Regional Sales Manager Newsletter

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1 Issue 2 TOPICAL DERMATOLOGICS FOR THE SKIN CARE PROFESSIONAL January 25, 2010 Message from the CEO In this month s newsletter, we ve tried to include information you will need to effectively answer at least some of the questions that may come up during your sales calls. One question that is sure to be asked is how does our Therosol technology prevent inflammation? In this newsletter I go into some depth about what causes skin inflammation and how to treat it. There is quite a bit of science in my explanation, so I apologize in advance if this is a little hard to wade through. The reality is that DermaMedics is a therapeutic company and you are more like pharmaceutical reps than skin care sales reps. I know you want to feel knowledgeable about skin problems and skin care when you are speaking to professional accounts, and we want to provide whatever information you need to reach your comfort level. We ve also included a Q&A section where we answer other questions that might come up during your sales calls. In the Competitive Technology section this month we cover hyperpigmentation and the treatments for it. Skin lightening products are a huge market (>$3 billion worldwide) and in the U.S. the only effective OTC drug for getting rid of age spots is hydroquinone. As discussed in the newsletter, hydroquinone is one drug the FDA intends to ban from OTC products in the next year or two. DermaMedics skin lightening product works better than hydroquinone and doesn t have the safety issues hydroquinone does. So this product should become a big seller for you. All the DermaMedics products have now been made, inventoried and are ready for sale. To help you with your sales, we have retained a PR firm, headed by Julie Berry, to build the DermaMedics brand nationwide. Having worked with Julie before, I know she will rapidly increase the awareness or our products to both the medical community and to the prestige skin care media. It s an exciting time for DermaMedics and I know 2010 is going to be a year of dramatic growth. Thanks for being part of the DermaMedics team. Please let us know what we can do to make your sales efforts more productive. DermaMedics Q & A What is Therosol? Therosol is a small chemical compound that is found in several plants. DermaMedics scientists discovered that it has remarkable antiinflammatory as well as anti aging properties. Is Therosol Safe? Therosol has been used as a food flavoring chemical for over 50 years, and in the U.S. anything added to food must undergo extensive safety testing. Therosol has been tested for safety by the National Toxicology Program of the Health and Human Services, and has been found to be completely safe when taken either orally or applied topically. It is nonirritating and non sensitizing. Is Therosol proprietary to Derma Medics? Yes, the company has filed international patents to protect its use. No one can use Therosol in their products without violating our patent claims. How Does Therosol Block Inflammation? Therosol blocks the production of many inflammatory hormones, cytokines and chemokines that cause inflammation. It also blocks the ability of these same cytokines and chemokines to activate other cells in the skin and also prevents them from activating the movement of immune cells into the skin from the bloodstream. By preventing the runaway cascade of inflammatory events, Therosol resets the skin to a non inflamed resting state. If Your Products Prevent Inflammation, Will They Reduce or Prevent the Anti aging Benefits of the Laser Treatments? No. The laser procedure works by wounding the skin. The skin responds to this in two phases. In phase 1, immediately after the Inside this issue: DermaMedics Q & A Website Update 2 Update on Samples & Full Size Product Policy Important Information needed for New Accounts Competitive Products Continuing Education Inflammation The First Office Visit 1,2, 10 LASER wounding event, the skin triggers an inflammatory response, and this causes the release of many inflammatory hormones, including prostaglandin E 2 (PGE 2), perhaps the worst inflammatory hormone your skin can produce. PGE 2 is a major player in sunburn and has now been linked to the onset of skin cancer. In addition to the production of inflammatory hormones, during phase 1 immune cells are recruited into the area of the skin treated by the LASER, and these cells, along with skin cells secrete many enzymes which actually destroy collagen and elastin in the dermis. Finally, the inflammatory hormones produced in phase 1 SHUT OFF the production of collagen and elastin by fibroblasts in the skin. This inflammatory phase subsides after a couple of days, and then the skin enters phase 2, the re building phase. In phase 2 the fibroblasts turn on and start making collagen and elastin, and the skin renews itself. DermaMedics products reduce the level of inflammation in phase 1, and completely block PGE 2 production. (See Page 2) 3 3 4,6,7 4,5,8, 9 9, 10

2 Page 2 Cont d DermaMedics Q & A The patient experiences a dramatic reduction in inflammation, swelling and pain. Thus, phase 1 is shortened and the level of inflammation is reduced. Since DermaMedics products are also anti aging, Therosol will actually stimulate collagen production, so the recovery time in the skin is shortened. What is an Antioxidant and What is a Free Radical? Is Therosol an Antioxidant? An antioxidant is a molecule (chemical) that can prevent the oxidation of another molecule. Typically, OXIDATION means losing an electron while REDUCTION means gaining an electron. Oxygen can generate free radicals in tissues, so even though we depend on oxygen to survive, it is a very reactive chemical that produces free radicals. Examples of free radicals are hydrogen peroxide, hydroxyl radical, superoxide ion, and hyperchlorous acid (yes pretty much the chlorine form you put in your swimming pool). What this means is that these free radicals are missing an electron and that makes them unstable (kind of like a ceiling fan that s missing a blade). Chemicals don t like to be unbalanced or unstable so the free radicals run around the body (or skin) looking for an electron to steal so it can be stable. When a free radical bangs into something that will give up its electron, like an enzyme, protein or lipid, that protein or lipid now becomes an unstable free radical, and it then looks for an electron to steal. As you can see this results in a chain reaction and at the end of the reaction a lot of important tissue proteins and lipids are oxidized and damaged. This is often irreversible. An antioxidant PREVENTS oxidation by donating an electron to the free radical thus breaking the chain reaction. Fortunately, antioxidants are stable even when they ve lost an electron so they don t go out and search for an electron to steal. They wait patiently until certain enzymes in your cells give them an electron and restore them to their former state. Now they are ready to donate another electron to a free radical. Some of the best antioxidants (and most common) are Vitamin E, Vitamin A, and Vitamin C. You ve also heard a lot about polyphenols and resveratrol in red wine, and blueberries, etc. Many fruits and wines contain polyphenols that are wonderful antioxidants. The drink Mona Vie is loaded with the Acai berry which is a good antioxidant. So is Therosol an antioxidant? Yes, it is. Do all antioxidants have anti inflammatory activity? No, they don t. Most antioxidants cannot block inflammation. They simply bind free radicals. Therosol is unique in that it is an anti oxidant as well as an anti inflammatory. What s the difference between Therosol and Therosol III complex? Therosol is a single chemical compound that is present in all DermaMedics products. It has pronounced anti inflammatory effects. Therosol III is a mixture of 3 Therosol like compounds: Therosol, Therosol E and Therosol V. The combination of these 3 produces synergistic anti aging effects on skin cells. That s why this particular combination is in our anti aging product, Restorative Serum. (See Page 10) DermaMedics Website Update- You should all have received an on December 17 that included your sign in information as well as some instructions for the new website. Please contact Jennifer Hinz at jhinz@dermamedicsprofessional.com if you have not received this information. There have been a couple updates to the DermaMedics website since the last newsletter. The website is now able to process orders paid with check or on Net 30 Day Terms. To place an order for one of your accounts using one of these features, simply sign into the website using your own login information. Add the item they need into your Shopping Bag. Once all items are entered into your Shopping Bag, click on the red View Bag link toward the top right hand corner of the screen. You are now in the Shopping Bag area. Click Proceed to Checkout. On this page is where the option to check out as one of your Professional Accounts is located. At the top states Check out as: with a drop down menu next to it. When you have Professional Accounts set up, they will be listed in this menu. You then select the Professional Account placing the order. They re billing/shipping information will automatically update with their information. Click Proceed to Next Step. Here you will have the option to check out via credit card, check, or Net 30 Day Terms. By placing the order online before collecting their payment, you can get an exact total with shipping for the purchase.

3 Issue 2 Page 3 UPDATE On Samples and Full Size Product Policy MONTHLY SAMPLES As was covered in the last newsletter, DermaMedics will provide samples to all Sales Managers, every month without charge until April, and then continuously after that, as long as sales quotas are met. However, each Sales Manager needs to contact the office to request these monthly samples. If a Sales Manager has plenty of samples, there is no point in sending out more until these are gone. Therefore, it is more efficient for the company to mail out samples every month only when requested. LEAVING SAMPLES AT OFFICES Past sales experience shows that unless someone in a decision making position at the office you are calling on actually sits down with you and spends some time finding out about the products DermaMedics has to offer and what they are used for, there will be no point in leaving behind a lot of samples. No one in the office will look at them or use them. If you demonstrate the samples to the office staff and they are enthusiastic, then you should leave enough samples for each person in the office to try. In addition, the best thing that can happen is to have the physician or aesthetician (some do laser procedures) try the Calm and Correct Serum on a patient or two. That is what the back bar supplies are for. If the office has more than one operatory and wants more back bar to sample, simply call the office and we ll get it out to you to take to the office. The best advertising for us is to have offices try our products. Every patient will love the feel of them. FULL SIZE PRODUCTS If an office has specific needs, like Calm and Correct Serum for Levulan treated patients, we will provide back bar size product for the physician to use after the procedure and product for the patient to take home. Also, if they have a couple of patients they want to try one of our products on (like for infant eczema), we ll provide fullsized products for that. If that situation comes up, just call the office. Important Information Needed For New Accounts As you set up new accounts, there is some information the office must have to set the accounts up correctly. Please search feature, which allows any customers coming to the site to find a seller that offers our products.) make sure all of the information below is 5. PHONE NUMBER provided to the office: 6. OPTIONAL WEBSITE (If the account has a website, be sure to include 1. TAX ID that information. In the search feature, 2. FULL NAME OF OFFICE MANAGER OR PERSON RESPONSIBLE FOR ORDER ING. the website and telephone number as well as address will be viewable to any potential customers.) 3. CORRECT ADDRESS OF AC COUNT (Each account must have an on file. The account cannot be entered into the website without a unique address.) Once all Sales Managers become familiar with the website back end, they will be able to create the accounts themselves. 4. EXACT ADDRESS OF ESTABLISHMENT (This address is used by the website to put the business on a map in the But for the present time, Jennifer will be inputting all of this data to establish new accounts. For the first $500 order we receive from one of your new accounts, we will include with the order $100 worth of full size products!! The products will be selected by us. This will allow us to include items not on the account s order, giving them a sampling of products they may not have normally selected or thought they needed until they try them that is! If you have any questions regarding what information is needed when setting up a new account please feel free to contact Jennifer at or jhinz@dermamedicsprofessional.com.

4 Page 4 Competitive Products Treatments for Hyperpigmentation THE PROCESS OF SKIN PIGMENTAITON As you know, the skin has 4 layers, and starting from the surface we have 1) the stratum corneum (or barrier), 2) the epidermis, 3) the dermis, and 4) fat layer. The way your skin tans and the process of skin pigmentation occurs as follows. First, when sunlight hits the skin it penetrates to the bottom of the epidermis where it stimulates specialized cells, called melanocytes. These cells are found at the lowest part of the epidermis right next to the top part of the dermis. The UV radiation stimulates melanocytes to start manufacturing a brown pigment, called melanin. The enzyme that is responsible for making melanin is called TYROSINASE, and it is found inside melanocytes. The UV radiation actually works by turning on this enzyme. So the enzyme becomes active, makes melanin, and this melanin is packaged into vesicles, called melanosomes, that look something like little basketballs. The melanosomes get filled up with melanin and are then secreted from the melanocytes and eaten by keratinocytes. The keratinocytes carry the ingested melanosomes, full of melanin, to the surface of the skin and deposit the melanosomes on the surface to give you that nice tan. HYPERPIGMENTATION PROBLEMS Although the pigmentation process sounds very organized and efficient, as we get older, for some reasons that aren t known, clusters of melanocytes in the skin decide to start manufacturing melanin without being stimulated by the sun. As we re all aware, as we get older, our skin develops pigmented areas, or spots. These are commonly called age spots, but actually have more clinical names. A pigmented area, or spot, is called a LENTIGO or LENTIGENES (plural). These are benign areas of the skin where pigment cells, called melanocytes, are manufacturing too much melanin. Lentigenes may be flat or slightly raised. They can vary in size but are often 5 mm in diameter or larger. In contrast, freckles (ephilides) are flat pigmented spots that are small in size and which become prominent when the skin is exposed to sun and fade or disappear in the winter months. A lentigo looking brown spot that is scaly and rough is likely a pigmented SOLAR KERATOSIS. The roughness is due to keratinocytes that have proliferated at a high rate and are forming a pigmented crust on the skin s surface. In addition to Lentigenes, solar keratoses, and freckles, there is another type of skin hyperpigmentation that is frequently observed in pregnant women and in women on birth control pills. This area of pigmentation frequently covers a broad area and is not always circular in shape. This hyperpigmentation is called MELASMA or often, CHLOASMA. Like Lentigenes, melasma is caused by an increase in melanin production by skin melanocytes. Although some evidence suggests there are more melanocytes in a pigmented area on the skin, it is more likely that the number of pigment cells is the same, but in areas of lentigenes or melasma, the melanocytes are simply more active and make more melanin. The reason for increased activity of melanocytes is not known. In regard to treating pigmented spots on the skin, it important to realize that if the melanocytes and the melanin (the pigment produced by melanocytes) (See Page 6) Continuing Education The Process of Skin Inflammation As DermaMedics Sales Managers, you represent a molecular biology based biopharmaceutical company that specializes in the development of topical non steroidal anti inflammatory products. And in this capacity you are selling much more than simple skin care products. You are essentially pharmaceutical sales reps who are selling topical therapeutic products that are every bit as good as prescription products. That having been said, it is important that when you call on accounts, you have the knowledge to discuss inflammatory skin problems, answer questions about what causes skin inflammation and be able to explain to the physician or office staff how our products effectively treat these problems. Although I covered inflammation a little during training, a thorough understanding is important if you are to be able to answer the question HOW DO YOUR PRODUCTS INHIBIT INFLAMMA TION? The purpose of this Continuing Education section is to provide the answer to this question. THE PROCESS OF INFLAMMATION The process of skin inflammation typically begins at the skin s surface as a result of some stimulus that triggers an inflammatory response. (See Page 5)

5 Issue 2 Page 5 Cont d Continuing Education Inflammation Some of these stimuli are: 1) sunlight (UVR), 2) allergens (poison ivy), 3) irritants (soap, perfumes), 4) bacteria, and 5) yeast. In addition to these causes, simply having dry skin, which causes the skin s barrier to crack, can cause inflammation (some forms of eczema). There are two general types of inflammation: acute and chronic. Acute inflammation is typically caused by exposure to UV radiation from the sun, to LASER radiation, chemical peels, chemical irritants like soap, or to allergens. This type of inflammation typically goes away in 1 2 weeks as the triggering stimuli is removed and skin repairs itself. On the other hand, chronic inflammation is much more severe, can last a lifetime and can cause extensive skin damage. Examples of this are psoriasis, atopic dermatitis (the worst form of eczema), and rosacea. Most chronic inflammation is due, at least in part, to a long lasting autoimmune response that was triggered by something in the skin. Little is known about what this trigger might be. When a stimulus trigger comes in contact with the skin (or in the case of UVR goes through the skin) this event causes a release of inflammatory mediators from skin cells. Recall that your skin has 4 layers, and from the outside down these are : 1) the barrier layer or stratum corneum, 2) the epidermis, 3) dermis, and 4) fat layer. A triggering event on the surface of the skin causes keratinocytes in the epidermis to make and secrete a variety of inflammatory mediators (hormone like proteins) called either cytokines or chemokines. Cytokines, like IL 1, IL 6, and TNF alpha, are proteins that travel to other cells in the skin, such as fibroblasts and mast cells in the dermis and stimulate these cells to produce more cytokines and chemokines, as well as hormones and enzymes (like MMPs). The result of this very rapid production of inflammatory mediators is an increase in histamine, skin swelling, pain or itching and vasodilation. These same inflammatory cytokines also travel to the cells that make up the blood vessels and stimulate them to make specialized proteins called Adhesion Molecules. Adhesion molecules then attach to immune cells like monocytes and neutrophils floating through the bloodstream and cause them to stick or adhere to the blood vessel wall. Once attached to the wall, the immune cells worm their way through the blood vessel and out into the skin. This efflux of immune cells out of the blood vessel and into the skin occurs within 48 hours after the initial triggering stimuli. Once out of the blood vessel, monocytes and neutrophils travel through the skin along a roadway of chemokine crumbs that direct the immune cells to the site of injury, with the goal of fighting and killing invading bacteria. However, most skin inflammation (UVR radiation, LASER treatments, eczema, etc.) does not involve an invading bacteria so when the immune cells get into the skin there is nothing to fight. Instead they release their enzymes, histamine, cytokines and other chemicals into the skin where damage to the surrounding skin cells unfortunately occurs. In an acute response this damage is resolved in a week or two as the triggering stimuli is removed (LASER turned off) and the skin and immune cells stop producing inflammatory mediators. In chronic inflammation, like psoriasis, the response is not turned off and the influx of immune cells into the skin continues and increases (T lymphocytes move into the skin as well) and the skin undergoes considerable damage. HOW IS INFLAMMATION TREATED? As you can see, the process of inflammation involves many cell types, and many cytokines, chemokines and hormones. So how to treat inflammation? The obvious ways are: 1) prevent the production and release of inflammatory mediators, or 2) prevent released inflammatory mediators from acting on other cells like fibroblasts, blood vessel cells and immune cells, and 3) prevent immune cells from responding to inflammatory cytokines and chemokines. All prescription drugs on the market today act on one or more of these 3 events. Topical corticosteroids, like Betametasone, Clobetasol, or Cortisol all work by reducing the level of inflammatory mediators like IL 1, IL 6, PGE 2, and TNF alpha and they also very good at shutting down and destroying immune cells including monocytes, B lymphocytes and T lymphocytes. In short, they are immunosuppressive. While steroids can reduce inflammation, because they also damage the immune system, the patient is at higher risk for skin and other infections. Further, topical steroids inhibit fibroblast functioning and this means that the cells stop making collagen and elastin. They also stop growing and dividing. The end result is that the skin becomes thin, and for this reason, topical steroids are never prescribed for long term use. (See Page 8)

6 Page 6 Cont d Competitive Products: Hyperpigmentation is in the epidermis, this hyperpigmentation is more easily treated. If, however, the pigment is in the dermis, this is more like a tattoo and it is very difficult to get rid of it. Topical skin lightening lotions can be used for EPIDERMAL hyperpigmentation but not for DERMAL hyperpigmentation. For dermal hyperpigmentation, LASER treatments are the best choice. COMPETITIVE PRODUCTS FOR SKIN LIGHTENING Skin lightening products contain actives that work one of three ways: 1) they inhibit tyrosinase activity, 2) they block the transfer of melanosomes to keratinocytes, or 3) they accelerate skin exfoliation to remove the melanin that is at the surface of the skin buried away within the stratum corneum. Almost ALL skin lightening products on the market, either as prescription, OTC drugs or cosmetics, contain ingredients that INHIBIT the activity of tyrosinase. The gold standard ingredient is HYDROQUINONE. This ingredient is an OTC drug at concentrations of 2% or less, and a prescription drug at concentrations greater than 2%. Any product with hydroquinone in it is a DRUG, and must adhere to either the OTC rules or Rx rules. The problem with hydroquinone is that it is: 1) irritating, 2) makes your skin sun sensitive, 3) is linked to cancer, and 4) can cause ochronosis, a persistent blue black pigment. There are many OTC skin lightening products on the market that contain 2% hydroquinone, but the FDA has issued a statement declaring hydroquinone unsafe and has made it clear that their intention is to REMOVE all OTC hydroquinone products from the market. The fate of prescription drugs that contain hydroquinone is unclear but at present, they are being left alone. In Europe and in Asia, hydroquinone products have already been banned. In regard to prescription drugs, the best selling skin lightening prescription is Tri Luma, which contains hydroquinone, a steroid, and Retin A. While effective, it is very irritating to the skin. Obagi has a skin lightening system that is hydroquinone based. It is also a prescription product. In regard to cosmetic products for skin lightening, there are many on the market, but none work well, despite what their advertising claims. Remember that as a cosmetic and not a drug, the marketing claims must be restricted to reducing the appearance of age spots or reducing visible age spots. Many cosmetic skin lightening products contain the chemical ARBUTIN, which is nothing more than glycosylated (sugarcontaining) form of hydroquinone. It does inhibit tyrosinase, but since it s water soluble it doesn t penetrate the skin well, and its topical efficacy is, therefore, questionable. Other whitening ingredients that are often put into skin lightening products and which inhibit tyrosinase include vitamin C, licorice extract, mulberry extract, and kojic acid. Kojic acid is the best of these ingredients. Vitamin A derivatives are also put into these products but since these are NOT Retinoic Acid, but weaker derivatives, their efficacy is questionable. Every day a new plant derived tyrosinase inhibitor is discovered and put into a skin lightening product. The bottom line is that none of them work well. Of all the skin whitening products on the market over 90% work, in theory, by blocking tyrosinase. There are other skin whitening products that contain niacinamide (Vitamin B3) that inhibits the transfer of melanosomes to keratinocytes. Although there is some good lab data on this, clinical data for topical products with niacinamide working well is lacking. The only good data comes from Unilever, which for years has marketed a product called Fair and Lovely. This contains 5% niacinamide and does seem to lighten skin. Unilever had a patent on this but it expired. Many skin lightening products contain, in addition to a tyrosinase inhibitor, salicylic acid, or an alpha hydroxyl acid. These are designed to accelerate skin turnover, thereby increasing the sloughing of skin containing melanin. This will help lighten the skin, but ONLY if tyrosinase is turned off, so that the cycle of melanin production and transfer to keratinocytes is broken. DERMAMEDICS SKIN TONE BRIGHT ENER WORKS TWO UNIQUE WAYS Unlike any cosmetic, OTC drug or prescription drug skin lightening product on the market today, DermaMedics Skin Tone Brightener contains a plant bioactive ingredient that inhibits the production of melanin in melanocytes by two novel mechanisms: 1) Therosol E shuts OFF the production of tyrosinase, and 2) Therosol E blocks mela

7 Issue 2 Page 7 nin synthesis at the step where a colorless intermediate is converted to melanin. Mechanism 1: Inhibition of Tyrosinase Synthesis Recall that almost all skin lighteners inhibit the ACTIVITY of tyrosinase. This means that the enzyme is there and working but that the inhibitor comes into the melanocyte and interferes with the enzyme s ability to make melanin. However, there is no inhibitor that shuts off tyrosinase activity 100%. Most work at the level of 10 30% inhibition. That means that there is still plenty of active enzyme around to make melanin. In contrast Therosol E shuts of the SYNTHESIS of tyrosinase. That means that the melanocyte has NO enzyme and can t make any melanin. There s no need for an inhibitor of the enzyme because there isn t any enzyme. Therosol E reduces tyrosinase synthesis by over 80%. Mechanism 2: Inhibition of Post Tyrosinase Steps in the Melanin Synthesis Pathway As mentioned, tyrosinase is the enzyme that makes melanin, and it is considered the rate limiting enzyme. That means that it is absolutely required for melanin production. However, the entire process of making melanin consists of 7 steps. The first 2 steps are controlled by tyrosinase but the last 5 steps are enzyme independent. In other words, once tyrosinase 6th intermediate step is COLORLESS. Therosol E blocks the conversion of the colorless intermediate 6 into the brown pigment, melanin. The ability of Therosol E to block melanin two ways is the reason the product is so effective in reducing and eliminating hyperpigmentation spots. There is no product on the market that works this way. CONCLUSION 1. The most effective skin lightening active is HYDRO QUINONE. Hydroquinone is present in OTC topical products at a maximum of 2% and in Prescription products at up to 4%. 2. Obagi has a 4% skin lightening prescription product. Others have 2% OTC products. 3. The FDA wants to remove all OTC hydroquinone containing products. Prescription products are not affected yet by the FDA declaration. 4. Cosmetic skin lightening products do NOT contain hydroquinone. Many contain a glycosylated form of hydroquinone called ARBUTIN. Arbutin does not penetrate into the skin readily, and is not very effective. Other ingredients are kojic acid, retinol, vitamin C, licorice, and Mulberry. None are very effective. 5. Skinceuticals has a kojic acid skin whitener that also contains emblica, another purported tyrosinase inhibitor. SkinMedica has a 4% hydroquinone prescription product. 6. Unlike any other product, DermaMedics Therosol E technology works 2 ways to block melanin production: 1) blocks the synthesis (production) of tyrosinase, and 2) arrests melanin production at a colorless intermediate. Depigmentation of Human Melanocytes in culture treated for nine days with Therosol E. TH 213 is Therosol E. has made intermediate 2 that intermediate must be converted to other chemical compounds in 5 more steps before the final chemical, melanin, is produced. These last five steps proceed automatically without the need for any enzyme. The

8 Page 8 Cont d Continuing Education Inflammation Newer prescription products on the market include PROTOPIC (tacrolimus) and ELIDEL (pimecrolimus). These are often prescribed for eczema, even in young children. Both of these topical drugs are strong immunosuppressive agents, and thus, the risk of infection and even cancer is elevated. The FDA recently issued a black box warning for these drugs stating that the risk for lymphoma and skin cancer is higher in patients using these products. Very recently, a group of injectable biologic response modifiers have been approved for use in treating chronic skin problems like psoriasis. These injectable drugs are the strongest immunosuppressive agents available. Many of them act by binding to and blocking the action of TNF alpha, a cytokine that stimulates immune cells. The drug REMICADE is one of these TNF alpha blockers. The immunosuppressive effects of this drug cause increased risk of infection, cancer and TB (tuberculosis). Some patients have died from complications caused by this drug. HOW THEROSOL WORKS TO REDUCE INFLAMMATION When DermaMedics set out to look for new antiinflammatories, we had 3 objectives: 1) identify compounds that are naturally found in plants, 2) identify compounds that had been extensively tested for safety, and 3) identify compounds that could reduce the production and action of a wide variety of inflammatory compounds back to their resting state, but which would not be strongly immunosuppressive. Therosol, and related chemical compounds, turned out to meet all 3 criteria. First, Therosol is found in several edible plants, and therefore has been ingested for years with no safety issues. Secondly, Therosol and related chemical compounds have undergone rigorous safety testing by the National Toxicology Program, which is supported by Health and Human Services. Since Therosol is used as a fragrance and a flavoring agent in foods, it falls under the EAFUS list (Everything Added to Foods, U.S.). As a food ingredient it has had to undergo extensive safety testing, and a 32 page safety dossier on it is available. It has turned out to be extremely safe when used on the skin or eaten in foods. It is nonsensitizing and non irritating. In regard to objective 3, our extensive screening program looked at the effect of Therosol in: 1) blocking the PRODUC TION of inflammatory cytokines and chemokines in human skin cells and in human immune cells, and 2) blocking the ACTION of inflammatory cytokines and chemokines on other skin and immune cells. A brief description of how these studies are done may be useful. These studies are all done with human cells that are grown in culture in dishes. We use human keratinocytes, fibroblasts, melanocytes, and immune cells. So for a typical experiment we initiate an inflammatory response by treating the cells with a UV lamp (yes, it s a sunlamp just like in a tanning salon). The cells respond to the UV light by producing inflammatory cytokines and chemokines. These are secreted into the liquid growth medium and we use a variety of sensitive assays to measure the amount each inflammatory hormone that has been secreted. A duplicate set of cell cultures are also treated with UV light but in this case, the cells are also treated with Therosol. If Therosol blocks inflammation, then the cells will not produce the inflammatory cytokines and chemokines, and when we assay the growth medium we will not find any cytokines or chemokines present. We can also stimulate cells with allergens, chemical irritants, etc. so we can get a very good picture of how effective Therosol is in blocking Lotion without Therosol Therosol lotion blocks UVR inflammation. Lotion with Therosol

9 Issue 2 Page 9 inflammation. Using this approach as well as much more sophisticated analysis including DNA gene array analysis, we can determine precisely what inflammatory events Therosol can block. We can also determine if Therosol can block the ability of an inflammatory hormone (like TNF alpha) to trigger inflammation in a target cell. By finding that Therosol could block BOTH the PRODUCTION of TNF alpha as well as TNFalpha ACTION on target cells, we knew that Therosol would probably be a good psoriasis treatment, because TNF alpha is a major cause of psoriasis. So, what we know is that Therosol: 1) blocks the OVER PRODUCTION of inflammatory cytokines (IL 1, TNF alpha, IL 6), chemokines (MCP 1, IL 8) and inflammatory hormones like PGE 2 in skin cells, particularly keratinocytes and fibroblasts, and in immune cells like monocytes, neutrophils and T cells. So levels of these compound remain at resting levels. 2) Therosol PREVENTS inflammatory cytokines and chemokines from being able to stimulate their target cells (like the blood vessel cells and immune cells). Thus, even if inflammatory hormones are made they can t cause inflammation because they can t trigger inflammation in target cells. 3) Therosol does NOT totally suppress the immune system. Rather, Therosol lowers the production of the above cytokines and chemokines, back to the RESTING level that all cells have. If they are needed to fight an infection the cell can still make them. This is unlike Protopic and Remicade which TOTALLY wipe out the production of any inflammatory hormones so even if you had an infection your skin cells and immune cells couldn t respond by mounting an inflammatory response. 4) Therosol blocks PGE 2 production completely. This is a very bad hormone that is responsible for heart disease, as well as other kinds of chronic inflammation (that s why COX 2 inhibitor drugs are a multi billion dollar business COX 2 is the enzyme that makes PGE 2). Remember VI OXX? This billion dollar product was a COX 2 inhibitor that unfortunately had some side effects. PGE 2 is the hormone that causes sunburn and redness, and is also a major cause of skin cancer. Therosol blocks PGE 2 levels effectively and since PGE 2 is linked to skin cancer, Therosol likely reduces skin cancer risk. In radiation patients imagine how much PGE 2 is being produced by the radiation. The First Office Visit As you have no doubt experienced by now when making calls, the ONE product that Medical Spas and physician offices do not have but need badly is a product to reduce and prevent inflammation. So the first visit to any office should focus on our anti inflammatory technology. You don t need to even discuss the rosacea, hyperpigmentation of anti aging products first. Once you get them interested in the antiinflammatory technology and products we have, then they ll get interested in the rest of our products. I think the best initial approach may be the following: Introduce yourself and explain that DermaMedics is a very new company that was formed initially to develop non steroidal anti inflammatories for cancer patients, specifically for them to use to prevent radiation burns. And in this regard, the company was amazingly successful in discovering a family of botanically derived chemical compounds with pharmaceutical level potency. The company s topical product, DermaRad Relief, was found to completely block radiation burns. The product went through an IRB (stands for Institutional Review Board) approved clinical study to assess its effectiveness in preventing burns from breast cancer radiation. An extension of this study to look at the effectiveness of the product in preventing radiation burns in patients being irradiated for different types of cancer (e.g. throat, lung, prostate, colon, and bone cancer) is now underway at Integris Bap tist Hospital in Oklahoma City. The product has now been used in over 30 cancer clinics including MD Anderson. It is the only product in the world that can prevent the worst form of burns, i.e. radiation burns. It was THAT clinical success that prompted the company to look for other applications of this remarkable anti inflammatory technology, and that led to the development of products that we now offer. If the product can block radiation burns, it can block laser burns, peel burns, inflammation from IPL treatment, etc. Moreover, the technology treats inflammation from eczema, rosacea, acne, and even psoriasis. Pilot clinical studies have been done for rosacea (See Page 10)

10 Page 10 Cont d DermaMedics Q & A Who Designs the Therosol formulations? Dr. Fuller formulates all of the DermaMedics products. What makes DermaMedics products different from other skin care products? DermaMedics products are the result of 22 years of skin biochemistry research at a major medical school DermaMedics products contain novel, patented, nonsteroidal anti inflammatory and anti aging bioactives that are clinically proven to treat skin problems and which cannot be found in any other products. Therametics formulations are engineered to optimize the skin penetration of each bioactive ingredient so that the bioactives can reach and correct skin damage occurring far below the skin s surface Why Doesn t DermaMedics Put Plant Extracts in Their Products? Plant extracts may contain 1 or 2 chemical compounds that are well known to be beneficial to the skin, but the same extract will also contain hundreds of other unknown chemical compounds. For example, an extract of green tea leaves will contain the beneficial ingredient EGCG, but at very low concentrations. That same extract will contain over 100 other chemical compounds that are unknown and may either be good for the skin or bad for it. Many crude plant extracts cause skin sensitization and allergic reactions. Since plant extracts are nothing more than parts of a plant pulverized in water or other solvent, and then filtered to remove particulate material, they are complex mixtures of hundreds of unknown chemicals with unknown effects on your skin. DermaMedics puts only pure, ingredients in their product formulations. Cont d-the First Office Visit and psoriasis and are ongoing for other inflammatory skin problems. In addition, the Therosol compounds in our products have analgesic activity when applied to the skin, thereby reducing pain and itch. Finally, given the link between skin inflammation and aging, DermaMedics scientists looked at the possible anti aging effects of this technology and found that this Therosol family of compounds could stimulate collagen and elastin production, block enzymes that damage the skin s matrix (enzymes like MMPs) and, in addition, recent data suggests that the Therosol technology can accelerate wound repair. So we re a very new company, that is building products to help physicians help their patients. And, if the physician wants to try any of our products on patients (like Calm and Correct after a laser, peel or IPL; or Redness Reduction on a rosacea patient), we ll be happy to supply a full size product. Seeing is believing. 655 Research Parkway, Suite 546 Oklahoma City, OK Toll Free: Local: