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The advantages of Arthromac A chemical-free treatment manufactured in Europe with a non-animal, ultrapure, high molecular weight, French-origin hyaluronic acid. ••• Non-animal origin Several competing products, including the actual world's leading brand, are manufactured from a HA of animal origin (cock’s comb) which has a high animal protein content, leading to possible allergic reactions. ARTHROMAC ® is made of a non-animal HA obtained by biofermentation which is the today’s source of choice due to its full biocompatibility. ​ ••• No chemical agent Unlike other viscosupplements, ARTHROMAC ® is not cross-linked with chemical agents such as 1,4-butanediol diglycidyl ether (BDDE), formaldehyde, divinyl sulfone etc. ARTHROMAC ® is naturally cross-linked without any chemical agent through our proprietary technology X-Click Technology. ​ ••• Ultrapure HA The HA used in the manufacturing of ARTHROMAC ® is produced in France and has the highest purity available in the market today (≤0.005 I.U/mg). ​ ••• Very High Molecular Weight The HA in ARTHROMAC has a molecular weight between 3 and 4 millions Dalton, providing a better effectiveness compared to products with lower molecular weight HA. ​ ••• Optimal sterilization cycle ART HROMAC is sterilized by our proprietary autoclave steam sterilization process “Flash cooling system” making it possible to have a cooling time 90% faster than with standard autoclave, thus preserving the integrity of the HA from excess heating. ​ ••• Strict q uality control ARTHROMAC ® is manufactured in Europe under strict quality control and meets the requirements of the highest technical standards. It conforms to the European Medical Devices Directive MDR and an optimized risk management process that goes above and beyond regulatory compliance has been implemented. Interested in distributing Arthromac or finding a supplier for your medical practice? contact@arthromac.com Customer service Whatsapp

Frequently asked questions ••• How is Arthromac® given ? Administered by a single injection into the affected joint. The procedure takes approximately 10 minutes and is performed by a physician or other qualified health care professional experienced in intra-articular injections. ​ ••• How long will the effects of Arthromac® last ? The durability varies from several months to more than a year depending on : - the patient’s condition an d age - the patient’s lifestyle - the severity of the osteoarthritis - the type and size of the affected joint - the technique of injection ​ It should also be noted that the effectiveness of a viscosupplement increases with the number of treatment courses. How will the doctor prepare my joint for injection ? Before injecting ANTALVISC® into your joint, the doctor will : - clean your joint with disinfectants - apply a local anesthetic to your joint - withdraw any excess fluid from your joint. ​ ••• Is Arthromac® injection painful ? The injection is relatively painless. The topical application of an anesthetic agent is possible to improve patient comfort. ​ ••• What type of joints can be treated with Arthromac® ? All synovial joints affected by osteoarthritis can be treated. Particularly the knee and hip, but also the ankle, shoulder, elbow, wrist, fingers, toes, and the temporomandibular and facet joints. ​ ••• What degrees of severity of osteoarthritis can be treated ? ARTHROMAC® can be used for the treatment of all grades of osteoarthritis. ​ ••• Are there any adverse events following Arthromac® injection ? Following injection, transient pain and swelling of the injected joint may occur. These temporary reactions which generally subside over 72 hours do not have to be the source of concern and can be simply treated by resting and applying ice to the injected joint. Arthromac® does not have the serious side effects associated with NSAIDs and corticosteroids. ​ ••• What are the recommendations to follow after Arthromac® injection ? After the injection, you can resume normal day-to-day activities, but an articular rest of approximately 24 hours is rec ommended (no strenuous exercise). ​ ••• How effective is Arthromac® compared to NSAIDs and corticosteroids ? Arthromac® provides comparable pain relief to NSAIDs and corticosteroids during the first weeks, with a much longer duration of action (up to 15 months). Moreover, contrary to NSAIDs and corticosteroids, ANTALVISC® provides : - a correction of the stiffness and an improvement of the mobility - a complete safety. Numerous side effects and counter-indications are linked to the use of NSAIDs and corticosteroids - chondroprotective and wound healing properties, enabling to protect and repair cartilage - an easier evacuation of cartilaginous remains Clinical studies also show that the use of NSAIDs or corticosteroids in combination with viscosupplementation is more effective for reducing pain than NSAIDs or corticosteroids alone. ​ ••• When will I start to feel pain relief ? Everyone responds differently, but the pain relief generally starts between 2 and 4 weeks after the injection. ​ ••• Can both my knees be treated with Arthromac® ? Yes, you can receive one injection in each individual knee at the same time, or at different times. ​ ••• Can I repeat the treatment ? Yes, if the symptoms return after several months, the injection of Arthro mac® can be repeated safely and effectively for a new period of pain relief (generally longer than the previous one). ​ ••• Are there other indications for Arthromac® use ? Besides being used for the treatment of osteoarthritis, Arthromac® may also be indicated for post-surgical management, particularly in the reduction of post-arthroscopic pain. ​ ••• Who can inject Arthromac® ? A medical practitioner familiar and trained in the intra-articular injections. Medical specialists include (but not exclusively): rheumatologist, orthopaedic surgeon, radiologist, musculoskeletal physician, sports physician, general physician. ​ Interested in distributing Arthromac or finding a supplier for your medical practice? contact@arthromac.com Customer service Whatsapp

Get back to an active life What is Arthromac OSTEOARTHRITIS JOINT PAINT RELIEF ARTHROMAC® is a product for viscosupplementation, which is a safe, effective, and well-established treatment for osteoarthritis (OA) consisting in injecting a hyaluronic acid-based solution into the affected joint. It relieves pain, restores articular function and protects cartilage. A single, intraarticular injection of Arthromac® provides a rapid and powerful osteoarthritis pain relief that can last up to 12 months How does it work RESTORING JOINT LUBRICATION In osteoarthritis (OA) joints, the quality and quantity of hyaluronic acid (HA), a major component of the synovial fluid responsible for the lubrication and cushioning in joints, are diminished. As a result, the synovial fluid has lower viscosity and elasticity, decreasing its ability to lubricate the joint and absorb shocks. ​ ARTHROMAC® replaces and supplements the unhealthy synovial fluid to increase the quality and quantity of the endogenous HA and to restore its viscoelastic properties. ​ ARTHROMAC® lubricates and cushions the joint and protects the cartilage, thereby reducing pain, improving mobility and articular function, and retarding progression of OA. What is osteoarthritis A COMMON DISORDER TO TREAT Osteoarthritis (OA) is the most common joint disorder and a leading cause of chronic disability. Its prevalence increases with age and the common symptoms are pain, stiffness and loss of motion. OA most often affects knees, hips, spine, hands and feet, but can affect almost any joint in the body. ​ OA is the result of mechanical and biological events that destabilize the balance between synthesis and degradation of cartilage and which affects all articular structures. OSTEOARTHRITIS JOINT Cartilage wears away: The cartilage is eroded by the forces of friction and compression. Synovial fluid becomes less healthy: The fluid becomes thinner and less elastic, losing its ability to provide a good cushion. Exposed bone: Over time, the bone surfaces may rub together. Bone spurs: Osteophytes can form and grow ​ OA is a chronic condition that gradually worsens over time and can become rapidly painful and incapacitating. ARTHROMAC® will prevent and slow its progression and will reduce joint pain and stiffness. Our viscosupplement range TECHNICAL INFORMATIONS ​ ••• INDICATION: Prevention and treatment of osteoarthritis ••• HA CONCENTRATION: 20 mg/m l ••• HA ORIGIN: Non-animal ••• HA MOLECULAR WEIGHT: Between 3 and 4 million Dalton ••• ADMINISTRATION: Single intraarticular injection ••• ACTIONS: Pain relief, mobility improvement, cartilage p rotection ••• DURATION OF EFFECTS: Up to 9 months* ••• PRIMARY PACKAGING: Sterile 3 mL prefilled glass syringe with finger grip ••• SECONDARY PACKAGING: Sterilized medical grade blister in carton box ••• STORAGE: Between +2°C and +25°C ••• SHELF LIFE: 3 years * depending on several factors such as the severity of the osteoarthritis, the type and size of the affected joint, the patient’s condition and age, the patient’s lifestyle, the patient’s genetic profile and the technique of injection. ​ Bespoke Support and Sales ​ Interested in distributing Arthromac or finding a supplier for your medical practice? contact@arthromac.com Customer service Whatsapp

Say goodbye to joint pain A single injection of Arthromac provides a quick, powerful and long-lasting joint pain relief 1/3 What is Arthroma c VISCALGIC est un produit de viscosupplémentation administré par voie orale et indiqué pour améliorer le confort et la mobilité articulaires et pour maintenir la bonne santé du cartilage. VISCALGIC délivre une quantité substantielle d'acide hyaluronique (AH) à l'intérieur des tissus articulaires pour réduire la raideur et améliorer la fonction articulaire. ​ L'AH oral est absorbé et distribué dans les os, le cartilage et le liquide synovial et est retenu dans ces tissus pendant des périodes prolongées. En conséquence, la quantité et la qualité de l'AH sont restaurées, assurant ainsi une bonne lubrification et absorption des chocs dans l'articulation. Learn more about Arthromac® 1/4 Actions of Arthromac Quickly and lastingly relieves joint pain Decreases stiffness for more mobility Protects cartilage against degradation A natural cross-linking Our proprietary cross-linking process X-Click technology makes it possible to transform linear HA into a stabilized 3D HA without any chemical agents. As a result, the injected HA will have a greater residence time in the joint while keeping its natural biological and rheological properties for more effectiveness and a complete safety . ​ ​ Why choosing Arthromac Complete safety Non-animal, french-origin HA from the highest purity available on the market and no chemical cross-linking. High quality HA Very high molecular weight of 3-4 million Daltons protected by our "Flash cooling system" during sterilisation. X-Click Technology Physical cross-linking preserving the natural viscoelastic and biological properties of the HA. Made in Europe Manufactured in Europe under strict quality control and according to the European Medical Devices Directive.

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Our technology A safe and effective cross-linking ​ Arthromac® products are made with a hyaluronic acid produced in France , with the highest level of purity available in the industry today, and cross-linked through a proprietary process using no chemical agent called X-Click Technology. About HYALURONIC ACID Hyaluronic acid (HA), a linear polysaccharide that occurs naturally in the synovial fluid and cartilage, is fully biocompatible and has remarkable properties for the treatment of osteoarthritis . However, once injected into the tissues, a natural and unmodified molecule of HA will be rapidly degraded and absorbed. ​ This depolymerization which transforms long HA chains (polysaccharides) into smaller HA units (oligosaccharides) is due to enzymes (hyaluronidases), free radicals, heat and mechanical stresses. Therefore, to increase the residence time of HA and its beneficial action in the tissues, it is crucial to protect it against these enzymatic, oxidative, thermal and mechanical degradations by a process of cross-linking (reticulation). About CHEMICAL CROSS-LINKING To improve the duration of HA in vivo, a common method is to form a hydrogel by covalently cross-linking the HA polymer chains into a three-dimensional network. Unfortunately, this cross-linking process involving chemical agents (such as such as 1,4-butanediol diglycidyl ether (BDDE), formaldehyde, divinyl sulfone etc.) impairs the biocompatibility, the ease of injectablity, as well as the natural viscoelastic and biological properties of the HA molecule. The later will have an impaired biocompatibility with a greater risk of hypersensitivity reactions [1-5], a more rigid structure, a lower water-binding capacity, and a lower capacity on the production of extracellular matrix components [6] . Such adverse events and disadvantages are avoided with the use of a physical cross-linking instead of a chemical one [1, 7, 8]. About our exclusive technology PHYSICAL CROSS-LINKING NOVATEX BIOENGINEERING, an Astagen Therapeutics division, through its collaboration with the CNRS (The French National Centre for Scientific Research), has developed a new cross-linking technology, called X-Click technology, making it possible to physically transform a linear HA into a stabilized three-dimensional HA network without any chemical agents . This proprietary technology is based on the click chemistry [9] and used crystallization to create intermolecular and intramolecular hydrogen bonding (Fig 1). ​ ​ ​ ​ ​ ​ This physical hydrogel is a good alternative because of the absence of organic solvents and toxic cross-linking agents [10-14]. As a result, the HA cross-linked with X-Click Technology is non-toxic, fully biocomptabible, easy to inject, with unaltered viscoelastic and biological properties [15,16]. Fig. 1. Hydrogen bonding between –COOH groups in HA cross-linked by X-Click Technology CLASSICAL METHOD Chemical cross-linking X-CLICK TECHNOLOGY Physical cross-linking without chemical agent LOSS OF THE NATURAL VISCOELASTIC AND BIOLOGICAL PROPERTIES OF THE HA ​ Rigid structure (low injectability and elasticity) No stimulation of HA synthesis HIGHER RATE OF ADVERSE EVENTS PRESERVATION OF THE NATURAL VISCOELASTIC AND BIOLOGICAL PROPERTIES OF THE HA ​ Dynamic structure (ease of injectability, good elasticity) Stimulation of HA synthesis LOWER RATE OF ADVERSE EVENTS VS REFERENCES: 1. W.E. Hennink, C.F. van Nostrum, Adv. Drug. Deliver. Rev. 54 (2002) 13–36. 2. Jeong Min Lee and Yu Jin Kim. Foreign Body Granulomas after the Use of Dermal Fillers: Pathophysiology, Clinical Appearance, Histologic Features, and Treatment. Arch Plast Surg. 2015 Mar; 42(2): 232–239. 3. Fidalgo J, et al. Detection of a new reaction by-product in BDDE cross-linked autoclaved hyaluronic acid hydrogels by LC-MS analysis. Med Devices (Auckl) 2018;11:367–376. doi: 10.2147/MDER.S166999. 4. Keizers PHJ, et al. A high crosslinking grade of hyaluronic acid found in a dermal filler causing adverse effects. J Pharm Biomed Anal. 2018;159:173–178. doi: 10.1016/j.jpba.2018.06.066. 5. Yeom J, et al. Effect of cross-linking reagents for hyaluronic acid hydrogel dermal fillers on tissue augmentation and regeneration. Bioconjug Chem. 2010;21:240–247. doi: 10.1021/bc9002647. 6. A. Tezel, G.H. Fredrickson. The science of hyaluronic acid dermal fillers. Journal of Cosmetic and Laser Therapy, 10 (1) (2008), pp. 35–42 7. A. Clark, S. Ross-Murphy, Structural and mechanical properties of biopolymer gels, in: Biopolymers, Springer, Berlin-Heidelberg, 1987, pp. 57–192. 8. C. Chang, L. Zhang, Carbohydr. Polym. 84 (2011) 40–53. 9. H. C. Kolb, M. G. Finn and K. B. Sharpless (2001). «Click Chemistry: Diverse Chemical Function from a Few Good Reactions». Angewandte Chemie International Edition 40 (11): 2004–2021. 10. Chemical mutagenesis testing in Drosophila. IX. Results of 50 coded compounds tested for the National Toxicology Program. Foureman P, Mason JM, Valencia R, Zimmering S Environ Mol Mutagen. 1994; 23(1):51-63. 11. West JD, Stamm CE, Brown HA, Justice SL, Morano KA. Enhanced toxicity of the protein cross-linkers divinyl sulfone and diethyl acetylenedicarboxylate in comparison to related monofunctional electrophiles. Chem Res Toxicol. 2011 Sep 19;24(9):1457-9. doi: 10.1021/ tx200302w. Epub 2011 Aug 8. 12. Cancer risk assessment P020023 www.fda.gov 13. National Toxicology Program (June 2011). Report on Carcinogens, Twelfth Edition. Department of Health and Human Services, Public Health Service, National Toxicology Program. Retrieved June 10, 2011. 14. T. Coviello, P. Matricardi, C. Marianecci, F. Alhaique, J. Control. Release. 119 (2007) 5–24. 15. S. Van Vlierberghe, P. Dubruel, E. Schacht, Biomacromolecules 12 (2011) 1387–1408. 16. Internal data. X-Click-technology technical file. Novatex Bioengineering

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Become a distributor A safe technology ••• Only one injection The single injection regimen reduces patient inconvenience ••• Non-animal origin ARTHROMAC is manufactured from a HA obtained by biofermentation and of the highest purity attainable ​ ••• Full biocompatibility ARTHROMAC is completely natural, biocompatible, bioresorbable and non-allergenic ​ ••• Simple, quick, with no downtime The procedure takes only few minutes and daily routine can be resumed immediately after the injection ​ ••• Non-surgical treatment ARTHROMAC is an office-based procedure that helps to avoid or delay the need for major surgery ​ ••• Drug-free and non-systemic ARTHROMAC avoids the adverse and undesirable effects linked to the use of NSAIDs and corticosteroids or associated with systemic administration ​ ••• Non-toxic cross-linking system ARTHROMAC is cross-linked through a proprietary technology without any toxic agents such as BDDE, formaldehyde, divinyl sulfone etc. which are used by numerous competitors ​ ••• Minimum rate of adverse events Clinical and practice data indicate that ARTHROMAC has a lower rate of adverse events in comparison with other competitors ​ ••• Rigorous control of the manufacturing process ARTHROMAC is manufactured in France under the highest quality standards with top qualified engineers and latest technology ​ Clinical results I will improve and draw again the bad graphics of arthromac. I just add viscalgic

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