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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?
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Biologics and Biosimilars Congress 2017 in Berlin

Apr 12, 2017

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Janko Brand
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Page 1: 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?

Page 2: Biologics and Biosimilars Congress 2017 in Berlin

Classical ELISA

TAB

Antigen

Biologics&Biosimilars Congress 2017 2

Challenge

1st AB

2nd AB HRP

Page 3: Biologics and Biosimilars Congress 2017 in Berlin

Classical ELISA

2nd AB HRP

TAB

Antigen

1st AB

Biologics&Biosimilars Congress 2017 3

Challenge

Page 4: Biologics and Biosimilars Congress 2017 in Berlin

Classical ELISA

2nd AB HRP

TAB

Antigen

1st AB

Biologics&Biosimilars Congress 2017 4

Challenge

Page 5: Biologics and Biosimilars Congress 2017 in Berlin

TAB Antigen

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

Plate Coating Streptavidin Poly Streptavidin Biotin …

Resources

Biologics&Biosimilars Congress 2017 5

Conjugate 1 Linker lengths …

Conjugate 2 HRP Poly HRP …

Development platform

Page 6: Biologics and Biosimilars Congress 2017 in Berlin

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

Biologics&Biosimilars Congress 2017 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

Page 7: Biologics and Biosimilars Congress 2017 in Berlin

Solution/Pipetting scheme

Biologics&Biosimilars Congress 2017 7

Antigen CALIBRATORS

Topping up Samples with Antigen CALIBRATORS

TAB CALIBRATORS

Page 8: Biologics and Biosimilars Congress 2017 in Berlin

Biologics&Biosimilars Congress 2017 8

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.

Page 9: Biologics and Biosimilars Congress 2017 in Berlin

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

Page 10: Biologics and Biosimilars Congress 2017 in Berlin

~ 1 % of the world population are affected

Adalimumab/TNFa in RA

Biologics&Biosimilars Congress 2017 10

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)

*

**

Page 11: Biologics and Biosimilars Congress 2017 in Berlin

Adalimumab/TNFa in RA

Biologics&Biosimilars Congress 2017 11

Page 12: Biologics and Biosimilars Congress 2017 in Berlin

DAS28/Boost in RA

Biologics&Biosimilars Congress 2017 12

Page 13: Biologics and Biosimilars Congress 2017 in Berlin

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.

Biologics&Biosimilars Congress 2017 13

*

Page 14: Biologics and Biosimilars Congress 2017 in Berlin

Consequences RA Study

Biologics&Biosimilars Congress 2017 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 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

Page 15: Biologics and Biosimilars Congress 2017 in Berlin

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

Biologics&Biosimilars Congress 2017 15

N=260 N=260

Page 16: Biologics and Biosimilars Congress 2017 in Berlin

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

Biologics&Biosimilars Congress 2017 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 spontaneous urticaria.

Page 17: Biologics and Biosimilars Congress 2017 in Berlin

PCSK9/Evolocumab and Alirocumab in high LDL

Biologics&Biosimilars Congress 2017 17

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

Page 18: Biologics and Biosimilars Congress 2017 in Berlin

Alirocumab- HRP

Evolocumab

PCSK9

Biologics&Biosimilars Congress 2017 18

PCSK9/Evolocumab and Alirocumab in high LDL

Evolocumab- HRP

Alirocumab

PCSK9

Page 19: Biologics and Biosimilars Congress 2017 in Berlin

Future Project IL6 and sIL6R

Biologics&Biosimilars Congress 2017 19

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

Page 20: Biologics and Biosimilars Congress 2017 in Berlin

Preclinical recoveryELISA application

Biologics&Biosimilars Congress 2017 20

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

Page 21: Biologics and Biosimilars Congress 2017 in Berlin

Feasibility Package

recoveryELISA Development

Biologics&Biosimilars Congress 2017 21

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

Page 22: Biologics and Biosimilars Congress 2017 in Berlin

Biologics&Biosimilars Congress 2017 22

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!