Creating Next Generation ADCs with Industry Leading DAR ...€¦ · Biotechnology News, Vol. 37, No. 4, February 2017 Kadcyla’sglobal sales is expected to reach over $1 bn in 2017

June 29, 2017

Jeiwook Chae, Ph.D.Chief Business Development Officer

LegoChem Biosciences, Inc.

Creating Next Generation ADCs with Industry Leading DAR Precision and Plasma Stability

GBC Korea 2017 | LegoChem Biosciences, Inc | 2

Agenda

▪ Backgrounder: Landscape of ADCs

▪ ADC Regulation Overview: Regulatory Requirements of ADCs by the US FDA

▪ LegoChem Bio’s ADC; site-specific conjugation and linker technologies and more


Backgrounder: Landscape of ADCs


ADC: Antibody-Drug Conjugates

ADC binds to Antigen Endocytosis

Proteolysis Drug release

ADC is an ideal drug for its high potency and specificity to the target antigen


Milestones: FDA approved ADCs

IND submission FDA approval

1993 7 years

Gemtuzumab ozogamicin (Mylotarg) (accelerated approval)(withdrawn in 2010)

Brentuximab vedotin (Adcetris)(accelerated approval )

2006 20116 years

2000

Anti-CD30(Chimeric IgG1)

Peptide MMAE

S

Anti-CD33(humanized IgG4)

Hydrazone Calicheamicin

2005 2013

Ado-trastuzumab emtansine (Kadcyla)(T-DM1)

8 years

Anti-HER2(Humanized IgG1)

DM1Thioether

N

Source: Wen Jin Wu, MD, PhD, Senior Investigator, US FDA, “Regulatory considerations and Case Studies for Antibody Drug Conjugates”, Feb 2017


FDA-approved ADCs: old failure and new success

1) Mylotarg (Pfizer): anti-CD33 gemtuzumab conjugated to calicheamycin (AML)

2) Adcetris (Takeda-Millenium / Seattle Genetics)

3) Kadcyla (Roche-Genentech / ImmunoGen)

FDA approved: Aug 2011 for relapsed Hodgkin lymphoma• 75% objective response rate in HL patients• 1/3 of the responders had complete remission

FDA approved: Feb 2013 for Herceptin breast cancer• 5.8 month longer survival than standard therapy• Significant longer progression-free survival

FDA approved: 2000, withdrawn 2010, resubmitted 2017


ADC Market - Current and Future Sales

Units: Millions USD

ADC 2013 2014 2015 2016 2017(F) 2018(F) 2019(F) 2020(F) 2021(F) 2022(F)

Kadcyla 253 586 800 864 1,089 1,208 1,339 1,476 1,596 1,709

Adcetris 273 414 557 648 773 991 1,181 1,369 1,580 1,788

Source: Global Data (Accessed April 2017), Roche Annual Report, Seattle Genetics Annual Report; Manning, D. "Antibody-Drug Conjugates: Catalysts for Chemistry", Genetic Engineering & Biotechnology News, Vol. 37, No. 4, February 2017

Kadcyla’s global sales is expected to reach over $1 bn in 2017.

With 7-10 new commercial ADC launches projected in the next decade, the global ADC market is estimated at $10 billion annually after 2024.

500

1,000

1,500

2,000

2,500

3,000

3,500

2011 2012 2013 2014 2015 2016 2017(F) 2018(F) 2019(F) 2020(F) 2021(F) 2022(F)

ADC (Kadcyla, Adcetris) Sales Forecast

Kadcyla Adcetris

Millions


Number of ADCs in active clinical testing

Source: ADC Beacon, World ADC Berlin, Feb 2017


Increasing ADC IND submissions at US FDA


Nu

mb

er o

fA

DC

IND

s 4540353025201510

50


Number of ADCs by disease indication

Notes:• Phase 2 trials include any trials that are phase 1/2 • Adcetris is in trials for solid tumors as well as licensed for hematological cancer



Increasing diversity of payloads

Notes:• At least 19 different payloads for ADCs have been tested in clinical trials• Rapid expansion since 2013• Several ADCs have not disclosed payload details



ADC component: Payloads


Nu

mb

ero

fp

rod

uct

s

454035302520 1510

50

Other

Traditional chemotherapies

Enzyme targeting agents

DNA targeting agents

Microtubule targeting agents


ADCs in development


Regulatory Requirements of ADCs by US FDA


ADC Regulation Overview

• There is no specific Regulatory Guidance to Industry on ADC development

• FDA follows existing guidelines for small drugs and monoclonal antibodies toregulate ADC

• ADC review is a collaborative effort across product quality offices at FDA:

o Office of Biotechnology Products (OBP)/Office of Pharmaceutical Quality(OPQ) of CDER: antibody intermediate, and the drug substance (DS) and drug product (DP)

o Small molecule review groups in OPQ: review of the adequacy of the payload andlinker, conjugation reaction and aspects of the control strategy



ADC success depends on optimization of each component

Source: Chari RV. Accounts of Chemical Research, 2008;41:98-107; Teicher BA. Current Cancer Drug Targets, 2009;9:982-1004

Attachment Site

Linker Payload

Antibody Linker / conjugation Drug (Payload)

• Target specificity (tumor):Drug delivery

• Target binding affinity: Unaltered compared to naked mAb

• Internalization: Rapid process

• Target expression: High on tumor cell surface, low in normal tissues

• Stable in plasma and labile in target cells to release drug in the active form

• Stable upon storage

•High potency

•Linkable

•Water soluble

•Validated mechanism of action


Characterization of mAb intermediate and ADCmAb intermediate ADC-specific

Primary structure amino acid (aa) composition, N-terminal/C-terminal sequence analysis, peptide mapping

drug attachment sites

Conformationalstructure

size and charge variants, molecular weight drug load distribution anddrug/antibody ratio (DAR)

Posttranslational modifications

e.g., sialic acid determination, monosaccharide content and oligosaccharide profile analysis

Impurities product-related Impurities, e.g., dimers, aggregates and degradation products

process-related Impurities, e.g., microbialcontaminants, HCP, host cell DNA

free drug and its related substance, residual solvents, heavy metals and unconjugated mAb

Biological activity target specific binding and binding affinity, and effector function

cytotoxicity

• The expectations for the characterization of unconjugated mAb are the same whether or not it will be developed on its own or as part of an ADC

• Conjugation may impact on mAb: 1) binding affinity and effector function, 2) primary structure and posttranslational modifications , 3) size and charge variants.



ADC DS and/or DP release specifications

• Appearance, pH, osmolality, totalprotein

• Identity

– binding

– charge based

– peptide mapping

• Impurities – drug

– free drug and its related substances

– residual solvents

– heavy metals

• Drug/antibody ratio

• Purity/Impurities – mAb

– monomer, fragments and

• aggregates

– charge variants

– unconjugated antibody

• Particulate matter (USP<788>)

• Safety

– Endotoxin

– bioburden/sterility

– Binding

– cytotoxicity assay

• Potency



Drug/Antibody ratio (DAR) and drug load distribution (cysteine-linked ADC)

(Ouyang J. Antibody-Drug Conjugates, Methods Mol Biol 2013;1045:275-83.)

1. The hydrophobic interaction chromatography (HIC) method has been developed to determine the drug load distribution and DAR for cysteine-linked ADCs (similarly, MS-based method has been developed for lysine-linked ADCs)

2. Based on the drug load profiles, drug load distribution and DAR can be calculated3. Site of Attachment: Peptide map ‘fingerprint’ of drug-containing peptides shows consistency

between processes at different scales and sites

A representative HIC chromatogram



DAR and drug load distribution

➢ They are critical product quality attributes➢ They determine the drug quantity to which the patient is exposed➢ Various drug-loaded forms may differ in their PK/PD characteristics

(Basa L. Antibody-Drug Conjugate, Methods Mol Biol 2013;1045:285-293)


ADC Stability

• DS and DP stability studies‐ Stability testing methods and acceptance criteria‐ Test time/intervals‐ Storage conditions: long-term, accelerated and stressed‐ Stability indicating assays

• ADC serum stability‐ Linker stability

Source: Wen Jin Wu, MD, PhD, Senior Investigator, US FDA, “Regulatory considerations and Case Studies for Antibody Drug Conjugates”, Feb 2017; LegoChem Biosciences


Issues identified in pre-IND meeting packages

1.The sponsor considered the small molecule of ADC as DS

- The small molecule potion of ADC is considered as an intermediate, and

antibody conjugated with small molecule via a linker is considered DS.2.The mAb potion of ADC was functioning to target cancer cells and was notconsidered as an active molecule in the ADC. Therefore, the sponsor thoughtthe antibody component would not need further CMC characterization

-The mAb is a component of the mechanism of action of ADC. The expectations for characterization of the mAb intermediate are the same whether the mAb is used alone or as part of a conjugated structure.

3.The sponsor proposed to use “non-GMP DM1 reagent” in the GMP manufacturing of preclinical and clinical lots of ADC

- DM1 is not a reagent. It is a drug substance intermediate. Therefore, DM1

should be manufactured under GMP.

Source: Wen Jin Wu, MD, PhD, Senior Investigator, US FDA, “Regulatory considerations and Case Studies for Antibody Drug Conjugates”, Feb 2017; LegoChem Biosciences


ADC success depends on optimization of each component

Source: Chari RV. Accounts of Chemical Research, 2008;41:98-107; Teicher BA. Current Cancer Drug Targets, 2009;9:982-1004

Attachment Site

Linker Payload

Antibody Linker / conjugation Drug (Payload)

• Target specificity (tumor):Drug delivery

• Target binding affinity: Unaltered compared to naked mAb

• Internalization: Rapid process

• Target expression: High on tumor cell surface, low in normal tissues

• Stable in plasma and labile in target cells to release drug in the active form

• Stable upon storage

•High potency

•Linkable

•Water soluble

•Validated mechanism of action


LCB’s ADC


Unmet needs of ADC and LCB’s Solutions

Attachment Site

Linker Cytotoxin

Antibody Conjugation Linker Toxin

Limitation of conventional

ADCs

• Change of parental antibody’s properties (Aggregation ↑, toxicity ↑, stability ↓, T1/2 ↓)

• Random conjugation (heterogeneous mixture)

• Unstable linker • Premature toxin

release

• Conventional MOA• Less-potent for

different targets

Unmet needs & LCB’s

Solutions

✓ Preservation of parental antibody’s properties(Aggregation ↓, toxicity ↓, stability ↑, T1/2 ↑)

✓ Site-Specific Conjugation(homogenous)

✓ Plasma stable linker✓ Efficient toxin release

only within cancer cells

✓ Tailored Toxin for each ADC

✓ Differentiated Toxin with novel release MOA

Creating site-specific ADCs using LCB’s proprietary linker with superior plasma stability


Limits of First Generation ADCs

0 1 2 3 4 5 6 7 8 9

Drug Distribution

0 1 2 3 4 5 6 7 8 9

Drug Distribution

Highly Heterogeneous

• 80-90 Lysine residues/mAb

• ~50% of Lysine is available for drug conjugation

• >2000 isomers when 2 drugs are attached

• Loss of Lys charges mAb integrity is disturbed

Less heterogeneous than Lys-ADC

• 4 inter-chain Cysteine pairs/mAb

• 3 isomers generated when 2 drugs are attached

• Structural integrity of the antibody is disturbed

Cys-ADC

Lys-ADC

Higher drug-loaded species → antibody character ↓, ADC stability ↓, T1/2 ↓, aggregation ↑ → Therapeutic Index ↓


Thiol-Maleimide Conjugation

N

O

O

DrugmAb SH

mAb S

N

O

O

Drug

S

N

O

O

Drug

R

blood stream(pH ~ 7.4)R-SH

RSH : albumin cystein, GSH

Thiol-maleimide conjugate

“Recently, it was shown that a slow transfer of the drug from the ADC to albumin cysteines in the plasma occurs with alkyl-maleimide ADCs”

Bioconjugate Chem, 2010, 21, 5

Resulting in off-target toxicity → Therapeutic Index ↓


LCB’s next-generation ADC Platform (ConjuAll™)

LCB’s ADC Approach

Site-SpecificConjugation

Linker Stability

Efficient ToxinRelease

Universality(Ab carrier, Toxins)

Tailored DAR & hybrid toxins

✓ Defined DAR

✓ PK of ADC = mAb PK

✓ Simple 2-step process (Efficient production)

✓ Proprietary conjugation patent granted in the US

✓ Superior stability (best stability globally)

✓ Proprietary linker patent granted

✓ Efficient toxin release with cancer cells vs. competitors

✓ Using trigger for toxin release (beta-glucuronide/ cancer-specific lysosomal glucuronidase)

✓ Antibodies: Various antibodies including Herceptin, Mesothelin, CD19

✓ Toxins: Diverse toxins incl. MMAE, MMAF, PBD, etc.

✓ Extended applicability to Protein-Drug Conjugates (PDCs)

✓ Tailored DAR, defined distribution (DAR = 2, 4, 6, 8…)

✓ Allowing the use of hybrid toxins (Dual payloads) across different indications

DAR 2

DAR 4

DAR 6

DAR 8

Hybrid

Plasmid


Summary: LCB’s Solutions to conventional ADCs

LCB’s Linker Genentech’s Linker (Jan 2016)

Site-Specific Conjugation PK of ADC = mAb PK

Linker Stability

LCB’s Approach

Cancer-Specific Release

Toxin release by beta-glucuronide trigger

1

10

100

0 2 4 6 8 10 12 14

Pla

sm

a c

on

ce

ntr

ation

(μ

g/m

L)

Time (day)

ADC (rat PK, 3 mpk, IV)ADC14-0110_DAR2

Herceptin

LCB HER2 ADC

Summary of LCB HER2 ADC

Significantly better

▪ Efficacy

▪ DAR Stability

▪ PK Profile

compared to competitor’s HER2 ADC


HIC AnalysisLCB14-0110(Herceptin-LC-LBG*-MMAF, DAR2)

farnesyl pyrophosphate analog (FPP)

mAb-CAAX

mAb-CAAX-FPP

mAb-CAAX-FPP-linker-drug

Enzymatic Rxn.

Chemical Rxn.

LCB’s Linker-Drug

* LBG: LCB’s proprietary BG linker

Herceptin-LC-CAAX after prenylation

30ug loaded

Herceptin-LC-CAAX20ug loaded

LCB14-0110(ADC) 30ug loaded

LCB’s ADC preparation is highly efficient and homogeneous


HIC AnalysisLCB14-0110(Herceptin-LC-LBG*-MMAF, DAR2)

farnesyl pyrophosphate analog (FPP)

mAb-CAAX

mAb-CAAX-FPP

mAb-CAAX-FPP-linker-drug

Enzymatic Rxn.

Chemical Rxn.

LCB’s Linker-Drug


Herceptin-LC-CAAX after prenylation

30ug loaded

Herceptin-LC-CAAX20ug loaded

LCB14-0110(ADC) 30ug loaded

LCB’s ADC preparation is highly efficient and homogeneous


DAR AnalysisLCB14-0110(Herceptin-LC-LBG*-MMAF, DAR2)

a

a

Data generated by Prof. Young G. Shin


DAR2 is confirmed with intact protein analysis using Q-TOF


PK Profile and DAR stabilityLCB14-0110(Herceptin-LC-LBG*-MMAF, DAR2)


Drug-Antibody Ratio (DAR) in Monkey

Drug-Antibody Ratio (DAR) in Rat

Superb DAR stability

LCB14-0110

LCB14-0110 (N=2, infusion)


PK ProfileThio-trastuzumab vc-MMAE (Genentech)

Sukumaran et al., 2014

In Thio-trastuzumab vc-MMAE, relatively rapid decrease of higher DAR fraction observed in mice


PK Profile LCB14-0110(Herceptin-LC-LBG*-MMAF, DAR2)

Terminal half-life (day)

Herceptin Kadcyla LCB14-0110

Rat 12.5 (3 mpk) 3.8 (6 mpk) 9.8 (3 mpk)

Monkey 8.3 (3 mpk) 2.5 (3 mpk) 10.9 (3 mpk)

Human 28.5(4 2 mpk) 4 (3.6 mpk) TBD

AUC (µg*day/mL)

Herceptin Kadcyla LCB14-0110

Rat 481.1±104.3 (3 mpk) 426±28.1 (6 mpk) 366.9±69.2 (3 mpk)

Monkey 623.1±78.2 (3 mpk) 180 ±15.0 (3 mpk) 838.8±114 (3 mpk)

Human 578 (4 2 mpk) 300 (3.6 mpk) TBD

Much better PK profile than Kadcyla



In vivo Anti-tumor Efficacy (JIMT-1, Her2 2+)

HER2-ADC in Kadcyla-resistant

Breast Cancer Xenograft Model

* Data generated by Asan Medical Center

LCB’s anti-HER2-ADCs

Linker-toxin/DAR

LCB14-0110 LBG-MMAF/DAR2


single iv. dosing

0

500

1,000

1,500

2,000

2,500

3,000

0 10 20 30 40 50 60 70 80 90

Tu

mo

r vo

lum

e (

mm

3)

Day after treatment

PBS

Herceptin 5mpk

ADC14-0110 2mpk

ADC14-0110 5mpk

ADC14-0127 2mpk

ADC14-0127 5mpk

• Herceptin resistant, HER2 positive breast cancer cell-line (IHC : Her2 2+)• Herceptin has no efficacy at 5 mpk• Herceptin(5 mpk) ≪ LCB14-0110 ≪ LCB14-0127• DAR4 > DAR2 at 2 mpk & 5 mpk in terms of efficacy


LCB14-0110, 2mpk

LCB14-0110, 5mpk

LCB14-0127, 2mpk

LCB14-0127, 5mpk


Anti-HER2 ADCIn vivo Anti-tumor Efficacy (NCI-N87): LCB14-0110 (Herceptin-LC-LBG*-MMAF)

01280127

01130110

T-DM1

0133

Herceptin

PBS

HER2-ADC in Gastric Cancer

Xenograft ModelLCB’s anti-HER2-ADCs

Linker-toxin/DAR


LCB14-0113 LBG-MMAE/DAR2


LCB14-0128 LBG-MMAE/DAR4

LCB14-0133 VC-MMAF/DAR2

single iv. dosing

• Herceptin has no efficacy at 5 mpk• Herceptin(5 mpk) << T-DM1(2mpk) < ADC110, ADC113 << ADC127, ADC128• DAR4 > DAR2 at 2 mpk in terms of efficacy• MMAF≒MMAE at 2 mpk in terms of efficacy

* Data generated by Asan Medical Center

* LBG: LCB’s proprietary BG linker* LC: Light Chain


LCB14-0110, 2mpk

LCB14-0127, 2mpk

LCB14-0113, 2mpk

LCB14-0128, 2mpk

LCB14-0133, 2mpk

LCB14-0110LCB14-0113

LCB14-0127LCB14-0128

LCB14-0133


Anti-HER2 ADCIn vivo Anti-tumor Efficacy (PDX): Herceptin-LC-LBG*-MMAF

LBG-MMAF/DAR4

0

500

1000

1500

0 5 10 15 20 25 30 35 40 45 50

Tum

or

volu

me

(mm

3)

Days after treatment

HER2-ADC in Gastric Cancer PDX Model

PBS T-DM1 2 mpk DAR4 ADC 2mpk

single iv. dosing

HER2 positive, IHC3+, gastric cancer patient

Collaboration with Professor Choi Eun Kyung in Asan Medical Center


LC-LBG-MMAF shows excellent efficacy against HER2-positive, IHC3+Patient-derived gastric cancer model



Anti-HER2 ADCIn vivo Anti-tumor Efficacy (PDX): Herceptin-LC-LBG*-MMAF

LBG-MMAF/DAR4


Collaboration with Professor Choi Eun Kyung in Asan Medical Center

0

400

800

1200

1600

0 5 10 15 20 25 30 35 40

Tum

or

volu

me (m

m3)

Days after treatment

HER2-ADC in Gastric Cancer PDX Model

PBS

DAR2 ADC (5mg/kg, Q2Wx2)

T-DM1 (5mg/kg, Q2Wx2)

DAR4 ADC (5mg/kg, Q1D)

DAR4 ADC (5mg/kg, Q2Wx2)

DAR4 ADC (2mg/kg, Q2Wx2) HER2 positive, IHC2+, gastric cancer patient

Q2W iv. dosing

LC-LBG-MMAF shows excellent efficacy against HER2-positive, IHC2+Patient-derived gastric cancer model



Anti-HER2 ADCIn vivo Anti-tumor Efficacy (SK-OV3): LCB14-0110 (Herceptin-LC-LBG*-MMAF)

* Data generated in-house

HER2-ADC in Ovarian

Cancer Xenograft Model

single iv. dosing

0

500

1,000

1,500

2,000

2,500

3,000

3,500

0 5 10 15 20 25 30 35

Tu

mo

r V

olu

me (

mm

3)

PBS

Herceptin 5mpk

T-DM1 5mpk

ADC14-0110 5mpk



LCB14-110(LC-LBG-MMAF) shows excellent efficacy against ovarian cancer cell line SK-OV3


LCB14-0110, 5mpk


Key Comparisons Summary

Conventional Approaches LCB’s Approach

ADC structure▪ Heterogeneous Mixture -difficulties in

CMC (reproducibility, impurity profiles…)▪ With defined mAb-drug ratio w/o stereo

isomers

DAR ▪ Heterogeneous, ~4 (average) ▪ 2, 4 (higher, if necessary)

Conjugation method

▪ Mostly thiol-maleimide method▪ With disruption of mAb structure

(@cys or lys)

▪ No thiol-maleimide route employed▪ Minimum perturbation of original

structure

Linker chemistry▪ Unstable (retro Michael reaction of thiol-

maleimide) lowers therapeutic index▪ Cleavable (LBG) & non-cleavable▪ Highly stable


Efficacious and Stable ADC with Wider TI

1st generation technology with non-site-specific, unstable linker → Narrow Therapeutic Index (TI)

Source: Panowksi, Siler, et al. (2014) "Site-specific antibody drug conjugates for cancer therapy", MAbs, v.6(a); 2014 Jan 1 (modified by LCB)

Therapeutic Window

Toxic dose (MTD)

Efficacious dose (MED)

Therapeutic Window

Toxic dose (MTD)


Wider Therapeutic Window

Toxic dose (MTD)


Dru

g D

ose

Lowering toxicity through plasma stable linker and selective delivery to tumor cells

Increasing efficacy by efficient in-tumor toxin release and superior PK

1st generation ADCsChemotherapy LCB’s next-generation ADC


LCB Pipelines of ADCProduct / Target Indication Discovery Preclinical Partner Commercial Rights

AD

C P

rod

uct

s

HER2 Solid tumorLCB: Worldwide (ex China)

Fosun: Greater China

Undisclosed Solid tumor Takeda: Worldwide

Mesothelin Solid tumor LCB and Green Cross

Undisclosed Solid tumorLCB: Worldwide (antibody in-licensed from Samsung Medical Center)

Undisclosed ALL, NHL, DLBCL LCB and Novimmune

CD37 NHL, CLL, AML LCB and Nordic Nanovector

Undisclosed CLL, MCL, Solid tumor LCB and Ardeagen

Undisclosed Various LCB and Theranyx

Undisclosed CLL, MCL, Solid tumor LCB and ABL BIO

Undisclosed Solid tumor LCB and ABL BIO

Undisclosed Various LCB and Y Biologics

Undisclosed Solid tumor LCB and Company S

Undisclosed Solid tumor LCB and Company M

PNS* Undisclosed LCB and Seasun Biomaterials

* PNS: Peptide nucleic acid

Company S (EU)

Company M (EU)

Available for out-licensing

Available for L/O

Available for L/O

Available at candidate selection











LCB Collaborations

Over 10 ADC projects are underway in collaboration with partners with

antibodies or toxin/agents

Partner’s

Partner’s


About LegoChemBio

Leader in novel drug development with top researchers, technology, system, and global experiences

Who we are?

• In Brief

- Founded in May 2006

- IPO in May 2013

- 106 employees (58 in R&D)

- Capital KRW 4.97bn

- CEO Yong-Zu Kim, PhD

- HQ in Daejeon

• Experience from discovery

stage through development

to US FDA approval

• Global out-licensing

experience

• “Emerging Company of the

year (Biospectrum)

• “K-Brain Power” (MOTIE)

What is Core Competence?

• LegoChemistry TM:

Chemical synthesis

technique

• ConjuAll TM: Next-

generation ADC

Technology

• Focused in

antibiotics,

anticoagulant,

oncology, ADC

How we do?

• Project selection

know-how

• Gate Decision

System

What we have?

• Development:

- 1 Phase II

- 2 Phase I

- 3 Preclinical

- 1 Commercialized

- ADC technology

• Business

- 7 Out-licensed

- 10 MTA /

Research Collaboration

Your success is only limited by

your creativity.

Dr. Jeiwook Chae, Chief Business Development Officer

Phone +82 (0)42 861 0688 Fax +82 (0)42 861 0689 Email [email protected]

Thank you.

Documents

Creating Next Generation ADCs with Industry Leading DAR ...€¦ · Biotechnology News, Vol. 37, No. 4, February 2017 Kadcyla’sglobal sales is expected to reach over $1 bn in 2017