Moving Nanomedicine towards H2020 · Moving Nanomedicine towards H2020 Patrick BOISSEAU Business Development Nanomedicine, CEA-Leti, Grenoble (FR) Chair of Working Group Nanodiagnostics,

Moving Nanomedicine towards H2020

Patrick BOISSEAU Business Development Nanomedicine, CEA-Leti, Grenoble (FR)

Chair of Working Group Nanodiagnostics, ETPN

• Background

• Nanomedicine value chain

• Towards translational nanomedicine

• The future PPP Health

• Work plan 2012-2013

• Conclusions

2

Outline

05/11/2012 ETPN General Assembly London

• Only 14 months left before beginning H2020

• H2020 focuses on innovation and translation to industry

• Slow move of nanomedicine towards industrialization; increase of

– Clinical trials

– Approved products

3

Background


44 marketed Nano-delivery products Product Generic Formulation Indication Manufacturer

Abraxane Paclitaxel Polymeric

nanoparticles

Cancer

chemotherapy Celgene

Abelcet Amphotericin B Liposomal

formulation

Fungal infections

Elan/Alkermes, Enzon,

Cephalon

Adagen Adenosine

deaminase PEGylation

Enzyme replacement

therapy

Enzon, Sigma-Tau

AmBisome Amphotericin B Liposomal

Formulation

Oral and perioral

infections

Astellas/Gilead

Sciences

Amphotec Amphotericin B Liposomal

Formulation

Oral and perioral

infections

Three Rivers

Pharmaceuticals/ALZA

Avinza Morphine

sulphate

nanocrystal

formulation

Moderate to severe

pain Elan/Alkermes, Pfizer

Copaxone Glatiramer

acetate

Copolymer of lglutamic

acid, lalanine, l-tyrosine

and l-lysine)

Multiple sclerosis Teva Pharmaceuticals

Curosurf Poractant alfa Liposome Neonatal respiratory

distress

Chiesi Farmaceutici

SpA

DaunoXome Daunorubicin PEGylated liposome

Formulation

Cancer

chemotherapy Gilead Sciences

DepoCyt Cytarabine Sustained-release

Liposomes

Cancer

chemotherapy SkyePharma/Enzon

Depodur Morphine

sulphate Liposome

Pacira

Pharmaceuticals

Pacira

Pharmaceuticals

Diprivan Propofol Liposomes Induction of

anesthesia AstraZeneca

Doxil/CaelyX Doxorubicin PEGylated liposome

Formulation

Cancer

chemotherapy

ALZA/ OrthoBiotech/

Schering Plough

Elestrin Elestrin Estradiol

gel

Phosphate

nanoparticles

Menopausal

symptoms BioSante

Elyzol Metronidazole Dental gel Parodontitis Camurus Camurus

Emend Aprepitant Nanocrystal

Formulation

Anti-emetic

Merck & Co+

Elan/Alkermes

Epaxal Hepatitis A

vaccine Virosome technology

Prevention of

Hepatitis A infection Berna Biotech

Episil Bioadhesive

barrier Fluidcrystal Oral pain Sinclair/Teva

Estrasorb Estradiol gel Micellar

Nanoparticles

Menopausal

symptoms

Novavax/Espirit

Pharma

Focalin XR Dexmethylphen

idate hcl Nanocrystals ADHD

Novartis

Élan/Alkermes

Fosrenol Lanthanum

carbonate

Inorganic

Nanoparticles

End-stage renal

disease Shire

Genexal PM Paclitaxel Polymeric micelles Cancers Samyang

Product Generic Formulation Indication Manufacturer

Indaflex Indomethacin

Solid/lipid

nanoparticles Osteoarthritis AlphaRx

Inflexal V Subunit influenza

vaccine Virosome Influenza prophylaxis Crucell

Invega

Sustenna Paliperidone Nanocrystal Antipsychotic Janssen

Macugen Pegaptanib Pegylated anti-vegf

aptamer

Age-related

macular

degeneration

OSI Pharmaceuticals/

Pfizer

Myocet Doxorubicin

citrate complex Liposome encapsulated Cancer chemotherapy

Cephalon/Zeneus

Pharma/ Sopherion

Therapeutics

Megace ES Megestrol acetate Nanocrystal formulation Cancer therapy Elan/Alkermes+Par+Bristol-

Myers Squibb

MuGard Hydrogel mouth

rinse

Nanogel

Head and neck cancers Access Pharma

Naprelan Naproxen Nanocrystal formulation Arthritis, gout Elan/Alkermes

Nanoxel Paclitaxel Polymeric nanoparticles Cancer chemotherapy Dabur Pharma

Neulasta Filgrastim Pegylation Neutropenia Amgen

Oncospar Oncospar PEG-

Lasparaginase

Pegylation

Cancers

Enzon/Schering-

Plough

Pegasys Peginterferon alfa

2a

Pegylation

Hepatitis B, hepatitis C Roche/Nektar

PegIntron Peginterferon alfa

2b

Pegylation

Chronic hepatitis C Schering-Plough

Rapamune Sirolimus Nanocrystal formulation Immunosuppression Wyeth Élan/Alkermes

Renagel Sevelamer hcl Poly (allylamine) resin Hyperphosphatemia in

hemodialysis Genzyme

Salinum

Potassium,

magnesium,

chlorine

Oral liquid Xerostomia

Somavert Pegvisomant Polymer protein conjugate Acromegaly Pfizer

Ritalin LA Methylphenidate

Hcl

Pulsatile release

Nanocrystal formulation ADHD Elan/Novartis

Survanta Beractant Liposome encapsulated Neonatal respiratory

distress Abbott

Tricor Fenofibrate Nanocrystal formulation Lipid reduction Abbott Élan/Alkermes

Triglide Fenofibrate Nanocrystal formulation Lipid reduction

SkyePharma/ First Horizon

Pharmaceuticals/Sciele

Pharma

Verelan/

Verelan

PM

Verapamil Elan’s SODAS

Multiparticulate technology Hypertension Elan/Alkermes Schwarz

Source BCC Research

05/11/2012 ETPN General Assembly London 4

18 marketed Pharmaceutical products

Product Composition Indication Company

Annual

Sales

($ Millions)

Abelcet Amphotericin B/lipid Fungal infections Enzon 23

Ambisome Liposomal

amphotericin B Fungal infections Gilead 350

Doxil, Caelyx Liposomal

doxorubicin Kaposi’s sarcoma Ortho, Schering-Plough 360

Depocyt Liposomal cytarabine Cancer Skyepharma 170

Visudyne Liposomal verteporfin

Age-related macular

degeneration QLT, Novartis 150

Estrasorb Estradiol in micelles Menopause Novavax 130

Adagen PEG-adenosine

deaminase Immunodeficiency Enzon 33

Neulasta PEG-GCSF Neutropenia Amgen 500

Oncospar PEG-asparaginase Leukemia Enzon 65

Pegasys PEG- α -interferon 2a Hepatitis C Nektar, Roche 1,650

PEG-Intron PEG-α -interferon 2b Hepatitis C Enzon, Schering-Plough 975

Macugen Pegylated anti-VEGF

aptamer

Age-related macular

degeneration OSI Pharmaceuticals, Pfizer 175

Somavert PEG-HGH Acromegaly Nektar, Pfizer 325

Copaxone Copolymer of amino-acids Multiple sclerosis TEVA 3,250

Renagel Crosslinked

poly(allylamine) resin

Chronic kidney

Disease Genzyme 575

Megace ES Nanocrystalline

megestrol acetate Eating disorders Elan, Par 55

Rapamune Nanocrystalline

sirolimus Immunosuppression Elan, Wyeth 340

Abraxane Paclitaxel proteinbound

nanoparticles Cancer Abraxis, AstraZeneca 675


15 marketed Imaging/diagnostic & biomaterial Product Composition Indication Company

In vivo Imaging

Resovist Iron nanoparticles Liver tumors Schering, Berlin

Feridex/Endorem

Iron nanoparticles

Liver tumors

Advanced Magnetics,

Guerbet

Gastromark/Lumirem

Iron nanoparticles

Imaging abdominal

structures

Advanced Magnetics,

Guerbet

In Vitro Diagnostics

Lateral flow tests

Colloidal gold

Pregnancy, ovulation, HIV

etc

British Biocell,

Amersham/GE,

Nymox

Clinical cell separation

Magnetic nanoparticles

Immunodiagnostics

Dynal/InVitrogen,

Miltenyl Biotec,

Immunicon

Biomaterials

Ceram X duo Nanoparticle composite Dental filling material Dentspley

Filtek Supreme Nanoparticle composite Dental filling material 3M Espe

Mondial

Nanoparticle-containing

dental prosthesis

Dental restoration Heraeus Kulzer

Premise

Nanoparticle composite Dental repair

Sybron Dental Specialities

Tetric Evoceram Nanoparticle composite Dental Repair Ivoclar Vivadent

Ostim Nano-hydroxy apatite Bone defects Osartis

Perossal Nano-hydroxy apatite Bone defects Aap implantate

Vitoss Nano-hydroxy apatite Bone defects Orthovita

Acticoat Silver nanoparticles Antimicrobial wound care Nucryst

Active Implants

Pacemaker Fractal electrodes Heart failure Biotronik


http://www.centerwatch.com/drug-information/fda-approvals/drug-areas.aspx?mp=empty

>70 Nanomedical Products in Clinical trials Cardiovascular

Diseases Endocrinology Hematology

Immunology

Infectious Diseases Musculoskeletal Neurology Oncology

NCE Brilinta (ticagrelor); AstraZeneca; For the

reduction of thrombotic events in patients with

acute coronary syndrome, Approved July 2011

NCE Afinitor (everolimus); Novartis; For the

treatment of advanced pancreatic

neuroendocrine tumors, Approved May 2011

NANO Adcretris (brentuximab vedotin); Seattle

Genetics; For the treatment of Hodgkin

lymphoma and anaplastic large cell lymphoma,

Approved August 2011

NCE Arcapta (indacaterol maleate inhalation

powder); Novartis; For the treatment of airflow

obstruction resulting from chronic obstructive

pulmonary disease, Approved July 2011

AB Actemra (tocilizumab); Genentech; For the

treatment of systemic juvenile idiopathic arthritis,

Approved April 2011

NCE Abstral (fentanyl sublingual tablets);

ProStrakan; For the treatment of breakthrough

cancer pain in opioid-tolerant patients, Approved

January 2011

NCE Abstral (fentanyl sublingual tablets);

ProStrakan; For the treatment of breakthrough

cancer pain in opioid-tolerant patients, Approved

January 2011

NCE Edarbi (azilsartan medoxomil); Takeda; For

the treatment of hypertension, Approved

February 2011

NCE Juvisync (sitagliptin and simvastatin);

Merck; For the treatment of type II diabetes,

Approved October 2011

NCE Ferriprox (deferiprone); Apotex; For the

treatment of transfusional iron overload due to

thalassemia, Approved October 2011

AB Benlysta (belimumab); Human Genome

Sciences; For the treatment of systemic lupus

erythematosus, Approved March 2011

NCE Duexis (ibuprofen and famotidine); Horizon

Pharma; For the relief of rheumatoid arthritis

and osteoarthritis and prevention of gastric

ulcers, Approved April 2011

NCEGralise (gabapentin); Abbott; For the

treatment of postherpetic neuralgia, Approved

February 2011

NANO Adcretris (brentuximab vedotin); Seattle

Genetics; For the treatment of Hodgkin

lymphoma and anaplastic large cell lymphoma,

Approved August 2011

NCE Xarelto (rivaroxaban); Bayer; For the

prophylaxis of deep vein thrombosis during knee

or hip replacement surgery, Approved July 2011

NCE Sutent (sunitinib malate); Pfizer ; For the

treatment of pancreatic neuroendocrine tumors,

Approved May 2011

AB Soliris (eculizumab); Alexion; For the

treatment of atypical hemolytic uremic

syndrome, Approved September 2011

NCE Complera

(emtricitabine/rilpivirine/tenofovir disoproxil

fumarate); Gilead; For the treatment of HIV-1 in

treatment-naive adults, Approved August of

2011

Nephrology

Urology

NCE Horizant (gabapentin enacarbil);

GlaxoSmithKline; For the treatment of restless

legs syndrome, Approved April 2011




Dermatology

Plastic Surgery

NCE Tradjenta (linagliptin); Boehringer

Ingelheim; For the treatment of type II diabetes,

Approved May 2011

NCE Xarelto(rivaroxaban); Bayer; For the

prophylaxis of deep vein thrombosis during knee

or hip replacement surgery, Approved July 2011

NCE Daliresp (roflumilast); Forest

Pharmaceuticals; For the treatment of chronic

obstructive pulmonary disease, Approved

February 2011

NBE Nulojix (belatacept); Bristol-Myers Squibb;

For the prevention of organ rejection following

kidney transplant, Approved June 2011

NCE Lazanda (fentanyl citrate) nasal spray;

Archimedes; For the management of

breakthrough cancer pain, Approved June 2011

NCE Lazanda (fentanyl citrate) nasal spray;

Archimedes; For the management of

breakthrough cancer pain, Approved June 2011

peptide Firazyr (icatibant); Shire; For the

treatment of acute attacks of hereditary

angioedema, Approved August of 2011 Gastroenterology Otolaryngology NCE Dificid (fidaxomicin); Optimer

Pharmaceuticals; For the treatment of

Clostridium difficile-associated diarrhea,

Approved May 2011

AB Soliris (eculizumab); Alexion; For the

treatment of atypical hemolytic uremic

syndrome, Approved September 2011

NCE Onfi (clobazam); Lundbeck; For the

adjunctive treatment of seizures associated with

Lennox-Gastaut syndrome, Approved October

2011

NCE Sutent (sunitinib malate); Pfizer; For the


Approved May 2011

NCE Gralise (gabapentin); Abbott; For the


February 2011




NCE Vandetanib (vandetanib); Astra

Zeneca; For the treatment of thyroid

cancer, Approved April 2011

NCE Edurant (rilpivirine); Tibotec; For the

treatment of HIV-1, Approved May 2011 Pharmacology

Toxicology

NCE Oxecta (oxycodone HCl); Pfizer; For the

management of acute and chronic moderate to

severe pain, Approved June 2011

NANO Sylatron (peginterferon alfa-2b); Merck;

For the treatment of melanoma, Approved April

2011

CELL laViv (azficel-T); Fibrocell Science; For the

improvement of nasolabial fold wrinkles in

adults, Approved June 2011

NCE Dificid (fidaxomicin); Optimer


Clostridium difficile-associated diarrhea,

Approved May 2011

Pulmonary

Respiratory Diseases

Peptide Firazyr (icatibant); Shire; For the

treatment of acute attacks of hereditary

angioedema, Approved August of 2011

NCE Oxecta (oxycodone HCl); Pfizer;

For the management of acute and

chronic moderate to severe pain,

Approved June 2011

NCE Potiga (ezogabine); Valeant

Pharmaceuticals; For the treatment of partial-

onset seizures, Approved June 2011

NCE Vandetanib (vandetanib); Astra Zeneca;

For the treatment of thyroid cancer, Approved

April 2011

NANO Sylatron (peginterferon alfa-2b); Merck;

For the treatment of melanoma, Approved April

2011

NCE Duexis (ibuprofen and famotidine);

Horizon Pharma; For the relief of rheumatoid

arthritis and osteoarthritis and prevention of

gastric ulcers, Approved April 2011

NCE Arcapta (indacaterol maleate

inhalation powder); Novartis; For the

treatment of airflow obstruction

resulting from chronic obstructive

pulmonary disease, Approved July

2011

NCE Gralise (gabapentin); Abbott; For the


February 2011

Rheumatology

NCE Viibryd (vilazodone hydrochloride); Clinical

Data; For the treatment of major depressive

disorder, Approved January 2011

NCE Xalkori (crizotinib); Pfizer; For the

treatment of ALK+ non-small cell lung cancer,

Approved August of 2011

antibody Yervoy (ipilimumab); Bristol-Myers

Squibb; For the treatment of metastatic

melanoma, Approved March 2011

17 NCE Incivek (telaprevir); Vertex; For the

treatment of genotype 1 chronic hepatitis C,

Approved May 2011



chronic obstructive pulmonary disease,

Approved February 2011

NCE Incivek (telaprevir); Vertex; For the

treatment of genotype 1 chronic hepatitis C,

Approved May 2011

AB Actemra (tocilizumab); Genentech;

For the treatment of systemic juvenile

idiopathic arthritis, Approved April 2011

Pediatrics

Neonatology

AB Yervoy (ipilimumab); Bristol-Myers Squibb;

For the treatment of metastatic melanoma,

Approved March 2011

NCE Zelboraf (vemurafenib); Roche; For the

treatment of BRAF + melanoma, Approved

August of 2011

NCE Rectiv (nitroglycerin) ointment 0.4%;

ProStrakan; For the treatment of chronic anal

fissure, Approved June 2011

NCE Xalkori (crizotinib); Pfizer; For the

treatment of ALK+ non-small cell lung

cancer, Approved August of 2011

NBE Nulojix (belatacept); Bristol-Myers Squibb;

For the prevention of organ rejection following

kidney transplant, Approved June 2011

NCE Duexis (ibuprofen and

famotidine); Horizon Pharma; For the

relief of rheumatoid arthritis and

osteoarthritis and prevention of gastric

ulcers, Approved April 2011

AB Actemra (tocilizumab); Genentech;

For the treatment of systemic juvenile

idiopathic arthritis, Approved April 2011

NCE Zelboraf (vemurafenib); Roche; For the

treatment of BRAF + melanoma, Approved

August of 2011

Obstetrics

Gynecology

NCE Sutent (sunitinib malate); Pfizer; For the


Approved May 2011 Pharmacology

Toxicology

NCE Victrelis (boceprevir); Merck; For the

treatment of chronic hepatitis C genotype 1,

Approved May 2011



chronic obstructive pulmonary disease,

Approved February 2011

NCE Zytiga (abiraterone acetate); Centocor

Ortho Biotech; For the treatment of prostate

cancer, Approved May 2011

NCE Makena (hydroxyprogesterone caproate

injection); Hologic; For the prevention of risk of

preterm birth, Approved February 2011

NCE Victrelis (boceprevir); Merck; For the

treatment of chronic hepatitis C genotype 1,

Approved May 2011

NCE Oxecta (oxycodone HCl); Pfizer;

For the management of acute and

chronic moderate to severe pain,

Approved June 2011

NCE Onfi (clobazam); Lundbeck; For

the adjunctive treatment of seizures

associated with Lennox-Gastaut

syndrome, Approved October 2011









http://www.centerwatch.com/drug-information/fda-approvals/drug-details.aspx?DrugID=1158&mp=empty






















































































































































Global nanomedicine market

• $63.8 billion in 2010 and $72.8 billion in 2011

– +14%

• Expected growth to $130.9 billion by 2016

– +12.5%/year between years 2011 and 2016

• Nanomedicine: 10% of pharma sales Source: BBC Research

05/11/2012 8 ETPN General Assembly London

11

The nanomedicine value chain

Patient

Needs

• Clinical trials

• Translation

• Regulatory Issues

• Reimbursement

• Qualified products

and services

• Qualified products

and services

Basic

Research

Applied

R&D

Industrial

Implement.

Clinical

Implement.


12

The nanomedicine stakeholders

Basic

Research

Applied

R&D

Industrial

Implement.

Clinical

Implement.

05/11/2012

Academia

Research & technology institutes

SMEs

SMEs Large

companies Hospitals

Participation to ETPN

Players

ETPN General Assembly London

Academia

Nano based technologies,

research, concepts ….

Industry

Market

Translation hub

Pre-clinical studies, Clinical

studies, IP, Manufacturing,

Business Development, Regulation

The situation in Europe

Innovation


• Liaising Academia with industry

• Establishing a supply chain of innovative SMEs

• Support of the early preclinical or clinical proofs of concepts before transfer to large companies

What does translation mean?


• Education of academia to industrial development constraints

• Evaluation of projects with the industrial perspective

• Better connection/interface between SMEs and large companies

What does translation require? (from an industrial perspective)


Towards an open innovation model

Large companies

Academia

SMEs


Integration in the PPP Health model

PPP Health (EC/industry)

Diagnostic (industry)

Nanomedicine (industry, academy)

Pharmaceuticals (industry)

Specific activities

Joint activities

Specific activities

Specific activities

Joint activities


• Nano-characterization

– Physical, chemical and biological evaluation

– Synchronization with EMA

– Mirror site to US/NCL

• Manufacturing of clinical batches

– Scale up of manufacturing process

– From lab to GMP unit

• Regulatory issues

Specific activities of nanomedicine


• Education on translation

– Industrial translation experts

– Paid by EC to industry

• Show case of SMEs to large companies

• Joint R&D projects

• Early pre/clinical trials

Joint actions with pharma and diag


• R&D infrastructure – With trained team and facilities working according to the highest standard

– From early non clinical proof of concept to end of Phase 1/Pilot Study

• Services – Characterization (Phys., Chem. & Bio)

– Industrial prototyping

– Industrialization, early manufacturing

– Safety package

– Pre-clinical development

– Regulatory

– QC

– Research to sustain development

– Market access

05/11/2012 20

The nanomed translational infrastructure


Facilitate the emergence

of a

profitable nanomedicine

sector in Europe

05/11/2012 21

Our objective


❶ Increase resources of ETPN

❷ Bridge academia, SMEs and

large companies

❸ Make nanomed products ready for clinical trials

❹ Shape R&D funding

Priorities for 2012-2013


• Membership

– Strong focus on SMEs

• Objective: +25 SMEs

– Contact with large companies

• Objective : + 2-3 large companies

• Management of EU projects

– Nanomed 2020

– Translation infrastructure

❶ Resources of ETPN Urgent action needed


• Education

– Tutorials on translation

– Undergraduate courses on translation

• Expose SMEs’ early clinical proofs of concept to large companies

• Evaluation of translation projects with participation of industry

• Tutoring of translation project with participation of industry

❷ Bridge academia, SMEs and companies


• Nanomed Translation (Hub) Infrastructure

– Characterization Lab

– GMP Manufacturing

– Support to a few selected early phase clinical trials Phase I

– …

❸ Make nanomed products ready for

clinical trials


• Update the Strategic Innovation & Research Agenda (ex-SRA)

– For the EC

– For the PPP Health

• Synchronize the SIRA with EFPIA and COCIR

• Contribute to the KETs programme (see Heico’s lecture)

• Contribute to the EC/Infrastructure programme

❹ Shape R&D funding


• Liaise with EC

– DG Research & Innovation

• Health

• NMP

– DG Infrastructure

• Synchronize the ETPN White Paper

– with EFPIA and COCIR

• Coordinate with Members States

– Mirror Group

05/11/2012 27

ETPN strategy towards H2020


Team up with other stakeholders and groups

Implementation of joint activities:

• European Summit for

Nanomedicine

• Policy – Industry Tables

• High-Level meetings on

Future Medicine

• Other actions …


29

ETPN as mediator – the translation triangle 1. Nanomedicine into clinical practice via industry

2. Align up-stream R&D with industrial needs

3. Bridge academia and industry and clinicians on

Market needs

S&T bottlenecks

Approval process

Technology roadmaps

4. Suggest industry inspired call topics to the EC and to ERANET EuroNanoMed

Clin. trial Clin. trial

Clinics

Academia Industry Translation

Clin. trial Clin. trial

CLINAM


05/11/2012 30

Federating the nanomed community

CLINAM


IT’S NOW OR

NEVER 05/11/2012 ETPN General Assembly London 31

Conclusion

Let’s be ambitious


For more information visit: www.etp-nanomedicine.eu or contact [email protected]

Thank you for your support

and attention

Documents

Moving Nanomedicine towards H2020 · Moving Nanomedicine towards H2020 Patrick BOISSEAU Business Development Nanomedicine, CEA-Leti, Grenoble (FR) Chair of Working Group Nanodiagnostics,