itri-adc platform: antibody-drug conjugate proprietary ......kang-li wang ([email protected])...

版權宣告©工業技術研究院 Copyright © Industrial Technology Research Institute

ITRI-ADC Platform:抗体薬物複合体を設計し、開発するサービス

Contact:Kang-Li Wang ([email protected])Ping-Fu Cheng ([email protected])Drug Delivery Technology Dept.Biomedical Technology and Device Research Labs.Industrial Technology Research Institute, Taiwan

mailto:[email protected]?subject=About%20ITRI-ADC%20Platform

mailto:[email protected]

版權宣告©工業技術研究院 Copyright © Industrial Technology Research Institute ITRI BDL/2021 2

We can provide…

Proprietary Technology Service Platform

ITRI’s SSCLT Conjugator

No risk of loosing target affinity Highly homogeneous In vivo stable Easy to scale-up Applicable for universal IgG1

Customized ADC Design

Complete Preclinical StudiesIP statusUS/EP/CN/TW patent pendingJP patent no.: JP6771450B2

Technology Transfer Available!

Vast options of each part Functions based on needs Commercial or novel mAbs Experienced with strong capacity

Process development to liter scale Characterization In vitro to in vivo evaluations Regulation-based Cost-effective

版權宣告©工業技術研究院 Copyright © Industrial Technology Research Institute ITRI BDL/2021

Proprietary Technology:ITRI’s SSCLT Conjugator

Conjugator Lys-based Cys-based ITRI’s SSCLT

Example Kadcyla® Adcetris® ITRI HER-SSCLT24

Conjugation sites Non-specific lysines Hinge cysteines Specific hinge cysteines

Binding affinity interruption Possible Less risk No risk

Drug/Antibodydistribution

Mixture(Randomly 0 – 8)

Mixture(Randomly 0, 2, 4, 6, 8)

Homogenous(DAR4 >75%)

Conjugation reaction Amide coupling Reversible

thiol-maleimide couplingIrreversible

dual thiol coupling

In vivo stability OK Poor Good

3

DAR4 dominant

Homogenous DAR distribution without further isolation

Superior plasma stabilitythan marketed ADC


Service Platform:Customize Your ADC

4

Conjugator• ITRI’s SSCLT• Conventional Lys-based • Conventional Cys-based

Linker• Non-cleavable• Cleavable• ITRI’s Hydrophilic Linker• ITRI’s Branched Linker

Drug• MMAE/ MMAF• DM1/ DM4• Ducamycin• SN38• Other drugs

(e.g. Immune modulators or photosensitizers)

Antibody• Anti-HER2• Anti-EGFR• Anti-MSLN• Anti-EpCAM• Novel mAbs

To create ADCs based on your needsWe provide vast options in antibodies and linker-drugs

with full design and synthesis capacity


Scales

Process Development • Linker-drug preparation• Conjugation optimization• Formulation design (solution or lyophilized powder)☺ Providing bio-similar of marketed ADC is possible!

μL reaction mL scale (mg – g) Liter scale (>10 g)

Service Platform:Complete Preclinical Studies

AntibodyPeptide mapGlycosylationPurityPotency

DrugIdentityPurityPotency

Linker-DrugIdentityPurity

ADCDARPeptide mapGlycosylationFree drug Free linker-drugPurityPotency

Characterization


Pharmacodynamics (PD)

In vitro cytotoxicityIn vivo tumor suppressionMultiple animal tumor models

Pharmacokinetics (PK)

In vitro plasma stabilityIn vivo blood concentrationIn vivo bio-distribution

Toxicology (Tox)

Maximum tolerance dose (MTD)HypersensitivityOrgan and tissue toxicity(rodent and NHP)

Pharmacological evaluations

Service Platform:Complete Preclinical Studies

Our experiences 80+ linker-drugs have been designed and synthesized. 5+ commercial and novel mAbs have been conjugated. 2 in-house ADCs are in IND-enabling stage. 3+ bio-pharmaceutical companies choose our services in ADC development.


CASE EXAMPLE: ITRI HER-SSCLT24

7


Promising Properties of ITRI HER-SSCLT24 Anti-HER2 mAb + ITRI’s SSCLT conjugator (DAR = 4)

8

HER2- HER2+ HER2+, Kadcyla®-resistant

Exactly the same PK profiles with mAb

Good specificity and overcome the resistance

High MTD shows good safety

Kadcyla®

HER-SSCLT24

100-fold dose

DAR4 >80%

Homogenous DAR distribution without further isolation

Kadcyla®

HER-SSCLT24


Excellent Anti-tumor Efficacy Among Anti-HER2 ADCs

9

JIMT-1: Kadcyla®-resistant breast cancer

Clin. Cancer Res. 22(20): 5097 (2016)Mol. Cancer Ther. 19(9): 1833 (2020)

Mol. Cancer Ther. 18(10): 1721 (2019)


ABOUT US –ITRI DRUG DELIVERY DEPT.

10


About Us –ITRI Drug Delivery Technology Dept.

What we are doing…Customized formulation solution

Unmet need product development Drug delivery technology innovation

PLGA/PolymericFormulation

Who we are…90%+ with MS or PhD

Strong preclinical capability and facilitiesExperienced in working with the industry

11


Program Candidate Indication

Discovery Preclinical Clinical

CommercialLead finding

Lead optimization

IND-enablingstudy IND Phase

1Phase

2Phase

3

TransdermalDelivery

Liposomal Gel Acnes Technology Transferred

CINV Patch Parkinson; CINV Technology Transferred

TargetingNanomedicine

2B3-101 Brain tumor Technology Transferred

2B3-201 Multiple sclerosis Technology Transferred

Gene Delivery siRNA Solid tumor Technology Transferred

PLGAMicroparticle

OBM477 Schizophrenia Technology Transferred

BDPM Dementia Technology Transferred

Polymeric Micelles SCP201 Solid tumor Technology Transferred

Eye dropHPC8C30L4H Uveitis (anterior)

HPC7C25A8H AMD (posterior)

ADCsEGFR-ADC HNSCC

HER2-ADC Breast cancer

Oral Solid Dispersion

BCSII Hypolipidemic

BCSIII Diabetes

Immunotherapy APDC Lung cancer

About Us –ITRI Drug Delivery Technology Dept.

12


Any Problem About ADC?

Let ITRI Help You!

13

Contact:Kang-Li Wang ([email protected])Ping-Fu Cheng ([email protected])

mailto:[email protected]?subject=About%20ITRI-ADC%20Platform

mailto:[email protected]

itri-adc platform: antibody-drug conjugate proprietary ......kang-li wang ([email protected])...

Documents