Download licensing opportunity propylene glycol free minoxidil

Propylene Glycol Free Minoxidil Topical Formulation Licensing Opportunity
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LICENSING OPPORTUNITY
PROPYLENE GLYCOL FREE MINOXIDIL TOPICAL FORMULATION FOR HAIR
LOSS BASED ON PATENTED TECHNOLOGY
•
NO PROPYLENE GLYCOL → NO SCALP IRRITATION, NO GREASY HAIR
•
BIOEQUIVALENT ABSORPTION TRHOUGH THE SKIN COMPARED TO REFERENCE
PRODUCTS
•
NO RESIDUAL CRYSTALLINE PRECIPITATE IN SCALP
•
EASY AND COST-EFFECTIVE PRODUCTION AT A COMMERCIAL SCALE
•
INTELLECTUAL PROPERTY RIGHTS UNTIL 2031
THE COMPANY
Bionanoplus was founded in 2011 and combines the enthusiasm of a young company
with more than 10 years of experience in the nanotechnology and drug delivery fields in
academic institutions. Bionanoplus was born in the spirit of avoiding nanoparticles
industrial scale-up issues that are decisive factors in many project failures. For this
reason, we developed several technology platforms that allow the manufacturing of
stable and homogeneous nanoparticles without the use of volatile organic solvents or
special equipment, thus ensuring a cost-effectiveness and adequate scalability from lab
to final production. In addition, all the materials used in the manufacturing of our
nanoparticles compile with the regulatory requirements and are present as common
excipients in many pharmaceuticals.
The staff of Bionanoplus is formed by 8 people with extensive experience in scientific
innovation and intellectual property management. Backing us up are more than 50
research articles in peer-reviewed journals and 6 patents.
At the beginning of 2013, Bionanoplus was certified as compliant with the principles of
Good Laboratory Practices (GLPs), a new step on the road to excellence on which we are
embarked.
BIONANOPLUS – Pol. Mocholí · Plaza Cein Nº5, nave B14 · 31110 Noáin · Navarra · Spain
Propylene Glycol Free Minoxidil Topical Formulation Licensing Opportunity
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MINOXIDIL & HAIR LOSS BACKGROUND
Minoxidil is the only topical medication approved by the international regulatory
agencies for the treatment of hair loss since the early 1990's. Minoxidil is available in
both 2% and 5% concentrations and has clinically proven to slow the progression of hair
loss and regrow hair after topical application. It is recommended that males use
minoxidil 5% whilst females use minoxidil 2%.
The most common side effect of minoxidil hair loss treatment is the scalp irritation and
redness. All current minoxidil commercial formulations are made with alcohol-based
agents as a media to maintain a stable composition, being propylene glycol the basic
ingredient of these formulations. Propylene glycol is the main cause for scalp irritation
and redness. In addition, minoxidil hair loss treatment side effects also include having
greasy hair that may also be sticky and are hard to manage. Propylene glycol is also the
reason for this wet appearance and oily and sticky to the touch.
Minoxidil needs to be applied twice daily and must be used indefinitely for continued
support of existing hair follicles and the maintenance of any experienced hair regrowth.
Thus, for successful long-term use it is important to avoid uncomfortable side effects
and allow a pleasant use on the cosmetic level.
PRODUCT DESCRIPTION
Bionanoplus’ propylene glycol free minoxidil formulation is a hydroalcoholic solution
with low viscosity suitable for topical use in which all the excipients are approved by
the international regulatory agencies for human topical use. The exact composition of
the formulation is showed in the table below.
% Minoxidil (w/v)
% Gantrez ES
(w/v)
% Ethanol (v/v)
% Carrier (v/v)*
% Water (v/v)
2 or 5
0.75 - 1
50 - 60
10 - 25
Q.S.100
*Information available under a confidential disclosure agreement.
BIONANOPLUS – Pol. Mocholí · Plaza Cein Nº5, nave B14 · 31110 Noáin · Navarra · Spain
Propylene Glycol Free Minoxidil Topical Formulation Licensing Opportunity
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The formulation can be easily and cost-effective produced at a commercial scale with
standard processes of solution preparation. Bionanoplus has scale-up the process from
250 mL to 2 L without any significant technical issue.
BIONANOPLUS’ MINOXIDIL FORMULATION IS PROPYLENE GLYCOL FREE AND STABLE AT
ROOM TEMPERATURE
Bionanoplus’ minoxidil formulation does not contain any propylene glycol and is stable
for at least one year at room temperature in transparent glass vials.
Initial Point
6 Months
12 Months
5.1 ±0.1
4.9 ±0.2
4.9 ±0.1
Transp. No pp. CL
Transp. No pp. SYC
Transp. No pp. SYC
Minoxidil Content
(% by HPLC)
Macroscopical
characteristics*
* Transp= Transparent; No pp = No precipitation; CL= colorless; SYC= Slight yellow color.
This propylene glycol free minoxidil formulation doesn’t produce any scalp irritation
and is significantly less oily and sticky than current commercial formulations. Therefore,
Bionanoplus’ formulation presents both, a safety profile and cosmetic level which
constitutes an unquestionable advantage for the patient using long-term treatment.
NO RESIDUAL CRYSTALLINE PRECIPITATE POST SOLVENT EVAPORATION COMPARED TO
COMMERCIAL PRODUCTS
Minoxidil is somewhat soluble in both propylene glycol and alcohol, but nearly insoluble
in water. Commercial formulations are supersaturated propylene glycol/minoxidil
solutions that even tend to precipitate out some of the minoxidil at room temperature.
Propylene glycol of commercial products evaporates after application and minoxidil
precipitates on the scalp producing an unaesthetic dandruff effect and enhancing
BIONANOPLUS – Pol. Mocholí · Plaza Cein Nº5, nave B14 · 31110 Noáin · Navarra · Spain
Propylene Glycol Free Minoxidil Topical Formulation Licensing Opportunity
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irritation. In contrast, Bionanoplus formulation doesn´t precipitate in a crystalline form
after application and evaporation of the solvent.
Figure 1: Comparison of crystalline precipitation of minoxidil in pork skin post solvent
evaporation between Bionanoplus formulation and commercial products. A) Observation
of minoxidil 5% formulations by optical microscopy. B) Observation of minoxidil 2%
formulations by scanning electron microscopy.
SYSTEMIC EXPOSURE OF MINOXIDIL AFTER TOPICAL ADMINISTRATION IS NOT HIGHER
THAN COMMERCIAL PRODUCTS THEREFORE NO SYSTEMIC EFFECTS ARE EXPECTED
In the 1970s Minoxidil was a drug used to treat hypertension, classified as a potassium
channel opener with effects on expansion of peripheral vascular. For this reason,
another minoxidil topical administration treatment side effect is changes in the blood
pressure and, consequently, minoxidil absorption into the blood after topical
administration must be as low as possible. Despite its higher skin residence time,
Bionanoplus’ minoxidil absorption into the blood after its topical administration is
BIONANOPLUS – Pol. Mocholí · Plaza Cein Nº5, nave B14 · 31110 Noáin · Navarra · Spain
Propylene Glycol Free Minoxidil Topical Formulation Licensing Opportunity
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bioequivalent to commercial products and, in consequence, shows a consistent safety
profile.
Figure 2: Comparison of minoxidil absorption into the blood over 24 hours. Penetration of
minoxidil through the epidermis was evaluated in Franz diffusion cells using fresh pork ear
skin. The absorption grade was evaluated measuring minoxidil levels in the receptor
compartment (similar to blood) over a 24 hours period. LACOVIN® (Galderma) is a standard
formulation of minoxidil with propylene glycol. ALOPEXY® (Pierre Fabre) is a formulation
with gamma-cyclodextrin which enhances the solubility of minoxidil in water and decreases
the requirement for propylene glycol.
REGULATORY AFFAIRS
The legal basis for submission of a marketing-authorization of the Bionanoplus’ minoxidil
formulation is the approved reference listed drugs which contains minoxidil for topic
use.
Bionanoplus’ minoxidil formulation is a hydroalcoholic solution for topical application
with non-active ingredients that differ from the reference listed drug product, thus the
regulation specifies that this difference must be characterized and it has to be provided
BIONANOPLUS – Pol. Mocholí · Plaza Cein Nº5, nave B14 · 31110 Noáin · Navarra · Spain
Propylene Glycol Free Minoxidil Topical Formulation Licensing Opportunity
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information demonstrating that do not affect the safety or efficacy of the proposed drug
product. According to the different international regulatory agencies, there are two
options to provide this information:
1. Results from an in vivo bioequivalence study.
2. A waiver of the in vivo bioequivalence study supported with expert justifications
and/or data from in vitro assays.
Bionanoplus believes that it is not necessary to obtain clinical data and that the second
option would be easier and faster because:
1. The formulation has the same active ingredient in the same concentration and
dosage form as the reference listed drug product.
2. There is a considerable knowledge about the efficacy and safety of the active
substance collected during more than thirty years of topic use for the treatment
of hair loss.
3. All the non-active ingredients are approved by the international regulatory
agencies for human topical use and are currently present as common excipients
in many pharmaceuticals.
4. Minoxidil is a locally acting product that exerts its effect at the site of application.
As in this case, a change in non-active ingredients may influence the safety of the
product modifying the penetration of the active, thus this effect needs to be
carefully investigated. For locally acting well-known active substances as
minoxidil, the international regulatory agencies do not consider necessary full
toxicological and clinical data if it is not expected that the amount of active
ingredient reaching the systemic circulation is higher than for the original
product. An in vitro assay in Franz diffusion cells has shown that Bionanoplus’
minoxidil absorption into the blood after its topical administration is
bioequivalent to the reference listed drug product and, therefore, it is not
necessary to obtain clinical data.
In any case, before submission of a marketing-authorization, it is recommended to
request scientific advice from the corresponding regulatory agency.
BIONANOPLUS – Pol. Mocholí · Plaza Cein Nº5, nave B14 · 31110 Noáin · Navarra · Spain
Propylene Glycol Free Minoxidil Topical Formulation Licensing Opportunity
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INTELLECTUAL PROPERTY STATUS AND PARTNERSHIP CONDICTIONS
Bionanoplus holds the intellectual property rights of this propylene glycol free Minoxidil
topical formulation worldwide in the patent PCT/EP2012/056900 (priority date
15/04/2011). The second written opinion of the International Preliminary Examining
Authority (April 2013) has established novelty, inventive step and industrial applicability
in all the key claims.
Bionanoplus seeks to license the further development and commercialization of its
minoxidil formulation for hair lost treatment.
The ideal partner would be:
•
A company with a strong therapeutic focus in the dermatology market.
•
Willing to commit investment to develop the product worldwide.
•
Marketing experience with capacity to put on the market place the product
directly or through alliances.
Bionanoplus is open to different format of partnering modalities including:
•
Worldwide exclusive licensing.
•
Country based exclusive licensing.
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Opt-in rights + research fee.
CONTACT DETAILS
Hesham Salman
Ricardo Palacios
CEO
Business Development Manager
[email protected]
[email protected]
BIONANOPLUS – Pol. Mocholí · Plaza Cein Nº5, nave B14 · 31110 Noáin · Navarra · Spain