MAM-1004-1/Budesolv is a nasal spray containing the corticosteroid budesonide solubilized with Marinomeds proprietary Marinosolv solubilization technology. Budesolv is intended to treat severe allergic rhinitis and has met all endpoints in a phase III clinical trial. Due to the solubilized, readily available form, a therapeutic effect could be achieved with a significantly lower dose (85% lower than comparable marketed products). Furthermore, the increased bioavailability allows a significantly faster onset of action: Budesolv led to a noticeable reduction in allergic nasal symptoms and a significant reduction in asthmatic symptoms in less than three hours after the first dose. The unique Marinosolv-formulation offers further advantages: due to the dissolved form of the active ingredient, shaking is not necessary and the risk of misdosing is greatly reduced. The formulation is free of potentially irritating preservatives and well tolerated. Furthermore, the reduction of the amount of active pharmaceutical ingredient contributes to sustainability, as less drug substance pollutes the environment, particularly the wastewater.
|Active pharmaceutical ingredient||Budesonide (corticosteroid)|
|Development phase||Filing in preparation|
Allergic rhinitis (AR) is one manifestation of a type I hypersensitivity reaction caused by an immune reaction to otherwise innocuous agents such as pollen or house dust mites. The disease can occur both perennially (e.g. house dust mite allergy) or seasonally (e.g. grass pollen allergy). In the past decades, a globally rising trend of AR has been observed with widely varying prevalence, particularly in the developing countries. Up to 30% of the global population may be affected. While allergic rhinitis refers to an inflammatory process of the nasal passages, symptoms involve the nose and may extend beyond to affect the eyes, ears, sinuses and bronchi. Commonly reported nasal symptoms include nasal itching and congestion, runny nose and sneezing. Often, AR will involve the conjunctivae; such patients may experience itching, tearing and red eyes. About 40% of AR patients also suffer from asthmatic symptoms like cough, wheeze and dyspnea. In fact, AR is considered an independent risk factor for subsequent asthma. Some studies have shown that treatment for AR can reduce healthcare costs and lead to a better asthma control.
Apart from allergen avoidance and physical measures, current therapy of AR comprises two main treatment options: Pharmaceuticals targeting the effects of messenger substances secreted by mast cells or hypersensitization to specific allergens. Anti-allergic pharmaceuticals can be divided into three categories: Antihistamines prevent histamine from binding to its receptor, mast cell stabilizers (e.g. cromoglycate) are supposed to reduce the secretion of messengers, and glucocorticoids inhibit the production and release of proinflammatory substances such as TNF-alpha.
Poor solubility and associated poor bioavailability result in delayed onset of action, especially when applied locally in the nose. The suspension with undissolved particles used must be applied for a number of days before an effect occurs.
- Faster onset of action
- Reduced dose
- Suitable for sensitive tissues such as the nasal mucosa
- No shaking necessary
- Decreased risk of misdosing
|Active pharmaceutical ingredient||Tacrolimus (immunosuppressant)|
|Indication||Severe inflammatory ocular surface diseases|
|Development phase||Phase II clinical study|
MAM-1003-1/Tacrosolv is a topically applied, anti-inflammatory and immunomodulating ophthalmic solution, containing Tacrolimus solubilized with Marinomeds proprietary Marinosolv solubilization technology. Tacrolimus is a well-known calcineurin inhibitor and highly potent immunosuppressant used in organ transplantation as well as inflammatory eye and skin conditions. However, Tacrolimus is a highly lipophilic substance with very low water solubility. Based on the proprietary Marinosolv technology, Marinomed has developed a novel aqueous formulation, which allows the complete solubilization of the compound using known excipients. Thus, Marinosolv is able to unfold the full potential of Tacrolimus even at very low concentrations.
It could be demonstrated that the topical application of Tacrosolv results in higher concentrations of Tacrolimus in ocular tissue compared to Talymus (Tacrolimus in suspension), a product marketed in Asia to treat vernal keratoconjunctivitis. Even though the concentration of the drug was reduced up to 95%, sufficient concentrations of the drug were detected in different tissues of the eyes, such as conjunctiva and cornea. An exploratory phase II clinical trial for dose finding was performed in the model indication of allergic rhinoconjunctivitis. The higher dose group demonstrated a significant relief of allergic symptoms in the eyes and also in the nose already after eight days of treatment.
Based on its anti-inflammatory and immunomodulatory effect, Tacrosolv offers great potential as treatment in different ocular surface diseases, such as dry eye disease, ocular graft versus host disease, severe refractive conjunctivitis, vernal/atopic keratoconjunctivits or herpetic stromal keratitis.
Management of anterior segment inflammatory eye diseases often involve the long-term use of topical and/or systemic corticosteroids, which can lead to raised intraocular pressure and associated complications such as cataract and glaucoma. Alternative treatment options include the use of immunosuppressive compound cyclosporin, which has a comparable safety profile to Tacrolimus but is ~100 times less potent.
- Faster onset of action
- Reduced dose
- Suitable for sensitive tissues such as eyes
- Suitable for a wide range of ocular diseases
The objective of this project is to develop an orally applied, well tolerated and locally effective innovative drug with an anti-inflammatory agent based on the Marinosolv technology. In addition, new biomarkers are to be defined to facilitate the identification of patients in the early stages of the disease and to document the effectiveness of a therapy by influencing the progression of the disease.
Autoimmune gastritis (AIG) is a chronic disease of the stomach that affects an estimated 2-5% of the general population, with women being more commonly affected (approximately 3:1). However, there is wide variation in the literature regarding the incidence of AIG. Due to inflammatory processes, there is degeneration of the gastric mucosa and progressive loss of the acid-producing cells of the stomach. This results in iron deficiency and, in advanced disease, vitamin B12 deficiency.
The disease is associated with a high loss of quality of life and is often diagnosed late, as symptoms in the early stages are often non-specific (e.g. nausea, dyspepsia, flatulence, pain). In later stages, neurological symptoms may occur due to vitamin B12 deficiency. In addition, chronic inflammation of the gastric mucosa can lead to neoplastic changes and thus to the development of various types of tumors.
Currently, a causal therapy for AIG does not exist. Treatment of patients with AIG is limited to vitamin B12 and iron substitution. Although this may alleviate the symptoms of deficiency, it does not stop the progression of the disease. An anti-inflammatory therapy applied directly in the stomach should eliminate the basis of the disease itself, stop the progressive degeneration of the gastric mucosa, increase the patients' quality of life and subsequently greatly reduce the risk of cancer in the stomach.
- First causal treatment for AIG
- May reduce the risk of stomach cancer in the progression of AIG
MAM-1001-4 nasal spray contains Carragelose, a polymer derived from red seaweed, which forms a protective layer on the nasal mucosa. This layer prevents allergen contact with the mucosa and thus reduces allergy symptoms. MAM-1001-4 acts quickly, exclusively locally and does not cause fatigue. A clinical study has shown that even a single, prophylactic application of the nasal spray leads to a significant reduction in allergy symptoms. In addition, its moisturizing properties and excellent safety profile make MAM-1001-4 the ideal choice for nasal mucosa irritated by allergy.
Allergic rhinitis (AR) is one manifestation of a type I allergic reaction caused by otherwise innocuous substances, such as pollen or dust mites. The disease can be seasonal (e.g. allergy to grass pollen) or year-round (e.g. allergy to house dust mites). In the milder courses, AR is usually limited to an inflammatory process of the nasal passages; characteristic symptoms of this disease include itching and nasal congestion, a runny nose, and sneezing.
Mild courses of allergic rhinitis benefit from physically acting therapy measures, such as nasal rinses with saltwater solutions or avoidance of the triggering allergens. In this case, the use of drugs is usually not necessary. For these mild courses, MAM-1001-4 offers safe, fast-acting and, thanks to Carragelose, longer-lasting protection against inhaled allergens for use at home and on the go. The protective film also moisturizes and soothes the irritated nasal mucosa.
- Rapid onset of action
- Acts only locally
- Suitable for pregnant women and children
- Free from preservatives
- Does not cause fatigue
- Clinically validated, excellent safety profile
- Has additional moisturizing properties
MAM-1001-3 eye drops contain Carragelose, which is a polymer extracted from red seaweed that forms a protective layer on mucosal surfaces. Carragelose has been well-established as broad-spectrum virus-blocking compound used in a marketed OTC product portfolio for the treatment of viral respiratory infections and has been shown to effectively inhibit a wide range of respiratory viruses. Next to its virus-blocking effectiveness, Carragelose shows excellent moistuirizing properties, which, together with its outstanding safety profile, makes it a perfect candidate for eye drops.
Dry eyes can be caused by a variety of triggers, such as a dry indoor environment, contact lenses or air conditioning. Especially screen-associated irritation and dryness of the eyes are gaining increasing awareness. Dry eyes can cause burning or stinging of the eyes and can lead to inflammation and damage of the eye in the long term. Next to its protecting and lubricating properties, Carragelose eye drops may also be suitable for the treatment of viral conjunctivitis. Viruses cause up to 80% of all cases of acute conjunctivitis, of which 65-90% are caused by various types of adenoviruses. To date, there is no causative treatment for adenovirus-induced ocular infections available. Carragelose has been shown to inhibit several adenovirus strains known to induce keratoconjunctivitis.
Marketed eye drops for dry eye relief contain moisturizing compounds such as hyaluronic acid. The water retention properties of Carragelose have been described as excellent and Carragelose forms soft gels in contact with water. Based on these properties, Carragelose is an exceptionally moisturizing substance and, together with its excellent safety profile, a perfect candidate for lubricating eye drops.
Furthermore, the virus-blocking effectiveness of Carragelose might provide the first causative treatment for viral keratoconjunctivitis. Currently, most cases of viral keratoconjunctivitis are treated with antibiotics to treat a potential bacterial infection. Carragelose is a broadly active, topically acting and safe virus-blocking substance, making it a promising candidate for a causative treatment of viral keratoconjunctivitis.
- Clinically validated, excellent safety profile
- Combines moisturizing and broadly active virus-blocking properties
- Promising candidate for a causative treatment of viral keratoconjunctivitis