identify the drug dose for each patient individually ... · patients brand etal laine etal biotez...
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Identify the drug dose for each patient individuallyChallenge: Detect free antigen and free drug concentration during therapy
I´m so different, so why is themedication dose the same?
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Classical ELISA
Challenge
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1st AB
Antigen
TAB
2nd AB HRP
Classical ELISA
2nd AB HRP
1st AB
Antigen
TAB
Challenge
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Classical ELISA
2nd AB HRP
1st AB
Antigen
TAB
Challenge
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Additive LibraryAntigen, TABAntigen/ TAB complex StabilizationMatrix adjustments
Plate CoatingStreptavidinPoly Streptavidin Biotin …
Resources
Conjugate 1Linker lengths …
TAB Antigen
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Conjugate 2HRPPoly HRP …
Development platform
TAB
Capture AB
Antigen
60µl Serum
BioTeZ Algorithm
Non linear regression,Michaelis-Menten &Law of mass action
96 well plate&reader
Solution
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Source: Strohner, Pavel, Stephanie Korn, Roland Buhl, and Gunther Becher. “The Recovery-
ELISA--a Novel Assay Technique to Monitor Therapy with Humanized Antibodies: The Example
of Omalizumab.” Journal of Immunoassay & Immunochemistry 34, no. 1 (2013): 83–
93. doi:10.1080/15321819.2012.683501.
The recoveryELISA® (CE marked IVD) is a combination of a sandwich ELISA and a competition ELISA
TAB- poly HRP
Solution/Pipetting scheme
AntigenCALIBRATORS
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Topping up Samples with AntigenCALIBRATORS
TABCALIBRATORS
Free Target concentration as indicator of patients drug
need.
Neutralization rate gives information's
about the ability of the drug to neutralize free
target antigens and allows prediction of
dose variations effects.
A low neutralization rate can serve as
indicator for anti-drug antibodies (ADAs).
Solution
Free Drug concentration shows individual drug
dose to meet the therapeutic window to avoid over and under
treatment.
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Administered drug dose and measured free drug
show individual drug absorption and drug
metabolism.
Therapeutic free Drug Monitoring (TDM)
Therapeutic free Antigen Monitoring (TAM)
Therapeutic Drug/Antigen Monitoring
Solution Summary
9 Source: www.thenewpoundcoin.com
~ 1 % of the world population are affected
Adalimumab/TNF in RA
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Source: *www.healthline.com **Sacks, Luo and Helmick, Arthritis CareRes
Observational clinical study cohort of 17 patients treated with adalimumab dose (40mg) every 14 day or according to the rheumatologist every 7 days (BOOST)
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Adalimumab/TNF in RA
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DAS28/Boost in RA
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Consequences RA Study
* Key findings towards optimising adalimumab treatment: the concentration–effect curve Pouw et al Ann Rheum Dis. 2015 Mar;74(3):513-8. doi: 10.1136/annrheumdis-2013-204172.13
*
Consequences RA Study
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Patients Brand et al Laine et al BioTeZ
Cohort Size (N) 17 1137 50
Supra-Therapeutic 18% 22% n.d.
Therapeutic Window 47% 42% n.d.
Sub-Therapeutic 35% 36% n.d.
Laine J. et al Cost-effectiveness of routine measuring of serum drug concentrations intreatment of RA patients with TNF-α blockers Targets and Therapy
Brand et al Improved dose decision in TNFa-inhibiting therapy with comprehensive diagnostics data Under review at The Journalof Rheumatology
Treatment following existing guideline DAS28 as main disease indicator
Follow up study on RA patients with Horizon2020 & Innovationsfond proposals
Open label treatment including diagnostic data and real world evidence
RA Cohort
Consequences RA Study
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N=260 N=260
IgE
IgE
Examines the underlying mechanisms of Fast vs. Slow responders to first injection of Omalizumab chronic spontaneous urticaria (CSU) patients.
Omalizumab HRP
IgE/Omalizumab in CSU
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Source: Gericke et al J Allergy Clin Immunol. 2016 Nov 9. doi: 10.1016/j.jaci.2016.07.047. Serum autoreactivity predicts time to response to omalizumab therapy in chronic spontaneousurticaria.
PCSK9/Evolocumab and Alirocumab in high LDL
Source: PCSK9 Inhibitors PradeepNatarajan, Sekar KathiresanDOI: http://dx.doi.org/10.1016/j.cell.2016.05.016
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Evolocumab- HRP
Alirocumab
PCSK9
Alirocumab- HRP
Evolocumab
PCSK9
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PCSK9/Evolocumab and Alirocumab in high LDL
Future Project IL6 and sIL6R
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Chalaris et al Interleukin-6 Trans-Signaling and Colonic Cancer Associated with Inflammatory Bowel DiseaseArticle in Digestive Diseases 30(5):492-9 · October 2012DOI: 10.1159/000341698
Preclinical recoveryELISA application
In Vivo Drug stability testsDrug/Antigen binding identification
In early biological development stagesPreclinical phases
60µl Serum ≈100µl blood are needed
Source: https://en.wikipedia.org/wiki/Laboratory_rat#/media/File:Wistar_rat.jpg20
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Thank you for your attention!
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Presented at the 3rd Biologics and Biosimilars Congress.
To find out more, visit:www.global-engage.com