20140828 future chemistry pieter nieuwland
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description
Transcript of 20140828 future chemistry pieter nieuwland
FutureCh
emistry
FutureChemistry Holding BV
Incorporated December 2007
100% privately owned
Housed in Mercator III; assembly, laboratory and office facilities
Collaborations with Radboud University and Radboudumc
Focus on exploiting flow chemistry
Confidential
FutureCh
emistry
Our design philosophy
• Easy and fast set‐up• ‘Understanding on first sight’• Modularity
Inline analysis Gas‐liquid Photo chemistry
FutureCh
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Flow chemistry: an enabling technology
Nanoparticles
Pharmaceuticals
PET tracers Key activities‐ Flow chemistry instruments ‐ PET tracer for imaging‐ New chemical products
PorousGelatinParticles
FutureCh
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FutureChemistry’s FlowSafe
Patents pending
FF+DC
FF
Efficient chemistry Accelerate R&D Compliance
18FLT
Radio tracer report
Example: Fluorothymidine (18FLT) Target: High proliferating cells Mode: DNA synthesis
FutureCh
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RAD
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0,50
1,00 CPS *1000
Reg #1
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UV_A (215 nm)
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2,00mAU *1000Required:
radiochemical purity >95% [18F]‐fluoride <5% Specific activity >3.750 GBq/mmol [K222] <25 µg/mL Acidity pH = 6‐8
Showcase:FLT‐Production with FlowSafe (known tracer)
Ready for injection into subject
Results: Starting activity 2.5 GBq (68 mCi) Radiochemical yield 95% Radiochemical purity >99% Quantity 150 MBq (4 mCi) (non corrected) Volume 0.3 mL Specific activity 5.760 GBq/mmol [K222] <25 µg/mL Acidity pH = 6.7 Production time (including purification) 90 min
Figure 1: HPLC‐profile of FLT
FutureCh
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Study design: Biodistribution in mice having a FaDu tumor FLT‐uptake after 45 minutes PET/CT image (20 min) Injection 10.0 MBq/0.2 mL 0.9% NaCl (270 μCi)
PET/CT imaging (known tracer)
ConfidentialFigure 2: PET/CT image
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Current trajectory
Discovery Preclinical Clinical (I-III)
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• Costs add up from preclinical phase• Earlier selection leads to cost reduction and better value creation
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Current method
Drug candidate Radio tracer Molecular Imaging
ProsEarly decision makingLogical step to clinicalLess experimentsHigh sensitivity and resolution
ConsLong development neededHigh direct costs
FutureCh
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New method
+ =
‘Time to Image’
tot 2014 2015
6‐9 monts 2‐4 weeks
ProsEarly decision makingLogical step to clinicalLess experimentsHigh sensitivity and resolution
SolutionShorter developmentLower direct costsUnique methodIntellectual property
FutureCh
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Improved trajectory
Discovery Prekliniek Kliniek (I-III)
• Earlier ‘funneling’ reduces unnecessary leads
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Accelerating drug development by fast radiolabelling
Focus:
Shorter development cycles for implementation and development of PET‐tracers
Production for pre‐clinical imaging
DC1 DC1FF FF
FF FF =18F=19F
Drug Candidate Tracer ProductionFast Tracer Development PET imaging studies
Patents pending
FF+
= drug candidateDC1FF
FutureCh
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Molecular imaging service
Molecular Labeling (18F) Administration
Molecular imaging
Biomolecule orsmall molecule
FutureChemistry
Drug Developer
Question: where will my new drug candidate/biomarker be distributed in vivo?
Biodistribution data
FutureCh
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Time‐to‐image:Accelerating drug development
TTI wordt mede mogelijk gemaakt dankzij een bijdrage uit het
Europese Fonds voor Regionale Ontwikkeling (EFRO)
FutureCh
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Imaging for schizophrenia
GOAL:Synthesize a radiotracer of an HDAC inhibitor and identify the locations of this radiotracer in the APO‐SUS and APO‐UNSUS rats through PET imaging, and determine its bioavailability and biodistribution in the brain.
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genome-wide approaches
gnawing
DNA
RNA
(phospho)protein
HDAC inhibitors are candidates asschizophrenia drugs
molecular profiles
FutureCh
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Molecular imaging service
Molecular Labeling (18F)
Administration
Molecular imaging
Biomolecule orsmall molecule
FutureChemistry
Drug Developer
Biodistribution data
Radboud Translational Medicine B.V.
FutureCh
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Ambitions
• Offer FAST access to radiolabelled compounds and imaging
• Make preclinical imaging much more attractive as an early drug development tool
• Allow drug developers to make decisions in an earlier stage
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FutureCh
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Challenges
• Meet strict timelines• Offer contract research, while balancing flexibility and
cost‐effective routine• Increase awareness of benefits of imaging• Build up credibility
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