MARINOSOLV – Solution of hardly soluble steroids in aqueous
formulations suitable for intranasal application
Marinomed Biotechnologie GmbH
in a nutshell
Key facts
• Founded: 2006 as spin-in from the Veterinary
University Vienna
• Location: Campus of the University of Veterinary
Medicine, Vienna
• Workforce: 25 FTEs
• Developed the proprietary MAVIREX, MARINOSOLV
and IMMUVIREX platforms
• MAVIREX based on Carragelose®: Targeting 200
different respiratory virus strains – products are
marketed worldwide via partnerships
Marketed product portfolio*
• MARINOSOLV is a patent-protected technology
platform enabling novel aqueous formulations of
hardly soluble compounds.
• IMMUVIREX: comprises early programs targeting
immunological or infectious diseases
• Excellent IP portfolio
* brands are owned by partners
Innovative biopharmaceutical company focused on anti-viral and immunological
treatments
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MARINOSOLV – Platform technology for
formulation of insoluble locally applied drugs
MARINOSOLV – solving problems - delivering drugs
• What is MARINOSOLV?
• Patent-protected technology platform enabling novel
aqueous formulations of hardly soluble compounds
• Key Features of MARINOSOLV?
• Compatible with applications in eyes, nose, and lungs
• Higher availability and faster onset of action of active
compounds in the target tissues.
3
MARINOSOLV – Platform technology for
formulation of insoluble locally applied drugs
MARINOSOLV – solving problems - delivering drugs
Characteristics of MARINOSOLV
•
Patent-protected technology platform enabling novel aqueous formulations of
hardly soluble compounds
•
Increase of solubility
•
Steroids: 10-200-fold (Budesonide, Fluticasone propionate)
•
Macrolide immunosuppressants: 30-200-fold
(Cyclosporin A, Tacrolimus, Pimecrolimus)
Photo: Rhinocort Aqua (Astra
Zeneca) nasal spray (left) and
MARINOSOLV enabled
Budesonide nasal spray (right).
Source: Marinomed
•
Higher availability of compounds in the target tissues
•
Ex-vivo and in-vivo data in pigs for availability of compound
•
Supportive efficacy data from murine inflammatory lung model available
•
Ready to enter phase II
•
Compatible with intranasal application, formulation contains only well-known
components that are used in the pharmaceutical industry
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Key USPs of the new technology MARINOSOLV
•
Advantages of dissolved compounds versus a suspension
• Intranasal application of dissolved highly insoluble steroids are feasible resulting in
low systemic availability and high local activity
• The availability of the compounds applied as suspension is relatively low resulting in a
late onset of action => dissolved compounds elicit a fast onset of action
• In currently marketed products exemplified by Budesonide or Fluticasone propionate
a huge excess of compound is applied compared to the dissolved proportion of the
API => reduction of the total dose is possible
• With suspensions improper dosing occurs because patients forget to shake the
product
• Combination with other APIs more easy to achieve (e.g. combination with antihistamines)
• Patent protection
• Sterile production with filtration is possible and preservatives can be omitted
• Potential for COGS reduction based on cheaper production processes
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FLUORESCENTLY LABELED ESTRADIOL
AS MODEL SUBSTANCE
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Labeled estradiol ex-vivo, porcine nasal mucosa
Fluorescently labeled estradiol either dissolved using MARINOSOLV or as suspension
was applied onto porcine nasal mucosa (60 min), PBS was used as control for
autofluorescence of the tissue
Solution
Suspension
PBS (autofluorescence)
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STEROIDS – BUDESONIDE AND
FLUTICASONE PROPIONATE
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Increased permeability of dissolved Budesonide
compared to marketed product into porcine tissue
Budesonide dissolved using MARINOSOLV is detected in an increased amount
in comparison to the suspension or a cyclodextrin formulation.
80
Marinosolv
µg Budesonide/g tissue
70
ß-Cyclodextrin
60
Rhinocort aqua 64
50
40
30
20
10
0
0
15
30
45
60
min
Budesonide either dissolved using MARINOSOLV or as suspension (marketed product) or
Budesonide dissolved with cyclodextrins was applied onto porcine tissue (nasal mucosa)
and the concentration of permeated drug was determined over time with HPLC/MS
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Efficacy of dissolved Budesonide versus suspensions
in a murine lung inflammation model
Strong decrease of TNF-alpha production in a murine inflammatory lung model
A dose of 300 µg/ml dissolved Budesonide is more effective than the marketed
product with 1.28 mg/ml suspension when applied 3 hours before challenge
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Efficacy of dissolved Budesonide versus suspensions
in a murine lung inflammation model
Strong decrease of TNF-alpha production in a murine inflammatory lung model
A dose of 300 µg/ml dissolved Budesonide is more effective than the marketed
product with 1.28 mg/ml suspension even when applied 15 minutes post
challenge
11
Increased permeability of dissolved Fluticasonepropionate compared to a suspension into porcine
tissue
Fluticasone-propionate dissolved using MARINOSOLV is detected in an increased amount in
porcine nasal mucosa in comparison to the suspension
Fluticasone propionate either dissolved using MARINOSOLV or as suspension was applied
onto porcine tissue (nasal mucosa) and the concentration of permeated drug was
determined over time with HPLC/MS
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Efficacy of dissolved Fluticasone versus suspensions
in a murine lung inflammation model
Strong decrease of TNF-alpha production in a murine inflammatory lung model.
A dose of 10 μg/ml dissolved Fluticasone propionate is more effective than the
marketed product with 500 µg/ml suspension when applied 3 hours before
challenge
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Efficacy of dissolved Fluticasone versus suspensions
in a murine lung inflammation model
Strong decrease of TNF-alpha production in a murine inflammatory lung
model. A dose of 10 μg/ml dissolved Fluticasone propionate is more
effective than the marketed product with 500 µg/ml suspension even when
applied 15 minutes post challenge
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Summary dissolved Budesonide and Fluticasone
propionate
•
Dissolved steroids are more rapidly bioavailable compared to the
marketed product and Cyclodextrin (Budesonide data) shown in ex-vivo
experiments with nasal mucosa
•
Dissolved steroids are more efficacious compared to the marketed product
as shown in an inflammatory lung model in-vivo
•
Dissolved steroids have a faster onset of action and are even efficacious if
applied 15 minutes after an LPS challenge
•
Stability data available
•
Local tolerability data available
•
Regulatory advice from competent authority available
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Partnering interest for MARINOSOLV
• Enter into a partnership to enable the development of
outstanding intranasal products with clear USPs
• Development of known steroids such as Budesonide or
Fluticasone propionate
• Development of known compounds from other indications
which are currently not used in allergic rhinitis due to
solubility issues
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MARINOSOLV – Solution of hardly soluble steroids in aqueous
formulations suitable for intranasal application
Contact: BD&L
[email protected]
www.marinomed.com