biologics and biosimilars congress 2017 in berlin

Biologics&Biosimilars Congress 2017 1

Identify the drug dose for each patient individually Challenge: Detect free antigen and free drug concentration during therapy

I´m so different, so why is the medication dose the same?

Classical ELISA

TAB

Antigen


Challenge

1st AB

2nd AB HRP

Classical ELISA

2nd AB HRP

TAB

Antigen

1st AB


Challenge

TAB Antigen

Additive Library Antigen, TAB Antigen/ TAB complex Stabilization Matrix adjustments

Plate Coating Streptavidin Poly Streptavidin Biotin …

Resources


Conjugate 1 Linker lengths …

Conjugate 2 HRP Poly HRP …

Development platform

TAB

TAB- poly HRP

Capture AB

Antigen

60µl Serum

BioTeZ Algorithm

Non linear regression, Michaelis-Menten & Law of mass action

96 well plate&reader

Solution


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

Solution/Pipetting scheme


Antigen CALIBRATORS

Topping up Samples with Antigen CALIBRATORS

TAB CALIBRATORS


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. 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

Biologics&Biosimilars Congress 2017 9 Source: www.thenewpoundcoin.com

~ 1 % of the world population are affected

Adalimumab/TNFa in RA


Source: *www.healthline.com **Sacks, Luo and Helmick, Arthritis Care Res

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/TNFa in RA


DAS28/Boost in RA


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.


*



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 in treatment 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 Journal of 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



N=260 N=260

Omalizumab HRP

aIgE

IgE

Examines the underlying mechanisms of Fast vs. Slow responders to first injection of Omalizumab chronic spontaneous urticaria (CSU) patients.

IgE/Omalizumab in CSU


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 spontaneous urticaria.

PCSK9/Evolocumab and Alirocumab in high LDL


Source: PCSK9 Inhibitors Pradeep Natarajan, Sekar Kathiresan DOI: http://dx.doi.org/10.1016/j.cell.2016.05.016

Alirocumab- HRP

Evolocumab

PCSK9


PCSK9/Evolocumab and Alirocumab in high LDL

Evolocumab- HRP

Alirocumab

PCSK9

Future Project IL6 and sIL6R


Chalaris et al Interleukin-6 Trans-Signaling and Colonic Cancer Associated with Inflammatory Bowel Disease Article in Digestive Diseases 30(5):492-9 · October 2012 DOI: 10.1159/000341698

Preclinical recoveryELISA application


In Vivo Drug stability tests Drug/Antigen binding identification In early biological development stages Preclinical phases 60µl Serum ≈100µl blood are needed

Source: https://en.wikipedia.org/wiki/Laboratory_rat#/media/File:Wistar_rat.jpg

Feasibility Package

recoveryELISA Development


6 3 2

Additive,Linker&Coating Library Optimization in buffer system

We need: 2mg TAB, 2mg Capture AB &

0.3mg Antigen

Matrix Free Package

Sandwich in Serum, Plasma & Matrix Adjustment

We need: Patient samples

Algorithm Adjustment

Ready to use kits

More Services: Stability&cross reactivity tests, scale up and production

For each TAB/Antigen recoveryELISA

individually

Weeks

We deliver

Sample measurement as a service and deliver the

recoveryELISA results. We need: patients samples

Single kit components e.g. Poly HRP TAB or Plates


For assistance and more information's please contact

Dr. Janko Brand [email protected]

Come for a chat at booth # 5 Find us next to the poster # 13

Thank you for your attention!

mailto:[email protected]

biologics and biosimilars congress 2017 in berlin

Healthcare