Executive Summary

BUSINESS PLAN

PolyMicrocaps

PolyNanocaps

Executive Summary

The company:

PolyMicrocaps PolyNanocaps is a new familiar owned company devoted to introduce its proprietary patented technology and products to the main application of drug dissolution and drug delivery systems both in the pharmaceutical, veterinary, cosmetic and nutraceuticals field .

Acyclovir Dissolution in Saturated Solutions

0

0,2

0,4

0,6

0,8

1

1,2

1,4

1,6

1,8

2

020406080100120140

Acyclovir concentration (mg/ml)

Absorbance

Serie1

Serie2

Management Team :

CEO / CTO : Claudio Gustavo Cerati (Pharmacist, Litentiate in Pharmaceutical Industry, UBA University of Buenos Aires, Argentina)

Marketing Manager Argentina : Martin Gustavo Cerati

Marketing Manager Brazil : Kleber Oliveira Miranda

Target Market :

More than 50% of the APIs ( active pharmaceutical ingredients) and NCE ( new chemical entities ) developed by the pharmaceutical industry today are poorly soluble compounds . This has been a general tendency all over the years and will grow significantly in the coming years since many patents on drug syntesis of actually marketed APIs are going to expire and also generic drug manufacturers will need to employ economically feasible products , exipients or methodologies to be able to compete with shorter profit margins as market spreads.

Some methodologies leading to the improvement in drug solubilization include chemical or mechanical modification either of the drug by comminution , spray drying or recrystallization or to the exipients added, however, tey own signifcative limitations to the extent they may solubilize insloluble APIs or NCEs ; addition of surfactants or inclusion into cyclodextrins are alternative methodologies for drug solubilization.

Polymer nano and micro particle manufacture present a new and interesting solution , not only for drug solubilization but for drug permeability enhancement as well. Potential biowaiver extensions to drugs included into the BCS III (Biopharmaceutical Classification System III ) are limited to those drugs that can demonstrate rapid dissolution behaviour.

Product and competition:

The R&D mission was to solve an ancient problem related to many areas of the pharmaceutical industry field based in the direct relationship between drug dissolution and bioavailability. First researches made on this subject were made directly onto pharmaceutical products solving dissolution problems in scaled up products. Typical drug dissolution enhancement products rely on sample particle reduction or novel co-polymers like the one described under the trademark of Soluplus by BASF which is basically a graft co-polymer of polyethylene glycol , polyvinylcaprolactam and polyvinylacetate solid dispersions are only achieved by spray drying or coprecipitation which involves the use of organic solvents taken individually for example polyvinylacetate is soluble in a number of organic solvents like:ethyl ether , cetone, benzene, ethylene dichloride, methanol, methyl ethyl ketone , toluene, xylene and amyl acetate , all of them banned in the pharmaceutical industry and with residual limits under one part per million.

They recommend using their product by hot melt extrusion , the same thing happens with the Abbott product marketed Soliqs developed in collaboration with Knoll Pharmaceuticals for a melt extrusion .Typical melt extrusion process is carried on in a range of temperatures from 30C to 300C , being most common process temperatures in the range of higher ones , the only way to control API degradation is shortening it residence time in the extruder.

Hot melt extrusion process is not a common one process that can be applied in a small or medium sized pharmaceutical company and also is extremely dependant on technological constraints of the piece of equipment used.

Other commercial product which is looking for a place in the market is the one known as Solubest comprises a two step process in which the drug must be prepared as an homogeneous solution or suspension of the lipophyllic API and at least two different polymers in a mixed organic solvent-water system the second step is comprised by the well known methodology for the obtention of spherical particles and hollow spherical micro particles called spray drying , key parameters for achieving good results in terms of homogeneus size dispersion of the final solid micro spheres rely on the spray drying equipment and process parameters.Main advantages of improved API dissolution could be: drug dose reduction better bioequivalence , drug dosage reduction with the same pharmacological outcome reducing the risk of toxicity .

With few future pharmaceutical NCE (new chemical entities) in the pipeline of the

new API manufacturing companies it seems to be extremely important to adopt a solubilization technology at any point in the supply chain either in the very first point supplying the drug in a solubilized form with a higher final price or as a drug solubilization solution to the final user . This opens up two different commercial possibilities with very different final customers both of them very interesting and with high possibilities of growing business in the near future.

Solubest has yet signed an agreement with Dr Reddys for the application of their technology at the end of the syntesis process. In this occasion, Mr Zalcenstein CEO of Solubest said:

Were seeing a lot of competition in the solubility enhancement market, but at the same time demand is growing exponentially. With more and more new compounds in discovery, the problem of insolubility is becoming ever more acute,

Nearly 75% of the APIs in the preclinical stage (3900 NCEs) 75%

Fail in the preclinical stage and only 25% are promoted to phase I (1300 NCEs) 39% of those 1300 NCEs (507 NCEs) have poor drug solubilization properties

Number of products (NCEs) :

Font: www.pharmaprojects.com

As it could be seen , unless the total number of drugs out of the syntesis pipeline has continually been growing over the last ten years, 90% of the active ingredients are considered to have low aqueous solubility implying that PolyMicrocaps PolyNanocaps solubilization product and technology could have a potential impact up to that percentage of R&D of NCEs . The hydrophobic nature of NCEs forces the companies to make a research in the aim of obtaining and patenting different salts of the NCEs in the aim of identifying one of those salts presenting a similar safety margin than the base drug and better solubility-bioavailability . This screening process increases the yet high R&D expenses , also, the increase in the number of poor soluble drugs on the market (40% approximately) exhibits poor dissolution kinetics which leads to sub optimal bioavailability detected by a poor physician and patient perception and detected in vitro through dissolution tests carried on final product on market leading to the obligation of voluntarily recalling the product from market ; recently (30 september 2010 ) Sanofi Aventis Argentina had to recall four Coaprovel product lots (Ibesartan Hidrochlorothiazide) because of lack of acceptable dissolution profiles which forced the argentinian health authorities ANMAT to emit a warning message to the patients avoiding the use of the interdicted lots of product.

Font : http://www.anmat.gov.ar/Comunicados/Coaprovel.pdf

Taking a look at the comparative NCEs pipeline both of them show that only about 25% of them pass from preclinical to Clinical phase I

Font: http://www.pharmaprojects.com/therapy_analysis/annual-review-2010-mechanisms.htm

Taking into account the poor prospects observed in the previous graph and the fact that RD efforts are much more expensive , drug solubilization can afford savings up to U$S 18.5 billion by 2015 with an anual growth rate of 10,7% ( if solubilization techniques like the one offered by PolyMicrocaps

PolyNanocaps are used) increasing the potentility of NCEs with an expected increase to U$S 86,0 billion by 2015 , which represents a growthrate of 31% adding extra revenues to the pharma biotech industries.

The impact of dissolution technologies like the one offered by PolyMicrocaps

PolyNanocaps in the different phases of product lifecycle can be divided into three , the first one is the impact on the discover phase when used during preclinical efficacy and safety studies enhancing bioavailability and enabling NCEs for improved safety profiles and passing to Phase 1,2 and 3. Once in the Development phase, PolyMicrocaps PolyNanocaps can enable the provision of patient friendly dosage forms delivering large doses in small volumes and finally during life cycle of the product minimizing compliance issues like the one faced by Sanofi Aventis previously described.

Talking about the future trends and micro and nano manufactured drug delivery systems (DDS) it is expected a big growth starting in 2011 with the association of both micro and nanocarriers included or not into controlled release drug delivery systems which is expected to grow to a final revenue of U$S216 billion by 2015 with an average annual growth rate of 68% from 2012 to 2015 as can be seen in the following graph:

Series 1 refers to micro and nano enabled DDS whilst series 2 are referred to conventional DDS

Funds Requested:

PolyMicrocaps PolyNanocaps have invested all available personal assets into the product development and particular applications to APIs yet in the pharmaceutical market and operations to date. The need for capital is in the context of starting up and expanding manufacturing operations to a global level either in multinational and national pharmaceutical companies at three levels:

Level 1: API manufacturing companies

Level 2: Generic Manufacturing companies (OTC and ethic pharmaceutical manufacturing companies)

Level 3: Biotech Manufacturing companies

In order to comply with the objective described in Level 1 and Level 2 points and permeate the actual product dissolution market described previously with the introduction of the PolyMicrocaps PolyNanocaps technology , management team is seeking a $ 500000 equity investment for suggested 30% ownership of the company. All terms of financing are negotiable in order to meet the financial requirements of the investor.

Use of Proceeds:

Setting up a manufacturing area (pilot plant and process area)

Setting up a multipurpose( quality control/R&D) laboratory intended for subsequent process validations, QC of starting materials and R&D purposes.

Patenting ,Advertising and Promotion Projected Cost:

Technical magazines

Congresses and Conventions

Financial Projections:

Euros

2011

2012

2013

2014

2015

Equity (investment)

100000

100000

100000

100000

100000

Total Revenue(product sale royalties)

20000

40000

80000

90000

140000

Gross Profit(revenue cost of sales)

11000

20000

68000

85000

125000

EBIT

9000

16000

55000

78000

110000

Net Income(loss)

(91000)

(84000)

(45000)

(22000)

10000

Employment

10

20

30

40

40

Exit:

The company will attempt a public offering based on 2015 and upcoming year earnings.

Product and Services:

The PolyMicrocaps PolyNanocaps technology was presented under a Secrecy Agreement to Colorcon (US branch) for coating applications , samples of different products of the coating line were forwarded to them and tests were run at the New Jersey facility.

The PolyMicrocaps PolyNanocaps technology was presented under a Secrecy Agreement to ISP (Brazilian Branch) for drug dissolution applications. Copies of both documents can be found in the annex of the present document.

A licencing opportunity arises with the firm QuantiQ (Chemical Branch of Ipiranga) agreements with this company are under way.

The PolyMicrocaps PolyNanocaps product dissolution effectiveness has been largely evidenced by testing onto pharmaceutical commercial products and evidenced by dissolution profiles of insoluble drugs included in very different pharmaceutical dosage forms like : tablets, controlled release tablets, osmotic drug delivery systems, injectable controlled release DDS.

With scientific credibility , the product will not only build its position in the 10000 euros net income earning planned for 2015 year but will also strengthen its transition into a novel route of administration of drugs and products derived from the biotechnology pipeline such as it is the pulmonary route gaining access to the Level 3 companies described previously (Biotech manufacturing companies) with dry powder inhalation systems (DPI) .

Target markets yet detected were those described under the Level 2 (commercial pharmaceutical OTC and ethic products). A more broad expansion of PolyMicrocaps PolyNanocaps technology can be achieved through a join work with APIs manufacturing companies.

Uniqueness:

PolyMicrocaps PolyNanocaps technology and the formulations derived from this technology not only give an alternate solution to improving dissolution of highly lipophyllic or insoluble drugs but also acts in conjugation with low molecular drugs which prolongs their in vivo activity through increasing the half life of APIs .

Future research will be focused on the selective toxicity when antitumor agent APIs are going to be vehiculized using the PolyMicrocaps PolyNanocaps technology which the owners think have a big potential based on previous scientific research made in recognized universities in the field of polymer conjugation and its application to drug delivery using single polymers included into products obtained using PolyMicrocaps PolyNanocaps technology.

An active research field is yet open in the field of inhalation therapy were the PolyMicrocaps PolyNanocaps technology can be of a great use for the vehiculization of therapeutic proteins or peptides by the inhalation route taking into advantage the aerodynamic properties of these particles.

An important unique feature which distinguishes PolyMicrocaps PolyNanocaps technology from other dissolution enhancers is the fact that it doesnt require strong conditions such as those presented in hot melt extrusion to act as an effective API solubilizer independently of the variability in equipments since only a gentle mixing is needed.

As an example of Class IV , pharmaceutical active , hydrochlorothiazide is well known for presenting low solubility and low permeability as well .Albendazole is a very low solubility API whose dissolution properties can be enhanced through nanoencapsulation using PolyMicrocaps PolyNanocapstechnology.

Micro and nanocapsules of active drugs can be vehiculized in oral drug delivery systems , injectable delivery systems or inhalatory drug delivery systems as can be seen in references 2 and 4 ( mometasone and salbutamol microparticles adhered onto inhalable lactose particles ) .

Inhalatory use of Polymicrocaps micro and nanocapsules allows not only for a more readily soluble and permeable form of the drug but also a way of achieving uniformity in a solid mix of a few milligrams.

Inclusion of those nano and microcapsules into polymer matrix systems allows for an easy way of obtaining a sustained release formulation and at the same time achieving dissolution results on each dosing interval. This situation could be particularly interesting in class IV drugs since their low aqueous solubility and permeability can be overcomed by encapsulating them into micro and nanocapsules.

Remembering that only biowavers are granted only to those actives that are formulated as immediate release dosage forms and have also high aqueous solubility and high permeability (Class I).

It is also known that the absorbed dose fraction of a drug is determined by the dose-solubility ratio , oral absorption of class II drugs from the biopharmaceutical classification system would be strategically enhanced by adequate choose of excipients that can increase their aqueous solubility, NSAIDs analgesics like naproxen and ketoprofen are included into class II type of active pharmaceutical ingredients.

Dramatically increase in both naproxen and ketoprofen can be obtained by vehiculizing them into Polymicrocaps nano and microcapsules as can be seen in photomicrographs of references 3 and 6.

The importance of the interaction between APIs and pharmaceutical grade Excipients has been described by several authors not only regarding to drug dissolution but drug permeability as well .

Dissolution rate of a drug is a function of aqueous solubility and particle sizes, where diffusion coefficient of the API into the dissolution medium and particle surface are the most important factors to be taken into account .

Solid dispersions and solutions can be obtained through the interaction of appropriate excipients and APIs being directly related to the ratio excipient-drug.

A solid dispersion implies that not all the particle surface is amorphous leaving crystalline places or showing an amorphous surface while the internal part of the particle continues to be crystalline this is the reason why we talk of a solid solution and not a solid dispersion .

Whole amorphous solid solution obtained by the use of PolyMicrocaps PolyNanocaps technology assures whole amorphycity and thus reproducible dissolution speed .

PolyMicrocaps PolyNanocapsdissolution technology has been tested in many pharmaceutical products in Latin America (Argentina, Brazil and Colombia) with excellent dissolution profiles.

The basic ingredients of PolyMicrocaps PolyNanocaps technology are readily available from well known pharma excipients suppliers (ISP corp. for example).

Purchasers of the Product

Market Analysis

Antiretroviral Drug Market:

Some antiviral drugs like acyclovir are used in big concentrations since it has been described that acyclovir absorption from the GI tract may be a saturable dose dependant process (Bridgen,D. Fowle,A. Rosling,A, Developments in antiviral therapy, Academic Press, 1980, p.53-62.)

(Vergin, H. Kikuta, C. Arzneimittel-Forschung-Drug research 1995,45,508.)

However when vehiculized into PolyMicrocaps PolyNanocapsmicro and nanocapsules its dissolution behavior changes as can be observed in the following graph:

Acyclovir active drug

Acyclovir PolyMicrocaps PolyNanocaps

This is an specially complicated experimental situation which is encountered in many in vitro antiviral assays were high concentrations of drugs, viruses and cells are co incubated , the sensitivity of virus to non antisense varies depending on the nature of the virion proteins , trying to identify those oligonucleotides that work via antisense mechanism has been difficult and difficult to know whether those mechanisms are dominant in vivo resulting in antiviral activity. This is the case observed for HIV, herpes simplex and influenza.

Adsorption of proteins onto Acyclovir PolyMicrocaps PolyNanocaps

micro and nanoparticles , adsorption leads to improved performance in terms of activity and selectivity with respect to that shown by lipases adsorbed onto no nano structured carriers as well as increased enantioselectivity and pH and thermal stability ( Iseult Lynch, Kenneth A Dawson UCD Bio nano institute , University College Dublin, NanoToday Feb-Apr 2008 , Vol 3 , Number 1-2).

Concluding Remarks:

The market for antiretroviral drugs is expected to increase from $7.1 billion in 2005 to $10.6 billion by 2015, as new antiretrovirals are launched and the number of HIV-positive people increases, according to a report released on Thursday by the market research company Datamonitor .

Antihypertensive Drug Market:

Hydrochlorotiazide is a diuretic drug usually associated with antihypertensive drugs , like Valsartan , Ibesartan . In this last case ,it was necessary to develop a double layer tablet since the pH of the environment of Ibesartan was altered to allow for a better dissolution of it and this accounted for a dissolution problem for Hydrochlorotiazide as could be seen from the in vitro dissolution tests that conducted sanofi Aventis to recall four Co Aprovel product lots from the argentinian market.

If both Hydrochlorotiazide and Ibesartan should be

enclosed into PolyMicrocaps PolyNanocaps they wouldnt have the necessity of adding either alkalinizing agents to dissolve Ibesartan or a double layer tablet to avoid dissolution problems with Hydrochlorotiazide which in fact couldnt be solved by this mean.

The world hypertension market generated over $25 billion in 2004, with steady growth from the previous year. At that time revenues in the world hypertension market expected a grow to nearly $30 billion per year by 2010. This market is one of the largest and most important in the pharmaceutical industry. Furthermore, the treatment of hypertension is a central part of cardiovascular healthcare . It is expected to exceed $50bn by 2015, with novel treatments , however there exist significant hurdles and it is an advice that pharmaceutical companies must remain in expectation regarding marketing and pricing structures for their products since only the most aggressive companies will survive.

Antiinflamatory Drug Market:

Cox 2 type drugs show all low water solubility , in the case of Valdecoxib, a 50% fold increase in dissolution could be observed when compared PolyMicrocaps PolyNanocaps with the original Valdecoxib API (Glenmark Pharmaceuticals Inc.). Valdecoxib shows a UV maximum abosorption at 204 nm in water from which both products can be compared.

Valdecoxib solubility enhancement in the presence of PEG polymers was yet described by several researchers (Cheng

Sheng Liu , Journal of Chemical and Engineering Data,2005, Vol5 , N5 pp1736-1739).

The market for anti inflammatory drugs and specially those named NSAIDS was approximately $31,1 Bn by 2005 and at that time it was expected to grow to $48 bn by 2010, however the anti inflammatory market was dramatically shaken in 2004 with the withdrawal of Mercks multibillion drug Vioxx (Rofecoxib) followed by the withdrawal of another Cox 2 product : Pfizers Bextra leaving only one Cox 2 , Clebrex in the US pharma market.

Turning to the corticosteroid anti inflammatory market , each year 67 million prescriptions are written despite their multiple recognized side effects . For example in 2007 the combined annual sales for corticosteroids totaled $7,4 bn without including generics. Approximately 1,3 million people only in the US have rheumatoid arthritis with a drug market expected to reach $16 bn by 2010.

Mainly all dexamethasone formulations need

To be solubilized by inclusion into hydroxypropyl beta cyclodextrins complexes generally with a stoichiometric relation of 1:1, however, preparation methods influence the physicochemical properties of the final product when tested in different dissolution media which lead to partial dissolution and differences from lot to lot.

Antiparasitic Drug Market

ALBENDAZOL NANOCAPS

Albendazole is an antiparasitic drug owing both local and systemic action with low water solubility and bioavailability conducting to intra and inter variabilities. Albendazole dissolution is the limiting step in drug absorption, albendazole

PolyMicrocaps PolyNanocaps solves this problem .

Alternative Health Care Segment:

Dry Powder Ihalers (DPI)

represent a growing segment of inhalatory therapy with a rapid move from conventional MDI (metered dose inhalers) CFC or HFA propelled , to DPI in the next years. On finishing existing patents in his area , the possibility for generic manufacture raises with a big hope of success .

Marketing Plan :

Marketing strategies : The key benefit is that conventional drug dissolution helpers are exipients which attempt to obtain a solid dispersion of the insoluble drug typically using high amounts of the it and strong process conditions (melt extrusion) while PolyMicrocaps PolyNanocaps uses mild conditions and common piece of equipment usually found in Pharma companies.

Present and future product studies support this marketing strategy .

The company has already been approached by a technical marketing commercializing firm in Brazil ( QuantiQ) which whom strategies were developed for the local Pharma market and suppliers of the raw materials needed for product manufacture.

Marketing the PolyMicrocaps PolyNanocaps solubilized drug enclosed into a direct tabletting exipient for a Ready to Use material were the client only will have to dose it into the final dose form depending on which potency he requires.

The Ready to Use drug powder is a very attractive possibility but it means a jump from the regulatory point of view since it is not only an exipient product but a semi manufactured one to which general finished product analysis such as those described in the European Pharmacopoeia should be applied.

The company will create its own competition by developing sided trademarks and product labels for particular Drug Delivery Systems. For example when the drug to be solubilized using the PolyMicrocaps PolyNanocaps will be enclosed into an Osmotic Delivery System , it will be commercialized under any other trademark other than PolyMicrocaps PolyNanocaps.

This technology has also a broad application in Pharmaceutical Nanocoating Technology were some brands are yet being considered under Secrecy Agreements by multinational Pharma exipients companies.

With the companies described previously the trademark PolyMicrocoat was yet introduced and is actually undergoing tests .

Main advantages of the use of nanocoatings are: A) less working temperature B) less quantity of material for the same coating coverage C) better finishing of logo tablets.

Based on some special properties these nanocoatings have, an open portfolio of products were developed as follows:

PolyMicrocoat II : Introduction: As a result of the strong interaction found in nanomaterials, an improvement in the physical characteristics of film coated tablets could be obtained compared to Opadry II in terms of:

Mechanical resistance

Thermal resistance

Water vapor permeability

PolyMicrocoat Protect : Better moisture barrier than conventional polymer coatings

PolyMicrocoat White 630 : This product line offers all the properties of functional coatings vehiculizing actives obtained by the PolyMicrocaps PolyNanocaps technology into functional coatings which can easily be applied onto pellets or tablets .

In the field of inhalatory products, Inhas phere is a trademark under which inhalatory drugs like : Salmeterol, Salbutamol, Mometasone and future APIs will be commercialized.

It is clear that depending on the application pricing structure will be completely different . Price structure for a general PolyMicrocaps PolyNanocaps exipient Prodotto 1and its application to a formulation :

Solubilization exipients:

Polymersomes

IngredientsCostQuantitiesin Ftion% in formula Total Prod. Cost%Inc

ValdecoxibU$S613/kgValdecoxib50 gr47, 30,65U$S97,76

Exipient1 U$S23/kgExipient1 20 gr18,86 0,43 U$S1,37

Exipient2 U$S8,5 /kgExipient2 31 gr29,20 0,25 U$S0,79

Exipient3 U$S4,8 /kgExipient3 5 gr4,78 0,02 U$S

0,08

TOTALS 106 100 % 31,35 U$S100,0

VALDECOXIB POLYMERSOME FORMULATION COST ANALYSIS

VALDECOXIB POLYMERSOME FORMULATION COST ANALYSIS

Poly

Poly

M

M

icrocaps

icrocaps

Poly

Poly

N

N

anocaps

anocaps

REVENUE (after discounts) u$s 60/kg 100%

COST OF GOODS SOLD u$s 12,5 20,83%

(COGS)

MANUF. COSTS u$s 10,0 16,67%

GROSS PROFIT U$S 22,5 37,5%

SALES & MKT u$s 8,0 13,3%

R&D u$s 5,0 8,3%

G&A general and administrative u$s 2,0 3,3%

TOTAL EXPENSES u$s 15,0 24,9%

OPERATING PROFIT u$s 7,5 12,6%

PolyMicrocaps Profit and Loss Statement

Year 2011

Year 2012

Year 2013

Year 2014

REVENUE

Expected Sales Comm.Units.

600

1800

3500

10500

Unit price (u$s/ kg)

60

Final sales revenue (u$s)

36000

100%

COGS

Total Goods Sold COGS (u$s)

7500

Total Manuf.Costs (u$s)

6000

TOTAL

13500

37,50%

GROSS MARGIN

22500

62,50%

EXPENSES

Sales & Marketing (u$s)

4800

13,30%

R&D (u$s)

3000

8,33%

General and Administrative (u$s)

1200

3,33%

TOTAL

9000

24,96%

OPERATING PROFIT

4500

12,54%

Financing beyond Nanochallenge:

In the area of Campania there exists the chamber union which assist small and little sized companies in getting more competitive capacity and innovation. This union chamber provides the information about financing opportunities , legislation and politics.

It also assists companies in individualizing and selecting new international or European partners.

SALES PROJECTIONS & MARGIN ANALYSIS

Prodotto Uno

12-Oct-10

Mese 1

03:36 p.m.

Ene-11

Unit

s.k.u. 1

1.000

s.k.u. 2

300

Totale Unit

1.300

Prezzo

s.k.u. 1

130,00

s.k.u. 2

180,00

Fatturato

s.k.u. 1

130.000

s.k.u. 2

54.000

Totale Fatturato

184.000

Percentuale sul Totale

71,0%

COGS

Costo Unitario

s.k.u. 1

37,00

s.k.u. 2

48,00

Costo Materie Prime

s.k.u. 1

37.000

s.k.u. 2

14.400

Totale Costo Materie Prime

51.400

Profitti (0% del fatturato prodotti)

0

Totale COGS

51.400

GROSS MARGIN

132.600

Gross Margin % del Fatturato

72,1%

Marketing Function:

Promotion:

The pharmaceutical market is a regulated environment were promotion can only be done at the technical level through communications or poster expositions .

Advertising in technical newsletters or journals is other way to reach these people

Regulatory Health Hazard Analysis:

Operations:

All manufacturing facilities must comply with the joint IPEC- PQG Good Manufacturing Practices Guide for excipients . Sales projections predict a growth in sales of 25% which runs in accordance with the predicted necessary expansion of the production site and the funds needed for this expansion.

Product:

Product clockspeed can be analyzed taking into account the three different product lines proposed :

A) SOLUBILIZATION EXIPIENTS

B) FUNCTIONAL COATINGS

C) SPECIALIZED APPLICATIONS ( INHALATORY, ANTICOUNTERFEITING)

A) Solubilization exipients PolyMicrocaps PolyNanocaps:

These times can be adjusted in order to reduce the medium and lengthy clockspeed ones which could have a biggest impact in warehouse area needed to support the production volume expected.

B) Functional coatings PolyMicrocoat :

Functional coatings can occupy a less warehouse surface area based on shorter production times smaller expected production volumes.

B) Specialized applications PolyTcoat Inhas phere :

Smaller volumes of these products are a counterpart of their specialized use an in the special case of inhalatory application products , special warehouse conditions must be achieved related to humidity and temperature conditions.

Developing partnerships with companies working in the area of Campania and dealing with Pharma distribution and stocking can solve the problem.

Partnerships can also be developed with base materials suppliers like ISP ( International Specialty Products) with whom , PolyMicrocaps has already signed a confidentiality agreement for the joint venture develop of new special polymer products.

Process (Unit process ,Technology, Equipment ,Production System):

PolyMicrocaps PolyNanocaps production is an unitary process carried on in a closed reactor with a direct output to a dosator and final pachakging

Main process is carried on onto a Comasa Italy reactor for semi solids :

COMASA S.R.L. Va Enrico Sartori, 6/A | ( 43100 ) Parma (PR) - Italy Tel: + 39 - 0521 - 709011 | 621255 Fax: + 39- 0521- 705619

Semi solid reactor developed and constructed by Comasa Italy consist in an unit process reactor with an advanced process control technology.

The research interests belongs to the area of drug delivery. In particular, the most studied approach is the polymer conjugation to low molecular weight drugs or therapeutic proteins. The aim is to obtain conjugates with a prolonged in vivo activity that can be safely used in clinic. Polymer conjugation offers the possibility to prolong the plasma half-life of therapeutically active agents by increasing their hydrodynamic volume and hence decreasing their excretion rate from the body. Furthermore, polymer chains can prevent the approach of antibodies, proteolytic enzymes or cells to conjugated molecule.

The presently ongoing projects can be summarized as follows:

- Synthesis of antitumor-polymer conjugates. Particular interests are focused in development of new method for controlled drug release and in the exploitation of targeting residue to allow selective cytotoxicity of the carried drug.

- Studies of high loading polymers for the delivery of increased amount of drug molecules.

- Development of new polymers as potential alternatives to poly(ethylene glycol), PEG. Presently we are investigating polyacroloilmorpholine, polyoxazoline, poly glutamic acid, hyaluronic acid.

- Studies on new protein-polymer conjugates. The research is focused in the development of conjugates with new polymers and with new method of coupling, either chemical or enzymatic approach are investigated.

- Development of microparticles releasing growth factors for the development of tissue engineering biomaterials.

Status and offering of the company

Turning again to the state of the current pipeline, we see some reasons for cheer, and others for fear. Let us look at the clinical stages of development first. Figures for all Phases are up, which is encouraging given the economic circumstances. The rise at Phase II is not insignificant, at 7.9%. However, two points should be made which might temper our enthusiasm at this point. Firstly, as has been the case every year in the past decade, the increases seen at Phase I and Phase II have not fed through to a significant increase at Phase III. While one would expect considerable attrition between Phase II and Phase III, the fact is that an extra 22 compounds at Phase III, compared to an extra 134 at Phase II, is frankly disappointing. This is better than in some years though, when the Phase III figure remained resolutely flat. However, the increase is exactly cancelled out by fewer drugs at the pre-registration phase. Taken together, this would indicate that any explosion in the number of new launches should not be expected any time soon.

Trends in preclinical drug development are always more difficult to divine. The annual figure is more volatile, and subject to both changes in reporting practices by the industry, as well as editorial practices by the drug database. The drop seen this year might appear concerning, but it is worth pointing out that the 2010 figure is still above that seen in 2008 (not shown), and that the variation is probably not very significant. The fall this year may well be largely due to improved editorial practices here drug records have been examined more rigorously and more regularly over the past year, with the likely effect that a greater number of preclinical drugs will have been discovered to have been dropped or designated 'No Development Reported'.

Next we move to our annual league table of pharma companies, arranged not by amount of market capitalization or sales, but by the reported sizes of their R&D pipelines. Changes in the league table this year really come down to two events the two megamergers which completed towards the end of 2009. Rather unsurprisingly, Pfizer's acquisition of Wyeth leapfrogs the US-based giant to the top of the chart, although its lead over nearest rival GlaxoSmithKline is not as great as might be expected. The other big takeover, that of Schering-Plough by Merck & Co, only moves the latter one place up the ladder. What is interesting is that the Top 3 are now some way ahead of the next tier of companies, making these megapharma concerns something of a 'mini-league' of their own.

How much might some potential oft-mentioned future tie-ups affect things? Any merger between GlaxoSmithKline and fellow UK company AstraZeneca would clearly lift the combined firm way above the competition in terms of pipeline size, leaving aside any divestments which might be required for regulatory authorities to approve such a tie-up. Similarly, any all-Swiss mega company formed out of Roche and Novartis would also be top of the pile, but not by so much. What is striking from this year's table though is that, aside from the two aforementioned big deals, there has been relatively little M&A activity in the upper echelons of the industry, leading to a table remarkably similar to last year's. The only entry into the top ten is Bristol-Myers Squibb, which climbs in by dint of its takeover of Medarex. Only two companies in the top ten have seen a decrease in their pipeline sizes this year, indicating further growth in the really big companies with portfolios of over a hundred compounds.

In the remainder of the table, there is a notable preponderance of Japanese companies, accounting for nearly half of the other 15 places. Mergers or hook-ups between almost any of these companies would create a debut Japanese top ten pharma company, indicating that this market might be an interesting area to watch in the coming years.

With bigger pipelines in the Top 10 companies, are we seeing further concentration of the R&D effort in these giant multinationals? If this is the case, it is also true that the long 'tail' of small companies at the other end of the scale has also grown. Graph 3 shows the overall number of companies with active pipelines this year, and is perhaps the most optimistic piece of data to be found in this review. It shows another big increase in the number of firms operating in this space, with the figure of 2,207 representing a 5.9% increase from last year. The past five years have shown consistent growth in this metric. The growth, as in previous years, is attributable to the increasing numbers of small start-ups entering the fray. If we take the companies with just 1 or 2 drugs in their pipeline as being in all likelihood mostly start-ups of emerging niche companies, we can see that there are a massive 991 companies currently reported which fit this description, up significantly from the 2009 figure of 836. This would indicate that despite the harsh economic conditions and dearth of funds available to borrow, the pharmaceutical industry is still producing a steady flow of companies entering its space which is far outweighing the rate of acquisition. So with more drugs in the biggest companies' pipelines, and more companies with small pipelines, it seems the squeeze must be occurring somewhere in the middle.

Top therapies - cancer peaking?

...for the first time in the nearly twenty years over which we have been conducting these analyses, the inexorable rise of cancer R&D may have stalled...

Moving to the changing therapeutic focus of the industry's pipeline, Graph 4 represents this broken down by therapeutic group (note that if a drug has activity in more than one therapeutic group it will be counted in both). This shows that, for the first time in the nearly twenty years over which we have been conducting these analyses, the inexorable rise of cancer R&D may have stalled. With 2,608 drugs, it is still the biggest therapeutic area, but this year 26.8% of drugs in R&D have some anticancer activity, compared to 28% last year. Cancer has been taking an ever bigger piece of the action, so it will be interesting to see if this is a blip or whether we have reached a limit on how large a slice of the R&D pie cancer can take.

The runner-up of the therapeutic groups remains neurological, whose share of R&D is roughly unchanged from last year (19.9% compared to 19.8%). In third place, anti-infectives have posted a 0.8% increase to 17.6%. Interestingly, 23.9% of drugs in the pipeline can be categorized as biotechnological agents another share which has been rising year-on-year but appears to be approaching a plateau

Most of these trends are also reflected in the Top 25 table of the 219 individual therapeutic categories used to classify drugs in Pharmaprojects/Pipeline. This reveals the first ever declines in the two biggest anticancer categories, while upturns in vaccine development and antivirals appear to be contributing to the rise for anti-infectives. One of the big growth areas of recent years, antidiabetics, continues to increase, despite, as mentioned earlier, an increasingly-crowded marketplace. Other noteworthy trends in the table include the continuing decline of asthma R&D, which was in the top ten two years ago; similarly gene therapy is just hanging on in the Top 25. At its peak, gene therapy actually reached the number three position, its demise since testament to the failure of this strategy thus far to deliver tangible results on its early promise.

Top mechanisms of action (pharmacologies) few changes

Table 4 shows the Top 20 mechanisms of action (pharmacologies) employed by drugs in the May 2010 R&D pipeline. This table is, as ever, dominated by the broader categories used in the classification and is headed by the general 'Immunostimulant' category which is applied to most vaccine programmes. Following on from this are three categories in the top five which encompass a range of anticancer drug development strategies: Angiogenesis inhibitors, Apoptosis stimulants and Cell cycle inhibitors. The mechanism of action classification we use has undergone considerable revision and improvement this year, but despite this, there is very little movement in the table. The total number of mechanisms of action in use in the database now stands at 2,131, up very slightly from 2,122 last year.

A better measure of the level of innovation in drug development strategies can be gleaned from looking at the number of protein targets which drugs are designed to act upon, and particularly how this figure has changed in the past year. This now stands at 1,849, indicating that 97 new drug protein targets have been identified in the past twelve months. This is comparable to the previous year's increase of 102 new targets. So although there is no slowdown in innovation as measured by this metric, the once-expected surge in new targets which it was hoped would follow on from the completion of the Human Genome Project still seems to be waiting in the wings.

Weathering the storm?

...it is certainly a fascinating time to be following pipeline R&D, and as ever, Citeline Drug Intelligence will be there at the cutting edge, providing the data and trends for the industry...

Although many positions have been axed from the pharmaceutical industry in the past year, it would appear that R&D pipelines, have at least so far, survived relatively unscathed by the financial crisis and economic woes of the rest of the world. Although pipeline expansion might have slowed, innovative drug launches were scarce and the number of late-stage R&D drugs still looks a bit paltry, the fact is that there are more drugs in total, more drugs in clinical trials, more drug targets and more drug development companies than ever before. Compared to other industries, it would appear that pharma might be successfully weathering the storm thus far.

However, dark clouds may be gathering on the horizon. With the recession in developed countries having largely bottomed out, many economies now have to turn to the mountains of debt which have built up during the crisis, and cuts sometimes on an unprecedented scale are forecast. In many countries, talk of cutting of healthcare budgets is considered politically very risky, as the recent UK election campaign has keenly demonstrated. However, it is nave to think that that some of the cost-savings needed will not be sought from national pharmaceutical bills. This will pile further pressure onto an industry already facing loss of revenues from patent expiries and a blockage in the pipeline at Phase II. What the industry really needs to do is reduce attrition at Phase II via better candidate selection earlier on. If it cannot achieve this and our data this year indicates that there are few signs of improvement in this area as yet - it might then face a stark choice. With budgets for sales and marketing already pared back, should it scale back R&D to further cut costs, thereby running the risk of squeezing the supply of new products which are its lifeblood? Or should it play the long game and continue to spend heavily on its pipelines to ensure future growth? Will it try to get the best of both worlds via further mergers and acquisitions, despite their historically questionable benefit on return on investment? Whichever way the industry turns to protect its profits, it is certainly a fascinating time to be following pipeline R&D, and as ever, Citeline Drug Intelligence will be there at the cutting edge, providing the data and trends for the industry as they emerge.

Pharma R&D Annual Review 2010

Thirty years of tracking drug R&D

...the database was almost entirely dependent on the goodwill of certain individuals...

May 1st 2010 marks thirty years since Citeline Drug Intelligences first pipeline database product, Pharmaprojects, was published. A major innovation, this was the first time that anyone had attempted to collate and organize data on pharmaceutical R&D pipelines. The world in general was a very different place in 1980. The story of how things have changed is not just one of a radically different pharmaceutical industry, but one of unforeseeable changes in the way information is reported and in how the data collected is then delivered to the subscriber.

In 1980, although Pharmaprojects was held on a rudimentary database, this was used to produce a print-only product, redolent of an old-fashioned encyclopaedia. Printed updates were issued monthly, with a complex index system directing the user to the most recent version of the drug entry. It was cumbersome, slow, and used an awful lot of trees. Now, the Pharmaprojects data in its most advanced offering, Pipeline, is not only available online but is updated in real-time, instantly. A neat encapsulation of the technological revolution we have all felt the benefit of if ever there was one.

As for the data included in Pharmaprojects and its collection, this has undergone a similar revolution. With no internet in 1980, company Annual Reports were often the only sources of reliable pipeline information and they of course only came out once a year. Whilst certain journals and conference abstracts were also scanned (in their physical form, naturally), a major source of information for those early editors were so-called 'Company returns'. Here, a print-out of the drug information held by Pharmaprojects for each company was mailed to it, and the firm was asked to mark-up any updates or changes to be made. These were usually returned to us in the form of handwritten annotations. So the database was almost entirely dependent on the goodwill of certain individuals at the one in three pharma companies who graciously updated the information for us. Now, most companies regularly update their pipeline information directly on their web sites, and various tools ensure that we never miss even the smallest update. Again, the pace of dissemination of information has become instant.

And what of the pharmaceutical industry itself? The shifts have been no less seismic. Although issue 1 of Pharmaprojects has unfortunately been lost to posterity, there were around 1,000 drugs in the entire industry pipeline then barely a tenth of those seen today. There were also fewer than 500 companies, and those that there were operated primarily at a local level, with few of the multinationals seen today. Rational drug design, high-throughput screening and finding druggable targets from the human genome were great ideas rather than common practice, and we were still two years away from the first drug produced by recombinant DNA technology hitting the market (Lilly/Genentech's Humulin). The pace of discovery since has been astounding and the achievements of the industry manifold. Millions of lives have been saved as a result of its products. And yet companies seem to be continuously in crisis and having to adapt rapidly to survive.

It would probably be very foolish to attempt to speculate on how things will look in a further thirty years. Much has been made of increasingly personalised medicine, but this remains a potentially double-edged sword for the industry better drugs but with smaller markets. Spiralling healthcare costs, an aging population, more lifestyle-related diseases and further information technology revolutions are all issues which represent a mixture of challenges and opportunities for pharma R&D. Yet as ever, one feels that the pharmaceutical industry will continue to evolve in response to a changing world, and will also continue to have a hugely positive impact on human society.

riginally formulated as a liquid-filled capsule. Although it worked as a drug product, it required multiple doses per day, had gastrointestinal side effects, and needed refrigeration.

In 2005, Abbott launched an easier-to-use tablet form created by Soliqs, its drug delivery business unit in Germany. Soliqs began as a collaboration between BASF and Knoll Pharmaceuticals, a former BASF unit that Abbott acquired in 2001, to develop a melt extrusion technology now called Meltrex. Today, Soliqs also works with outside customers, offering nanoparticle and other delivery technologies.

Soluplus polymeric solubilizer is a graft copolymer comprised of polyethylene glycol, polyvinylcaprolactam and polyvinylacetate. This unique structure provides ideal interactions with APIs through hydrogen bonding, leverages stability and enhances solubility of drugs. Soluplus polymeric solubilizer can also be used to prepare solid dispersions by spray drying, melt granulation and coprecipitation.

The R&D mission was to develop a greaseless, odorless, topical cream which was measurably more effective at relieving pain than any other OTC (over the counter) topical product

Read more: Pharmaceutical Company Business Plan - Product, Market, Competition, Marketing, Production, Property and facilities, Patents and trademarks, Research and development http://www.referenceforbusiness.com/business-plans/Business-Plans-Volume-03/Pharmaceutical-Company.html#ixzz11m1yb0LK

Principal Products :

Drug Dissolution :

Coating Technology:

Anticounterfeiting :

Marketing Plan:

Financing Requirements:

Unit process (production) : 1 day (fast clockspeed)

Product analysis : 5 days ( medium clockspeed)

Product liberation: 10 days (slow clockspeed)

Unit process (production) : 1 day (fast clockspeed)

Product analysis : 3 days ( medium clockspeed)

Product liberation: 8 days (slow clockspeed)

Unit process (production) : 1 day (fast clockspeed)

Product analysis : 4 days ( medium clockspeed)

Product liberation: 9 days (slow clockspeed)

_1349590360.ppt

Polymersomes

Ingredients Cost Quantities in Ftion % in formula Total Prod. Cost %Inc

Valdecoxib U$S 613/kg Valdecoxib 50 gr 47, 30,65U$S 97,76

Exipient 1 U$S 23/kg Exipient 1 20 gr 18,86 0,43 U$S 1,37

Exipient 2 U$S 8,5 /kg Exipient 2 31 gr 29,20 0,25 U$S 0,79

Exipient 3 U$S 4,8 /kg Exipient 3 5 gr 4,78 0,02 U$S 0,08

TOTALS 106 100 % 31,35 U$S 100,0

VALDECOXIB POLYMERSOME FORMULATION COST ANALYSIS

PolyMicrocaps

PolyNanocaps

SHAPE \* MERGEFORMAT

SHAPE \* MERGEFORMAT