�2

Index

• i+Med

• Technological capacities

• Application examples of i+Med technologies

• Conclusions

BRIEF HISTORY

Brief History - i+Med

2014 Spin-off company of University of the Basque Country. Faculty of Pharmacy. Lascaray Research Center.

i+Med S.Coop. COOPERATIVE COMPANY OF SCIENTISTS

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BRIEF HISTORY2016 New location at Business Innovation center (BIC ARABA)

‣ 260m² laboratories + warehouse + clean room. ‣Certified company by AEMPS:

Medical devices manufacturer. ISO 13485. ‣Staff: 20 researchers in R&D

Dept., plus Management, Quality and Regulatory Depts.

Brief History - i+Med �4

OUR BUSINESS

Our business - i+Med

We offer our expertise in:

- Development, Manufacturing & Certification

- Product Design and Regulatory Support.

- Life cicle management.

- In-licensing of our developments

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‣New Drugs: CTD ‣Medical Devices : CE Marking

‣Cosmetics ‣Food Complements

OUR EXPERTISE

Our Expertise - i+Med �6

‣ Our scientists: Experts on encapsulation and controlled release of both hydrophilic and lipophilic substances from nanohydrogels and other carriers.

‣ Functionalization with active groups. ‣ Safe, validated and certifiable raw materials, formulations and methods. ‣ Robust, accurate and reproducible manufacturing processes. ‣ Patented process: Licensed microgel patents from UPV/EHU:

- WO 2008/145612 A1 - WO 2011/113989 A1

OUR EXPERTISE

Our Expertise - i+Med �7

Our Quality & Regulatory Depts.:

‣ legal market requirements,

‣ quality at manufacture,

‣ data feedback and registry,

‣ clinical trials design.

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Index

• i+Med

• Technological capacities

• Application examples of i+Med technologies

• Conclusions

TECHNOLOGICAL CAPACITIES

Technological capacities - i+Med �9

Customized matrices and nanocarrier systems adapted to the cargo:

Encapsulation + Vehiculization + Controlled release

‣ Our technologies can be adapted to a wide variety of active compounds

‣ Controlled release achieved even in sensitive tissues (mucoses, skin, inner ear…)

‣ We can manufacture a wide variety of formats: creams, ointments, injectables, gels, sprays, coatings, etc

TECHNOLOGICAL CAPACITIES

Technological capacities - i+Med �10

‣ Hydrogels / micro-nano hydrogels

‣ Cyclodextrins

‣ Liposomes

‣ Lipid nanoparticles (SLN, NLC)

‣ Micelles: triblock copolymers

‣ Hydroxyapatite nanoparticles

‣ Polymeric Nanoparticles:

* PLGA, PCL, PVA,

* nanospheres, nanocapsules

* Polyelectrolyte complexes (HA/CS/xantan/alginate/CHI)

‣ APIs: vitamins, peptides, growth factors, antiinflamatories, despigmentants, antioxidants, etc.

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Index

• i+Med

• Technological capacities

• Application examples of i+Med technologies

• Conclusions

APPLICATION EXAMPLE 1: HA NANOGELS

Application Expample 1: HA Nanogels - i+Med �12

‣ R & D Project in collaboration with Labquimac Group at UPV/EHU. To further exploit the knowledge of i+Med in Hyaluronic acid as raw material for nanocarriers development.

‣ EXPERIMENTAL:

water-in-oil microemulsion (W/O) based on the AOT/isooctane/H2O system.

AF: HA (4 mg/ml) in 0.2M NaOH OF: AOT/1-HP/Isooctane (25%/62.5%/12.5%),

APPLICATION EXAMPLE 1: HA NANOGELS

Application Expample 1: HA Nanogels - i+Med �13

‣ CHARACTERIZATION: TEM, RMN, DLS size & Zpotential

‣ RESULTS:

-Effect of crosslinking agent

-Swelling vs pH: Swelling factors of 12%, 17% and 47%, (DVS, BDDE, and PEGBNH2)

pH Particle size Z pot

APPLICATION EXAMPLE 1: HA NANOGELS

Application Expample 1: HA Nanogels - i+Med �14

‣ RESULTS:

Effect of HA Molecular Weight and BDDE Content:

-HA: 2.1MDa(HMW) and 751 kDa (LMW),

-BDDE contents: 0.2, 1, and 10 equivalents

a) NO EFFECT in particle size of HA MW or BDDE content at constant pH.

b) However with pH variation,

Swelling HMW (75%) << LMW (94%)

Zpot HMW (more negative) << Zpot LMW

%BDDE Swelling

APPLICATION EXAMPLE 2: RELEASE from INJECTABLE

Application Expample 2: Release from Injectable - i+Med �15

‣ Project for an International Pharma company.

‣ Project developed in close collaboration with the client from idea to development: IP protection, manufacture of clinical batches, clinical research dossier.

‣ Currently, Phase I clinical trials finished.

‣ Controlled release of the API for 2 weeks.

APPLICATION EXAMPLE 2: RELEASE from INJECTABLE

Application Expample 2: Release from Injectable - i+Med �16

STAGES performed at I+MED:

1. Lab scale development of carrier+API : preformulations & prototypes

2. Scale-up and pre-clinical development: pilot batches

3. Manufacture of clinical batches: GMP conditions for active molecules under Research. Send to hospitals to implant in volunteers.

‣ Synthesis and characterization at all stages, to comply with safety and efficacy requirements:

- Physico-chemical

- in vitro & in vivo controlled release studies

- Microbiological

- Biological

t (days)

APPLICATION EXAMPLE 2: RELEASE from INJECTABLE

Application Expample 2: Release from Injectable - i+Med �17

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Index

• i+Med

• Technological capacities

• Application examples of i+Med technologies

• Conclusions

CONCLUSIONS

Conclusions - i+Med �19

‣ Added R&D value in real life products for each administration route.

‣ Experience & knowledge on scale-up, manufacture, packaging design and selection, certification and product launch.

Customized solutions through scientific research, technological innovation and collaboration

Virginia Sáez , Ph.D

Project Manager / Senior Researcher

MSCA-IF-SE Fellow