Executive Summary The Mission
Andrews Inc. seeks a medicine to prevent and/or reverse human cellular aging, an underlying cause of many diseases, such as cancer, heart disease and osteoporosis, as well as aging itself.
After numerous successful proof-of-concept experiments, it is becoming increasingly accepted by the scientific community that inducing cells to produce the enzyme telomerase could treat many diseases associated with human aging, extend human healthspan and lifespan, and perhaps even reverse the aging process.
Andrews Inc., formerly known as Sierra Science LLC, holds enforceable patents on what are the strongest telomerase-inducing chemicals ever discovered. We also possess the only high-throughput screening assay ever developed that is able to detect telomerase induction in human cells. Using that assay, we have screened approximately 300,000 chemicals and have identified 39 chemical families that induce the telomerase gene. Based on those discoveries, our chemists have designed 10 unique, patentable compounds that are less toxic and more potent than any previously-discovered chemicals. The result is a well- developed tool for pharmaceutical and nutraceutical development and intellectual property that any potential acquirer or collaborator will value.
At the tips of every chromosome in the human body is a biological ―clock‖ called the ―telomere‖. When a cell divides, its telomeres get shorter as a normal part of cell division. As a cell‘s telomeres get shorter, it functions less effectively. Eventually, the telomere becomes critically short, cell division stops and the cell eventually atrophies and dies. Telomere shortening is a primary cause of many age-related diseases, including heart disease, arthritis, and COPD, while telomere shortening in the cells of our immune system progressively limits the body‘s ability to fight infectious diseases, as well as cancer.
The enzyme telomerase has been shown to re-lengthen telomeres. Telomerase cannot be added to cells directly, but there is a gene for producing telomerase in every cell of the body. This gene is active in reproductive cells, but in most cells it is turned off. Andrews Inc.‘s chemicals can turn it back on, and in time can be developed into pharmaceuticals.
The 2009 Nobel Prize for Medicine was awarded to the scientists who, in the mid 1980s, did research that later led to understanding the role of telomeres and telomerase1. Since the awarding of this Nobel Prize, public interest in telomerase-based anti-aging therapies has soared. Further fueling the
excitement over telomerase research was a January 2011 article in the journal Nature2 describing a study demonstrating that activating telomerase in mice actually reversed their aging—the clearest proof of concept yet that aging can be reversed through telomerase induction.
Dr. Bill Andrews, founder and President, leads the research effort at Andrews Inc. In 1997, Dr. Andrews led the team at Geron Corporation that became the first to discover human telomerase. For this achievement, he shared second place as 1997 United States Inventor of the Year. Dr. Andrews is a named inventor on 50 US-issued patents, 45 of which are telomerase related (more than any other inventor).
Products and Markets
Andrews Inc‘s pharmaceutical discoveries will have broad application in drug therapies for the diseases of aging such as cancer, a $65 billion market, cardiovascular disease, a $116 billion market, and arthritis, a $22 billion market. Prior to obtaining FDA approval for these therapies, Andrews Inc. expects to have products in the dietary supplement, cosmetic, research reagent, and pet markets. Andrews Inc. has recently discovered a nutraceutical compound that is active in our screen, has partnered with the distributor Isagenix to market that nutraceutical in a product called ―Product B‖. We began receiving royalties in October 2011, which will result in revenue of approximately $896,000 through November, 2012 (see graph on page 8).
In September 2009 Andrews Inc. entered the ―medicinal chemistry‖ phase of our research where novel telomerase-inducing compounds are custom designed. The company has prepared a $40 million, three-year plan to take us from this research phase to pre-clinical trials (which are typically funded by larger pharmaceutical companies):
Medicinal Chemistry – Begun in 2009 and currently outsourced, medicinal chemistry processes the telomerase-inducing chemicals discovered in our libraries into novel, potential deparDepartment:
Medicinal Chemistry – Begun in 2009 and currently outsourced, medicinal chemistry processes the telomerase-inducing chemicals discovered in our libraries into novel, potential drug candidates that are more potent and less toxic. Screening – Currently the focus of our in-house efforts, screening is the high- throughput testing of large libraries of synthetic crug candidates that are more potent and less toxic. Screening – Currently the focus of ouhemicals to identify telomerase- inducing chemical compounds.
Cell Culture – The testing for telomerase-inducing chemicals is done inside human cells. Our cell culture labs produce a continuous supply of healthy human cells for testing.
Research – Studies on a chemical‘s ability to extend replicative lifespan, the mechanisms that normally repress telomerase expression, and the applicability of telomerase-inducing compounds to other types of human cells, will improve our ability to design better drug candidates.
Mechanism of Action – Understanding how compounds induce cells to produce telomerase will help us produce better drug candidates.
Scientific Background and Platform
There are several recognized theories of aging of which telomere shortening is only one. Valuable research is being pursued on many of these theories; however, Andrews Inc. believes that, without resetting the telomere shortening ―clock‖, advances in these other areas of anti-aging medicine can only make limited gains in extending life and health span.
The clock of aging is found at the tips of all chromosomes. This chromosomal region is called the telomere, and like all DNA, is made up of units, called nucleotides, arranged like beads on a string. In continuously dividing cells3, such as skin cells and cells of the immune system, the telomeres shorten at about 50 nucleotides per year. Simply stated, people are born with telomeres 10,000 nucleotides long, and they die of old age when their telomeres reach 5,000 nucleotides. In the laboratory, telomere lengths as short as 5,000 nucleotides have been shown to cause cells to senesce and stop dividing. Such cells take on conformational and physiological changes very different from younger cells.
Aging-related changes are not only correlated with telomere shortening, they are caused by it. Telomeres interact with genes on the chromosomes to regulate
their functions. As the length of a telomere shortens, its ability to regulate genes is affected. In skin, for example, we observe a decrease in the production of collagen and elastin (proteins responsible for giving skin strength and elasticity) and an increase in the production of collagenase (an enzyme that further degrades the already diminished amounts of collagen) with aging. We have no control over this process. As cells continue to divide, telomeres continue to get shorter. This is why we continue to age even when we live the healthiest of lifestyles, reduce our caloric intake, inject ourselves with human growth hormone, and reduce our free radicals - methods commonly used to slow aging.
Stopping the Clock
Telomerase is an enzyme that adds nucleotides back onto telomeres. It is found in immortal cancer cells and germ line cells (which in humans are the egg and sperm cells), preventing these cells from aging. A 1998 publication in the journal Science4 showed telomerase could also prevent telomere shortening and aging in laboratory cultured skin cells and eye cells by inserting into these cells the gene that encodes telomerase. Andrews Inc. plans to introduce telomerase activity into cells without actually inserting the gene. This will be done by taking advantage of the fact that all human cells already contain the gene for telomerase. This endogenous gene is just turned off. Dr. Andrews is expertly trained in the art of regulating gene expression and has previously applied such technologies in the areas of heart disease, inflammation, and cancer. Andrews Inc.‘s mission is to develop a product that activates the endogenous hTERT, telomerase, gene, causing it to express the rate limiting protein component of telomerase. This protein component will then automatically combine with the abundant RNA component of telomerase to form the active telomerase enzyme. The result will be a pharmaceutical that transiently turns on the endogenous telomerase gene, combating aging and aging-related diseases.
A recent study led by Ronald DePinho, a cancer geneticist at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts, provided the most convincing proof yet that turning on the telomerase gene and lengthening telomeres could combat and/or reverses aging. As reported in Nature News5, ―Mice engineered to lack the enzyme, called telomerase, become prematurely decrepit. But they bounced back to health when the enzyme was replaced. The finding, published online today in Nature, hints that some disorders characterized by early ageing could be treated by boosting telomerase activity.‖ "What really caught us by surprise was the dramatic reversal of the effects we saw in these animals," says DePinho. He describes the outcome as "a near 'Ponce de Leon' effect" — a reference to the Spanish explorer Juan Ponce de Leon, who went in search of the mythical Fountain of Youth. Shriveled testes grew back to normal and the animals regained their fertility. Other organs, such as the spleen, liver and intestines, recuperated from their degenerated state.‖
Andrews Inc.‘s most valuable asset is a powerful high-throughput drug screen which took eight years to develop. To date, Andrews Inc. has screened more than 300,000 compounds from a carefully selected library of 320,000 compounds and has found chemical compounds in 39 chemical families that activate telomerase gene expression. Andrews Inc. is the only company with this screen and these compounds were the first chemicals ever discovered to activate telomerase gene expression. These compounds have been given a high priority for structure/activity relationship (SAR) and mechanism of action (MOA) studies. Andrews Inc. continues to screen compounds searching for more compounds that activate telomerase gene expression.
Since beginning SAR, Andrews Inc. has designed ten new, patentable chemical compounds, more potent and less toxic than all of those identified through the screening process. This is a major step toward developing a drug for pre-clinical testing.
In addition, Andrews Inc. has identified natural compounds that activate telomerase expression and has developed with the founder of Isagenix, a dietary supplement company, an anti-aging nutraceutical, while further screening natural compounds for telomerase activation for other future natural products. In addition, Andrews Inc. is collaborating with a New Zealand cosmetic formulator to develop a skin cream, expected on the market in 2014.
Andrews Inc. currently is the holder of five U.S.-issued, telomerase related patents. A patent on our best compound, designated internally as C0057684, and 2 others covering other strong hits are currently pending. Patent protection for all ―hits‖ is being aggressively pursued.
Products and Markets
The overall goal of Andrews Inc. is to cure human aging through development of a human pharmaceutical. An FDA approved compound is expected in 10 to 15 years. However, a number of product and licensing opportunities may be realized along the way, including products for research, drugs for cell and tissue transplants, dietary supplements, cosmetics and products for the veterinary market, all requiring less regulatory approval.
Andrews Inc. has no plan to manufacture or market products itself. Our discoveries in these areas will reach the market through licensing the manufacturing and distribution of our compounds to established suppliers. We expect to achieve financial success through revenues in the form of royalties, with which we intend to first fund continuing research.
On August 15, 2011, Isagenix Inc., a leading dietary supplement manufacturer and distributor, introduced ―Product B‖, a proprietary mix of natural products, co- developed by Andrews Inc. and John Anderson, the original founder of Isagenix. Senior Andrews Inc. employees are participating in the marketing of Product B and Andrews Inc. will continue to screen natural products for telomerase activation to develop improved generations of Product B. Royalties of $2.40 per customer per month started in October 2011, resulting in approximately $986,700 in royalty revenue through January 31, 2013:
140,000 120,000 100,000
80,000 60,000 40,000 20,000
Reagents for Research
A substance that induces transient expression of telomerase could be offered, without regulatory approval, as a product for
laboratory research. This product would enable
researchers to extend the lifespan of the human
cells they are studying, simplifying the research
process. This market is small, but steadily
growing as new, innovative uses for cells are
developed each year. Andrews Inc. estimates the
annual market for cell-growth products to presently
be about $250 million based on sales figures for Life Technologies, Inc., a leading supplier of reagents and molecular biology supplies.
Drugs for Use in Cell and Tissue Transplants
Two applications Andrews Inc. could target are bone marrow transplants6 and skin grafts7. Cells harvested from a patient or donor, then induced to divide many times and/or genetically engineered before being transplanted into the patient, experience rapid telomere shortening and senescence, limiting their useful lifespan8. Approximately 30,000 bone marrow transplants, used primarily for patients whose immune systems have been compromised by various cancer therapies, are conducted each year in the U.S9. The annual cost was expected to reach $1.3 billion in 2011.10
The market for skin grafts for burn victims was expected to grow to over $2 billion in 2001, according to a report by Frost & Sullivan10. Replacement skin, a small market initially because of lack of product availability, was expected to grow to 23% of the replacement organ market, or $500 million, by 2001.
The broad new field of stem cell technology, of which bone marrow transplants are a part, will also benefit from telomerase-inducing drugs. After stem cells are harvested from a person, the stem cells need to be grown, i.e. expanded, to produce more of them. During these cell divisions, the telomeres get shorter. When the stem cells are then re-injected into the patient, the cells are essentially older than the person from whom the stem cells were derived. A telomerase inducer will prevent this telomere shortening.
Telomerase inducers will also be important for induced pluripotent stem cells (iPS). iPS cells are a type of pluripotent stem cells artificially derived from non- pluripotent cells, typically an adult somatic cell, by inducing a "forced" expression of certain genes. Creation of the iPS cell was an important advancement in stem cell research, as it may allow researchers to obtain pluripotent stem cells, which are important in research and potentially have therapeutic uses, without the controversial use of embryos11.
BioTime, Inc. recently published, in collaboration with Andrews Inc., research indicating that iPS cells have shorter telomeres than true human embryonic stem cells. Andrews Inc. employees Bill Andrews and Laura Briggs are co-authors on this paper.
Andrews Inc. believes most or all of these transplants and stem cell therapies will require a drug or reagent to re-lengthen the cells‘ telomeres, a drug Andrews Inc. plans to be able to provide.
Animal Therapeutic Medicine Market
On the path to a medicine for human use, Andrews Inc. may produce a medicine that could be approved for animal use sooner and at lower cost than products requiring full FDA human pharmaceutical approval. Pharmaceuticals for animal use are regulated by the Center for Veterinary Medicine (CVM), a branch of the FDA. While clinical trials are required to establish the safety and efficacy of the
product, the standards are less demanding and, by law, CVM is required within 180 days of receipt of an application to either approve the application or advise why it cannot be approved. Because of this, many medicines ultimately intended for human usage find their first usage in animals.
Animals whose lifespans could be extended by a telomerase-inducing medicine include valued service animals such as Seeing Eye dogs and police dogs, prized animals such as thoroughbred horses, and household pets. Of these categories, Andrews Inc.
believes pets represent the most promising market because there are so many of them and they are valued as individuals by their owners12. According to IFAH- Europe, the value of the world animal health market in 2004 was 2.5% of the world human pharmaceutical market, $13.75 billion13.
Andrews Inc. believes a product to extend the lifespan of pets would enjoy a large market14, and could pave the way for marketplace acceptance of a medicine for humans, if it is observed to be safe and effective by both veterinarians and pet owners.
Human Pharmaceutical Market
The global pharmaceutical market is forecast to grow to $1,033 billion in 2014, an equivalent compound annual growth rate of 5.0% over the next five years.15. North America accounts for about half of the world pharmaceutical market. The U.S. market for anti-aging related therapies is estimated at $50 billion16; however, telomerase induction will offer therapies for all diseases related to cell division, not just aging. These include but are not limited to:
Cardiovascular Disease17 Cancer
Alzheimer‘s Disease Osteoarthritis Rheumatoid Arthritis
Macular Degeneration Osteoporosis Degenerative Disc Disease Lupus
Dyskeratosis Congenita Idiopathic Pulmonary Fibrosis Cri du Chat Syndrome Fanconi‘s Anemia
General Immunity Decline Muscular Dystrophy HIV/AIDS18
The markets for prescription drugs addressing these diseases total many billions of dollars. For example, in 2008, global sales of cardiovascular drugs exceeded $79 billion, global sales of cancer drugs exceeded $50 billion, and sales of drugs treating COPD (Chronic Obstructive Pulmonary Disease) exceeded $27 billion. 2008 sales of drugs to treat arthritis, including osteoarthritis and rheumatoid arthritis, exceeded $22 billion. The prescription drug markets for osteoporosis
and Alzheimer‘s disease exceeded $8 billion and $6 billion, respectively19. The global market for Cancer drugs is expected to cross $78 billion in 201220. The US market for Cardiovascular drugs was expected to cross $116.3 billion in 201021.The 2008 anti-aging skin-care market was estimated at $1.6 billion by Mintel International Group, an international market research organization22.
Telomerase activation offers pharmaceutical manufacturers a new, unique approach for developing disease therapies. These diseases and many more offer Andrews Inc. lucrative licensing opportunities.
A Product to Cure Aging
Although it is still too early in our research to select a disease target, HIV/AIDS is particularly attractive as a path to reach our goal to ―cure
aging‖. AIDS is a fatal disease because the patient‘s immune system is exhausted fighting the virus and the patient typically dies from a minor sickness like the flu, common cold, or an opportunistic infection, or from a cancer such as Kaposi‘s Sarcoma. The immune system fights disease through production of T-lymphocyte cells
via cell division. Rapid cell divisions cause immune cells to age rapidly and reach senescence prematurely. A telomerase-inducing drug to revitalize the immune system would allow the patient to continue to fight the virus indefinitely. This is particularly attractive because this anti-AIDS drug, once approved by the FDA, could relatively easily be extended into a general immune system rejuvenator. Immune system decline is widely regarded as a major cause of aging and is implicated in the many flu deaths in the elderly, for example. The Center for Disease Control estimates 200,000 people are hospitalized and 36,000 people die from the seasonal flu every year, many of them elderly23. Since immune system decline is a part of all human aging, the market for an immune system rejuvenator would be ―all humans.‖