Imaging Agents Biomarkers - Nutopya Blog

2015 - S.C. @ www.nutopya.com

Imaging agents biomarkers


« Biomarkers » imaging agents


« Biomarkers »

h"p://brb.nci.nih.gov/


Biomarker

DCE MRI FMRI FDG PET Volumetric CT

DWI MRI FLT PET Apoptosis PET

PERCIST Tumor Growth Dynamics

FluciclaGde K5 Flutemetamol Florbetaben Aposense CK18


C-Kit IHC

HER2 Gene expression

KRAS PCR

ALK FISH

BRAF V600E PCR

Solanezumab

Companion Biomarker


h"p://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnos>cs/ucm301431.htm


•  Manufacturing InformaGon -‐ Informa>on pertaining to the composi>on, manufacturer, stability, and controls used for manufacturing the drug substance and the drug product.

•  Animal Pharmacology and Toxicology Studies -‐ Preclinical data to permit an

assessment as to whether the product is reasonably safe for ini>al tes>ng in humans.

•  Clinical Protocols and InvesGgator InformaGon -‐ Detailed protocols for proposed

clinical studies to assess whether the ini>al-‐phase trials will expose subjects to unnecessary risks. Informa>on on the qualifica>ons of clinical inves>gators. Commitments to obtain informed consent from the research subjects, to obtain review of the study by an ins>tu>onal review board (IRB), and to adhere to the inves>ga>onal new drug regula>ons.

IND InvesGgaGve New Drug

h"p://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplica>ons/inves>ga>onalnewdrugindapplica>on/default.htm


ExperGses

GO NoGO

Medicinal chemistry Synthesis

Analy>cal Chemistry QC

Molecular Biology

Preclinical Imaging

Data Post-‐Processing Modelling

IND Lead ValidaGon

Toxicology

Galenic / Formula>on

Scale-‐Up

GMP Produc>on

Batch valida>on and release

IND Dossier PreparaGon

Clinical Imaging

Data interpreta>on and analysis

Pa>ent recruitment and management

CTA-‐FDA

Clinical trial prepara>on

Data sta>s>cs and report

GO NoGO

Discovery / Preclinical Early Clinical


Complex ecosystem


•  Need of populaGon analysis / epidemiology to proof healthcare expenses reducGons with therapy personalizaGon à Pa>ent associa>ons / Hospital / Global Purchase Office

•  Define intermediate endpoints that are consistent with a beVer care and response to therapy for paGents / Clarify and value the benefit risk raGo of imaging agents à  Simplify / ease regula>on from regulators à  Access dedicated experts Trial supports

•  Get appropriate funding for costly early phase trials including clinical imaging when aVriGon rate is low compare to therapeuGcs when entering phase III à  Get dedicated funding channels and incen>ves à  increase societal criteria for grants

Challenges


•  NeurodegeneraGve diseases

•  Oncology / Immuno-‐Oncology

•  Cardiology / metabolism / Diabetes

3 examples Case studies


Neuro: Alzheimer targe>ng agent

Medical need: –  Lack of techniques to diagnose early signs of

Alzheimer disease –  Only behavioural tests at advanced stage –  Need for a quan>ta>ve reproducible technique –  Need non invasive brain measurement

SoluGon: –  Imaging of the beta amyloid load in brain region

Candidates: –  Florbetapir (Amyvid) – Avid Lilly (Approved MA) –  AZPET – Fluoropharma –  Florbetaben – Piramal –  Flutemetamol – GE

–  Tau imaging agents Avid (ex siemens Biomarker poraolio)

h"p://www.technologyreview.com/view/422477/fda-‐panel-‐supports-‐new-‐diagnos>c-‐tool-‐for-‐alzheimers/


Onco: PSMA targe>ng agents

Medical need: •  screening of prostate cancer with a prostate-‐specific an>gen (PSA) blood test and or a digital rectal exam (DRE)

•  Metasta>c prostate cancer spread to lymph nodes and bones

•  FDG PET is limited in the detec>on of osseous metasta>c lesions

SoluGon: •  Imaging agent that targets the extracellular domain of prostate specific membrane an>gen (PSMA)

Candidates: •  MIP1404 – Progenics (Molecular Insigt) •  PSMA minibody-‐ ImaginAb •  CTT-‐54 – Cancer Targeted Technology

[123I] MIP-‐1072 imaging in a pa>ent with metasta>c prostate cancer at 4 h post-‐injec>on

h"p://www.sciencedirect.com/science/ar>cle/pii/S0305737212001284


Cardio: Unstable Plaque

Medical need: •  Standard angiography do not tell about the risk of plaque rupture and clots

•  Morphological imaging IVUS, OCT is s>ll invasive and not associated with plaque biology

SoluGon: •  Imaging of the biological ac>vity of unstable plaque: Inflamma>on, Fibrin, MMP, VCAM…..

Candidates: •  FDG •  TSPO GE-‐180 -‐ GE •  VasoPET – Fluoropharma •  EP-‐2104R – EPIX (discon>nued) •  P947 – Guerbet (Preclinic stage)

h"p://eurheartj.oxfordjournals.org/content/30/21/2566.long

h"p://pubs.acs.org/doi/abs/10.1021/mp300610s


Technology transfer process

Research Preclinical dvt

Early Clinical dvt

Late Clinical dvt

Market

Academia

SME – PPP Consor>a

Pharma/Diag industry

Pa>ents

POC POC

TRL 4 TRL 1-‐3 TRL 5 TRL 6 TRL 7 TRL 8-‐9

TranslaGon

-‐Preclinical -‐Manufacturing

-‐Clinical -‐Phase1,2a

-‐Clinical -‐Phase 2b, 3

Inspired from h"p://www.etp-‐nanomedicine.eu/

Imaging Agents Biomarkers - Nutopya Blog

Healthcare

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