paolo colombo, ceo info@plumestars.com plumestars srl

Paolo Colombo, CEO

info@plumestars.com

PlumeSTARS srl

2. There are 7.000 Rare Diseases in the world 25-30 M Americans live with a rare disease.

To cure these diseases orphan medicines are required.

The BIG IDEA!

To develop novel medicines to cure rare diseases by repurposing known drugs in innovative delivery systems.

3. Problem / Market Opportunity

• Mesothelioma (MPM) is a very aggressive pleura or peritoneum rare cancer.

• Over 43.000 people die every year worldwide for MPM.

• Patients have 12 months survival after diagnosis.

• PlumeSTARS has the opportunity to enter the market of MPM medicines thank to the EMA/FDA orphan designation of its novel product for local delivery of the anticancer cisplatin.

4. Solution (Hyalcis)

Hyalcis is a novel designed orphan medicinal product, consisting in a biodegradable film loaded with cisplatin, for loco-regional drug delivery. The film is implanted in thorax during surgery for primary tumor resection, with the objective to prevent or delay the local metastases of MPM.

PlumestarsS.r.l.|StradaInzani1,43125-Parma

Tel.3204344670-info@plumestars.com

DESCRIPTIONOFTHEPRODUCT

ThemedicinalproductobtainedtheEMAorphanmedicinedesignationin2017.EMAgavealsotheprotocolassistanceforthepreparationoftheregistrationdossier.Theapplicationfor

orphandrughasbeensenttoFDA.

Theproductunderdevelopmentisathinandflexiblepolymericfilm,sufficientlyresistanttobeappliedintrapleuralorinotherdistricts,adheringtothemesothelialorepithelialsurfaces.Forexample,theinvitroreleaseofcisplatinfromthefilmresultedprolongedforatleastthreedays,inreleaseconditionswheretheentirefilmwasimmersedinthedissolutionmedium.Invivo,acontinuousreleaseformorethan10dayscouldbeextractedfromtheplasmalevelcurveobtainedinPKstudyonasheepmodel.Thisprolongationprovidedhighlocalconcentrationsofdrug,where the residual tumour could be present. Therefore,hyaluronate-cisplatinfilm(HA-CisPt)isanovelcisplatindeliverysystem.Hyaluronicacid(HA),aphysiologicalcomponentofthe

extracellularmatrix,isabiocompatiblepolymer.

MAINADVANTAGES

Preclinicalstudiesonratsshowedthathyaluronatefilmsloadedwithcisplatinweresignificantlymoreeffectiveinreducingtumourrecurrenceandassuringhigherandprolongedplasmaticdrugconcentrationsthancisplatinsolution,withoutincreasingsystemictoxicity.

SubsequentpreclinicalstudiesconductedonSardiniansheepshowedthatpolymericfilmsapplicationinthepleuralcavitywaseasyandhomogenoustoplaceinthoraciccavityofthesheep.Plasmaticdrugconcentrationwasmuchhigherafterpolymericfilmstreatmentthandrugsolutionafter7-9days.

TECHNOLOGYKEYWORDSPolymericFilm,Drugdelivery,Loco-regionalAdministration,HyaluronicAcid,MalignantPleuralMesothelioma

CURRENTSTAGEOFDEVELOPMENTPreclinicalstudiesalreadybedone-TestedinlaboratoryTECHNICALANDSCIENTIFICPUBLICATIONSIntrapleuralpolymericfilmscontainingcisplatinformalignantpleuralmesotheliomainarattumourmodel:apreliminarystudy,EuropeanJournalofCardio-thoracicSurgery37(2010)557—565.

5. Hyalcis Benefits • Efficacy: reduction of local tumor metastases • Liver and renal toxicity lower than IV administration • Applicability to other drugs or other treatable cancers

No treatment Hyalcis

Operated Rat Chest Conditions

6. Competition/ Barriers to entry

Chemotherapy

+Surgery Radiotherapy

Intracavitary

chemotherapy Hyalcis

Efficacy

Fair

Proven in humans

Low

Palliative

Medium

Drug solution tested, marginal

effect

Highest

Demonstrated in animal, not yet in

humans

Toxicity

High

Proven severe harmful effects

n/a

High

Similar to IV therapy

Low

Demonstrated in animal

Safety & Effectiveness

Low

Heavy, complex treatment

Low

Radiations effects

Low

Potential fluid leakage

High

Precise and accurate

application

No other products for loco-regional treatment of MPM

7. Go To Market Strategy

Customers: thoracic surgery hospital depts; pharma companies. Market type: niche market of high economic and social value. Market size and value: 40,000 treatable cases worldwide potential market value of 1.200 M€, per year. Target market share: 25% in the third year from product registration.

Exclusive market after registration: 10 ys in EU and 7 ys in US

8. Roadmap

Studies and preliminary composition

of films

2007-2010

1st preclinical study on rats

2010

2nd preclinical study on

larger animals (sheep)

2012

Orphan medicinal

designation approved by

EMA

2016

Orphan medicinal

designation approved by

FDA

2017

EU Program, SME

Instrument Phase 1, financed

2019

Past milestones

9. Business Model

1. Find Investor to register Hyalcis directly in EU and USA and then sell the product to pharmaceutical company or hospital

2. Find a pharma industrial partner to license or sell the product on the base of lump sum and royalties on the market.

Two strategies:

10. Financial Overview

10M€ cumulated

revenues in the

first 3 years after

product

registration.

Year 1 2 3 4 5

Costs

Preclinical and clinical studies €120.000 €80.000 €0 €0 €0

Pharmaceutical studies €50.000 €50.000 €0 €0 €0

Industrialization and registration €1.500.000 €50.000 €50.000 €50.000

Investment in marketing €25.000 €50.000 €52.500 €60.375 €75.469

Fixed expenses €300.000 €900.000 €945.000 €1.086.750 €1.358.438

Variable Costs €0 €0 €5.000.000 €15.000.000 €25.000.000

Revenues

Revenues €0 €0 €10.000.000 €30.000.000 €50.000.000

Unit sales # 0 0 2.000 6.000 10.000

Cash flow (EBITDA)

Cash flow -€495.000 -€2.580.000 €3.952.500 €13.802.875 €23.516.094

Cumulative Cash Flow -€495.000 -€3.075.000 €877.500 €14.680.375 €38.196.469

Actualized cash flow

Discounted Cash Flow -€478.261 -€2.408.458 €3.564.929 €12.028.408 €19.799.920

Discounted Cumulative Cash Flow -€478.261 -€2.870.545 €791.455 €12.793.099 €32.160.402

Jobs created (PlumeStars only) 3 2 5 5 5

Net Present Value (*) €32.506.538

Internal Return Rate (IRR) 179% (*) Based on EBITDA, excluding taxes and dividends.

Financial table submitted to EU to apply for

SME Instrument Phase 1

11. Who we are

Paolo Colombo

The Headmaster, CEO

Fabio Borella

The Hipmaster

Eride

Quarta The Hacker

The pharmaceutical technology researchers of PLU are world recognized and patent owners in medicines constructed on drug delivery technology.

Laura

Monica The Hustler and Communication

12. The Ask & Use of Funds

• Investors

• Partners for development and marketing

• Researchers for new products’ discovery

Funding requirement: ~ 3M€ investment to bring the product to market: - 2.5 M€ for pharmaceutical, pre-clinical and clinical studies. - 0.9 M€ for industrialization and registration dossier preparation. - 100 K€ for initial marketing.

Paolo Colombo, Pharm D.; PhD; CEO

Eride Quarta, Pharm D.; PhD Student;

Temporary Lab at Biopharmanet –TEC, University of Parma

c/o Department of Food & Drug,

Parco Area delle Scienze 27/A , 43125 Parma (Italy).

info@plumestars.com

+39 320 43 44 670; +39 0521 905086

http://plumestars.com