Identify the drug dose for each patient individually ... · Patients Brand etal Laine etal BioTeZ Cohort Size (N) 17 1137 50 Supra-Therapeutic 18% 22% n.d. Therapeutic Window 47%

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?

1

Classical ELISA

Challenge

2

1st AB

Antigen

TAB

2nd AB HRP

Classical ELISA

2nd AB HRP

1st AB

Antigen

TAB

Challenge

3

Classical ELISA

2nd AB HRP

1st AB

Antigen

TAB

Challenge

4

Additive LibraryAntigen, TABAntigen/ TAB complex StabilizationMatrix adjustments

Plate CoatingStreptavidinPoly Streptavidin Biotin …

Resources

Conjugate 1Linker lengths …

TAB Antigen

5

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

6

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)

*

**

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

14

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

16

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

17

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