROLIFERATION: IMPORTANCE OF Na, K-ATPase a SUBUNITS AS DRUG TARGETS:

Dr. Robert A. Newman presented at the American Association for Cancer Research (AARC) annual meeting April 12-16, 2008 which this year was held in San Diego, California. More than 17,000 participants from 60 countries gathered to discuss an estimated 6,000 abstracts and to hear more than 500 invited presentations on new and significant discoveries in basic, clinical, and translational cancer research. Scientific award lectures, grant writing workshops, networking events, and educational sessions rounded out the comprehensive program. Presentation poster

Newman, R.A., et al. Cardiac Glycosides as Novel Cancer Therapeutic Agents. (An invited review); Molecular Interventions, 6(1) 2008.

Kondo, Y.; Newman, R.A., et al. Autophagic Cell Death of Human Pancreatic Tumor Cells Mediated by Oleandrin, a Lipid-Soluble Cardiac Glycoside; Integrative Cancer Therapies, 6(4); 2007.
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November 2007, Nerium Biotechnology, Inc. has signed a consulting agreement with Quintiles Transnational Corp. to pursue development and approval of oleander-based products in the United States. Quintiles, a global leader in pharmaceutical, biotechnology, and medical device product development as well as marketing-related services, has helped develop or commercialize many of the world’s best-selling drugs. With Quintiles assistance, Nerium plans to continue research, gather additional clinical data, and continue with new product development.