Medicilon Introduction-Preclinical CRO

MEDICILON
One-stop pharmaceutical
R&D service platform

We have established a comprehensive service
technology platform, which integrates compound
synthesis, compound activity screening, structural
biology, CMC, pharmacodynamics evaluation,
pharmacokinetics and toxicological safety evaluation.
IND
Enabling
Package
CMC
Development
Drug
Discovery
Preclinical
Research
IND
Enabling
Package

 Founded in
Zhangjiang, Shanghai
 Chemistry services
 Biology & Structural
Biology
 PK
 First integrated
service project, FTE
based
Medicilon is a leading Preclinical CRO in China,
with years’ experience in pharmaceutical
R&D outsourcing services.
 20,000 m2 new labs
 Joint Venture with
MPI Research
 US GLP standard
preclinical studies
 AAALAC certification
 Pharmacology
Services
 Established isotope
laboratory
 NMPA GLP
Certificated
 Provided packaged
services for NMPA
and FDA IND filing
 New drug
registration &
regulatory services
 Antibody drug R&D
services
 Expansion of tumor
center
 Chemical process
service

 10,000 m2 new labs
 Established
academician work
station
 Immuno-oncology
studies
 Inflammation and
CNS studies
 Safety evaluation
service for inhalation
drugs
 Safety evaluation
service for
ophthalmic drugs
 Clinical biological
sample testing
service
 cGMP API/DP
 FDA GLP certified
 40000 m2 Nanhui
R&D Center started
operation
 IPO
 Immuno-oncology integrated
solutions developed for oncolytic
viruses, RNAi, CAR-T and
vaccine research technology.
 PROTAC drug discovery
technology platform established.
introduced DEL RNA drug
screening technology, and AI
technology
 Established large animal
pharmacodynamic model
platform and cell & gene therapy
(CGT) platform
 Include in the MSCI China A-
Share Index
 Established high potency drug
laboratory, PROTAC in vitro
research and development
platform, nucleic acid drug
synthesis platform, etc.
 Medicilon (Hangzhou) inc.
officially in operation
 Medicilon (Baoshan) Inc. started
construction
 Nanhui R&D center expanded
MEDICILON

MEDICILON
Ph.D.
Shuangqing Peng
Ph.D.
CSO
Jinna Cai Ph.D.
CBO
Xuedong Dai
Ph.D.
IDSU EVP
Xingquan Ma
Ph.D.
Chemistry Senior VP
Jian Liu Ph.D.
President of
Drug Discovery
Xiaolong Qiu
Ph.D.
Process E. Director
Dan Wang Ph.D.
Head of Formulation/
Senior Director
Jing Deng
Ph.D.
Pharmacology & Bio VP
Xiancheng Zeng
Ph.D.
Toxicology VP
Christopher Stewart
DABT/Ph.D. Consultant
Yongmei Xu Ph.D.
Chemistry VP
(Hangzhou)
Zhigang Li
Ph.D.
Chemistry R&D VP
Jian Wang
Ph.D.
IDSU E. Director
Zhuo Mao
Ph.D.
Biology Director
Bao Liu
Ph.D.
API Senior Director
Jian Tang Ph.D.
Formulation
Senior Director
Jian Du Ph.D.
Analytical Head for CMC
Drug Substance
Wenxin Dong
Ph.D.
Pharmacology VP
Baohong Cao
Ph.D.
Pharmacology VP
Jingxuan Zhang
Ph.D.
Toxicology VP
Renzong Xie
Ph.D.
Toxicology VP, DABT

MEDICILON
years
R&D Experience
Since 2004
3100+
Scientists &
Research staff
87500+
m2 Laboratories
and Facilities
2000+
Clients
Worldwide
：
NMPA IND
Approved
80
Biologics
IND Approved
66
FDA
IND Approved
：
International
IND Approved
9
TGA
IND Approved
1
EMA & KFDA
IND Approved
227
Chemical Drugs
IND Approved
4
Traditional Chinese
Medicine Approved
*Data as of 2023.06
19
NMPA IND approved
in 2022
67
NMPA IND approved
in the past 3 years
168
International IND
approved in the past
3 years
46
International IND
approved in 2022

MEDICILON
Medicilon (Baoshan)
(Under construction)
located in Shanghai and Hangzhou
• More than of pharmaceutical R&D outsourcing service experience
Medicilon (Nanhui)
Bio-tech Park
(57,000 m2)
Medicilon (Chuansha)
Headquarters
(20,000 m2)
Medicilon Zhangjiang
High-tech Park
(3,000 m2)
Medicilon (Hangzhou)
(3,000 m2)
• Pharmacology Lab
• Isotope Lab
• Chemistry Lab
• Biology Lab
• CMC Lab
• GLP Animal Facility
• Chemistry Lab,
• Process Development Lab
• GMP Facility
• Animal Facility
• Chemistry Lab,
• Process Development Lab
• Biology
• Scale-up Process Chem
• API Process Chem
U.S. Boston
(Under construction)
• Medicinal Chem Labs
• DMPK Labs

Med Chem
Synthetic Chem
Scale up Process
Analytical Chem
Protein Science
Structural Biology
Biology Assay
Drug Discovery
DS/ API Process
DS/ API Quality
DS/ API Stability
DMF
DP Process
DP Quality
DP Manufacture
Generic Drug
CMC Development
Tumor
Digestive
Endocrine &
Metabolic
Inflammatory
Central Nervous
System
Absorption
Distribution
Metabolism
Excretion
In Vitro ADME
In Vivo DMPK
Toxicology
Reproductive
Genetic
Toxicology
Safety
Pharmacology
Toxicokinetics
Preclinical Research
MEDICILON

MEDICILON
Druggability
Study
Pharmacology
Study
Preclinical
Study
Clinical
Sample
Analysis
API DMF
Formulation
Development
Animal pre-BE
Clinical Sample
Analysis
Antibody Discovery Preclinical Study Clinical Sample Analysis
New
Drug
Generic
Drug
Biologics
Early Discovery

Antibody Drugs one-stop R&D
Service platform
Drug discovery and screening
Using Crystallization
Animal Disease Models for
Pharmacodynamics Research
New Drug Formulations and
Quality Consistency Evaluation
Protein/ Antibody Drugs PK
Research
Isotope Drug Metabolism
Research
Non-human Primate Safety
Evaluation
New Drug Safety Evaluation in
compliance to FDA regulations
MEDICILON

MEDICILON
PROTACs drug R&D platform
Oligonucleotide drug
R&D platform
ADC drug R&D platform
mRNA vaccine bioassay
technology platform
Inhalation drug delivery
R&D platform
Cellular immunotherapy drug
R&D platform
Ophthalmic drug delivery
R&D platform
MetID platform
Topical skin drug delivery
R&D platform

~ 1100 chemists and analytical chemists
~ 60 biologists
~ 41000 m2 Chemical Lab.
~ 4500 m2 Biological Lab.

 Protein Degradation Technology
(PROTAC Technology)
 ADC Synthesis
 siRNA/ASO Synthesis
 Photoreduction
 Electrochemistry
 Green Chemistry
 Catalyst Screening
New Drug R&D
Services Platform
 Compound Library
 Activity Screening
 Conventional/AI drug design
 Structure-effect relationship
studies
 Lead compound identification
 Preclinical Candidate Compound
(PCC) Identification
Medicinal Chemistry
 Preparation of special reagents,
intermediates and molecular
fragments
 Preparation of standards
 Synthetic design and preparation
of impurities or metabolites
 Synthesis of stable isotope
internal standards
 Synthesis of deuterated
compounds
Custom Synthesis
 Reference compound synthesis
 Hundred-gram scale high purity
sample synthesis for animal
studies
 Synthesis of kilogram-scale
samples
 Preparation process study of
target compounds
Scale-up Synthesis

 Dedicated to
research
 Flexible team
 Efficient
 Visible
progress
 Controllable
project
Dedicated R&D & Management Team
The Medicilon FTE team can serve clients
at different stages of drug development,
including generation and optimization of
lead compounds, identification and
optimization of lead compounds, synthetic
scale-up and chemical process studies.
Flexible adjustment based on
project requirements
This cooperation model is based on customer
and project requirements, and can flexibly
adjust the R&D staffing, experimental protocols,
project priorities, etc.
The fees charged for the FFS
model depend on the type of
specific experiment, the
method and the number of
compounds to be tested, etc.
Customization of needs
Timed completion of synthesis
from small-scale quantities
(milligrams to hundred-grams) to
medium-large scale quantities
(hundred-grams to kilograms)
Service
Model
Synthesis of various target
compounds
These classes include drug reference compounds,
lead compounds and their derivatives,
combinatorial chemical templates and other drug-
like compounds with or without references

FFS On-time
delivery rate
Chemical reaction
success rate
FTE delivers
approx.
compound
per person/week
Number of reactions
completed
per person/week
The chemistry department of Medicilon has 1500 employees:
 About 40% have a PhD or Master's degree
 More than 10% of the employees have a foreign education and/or
work experience
 Average working experience of
junior research staff (researchers) : 3-5 years
middle-level researchers (group leader level): 8-10 years
senior level (director level and above): 15-20 years
Medicilon Research Staff:
Chemical Synthesis Lab

PROTAC drugs：
Proteolysis-Targeting Chimeras, as known as PROTAC, is
a heterogeneous bifunctional small molecule compound
consisting of a target protein ligand, an E3 ubiquitin ligase
ligand and a Linker, with the two ligands linked to each
other by the Linker.
PROTAC technology has a unique mechanism:
PROTAC molecules specifically
recognize and bind target
proteins through a target protein
ligand (POl Ligand) at one end
of the molecule, and specifically
recognize and bind E3 Ligase
through an E3 Ligase Ligand at
the other end of the molecule.
Formation of the POI-PROTAC-
E3ligase ternary complex.
In this ternary complex, the
target protein POI is
ubiquitinated by E3 ligase, and
the ubiquitinated POI is
subsequently recognized and
degraded by the proteasome,
thereby inhibiting the function of
the target protein.
Medicilon PROTAC Services.：
1. Design & synthesis of the target protein PROTAC-POI
Medicilon has compiled the current popular POI ligands, E3ligase
ligands of different tissue types, and established a linker library
containing hundreds of linker molecules. In addition, Medicilon's mature
computer-aided drug design technology platform greatly improves the
quality of PROTAC-POI design and synthesis.
3. In vivo drug efficacy screening of PROTAC-POI
 CDX mouse tumor model
 PDX mouse tumor model
 PK/PD studies, pharmacological analysis, pharmacokinetic studies
and safety evaluation
2. In vitro screening of PROTAC-POI
 High throughput screening of
HiBiT-labeled-POI stable cell
lines
 Western Blot or In-cell Western
 HTRF or MSD
 AlphaLisa or HTRF
 NanoBRET
 Cytotoxicity assays

Challenges in PROTAC
Drug Discovery
 Lack of patterns and standards
 Chemical/synthetic Complexity
 How to quickly and effectively screen
for target protein
 Efficacy
 …
 Broad experience in design, synthesis
and validation
 Fast turnaround time
 High KPI & Productivity with competitive
pricing
 Validated PROTAC targets in Medicilon
IRAK4, AR, ER, IKZF1, IKZF2, IKZF3, BTK, EGFR, BRD4,
BCL-xL, CDK4, CDK6, SMARCA2, SMARCA4, AKT, ALK,
STAT3, SHP2, FGFR1, FGFR2, KRAS G12C, KRAS G12D
 API-CMC
 ADME/DMPK
 Pharmacology, toxicity, IND enabling
One-stop shop services

Medicilon has:
• Know-how: > 6 years PROTACs
experience
• Comprehensiveness: > 20
ongoing projects
• Team: > 300 dedicated well-trained
chemists
• Building Block: > 300 advanced
linkers Available
• Scaffold: > 150 E3 ligands available
including Cereblon, VHL, MDM2, IAP, etc.
Dedicated Purification team:
 >50 PROTACs purification system
 >95% purification success rate
 >80% recovery rate
 <48 h purification cycle time
Service scope：
 PROTACs Chemistry
 PROTACs in vitro Evaluation
 PROTACs in vivo Evaluation

Popular nucleic acid drug classes:
ASO siRNA mRNA Aptamer
Waters BioAccord LC-MS
System with ACQUITY
Premier UPLC
Equipment： Waters BioAccord LC-MS System for
Small Nucleic Acid Mass Spectrometry
The system includes an inert ACQUITY UPLC I-Class
PLUS system, a variable wavelength ultraviolet detector,
and a compact time-of-flight (ToF) mass spectrometer,
the ACQUITY RDa mass spectrometer. BioAccord offers
a wide range of solutions (complete protein and peptide
map analysis, MAM, glycosyl, oligonucleotide analysis,
as well as accurate mass number determination of small
molecules, impurity analysis, etc.), ease of use, stable
inter-system performance, compact size, and a
regulatory compliant informatics system, Waters_connect
Nucleotide monomer
Oligonucleotide
Delivery system
Oligonucleotide coupling
Sugar
Nucleobase
Backbone
Delivery system
synthesis
modification
R&D Capabilities
Medicilon's nucleic acid drug discovery platform is an
integrated and comprehensive platform for drug discovery,
manufacturing and preclinical research. Medicilon has built an
siRNA library with not only a rich inventory of monomers, but also a large
library of monomer synthesis blocks, which can rapidly complete the
synthesis of various types of modified monomers. Medicilon has a
professional small nucleic acid drug development team, and several siRNA
drug FTE projects have been completed and are in progress.

 Sugar: >80 monomer Units
O N
N
O
O
DMTrO
NHBz
dC(Bzl)-Me
O N
H
N
O
O
DMTrO
O
dT
O
N
O
DMTrO
N
N
N
NHBz
dA(Bzl)
dG(ibu)
O
N
O
DMTrO
N
N
N
O
N
H
P
N O N
P
N O N
P
N O N
P
N O N
O
O N
H
N
O
O
DMTrO
O
dU
P
N O N
O N
N
O
O
DMTrO
NHBz
dC(Bzl)
P
N O N
O
N
O
DMTrO
N
N
N
NHBz
P
N O N
O
2'-OMe-Bz-dA
110782-31-5
O N
N
O
O
DMTrO
NHBz
P
N O N
O
2'-OMe-Bz-dC
110764-78-8
O N
H
N
O
O
DMTrO
O
P
N O N
O
2'-OMe-dU
110764-79-9
O N
H
N
O
O
DMTrO
O
P
N O N
O
2'-OMe-dT
168611-18-5
O N
N
O
O
DMTrO
NHBz
P
N O N
O
166593-57-3
2'-OMe-Bz-5-Me-dC
O
N
O
DMTrO
N
N
NH
O
P
N O N
O
2'-OMe-iBu-dG
N
H
O
150780-67-9
O
N
O
DMTrO
N
N
N
NHBz
P
N O N
F
2'-F-Bz-dA
O N
N
O
O
DMTrO
NHBz
P
N O N
F
2'-F-Bz-dC
O N
H
N
O
O
DMTrO
O
P
N O N
F
2'-F-dU
O N
N
O
O
DMTrO
NHBz
P
N O N
F
2'-F-Bz-5-Me-dC
O
N
O
DMTrO
N
N
NH
O
P
N O N
F
2'-F-iBu-dG
N
H
O
136834-22-5 146954-75-8
O N
H
N
O
O
DMTrO
O
P
N O N
F
2'-F-dT
182700-06-7 182495-83-6
161442-19-9 144089-97-4

 Nucleobase modification:
N
N
O
O
O
R
O
O
P
O OH
3-methyluracil
N
NH
O
O
O
R
O
O
P
O OH
5-iodouracil
I
N
NH
S
O
O
R
O
O
P
O OH
4-thiouracil
N
NH
O
O
O
R
O
O
P
O OH
dihydrouracil
N
NH
O
O
O
R
O
O
P
O OH
5-bromouracil
Br
O
R
O
O
P
O OH
dichlorobenzene
Cl
Cl
O
R
O
O
P
O
OH
diaminopurine
N
N
N
N
NH2
NH2
O
R
O
O
P
O
OH
N-methyladenine
N
N
N
N
HN
N
NH
O
O
O
R
O
O
P
O OH
5-propynyluracil
O
R
O
O
P
O
OH
4,6-difluoro benzimidazole
N
N
F
F
HN
C
NH
O
O
O
R
O
O
P
O OH
Pseudouridine
N
NH
S
O
O
R
O
O
P
O OH
2'-thiouridine
(s2U)
N
N
O
NH2
O
R
O
O
P
O OH
5'-methylcytidine
(m
5C)
Me
N
NH
O
O
O
R
O
O
P
O OH
5'-fluoro-2'-deoxyuridine
F
O
R
O
O
P
O OH
N
N N
N
HN
Me
N6'-methyladenosine
(m
6A)
O
R
O
O
P
O OH
2',4'-difluorotoluyl
ribonucleoside(rF)
F
F
O
R
O
O
P
O OH
5'-nitroindole
ribonucleoside
N
NO2
N
N
O
O
R
O
O
P
O OH
6'-phenylpyrrolocytosine
(PhpC)
NH
Ph
O
R
O
O
P
O OH
N
N N
N
HN
N-ethylpiperidine
6'-triazole
modified adenine
N N
N
N
O
R
O
O
P
O OH
C
N
N N
N
NH2
N-ethypiperidine
7'EAA triazole
modified adenine
N
N
N
N
 Backbone modification:
O
R
O
O
P
O
Phosphorothioate
(PS, Rp isomer)
Base
O
R
O
O
Base
S
-
O
R
O
O
P
O
Phosphorothioate
(PS, Sp isomer)
Base
O
R
O
O
Base
S
-
O
R
O
O
P
S
Phosphorothioate
(PS2)
Base
O
R
O
O
Base
S
-
O
R
O
O
P
O
Methylphosphonate
(MP)
Base
O
R
O
O
Base
Me
O
R
O
O
P
O
Methoxypropylphosphonate
(MOP)
Base
O
R
O
O
Base
Me
O
R
O
P
O
5'-(E)-vinylphosphonate
(5'-(E)-VP)
Base
OH
P OH
O
OH
O
R
O
P
O
5'-Methylphosphonate
(5'-MP)
Base
OH
P OH
O
OH
O
R
O
P
O
(S)-5'-C-methyl with
Phosphate
Base
OH
P OH
O
OH
O
R
O
P
O
(S)-5'-C-methyl with
Phosphate
Base
OH
P OH
O
SH
NH
O
N
O
Base
O
HN
Peptide Nucleic Acid
(PNA)
O
R
O
O
P
N
Base
O
R
O
O
Base
OH
Ms
uPN
N
O
O
Base
P O
N
O
N
O Base
R
R
PMO
O
O
O
Base
O
O
Base
NH
O
Amide-backbone-1
O
O Base
O
O
Base
NH
O
Amide-backbone-2
O
O Base
O
O
Base
NH
O
Amide-backbone-3
R R
R
R
R
R
O
R
O Base
O
R
O
Base
S
O
HN
O
Sulfonamide-backbone
O
R
O Base
O
R
O
Base
P
O H
O
3'-Methylene H-Phosphonate
O
R
O
N
Base
O
R
O
Base
N
N
Triazole-backbone-1
O
R
O
N
Base
O
R
O
Base
N
N
Triazole-backbone-2
O
O
R
O
O
Base
O
R
O
Base
Triazole-backbone-3
N N
N
O
R
O
O
Base
O
R
O
Base
Triazole-backbone-4
N
N
N
O
R
O
N
Base
O
R
O
Base
N
N
Triazole-backbone-5
O

O
O
N
MC3
HO
N
O
O
O O
M5
LNP
 Lipid molecules show
immunogenicity in
human bodies
1500+
 Unmodified lipids cannot
be delivered to the target
GalNAc
 GalNAc does not show immunogenicity and is safer
 GalNAc targets to the ASGPR on liver cells and could be
uptaken through endocytosis
30+

A-Antibody:
Specific antibodies against a
tumor antigen that is
restricted in expression in
normal cells
D-Drug (Cytotoxic agent ):
Highly active antitumor drug
released after entering the target
cells and killing the target cells
C-Conjugate (Linker):
Coupling cytotoxins to antibodies
ADC coupling strategy:
The three main components of an ADC are the Antibody, the Linker
and the Payload.
Antibodies are responsible for target binding and can be monoclonal
antibodies, Fab antibodies, bispecific antibodies or nanobodies.
The linker connects the antibody to the payload. The linker is key to
ADC stability and is responsible for when the payload is released.
Payload is usually a highly active toxin molecule with a well-defined
mechanism of action. It has a killing effect on tumor cells.
Target:
CD33, CD30, Her2, Her3, Trop2, Nectin-4, CD79b, Muc1, FR,
Claudin18.2…..(Medicilon completed targets in blue）
Linker:
◆ Un-cleavable ◆ Cleavable
Medicilon offers 240+ fragments covering linkers and specialty linkers in
currently marketed ADCs
Payload (Listed category)：
 Calendula officinalis: MMAE; MMAF
 Medensin class：DM1；DM4
 Pyrrolobenzodiazepines & indochlorobenzodiazepines ：PBD
 Camptothecin：DX；SD38
Through in-house research and external collaborations, Medicilon can provide
all 6 toxins of the marketed ADCs. We can provide more than 20 derivatives of
the toxins in the marketed ADCs and synthesis of self-developed toxoid
Antibody Isotype：

Toxin
 DX8951f, SN-38, DM1, DM4,
MMAE/MMAF, Tubulysin M, PBD dimer,
Seco-Duocarmycin MA, PNU159682,
Doxorubicin analog, etc.
 Capability to handle novel toxin
50+
Linker
 Gly-Gly-Phe-Gly,VC-PAB, SMCC,
N-SMP, etc.
 Cleavable and un-cleavable
 Hydrophilic and hydrophobic
 Novel linker
200+
Payload
 SN-38-PEG-PAB, DXD-
GlyGlyPheGly, DXD-VCPAB DM1-
SMCC, DM1-SPP, DM4-SPDB, MC-
VC-PAB-MMAE/MMAF, MC-Val-
Ala-PBD, VC-PAB-Dolastatin 10, etc.
30+
 高活性实验室
 ADC lab with OEB4/5 Isolator
 5 mg, 50 mg, 500 mg antibody
level conjugation services
 Experimental cycle time : 2-4
weeks
 QC: SEC、HIC、LC-MS/MS etc
 DAR: 2-8
Medicilon can provide:

Electrochemistry:
 Ni-Catalyzed C-N coupling
 Ni catalyzed Sp2-Sp3
coupling
 Reduction of amide
 Heterocycles formation
 -OCF3, -SCF3, -CF3
 Fluorination
 Shono type oxidation
Photoredox Platform:
 C(sp3)-C(sp2) coupling reactions
 C(sp3)-C(sp3) coupling reactions
 Heteroatom arylations
 Enable Photoredox condition screening
 Build up flow-Photoredox reactor
 Follow up literature to expand the Photoredox
reaction scopes
Future Plan：
Medicilon has a professional technical team, the core
scientists have worked in the continuous flow field for
years. Medicilon (Shanghai) has an approx. 200 ㎡ of
continuous flow process development lab. The
reaction types that we can support include:
Continuous flow platform：
 Cryogenic metal organic
reaction
 Azide reaction，diazo
reaction
 Nitration reaction
 High temperature, high
pressure reaction
 Sulphonate reaction
 Bromination
Receive
screening
request
Prepare
screening
materials
Transfer
material to
Glovebox
Addition of
chemicals in
Glovebox
Add solvent;
then extraction
Cooling down
Heating plate
with stirring
Transfer samples
to LCMS plate
Run LCMS;
Data analysis
Result
feedback
Catalyst Screening Platform: Typical cycle time for catalyst screening is 72 hr

Analysis Services：  Chemistry  Processes  Chemistry or Processes
 SFC Separation for chiral compounds
(mg to kg scale)
 Compound preparation and purification
 Impurity preparation and structure
identification
 Routine analytical assays (LCMS, NMR,
HPLC, etc.)
 Compound solubility and stability study
 Various physical and chemical assays
(moisture, spin, IR, UV, etc.)
 HPLC, GC testing of chiral compounds
 Prep-HPLC
 NMR and quantitative NMR
 High-resolution mass spectrometry(QTOF)
 IPC support for processes
 Reference standard characterization
 Analytical method pre-validation and
method transfer
 Microorganisms, endotoxins and bioburden
 Reaction Safety Evaluation
 Analytical Method Development
 Testing of impurities and toxic
substances by HPLC and GC
 Moisture detection by KF
 GC, TGA, LOD for solvent residues

Instruments Type Number
NMR Bruker,400MHz
7 (150 personnel:1
instrument)
LC-MS Agilent 6125-ELSD/Shimadzu 2020-ELSD/Waters UPLC-Qda
65 (15 personnel:1
instrument)
HPLC Agilent/Shimadzu/Waters(DAD/VWD/RID/CAD/ELSD) 23
Prep-HPLC Waters 2545-QDa150ml/min/Gilson 281 50ml/min 46
GC-HS Shimadzu2010/PE680 (FID Detector) 3
GC-MS Agilent 5977A/Shimadzu GC-MS 2020 1
UPC2 Waters UPCC 5
Chiral HPLC Shimadzu 20AD 1
Prep-SFC Waters SFC80/SFC150/SFC350/SFC600 7
DSC/TGA METTLER 2
Waters BioAccord LCMS ACQUITY Premier UPLC-RDa 1
*Date as of 2023.02

Bruker
400 MHz NMR
Waters
HPLC
Waters
UPLC-MS
Shimadzu
LCMS-2020
Waters MS-guided
Prep-HPLC
Waters
SFC
PE ICP-MS
 Chromatography: UPLC, HPLC, LC-MS, GC, IC, SFC, UPCC, Prep-HPLC
 Solid state characterization: DSC, TGA, XRPD, PSD, Polarized light microscopy
 Analysis and identification: Nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR)
 General testing: moisture meter (KF), ultraviolet and visible spectroscopy (UV-Vis), Polarimeter
 Elemental and trace metal analysis: ICP-MS
 Small nucleic acid analysis: Waters BioAccord

High Potency Laboratory,
Department of Chemistry
Biotage Microwave Synthesis
Instrument
Gilson-prep-HPLC Thermo-CAD Ultimate 3000
UHPLC
Waters 2767 QDA
prep HPLC-ELSD
Waters UPLC (Chiral analysis) Gilson-GX281-
Prepared Liquid Chromatograph
Shimadzu HPLC - High Performance
Liquid Chromatograph

 E. coli Expression System
 Yeast Protein Expression
System
 Baculovirus Expression
 Mammalian Cell Protein
Expression Systems
 Recombinant Kinase
Preparation
 Recombinant Antibody
Expression
 Protein Crystallization Screening
 Protein-small molecule co-
crystallization condition screening
 Protein crystallization, co-
crystallization with ligands
 Three-dimensional structure
analysis
 FBDD Service
 Selenomethionine (SeMET)
medium
 Cell Level Assays
 Enzyme Level Assays
 PROTAC Molecular Screening
 High throughput screening →
CADD
 siRNA and mRNA drug discovery
 Gene therapy/cell therapy drugs
 Radioisotope analysis (3H, 33P,
32P, 35S, 125I, 14C)
 Intermolecular interaction force
detection/assay (Biacore 8K
based)
 Hybridoma Screening Platform
 Phage Display Platform
 Single B-cell sequencing
platform
 ADA Positive Antibody
Preparation
 Antibody Engineering
Modification
 Expression Cell Line
Construction
Antibody Discovery Platform
In Vitro Biology
Recombinant protein
expression & purification
Structural Biology Platform

Hit Compound
Discovery
Hit-Lead Lead
compound
optimization
Candidate
Compound
Confirmation
Preclinical evaluation
- filing
 Biology Division has been dedicated to drug discovery services for
over 19 years
 Serving over 300 clients annually
 Over 1000 screening methods established, generating over 2 million
data points per year
 Conducted conformational studies for more than 200 targets
 Cell library with over 400 tumor cell lines for drug sensitivity testing
 Rich knowledge base with more than 50 new experimental methods
and 5 new platforms per year
 Clinical biomarker detection system has been gradually improved,
with the ability to detect biomarkers in human blood and tissue
samples, and NanoString nCounter tissue mRNA detection platform
is under preparation
Service Advantages:
Cell
Assay
Enzymology
PD Markers
Analysis
Target
Verification
Antibody
Discovery
Protein
crystalliza-
tion

BLK
BMX
BTK
CSK
ITK
JAK1
JAK2
JAK3
LCK
LYN
SRC
TEC
TXK
TYK2
YES
CTK：
ALK
AXL
c-Kit
c-Met
CSF-1R
EGFR
FGFR1
FGFR2
FGFR3
FGFR4
Flt1/VEGFR1
Flt3
Flt4
HER2
HER4
KDR/VEGF
R2
PDGFR
alpha
PDGFR beta
RET
ROS1
TRKA
TRKB
TRKC
RTK：
AKT1
AKT2
AKT3
ASK1
PKA
PKC delta
PKC
gamma
PKN A
PKN B
PKN C
ROCK1
ROCK2
SGK
AGC：
CDK1
CDK2
CDK4
CDK5/P25
CDK6
CDK7
CDK9
CDK12
ERK1
ERK2
GSK3 beta
p38 alpha
CMGC：
CHK1
CHK2
MARK1
MARK2
MNK1
MNK2
CAMK：
Aurora A
Aurora B
CDC7
DCK
IKK beta
PLK1
WEE1
Other：
b-Raf
c-Raf
IRAK4
RIPK1
RIPK3
PI3K alpha
PI3K beta
PI3K
gamma
HPK1
MAP4K4
MEK1
TKL：
Atypical：
STE：
Method：
 HTRF assay
 ADP-Glo assay
 LanthaScreen assay
 Z’-LYTE kinase assay
i.e.
EGFR mutants: EGFR-L858R, EGFR-DEL19, EGFR-DEL19/T790M, EGFR-
L858R/T790M, EGFR-DEL19/T790M/C797S, EGFR-L858R/T790M/C797S
ALK mutants: ALK-G1202R, ALK-L1196M, ALK-F1174L, ALK-C1156Y, ALK-G1269A,
ALK-G1269S, ALK-G1202R/L1196M, ALK-T1151-L1152InsT

PDE1A
PDE1B
PDE2A
PDE3A
PDE4A1
PDE4B2
PDE4C1
PDE4D3
PDE5A1
PDE6C
PDE7A
PDE8A
PDE10A1
PDE Family：
PD-1
PD-L1
VEGF
Nectin-1
Nectin-2
Nectin-3
Nectin-4
NECL1
NECL2
NECL3
NECL4
NECL5
EPHA1
IGF-1R
HSA
FcRN
FcRI
FcRII
FcRIII
Factor B
HER2
TfR1
EPCR
STAT1
STAT3
STAT5
SPR Platform：
EPHA2
EPHA3
EPHA4
EPHA5
4-1BB
SHP2
ATIII
EGFR
Gp130
OX40
TIGIT
FOLR1
INSR
Thrombin
FVIIa
FIXa
Fxa
FXIa
FXIIa
Trypsin
Plasmin
TPA
Urokinase
Kallikern
Chymotrypsin
TAFIa
Protease:
AR
Bcl-xl
BRD4
Cathepsin
Cox1
Cox2
ER
FTO
HDAC1
HDAC2
HDAC3
HDAC4
HDAC5
Others:
HDAC6
HDAC8
HIF-1a
HIF-2a
HSP90
Kras-WT
Kras-G12C
Kras-G12D
PARP1
PARP2
PHD1
PHD2
PHD3
PPARα
PPARγ
PPARδ
ROR
ROS
RYR
SHP2
Tubulin
polymerization
Tyrosinase
WRN
XO
H+K+ATPase
IC 5 0 s c re e n in g o f T A K -0 6 3 a g a in s t P D E 1 0 A 1
0 .1 1 1 0 1 0 0 1 0 0 0 1 0 0 0 0
-2 0
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
C o n c e n tr a tio n o f c o m p o u n d s (n M )
In
h
ib
itio
n
r
a
te
(%
)
T A K -0 6 3 IC 5 0 = 5 .1 n M
B e n e F IX a c t iv a t io n b y F X Ia
F X Ia = 1 n M
T im e (m in )
O
D
4
0
5
n
m
0 2 0 4 0 6 0
0 .0
0 .2
0 .4
0 .6
0 .8 1 0 0 n M
5 0 n M
2 5 n M
1 2 .5 n M
6 .2 5 n M
3 .1 2 5 n M
1 .5 6 n M
0 n M

 Cytotoxic assay-CTG,CCK8,MTT
 Oris™ Cell Migration Assay
 Transwell cell migration assay
 Cell necrosis assay - TNF+SM164+z-VAD
 Apoptosis assay-FACS
 Cell cycle assay-FACS
 Phosphorylated protein assay-Western blot/MSD/HTRF
 Confocal-based ADC endocytosis assay
 pHrodo-based ADC endocytosis assay
 ADC bystander effect-FACS
 NanoBiT/NanoBRET reporter gene assay
 Dual luciferase reporter gene assayCytokine release
assay-ELISA/Luminex/MSD
 Human Blood Protein Phosphorylation Assay-FACS
 Protein degradation assay-HiBiT/In cell
Wesern/WB/HTRF
 Tricomplex formation-NanoBRET
 psiCHECK2 reporter gene assay-siRNA screening
 Liver tumor cell transfection/uptake assay-siRNA
screening
 Primary hepatocyte transfection/uptake assay-siRNA
screening
 Hepatocyte toxicity assay-siRNA off-target assay
 RNA-seq-siRNA off-target assay
 Car-T cell killing assay-FACS
 Car-T cell cytokine release assay
 Cell binding assay-antibody screening-FACS
 ADCC/ADCP/CDC-Antibody Screen-FACS
 B-cell activation/B-cell proliferation assay-isotope
method/fluorescence method
 T-cell activation/T-cell proliferation assay-isotope
method/fluorescence method
 Receptor binding assay - isotope method
 Ligand binding assay - isotope method
 Free uptake assay - isotope method
 Second messenger assay - cAMP/cGMP/IP3/Ca2+

Target expression analysis
Tissue-specific expression
analysis
Homologous isomer analysis
Target sequence analysis
Interspecies sequence
homology analysis
Single nucleotide
polymorphism analysis
Off-target effect analysis
saRNA-like
transcriptional activation
Seed sequence-mediated
off-target effects
Nucleotide sequence design
Design of novelty
modified nucleosides
Design of high knockdown
efficiency sequences
Sequence Design

 GalNAc structure optimization assay
GalNAc-ASGPR1 binding assay-SPR,
ELISA
HepG2 cell uptake-confocal
HepG2 cell binding-FACS
Primary hepatocyte uptake-qPCR
 siRNA structure optimization assay
psiCHECK2 luciferase reporter assay
Hepatocarcinoma cell line transfection-qPCR
Primary hepatocyte transfection-qPCR
Primary hepatocyte uptake-qPCR
Ago2 loading
 Hybridization dependent off-target effects：
psiCHECK2 luciferase reporter assay-
seed sequence
Cytotoxicity of target KO cell lines-CTG
RNA-seq
Microarray
 Hybridization independent off-target effects：
TLR3/TLR7/TLR8 dependent cytokine release
assay-PBMCs-ELISA/Luminex
HEK-Blue-TLR3/TLR7/TLR8 reporter assay
Complement activation assay
Primary hepatocyte and kidney cell toxicity
assay
off-target effects:
In vitro screening:

Protein Purifier AKTA Pure 25 SHIMADZU Liquid
Chromatography LC-20ADXR
Automated Pipetting
Workstation
Enzyme Markers
MEGAROBO Elisa
Plate Washer
BECKMAN COULTER
Flow Cytometer
GE Biacore 8K Ultracentrifuge

~ 230 Process Development Scientists
~ 120 Formulation Development Scientists
~ 8000 m2 Scale-up Lab.
~ 4000 m2 Formulation Lab. & GMP Facility

Lab.
people R&D team (synthesis, analysis, microbiology, project management, QA)
 Development, optimization and
production of drug intermediate
manufacturing processes
 Development, optimization,
production of API processes for
preclinical and clinical stage new
drugs for NMPA/FDA dual filing
 Development, optimization,
production of generic API
manufacturing process and filing
(DMF)
 Statistical and trial design using
QbD (Quality by Design) and
multivariate data analysis
 Quality studies of APIs and
intermediates
 Analytical method development
and validation
 Technology transfer and
process validation
 Process design space setting
 Process risk assessment and
control
 Impurity identification and
separation
 API stability testing
 Process safety evaluation
Service Scope:
 chemical process
research
 drug synthesis process
optimization
 pharmaceutical
process scale-up
 formulation process
scale-up
 chemical project R&D
outsourcing
 …

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Period | Months
01 | Pre-prescription study (conducted with laboratory test materials)
02 | Prescription & process screening (conducted with pilot batch materials)
03 | Process Optimization (conducted with pilot batch materials)
04 | Laboratory Test (conducted with pilot batch materials)
05 | Pre-stability Test
06 | Pilot test (non-GMP) (conducted with pilot batch materials)
07 | GMP Batch (with GMP batch materials)
08 | Formulation quality study
08 | Formulation quality study - Analytical method development
08 | Formulation quality study - Method Validation
09 | Stability Study
09 | Stability Study - Influencing factor experiment
09 | Stability Study – Acceleration stability
09 | Stability Study – Long-term stability
10 | Filing material collation

 Non-GMP、GMP、class D clean area for API production
 86 large floor-to-ceiling walk-in hoods for reactions, work-up,
filtration and drying
 Production lines: 5
 Reactor: GL: 48 x 100 L, 6 x 50 L, 7 x 30 L; SS: 3 x 100 L
 Reaction temperature: from -78⁰C to 250 ⁰C
 Rotary evaporator: 12 x 50 L, 9 x 20 L
 Drying chamber: 10 vacuum drying chambers
 Temperature control unit: 66
TGA Total Organic Carbon Analyzer
Infrared XRPD Glass reactor

DVS Dynamic water vapor
adsorption instrument
GC-MSMS ICP-MS SFC Chiral separation
TGA Reaction Calorimeter + DSC Ion Chromatography Liquid Analysis Laboratory

R&D Lab. + R&D pilot scale workshop
GMP Lab. + GMP solid workshop
Stage of Service
 New drug application (China-U.S.)
 New drug clinical trial phase II/III
 New drug NDA application
 New drug post-market changes
Formulation Form
 Solid: tablets, capsules, granules
 Semi-solid: ointments, creams, gels
 Liquid: injections, eye-drops, suspensions, tinctures
 New forms: slow-releaser, spray, inhalation, emulsion
Filing Category
 Class 1 new drugs (91 in development, 46 approved)
 Class 2 improved new drugs (6 in development, 1 approved)
 Class 3, 4 generic drugs (32 under research, 22 approved)
 Consistency evaluation
 Supplementary application
Content of Service
 Pre-formulation study
 Formulation process development
 Scale-up
 Quality and stability study
 Preparation of application materials

Inhalation Drug Administration, Ophthalmic Drug Administration,
Transdermal Drug Administration, Slow & controlled release
drug Administration, New Type Particle System Administration etc.
Rich experience in successful R&D of innovative drugs,
consistent evaluation, improved new drugs, dual reporting
experience in China and US, project management experience
Full set of formulation studies (R&D + clinical sample
production), safety evaluation, package material compatibility,
filter membrane validation, pre-BE and BE studies
Nanometer grinding equipment
Sample characterization
equipment: Nano particle size and
ZETA potential analyzer
Hot melt extruder
Spray Dryer
Hot Melt Extrusion, Micronization, Solubilization Technology,
In vivo & in vitro Comprehensive Evaluation

 A self-emulsifying drug delivery system (SEDDS) is a solid or liquid formulation consisting of a drug, an oil, a surfactant (SA) and a co-surfactant (COSA). It is
usually formulated as a soft or hard capsule. Due to the low free energy of emulsification, SEDDS can generate emulsion spontaneously by peristaltic action of
the gastrointestinal tract. Subsequently, the emulsion formed is absorbed via the lymphatic route. The oral bioavailability of SEDDS drugs is increased due to
bypassing the first-pass effect in the liver. Therefore, SEDDS has become an important strategy to improve the oral bioavailability of poorly water-soluble drugs.
 Typically, SEDDS include self-emulsifying drug delivery systems (SNEDDS), self-microemulsifying drug delivery systems (SMEDDS), and conventional self-
emulsifying drug delivery systems (CSEDDS).SNEDDS (< 100 nm), SMEDDS (100 nm - 250 nm), and CSEDDS (> 300 nm) are often judged by the size of the
emulsion particles formed after the addition of water.
Self- Emulsifying Drug Delivery System (SEDDS)
Solubility
In vitro
dispersibility
In vitro
dissolution curve
Pseudo three-
phase diagram
Drugs
Oil
SA
COSA
Other auxiliary
materials
Compatibility of raw
& auxiliary materials
In vitro
dispersibility
In vitro dissolution
Rheological
properties
Self-emulsification
time
Bioavailability
SEDDS
RJWJ-100 soft capsule produce equipment

0.00
100.00
200.00
300.00
400.00
500.00
600.00
0.00 2.00 4.00 6.00 8.00 10.00
Blood
concentration（ng/ml）
Time (h)
Project 1 API and soft gelatin administration
blood concentrations in dogs
Project Project 1
Technology SEDDS
Form Soft gelatin capsule
Oral
bioavailability
Approx. 10-times increase relative to
API-only dosing
0
2000
4000
6000
8000
10000
12000
0 2 4 6 8 10
Blood
Time (h)
blood concentrations in rodent
0.00
10.00
20.00
30.00
40.00
50.00
60.00
70.00
80.00
90.00
100.00
0 10 20 30 40 50 60
Blood
Time (h)
blood concentrations in dogs
Project Project 2
Technology SEDDS
Oral
bioavailability
API-only dosing
Project Project 3
Technology SEDDS
Oral
bioavailability
API-only dosing
API
soft gelatin
API
soft gelatin
API
soft gelatin

 GMP standard
 1000 ㎡ Oral solids workshop
 Fully functional & flexible production
 Especially suitable for the preparation of Phase I
clinical studies samples
GMP workshop for oral solid formulation:
Hot melt extruder, multifunctional fluidized bed (granulation, slow-
release coating), dry granulator, wet granulator, pulverizer, mixer,
Tablet press machine, coating machine, capsule filling machine,
aluminum-plastic packaging machine
GMP workshop - Topical semi-solid formulations：
Homogenizing & emulsifying machine, aluminum tube can sealing
machine
 Managed according to GMP regulations
 1000 ㎡ GMP analysis laboratory
 Release testing, analytical method validation,
stability study
GMP workshop (Class D cleanroom), GMP analysis laboratory, perfect QA system

New generation medicinal impactor Breathing Simulator Rheometer Transdermal diffusion tester
 Wet mixing granulator
 Dry type granulator
 Hopper mixer
 Blister packaging machine
 Rotary tablet press
 WBF-5 fluidized bed
 Automatic capsule filling machine
 Coating Machine
 Wet type granulator
 Tablet brittle tester
 Fluidized bed
 lyophilizer
 Single-punch tablet press
 Rotary tableting press
 Mixture unit
 Tablet hardness tester
R&D equipment Equipment for Production
 Auto dissolution tester (8)
 Cone penetration tester
 Particle detector
 Electron microscope
 Gas chromatograph
 Stability test chamber
Equipment for Quality Study

Instrument Type Number
NMR Bruker,400MHz 8+2
LC-MS Agilent 6125，6135/Shimadzu 2020-ELSD/Waters UPLC-QDa/ Thermo ISQ EM 70
HPLC Agilent/Shimadzu/Waters/Dionex(DAD/VWD/RID/CAD/ELSD/FLD) 96
UPLC Waters ACQUITY UPLC/Agilent 1290/Thermo Vanquish 4
Prep-HPLC Waters 2545-QDa,SQD2,PDA/ELSD/150ml/min/Gilson 281 331/332/306 48
GC-HS Shimadzu2010,2030/Agilent 7890B,8890/PE680 (FID/ECD/TCD) 16
GC-MS Agilent 5977A/Shimadzu GC-MS 2020 5
LC-MS/MS Agilent 1290-6470 QQQ 1
UPC2 Waters UPCC 5
Chiral HPLC Shimadzu 20AD/20AT/2030C 1
Prep-SFC Waters SFC80/SFC150/SFC350/SFC600 7
ICP-MS PE NexION 1000 2
IC Thermofish ICS5000+ 2
Polarimeter Anton Paar MCP5300/MCP300 3
Melting Point METTLER MP70 2
KF METTLER V30/SC30S 3
IR/UV PE Spectrum TWO/Lambda 365 4
DSC/TGA METTLER TGA2/DSC3 2
GC-MS/MS Ailent 8890-7000D 1
HS-LCMS Thermo QE Plus 1
DVS Intrinsic PLUS 1
Automatic Titrator METTLER EasyPlus 1
Balance Mettler XP6,XSR105/Satorius 10
XRPD Bruker D8 Advance 1
Thermal Safety Mettle RC1mx / THT ARC 2
Stability Charmber Memmer ICHL256/HPP1400/Freeer/Refrigerator 10
Waters BioAccord LCMS ACQUITY Premier UPLC-RDa 1 *Data as of 2023.03

~ 1200 PK & TOX Research Scientists
~ 150 Pharmacology Research Scientists
~ 30000 m2 GLP Lab.

 Established in 2008-2010 by a joint venture between
Medicilon and MPI
China's leading CRO
in preclinical research
U.S. leading CRO
in preclinical research
 Managed by MPI scientists, introduced the American
GLP management concept and the MPI SOP system,
trained extensively and deeply scientific staff
according to the SOPs.
 Organizational structure, operational management,
and quality management of the institution reached
international first-class standards.
 Toxicology experimental data verified by the US FDA.
MEDICILON

NMPA
AAALAC
Certificated
NMPA GLP
Certificated
(2011, 2012, 2015, 2019)
International
RQAP-GLP
US FDA GLP listed
(2017)
Clinical Pathology
SCCL Certificated
Bioanalysis Lab
NCCL Certificated
Bioanalysis Lab
NIFDC Certificated
Radiation Safety
License
MEDICILON

Species Rooms Number
1. NHP 61 2260
2. Dog 62 1720
3. Rabbit 14 520
4. Rodent 66 16000
5. Mini-pig 10 200
6. Rodent (PK) 27 8100
*Data as of 2022.11

>> Tumor animal models >> Non-tumor animals models
~ 1 5 0 Xenograft Models
~ 3 0 Humanized Models
~ 3 0 Syngeneic Models
~ 3 5 Orthotopic Models
~ 5 0 PDX Models
~ 4 0 CNS Diseases Models
~ 1 0 Inflammation & Immune System
~ 2 0 Cardiovascular & metabolic
~ 1 0 Digestive System Disease Model
~ 1 0 Ocular Disease Model
~ 5 Other disease models
 Support research on the efficacy of
*Data as of 2023.03

• Head & Neck Cancer • Oral epithelial cancer
• Nasopharyngeal
carcinoma stem cells
• Prostate Cancer
• Lung Cancer • Bladder Cancer
• Breast cancer • Ovarian Cancer
• Gastric Cancer • Endometrial Cancer
• Pancreatic Cancer • Cervical Cancer
• Kidney Cancer • Skin Cancer
• Liver Cancer • Melanoma
• Glioblastoma • Sarcoma
• Fibroma • Rhabdomyosarcoma
• Colon & appendix
cancer
• Myeloma
• Leukemia • Lymphoma
Tumor Neurological Disease
• Depression model
• Convulsive model
• Sedative-hypnotic-anxiolytic
model
• Parkinson's disease model
• Pain model
• Dementia model
• Schizophrenia model
Digestive System Disease
• Gastric acid secretion model
• Gastric ulcer model
• Ulcerative colitis
• Gastrointestinal dynamics model
Metabolic Disease
• Obesity and diabetes model
• Hyperuricemia model
• Liver fibrosis model
• Pulmonary fibrosis model
• Dyslipidemia model
• Non-alcoholic fatty liver
model
• Hepatobiliary model
Cardiovascular Disease
• Thrombosis, anticoagulation
model
• Stroke model
• Atherosclerosis model
• Anemia model
Inflammatory & Immune
Disease
• Arthritis and osteoarthritis model
• Osteoporosis model
• Psoriasis model
• Atopic dermatitis model
• Multiple sclerosis model
• Acute inflammation model
Other Disease Models
• Skin trauma model
• Kidney failure & kidney injury
model
• Gynecological disease model
Ophthalmic Disease Models

Type Cell Line
Breast cancer
2LMP, Bcap-37, BT-474, HCC1806, HCC70, HCC1569,
HCC1954, HCC70, JIMT-1, MCF-7
Bladder cancer
MDA-MB-231, MDA-MB-361, MDA-MB-468, MX-1,
SUM159, SUM149PT, ZR-75-1, ZR-75-30, HT-1197,
HT-1376, RT4, SCaBER, SW780, T24
Colon & cecum
cancer
COLO 201, COLO 205, COLO 320 DM, CW-2, DLD-1,
HCT-8, HCT-15, HCT-116, HT-29, LoVo,
Cervical cancer
LS1034, LS174T, LS411N, LIM-1215, NCI-H716, NCI-
H508, RKO, SW48, SW620, SiHa, Hela
Endometrium/
Hysterocarcinoma
AN3 CA, HEC-1-A, ME-180, MFE-280
Fibrosarcoma HT-1080
Gastric cancer
BGC-823, HGC-27, MKN-45, MKN-28, NCI-N87,
NUGC-3, SCH, SGC-7901
Glioblastoma U-87MG, U-87 MG-Red-Fluc(PE), LN-229
Hepatocellular
cancer
Bel-7402, Hep-3B, Huh-7, PLC/PRF/5, QGY-7703, SK-
HEP-1, SMMC-7721
Head & neck cancer FaDu, Detroit 562, CAL-27
Lung cancer
95-D, A-549, Calu-1, Calu-3, Calu-6, DMS114, HCC827,
MSTO-211H, NCI-H1299, NCl-H146,
NCI-H1581, NCI-H1650, NCI-H1688, NCI-H1975, NCl-
H209, NCI-H2122, NCI-H2228, NCI-H226, NCI-H292,
NCI-H3122, NCI-H358, NCI-H446, NCI-H460, NCI-
H520, NCI-H526, NCI-H69, NCI-H727, PC-9
Type Cell Line
Leukemia
CCRF-CEM, HEL, HL-60, K-562, Karpas-299, MV-4-11,
MOLT-4, MOLM13, THP-1
Muscle, Striated SJCRH30
Myeloma KMS-11, KMS-26, RPMI-8226, MM.1S
Melanoma
A375, A2058, C32, HMCB, MDA-MB-435s, SK-MEL-30,
WM-226-4
Ovarian cancer ES-2, HO-8910PM, PA-1, SK-OV-3, OVCAR-3
Oral epithelial
cancer
KB
Osteosarcoma MG-63, SJSA-1
Prostate cancer DU145, PC-3, LNCap, CL-1
Pancreatic cancer
AsPC-1, BxPC-3, Capan-1, Capan-2, CFPAC-1, HPAF-II,
MIAPaCa-2
Pharynx FaDu
Renal cancer ACHN, OS-RC-2, 786-O, A498

(PBMC + CD34+ HSC Humanized Models)
Type Cell Line
Brain cancer U-87 MG
Breast cancer HCC1954, MDA-MB-231, JIMT-1
Bladder cancer UM-UC-3
Colon cancer HT29, LoVo, Ls174T
Endometrium cancer Ishikawa
Gastric cancer NCI-N87
Liver cancer Hep G2
Lung cancer HCC827, NCI-H1975, NCI-H292, A549
Leukemia THP-1
Lymphoma Raji, TMD8, MOLM-13
Myeloma RPMI-8226, NCI-H929, MM.1S
Melanoma A375
Ovarian cancer OVCAR-3
Prostate cancer PC-3
Pharynx FaDu
Pancreatic cancer Capan-2
Renal cancer 786-O
Skin cancer A431
Thyroid/medulla TT
Type Cell Line
AML C1498,L1210, WEHI-3
Bladder cancer MB49
Breast cancer EMT6, JC,EO771(ATCC), 4T1,4T1-luc, C1271
Colon cancer CT26.WT, CT26.WT-luc, MC-38, Colon26, CMT-93
DLBCL lymphoma A20, P388D1, L5178-R (LY-R), E.G7-OVA
Hepatoma H22
Kidney cancer RENCA
Leukemia C1498, L1210, WEHI-3
Liver cancer H22, H22-Luc, Hepa 1-6
Lung cancer LLC1, LLC1-luc, KLN205
Lymphoma A20, EL4, L5178-R, E.G7-OVA
Mastocytoma P815
Melanoma B16-F10, Clone-M3
Myeloma J558
Renal cancer RENCA
Pancreatic cancer Panc 02
Plasmacytoma MPC-11

Type Cell Line
Brain cancer U87-MG, G261, U251, U87-MG-luc, G261-luc, U251-luc
Breast cancer MDA-MB-231, MDA-MB-231-luc, 4T1, 4T1-luc, HCC1954, HCC70, MDA-MB-361, MCF7
Bladder cancer UM-UC-3, MB49
Colon cancer HCT-116, LoVo, HT29-luc, HT29, MC38, MC38-luc, CT26.WT-luc
Glioblastoma U87-MG, U87-MG-luc
Gastric cancer Hs 746T
Kidney cancer A498
Leukemia K562, K562-luc, MV-4-11, MV-4-11-luc, THP-1, Nalm-6, Nalm-6-luc, MOLM-13, MOLM-13-luc, RL, MAVER-1, Karpas299, HL-60
Liver cancer H22, H22-luc, HuH-7, HuH-7-luc, Hep G2, Hep G2-luc
Lung cancer NCI-H460, NCI-H1650, NCI-H1975, NCI-H1975-luc, A549, A549-luc, LLC1, LLC1-luc
Lymphoma Raji, Raji-luc
Melanoma B16-F10, B16-F10-luc
Myeloma NCI-H929, MM.1S, NCI-H929-luc, MM.1S-luc
Osteosarcoma SJSA-1
Ovarian cancer SK-OV-3, SK-OV-3-luc
Pancreas cancer Mia-Paca 2, Mia-Paca 2-luc, Panc02, Panc02-luc
Prostate cancer PC3, PC-3-luc
Renal cancer A498

Type Cell Line
Breast cancer PDXM-201B, PDXM-202B, PDX-203B
Bladder cancer PDXM-231U, PDXM-232U
Colon cancer
PDXM-008C, PDXM-016C, PDXM-020C, PDXM-
021C, PDXM-057C, PDXM-060C, PDXM-075C,
PDXM-076C, PDXM-087C, PDXM-104C, PDXM-
095C, PDXM-084C, PDXM-072C, PDXM-069C,
PDXM-015C, PDXM-002C
Gastric cancer PDXM-091Ga, PDXM-092Ga
Lung cancer
PDXM-028Lu, PDXM-047Lu, PDXM-050Lu, PDXM-
053Lu, PDXM-054Lu
Lymphoma PDXM-241Ly, PDXM-242Ly
Liver cancer PDXM-211Li, PDXM-212Li
Pancreatic cancer PDXM-221Pa, PDXM-222Pa
PDX Model (Growth Curve)
PDX Model (MED-PDX-001C H&E (10X))

Disease Type Species
Antidepressant
Test
Inhibition of 5-HT, NA and DA uptake by brain synaptosomes
(sample screening, IC50 determination)
Rat
Forced swimming assay
(rats/mice, Noduls software, video screen analysis)
Mouse/Rat
Tail suspension assay (Noduls software, video screen analysis) Mouse
5-Hydroxytryptamine enhancement assay Mouse
Risperdalin-induced eyelid ptosis assay Mouse
Yohimbine toxicity enhancement assay Mouse
High-dose apomorphine antagonism experiment Mouse
Chronic mild unpredictable stimulus (CUMS) model Rat
New environment feeding inhibition experiment Mouse/Rat
Determination of MAO-A and MAO-B activity of monoamine
oxidase in the brain
Mouse
Protective effect on hippocampal neuronal cells in neonatal rats
(glutamate damage, hydrogen peroxide damage, glucose
hypoxia damage, dexamethasone damage, etc.)
Neonatal Rat
Effects on the synthesis and secretion of BDNF by SH-SY5Y
cells
SH-SY5Y cell
Anticonvulsant
Test
Yohimbine toxicity enhancement test Mouse
Pentetetrazol convulsions Mouse
Hordeum vulgare convulsions Mouse
Convulsions with Indocin Mouse
Sedative-
hypnotic
anti-anxiety
Synergistic effects with pentobarbital Mouse
Effect on subthreshold hypnotic dose of barbiturates Mouse
Re-sleeping test Mouse
Open-field experiment
(full camera monitoring, software processing)
Mouse/Rat
Elevated cross-maze method
(camera monitoring, software processing)
Mouse/Rat
Light and dark shuttle box method
(camera monitoring, software processing)
Mouse
Anti-Parkinson
Test
MPTP causes subacute PD model (bilateral disruption PD
model)
Mouse
Chronic PD model with MPTP+probenecid (bilateral PD model) Mouse
Oxidative tremor induced fibrillation model Mouse
Analgesia
Test
Hot plate method, photothermal tail shaking method, pressure
pain method
Mouse/Rat
Von Frey hairs method, bipedal balance pain measurement
method
Mouse/Rat
Acetic acid twisting model Mouse
Formalin-induced pain model Mouse
Adjuvant CFA-induced toe pain model Mouse/Rat
Carrageenan gum-induced toe pain model Mouse/Rat
LPS-induced pain model Mouse/Rat
Spinal nerve selective ligation (L5/L6) Rat
Sciatic nerve branch selective injury model (SNI) Mouse/Rat
Diabetic pain, incisional pain, cancer pain model Mouse/Rat
Anti-
dementia
Memory acquisition disorder model (6-channel mouse jumping
stage video screen analysis system)
Mouse
Poor memory consolidation model (6-channel mouse jumping
platform video screen analysis system)
Mouse
Memory reproduction disorder model (6-channel mouse dark-
avoidance video screen analysis system)
Mouse
Mouse bright and dark box method (4-channel mouse bright and
dark box video screen analysis system)
Mouse
Rat acquired memory impairment model
(Morris water maze video screen analysis system)
Rat
Determination of acetylcholinesterase activity in the brain Mouse
D-galactose-induced dementia model in mice Mouse
New object recognition experiment Rat
APP/PS1 mice
(Morris water maze, Cognition Wall)
Transgenic Mouse
Cellular level, molecular biology level In vitro test
Anti-
schizophre
nia
MK801 causes negative symptoms, positive symptoms of
schizophrenia
Mouse
Ketamine causes negative symptoms of schizophrenia Mouse
Stiffness test in rats Rat
Lower lip retraction test in rats Rat
Amphetamine-induced increased activity in rats Rat
Phencyclidine increased activity in rats Rat

Arthritis
Acute joint inflammation model in rats caused
by carrageenan gum
Rat
CIA-induced ankylosis model Mouse/Rat
CFA-induced gout-like arthritis (AIA) model Rat
Sodium urate-induced gouty arthritis model Rat
Hypocretin-induced arthritis model in rats (PIA) Rat
Osteoarthritis
model
Sodium iodoacetate (MIA)-induced
osteoarthritis model
Rat
pMMx-induced osteoarthritis model Rat
pMMx+ACLT-induced osteoarthritis model Rat
Osteoporosis
model
Osteoporosis model in desiccated female rats Rat
Glucocorticoid-induced osteoporosis model Rat
Retinoic acid A-induced osteoporosis model Rat
Psoriasis
Mouse vaginal epithelial mitosis model Mouse
Mouse tail scales model Mouse
IL-23 induced aberrant epidermal hyperplasia
model in mouse auricle
Mouse
Imiquimod-induced psoriasis-like model in mice Mouse
Atopic Dermatitis
(AD)
DNFB-induced chronic atopic dermatitis model Mouse
DNCB+OX-induced chronic atopic dermatitis model Mouse
DNFB-induced subacute eczema-like model Mouse
Fluport-induced acute eczema-like model Mouse
Multiple
sclerosis model
(MS, ALS)
EAE experimental allergic encephalomyelitis
mouse model
Mouse
Cuprizone-induced demyelination model
of mouse brain tissue
Mouse
Inflammatory
swelling model
Mouse auricular swelling model Mouse
Rat toe swelling model Rat
Capillary permeability assay Mouse/Rat
Carbon contouring assay Mouse
Yeast-induced fever model Mouse
Passive skin allergic reaction (PCA) Mouse/Rat

Obesity and
diabetes
High-fat, high-sugar diet-induced obesity
model
Mouse/Rat/
Hamster
Streptozotocin-induced diabetes mellitus Mouse/Rat
Spontaneously diabetic mice db/db, ob/ob
db/db Mouse，
ob/ob Mouse
ZDF in spontaneously diabetic rats ZDF Rat
Hyperuricemia
Potassium oxyhydrogenate-induced
hyperuricemia
Mouse/Rat
Adenine/hypoxanthine + potassium
oxyhydrogenate induced hyperuricemia
Rat
Uric acid-induced hyperuricemia Mouse
Hypoxanthine-induced hyperuricemia in mice Mouse
Adenine + ethambutol-induced hyperuricemia
in rats
Rat
Yeast-induced hyperuricemia Mouse
NAFLD（NAFL /
NASH）
HFD chow-fed model
Mouse/Rat/
Hamster
MCD chow-fed model Mouse
Compound factor-induced model Rat
Liver Fibrosis
TAA-induced hepatic fibrosis Rat
Compound factor approach induced liver
fibrosis model
Rat
ConA-induced liver fibrosis Mouse
Porcine serum-induced immunogenic liver
fibrosis model
Rat
Dyslipidemia
High-fat/cholesterol/fructose diet-induced
hyperlipidemia model
Hamster
Hereditary atherosclerotic APOE mice + high-
fat feeding
APOE Mouse
Thrombosis &
anemia model
Arteriovenous bypass thrombosis Mouse/Rat
Tail vein thrombosis in mice caused by
carrageenan
Mouse
Deep vein thrombosis in rats Rat
Carotid artery thrombosis Mouse/Rat
Coagulation time measurement Mouse
Renal failure induced anemia model in rats Rat
Iron deficiency anemia model Rat
MCAO Model
Cerebral ischemia-reperfusion model Mouse/Rat
Study of the time window of cerebral
ischemia-reperfusion
Mouse/Rat
Study of neuroprotective effect of cerebral
ischemia/reperfusion
Mouse/Rat
Anemia Model
Iron deficiency anemia model Rat
Nephrectomy (5/6) induced nephrogenic
anemia model
Rat
Adenine induced renal anemia model Rat

Gastric acid
secretion &
Gastric ulcer
disease model
Model of pylorus ligation-induced gastric
acid secretion and gastric ulcer Rat
Histamine-induced gastric acid secretion
model Rat
Model of gastric ulcer caused by ethanol Mouse/Rat
Model of gastric ulcer induced by non-
steroidal anti-inflammatory drugs Rat
Model of gastric ulcer induced by water
bundle stress Rat
Acetic acid-induced gastric ulcer model Rat
Cysteine-induced duodenal mucosal ulcer
model in rats Rat
Reflux esophagitis model Rat
Ulcerative colitis
TNBS-induced ulcerative colitis (cellular
immunoassay) Rat
Ulcerative colitis caused by DNBS (cellular
immunoassay) Rat
Ulcerative colitis model by DSS drinking
method Mouse
Gastrointestinal
dysmotility
Gastric emptying model (carbon emptying
method) Mouse/Rat
Intestinal dynamics measurement model Mouse/Rat
Functional dyspepsia model Rat
Diarrhea model Mouse
Disease Type
Animal models
Conjunctival tissue proliferation and NV
Diabetic retinopathy (DR)
Choroidal neovascularization (CNV) and subretinal fibrosis
Corneal neovascularization (Corneal NV)
Retinal neovascularization
Acute ocular inflammation models
Dry eye

Chronic
nephritis model
Heymann nephritis model Rat
IgA nephritis model Mouse
Serum disease nephritis model Rat
Renal failure and
kidney injury
model
Cisplatin-induced acute renal failure model Rat
Acute kidney injury model caused by
rhabdomyolysis
Mouse
Ischemic kidney injury model Rat
Nephrectomy (5/6)-induced renal failure
model
Rat
Adenine induced renal failure model Rat
Diabetic renal failure model
ZDF Rat,
db/db Mouse
Skin healing
Full-layer skin cut injury model
Mouse/Rat
Skin burn injury model Rat
Diabetic foot ulcer model
db/db Mouse
Leukocyte
reduction model
Cyclophosphamide induced
leukocytopenia model Rat/Mouse
Leukocyte reduction by cytarabine model Rat
Adriamycin leukopenia model Rat
Cisplatin leukocyte reduction model Rat
Pruritus model
Pruritus model caused by chloroquine,
dextran, histamine, etc. Rat/Mouse
Hair loss,
baldness model
Paraffin rosin + topical application of
testosterone propionate induced alopecia
model
Mouse
Testosterone propionate-induced alopecia
model Rat/Mouse
Imiquimod-induced alopecia areata model Mouse
Cyclophosphamide induced baldness model Mouse
Allergic rhinitis
model
OVA+aluminum hydroxide induced model Mouse
OVA+Paclitaxel cell-free vaccine induction
model
Rat
Respiratory
system model
Expectorant sputum experiment (phenol red
excretion method)
Mouse
Tracheal cupped cell staining count Rat
LPS-induced acute pulmonary edema model Mouse
Sexual
dysfunction
model
Sexual behavior test experiment (back
climbing experiment)
Rat
Erectile function test in normal rats Rat
Erectile function test in desiccated rats Rat
Prostate hyperplasia model Rat/Mouse
Gynecological
disease model
Uterine fibroid model Rat
Endometriosis Rat/Mouse
Mammary gland hyperplasia Rat
Hyperthyroidism
model
Secondary hyperthyroidism model Rat/Mouse

IVIS SPECTRUM Small Animal
In Vivo 3D Imager
BD FACSymphoy A3 Flow Cytometer
BD LSRFortessa Flow Cytometer –
18 Channels
BD FACSCelesta Flow Cytometer –
12 Channels
RAD SOURCE Small Animal X-Ray Irradiator Operating room (microscope + light
source + anesthesia machine)

Animal behavior test kit (Noldus) Open field experiments
Light and dark shuttle experiment
test (Noldus)
Small animal behavior testing
system
Morris Water Maze Doppler blood microcirculation
imager

>> In Vitro ADMET
 Metabolic stability (microsomes/S9/hepatocytes/plasma/whole blood)
 P450 enzyme inhibition (including TDI)
 P450 enzyme induction
 Enzyme phenotyping (recombinant enzymes/chemical inhibitors)
 Protein binding ratio (plasma/tissue/microsomes)
 Erythrocyte/plasma partition ratio
 Caco-2/MDCK permeability
 Transporters (P-gp/BCRP/OATs/OCTs/OATPs/MATEs/BSEP/MRPs)
 In vitro metabolite identification
 GSH-trapping
 BBB blood-brain barrier permeability Kp,uu (in vitro fraction)
 hERG
 Mini-Ames
 Rapid screening or IND support
>> In Vivo PK
 Mouse/rat/guinea pig/rabbit/dog/mini-pig/monkey
 Intravenous / subcutaneous / transdermal / intramuscular /
intraperitoneal / oral / sublingual / nasal / intravitreal / intrathecal drug
delivery
 Intravenous cannulation / infusion pump / bile duct cannulation
 Cassette administration/continuous microblood collection
 Multi-cycle cross BE/prescription screening
 Tissue distribution/blood-brain barrier permeability Kp,uu (in vivo fraction)
 Excretion studies/in vivo metabolite identification
 In vivo drug interactions
 PK/PD in tumor-bearing rats
 125I/14C/3H labeled isotope drug PK/tissue distribution/material balance
 Large animal monkey/canine ultrasound-guided liver biopsy
 Large animal monkey/canine muscle biopsy
 Rapid screening or IND support

 Small Molecule Bio-analytical Platform
 Biotechnology Drug Analysis Platform
 Supported IND declaration for over 100
domestic and foreign new drugs
 NMPA GLP certification
 US FDA GLP listed
Software systems:
protecting sample management
 Watson LIMS Laboratory Information
Management Software
 SensaTronics Temperature Monitoring System
• Full Validation
• Partial Validation
• Cross Validation
National clinical pharmacokinetic
laboratory biological sample testing
inter-room quality assessment

*Data as of 2022.11
 Sciex Triple Quad 7500：1
 Sciex Triple Quad 6500+: 18
 Sciex Triple Quad 5500: 10
 Sciex Triple Quad 4000：1
 Shimadzu MS 8050: 1
 Thermo Orbitrap Exploris 240：1
 Sciex API 4000：1
 Waters Acquity UHPLC: 20
 Shimadzu UHPLC: 12
 Thermo Vanquish UHPLC：1
 Thermo Orbitrap Exploris 240 : 1
 Waters Acquity UPLC Xevo TQ-XS：2
 Thermo Q Exactive HF-X：1
Support
LC-MS/MS
 Biotage Lycera Bead Mill Homogenizer
 MP Bio Fastprep-24 Bead Mill Homogenizer
 IKA ULTRA-TURRAX T25 Digital Disperser
 Agela SPE-M96 Positive Pressure Device
 Biotage SPE Dry 96 Sample Concentrator
 Eppendorf Refrigerated Centrifuges
 Milli-Q Integral 10
Sample Pre-treatment & Storage
 Global Clinical Trials
 Generic Bioequivalence (BE) Trials
 Preclinical GLP pharmacokinetic assays
 Early DMPK in vitro & in vivo screening
Thermo Orbitrap
Exploris 240
Thermo Q Exactive
HF-X
LCMS-7500
Triple Quad 6500+
Waters Acquity UPLC
Xevo TQ-XS
Triple Quad 6500+

 For protein, antibody, ADC, polypeptide, vaccine, and various cell
and gene therapy
 More than 200 bio-analytical methods for various macromolecules,
CAR-T, CAR-NK, lytic virus, etc. have been developed and
validated
 PK/TK/ immunogenicity (Total ADA, Nab)/ biomarker/cytokine
analysis was supported
 Comprehensive support for bioassays from early screening to
preclinical and clinical stages
Instrument and equipment
 MSD Sector Imager 6000/SQ120
 Molecule Devices M4/M5e/i3X
Plate Reader
 BioTek ELx405 Plate Washer
 Gyrolab xPlore
 CytoFlex FACS
 CTL ELISPOT
 QIAcuity One 5 Plex ddPCR
 Nanodrop NP-80
 Vi-CELL XR cell Counter
 PE Envision plate reader
 Luminex
 Biacore 8K
 ABI7500 qPCR
BD LSRFortessa Flow Cytometer
Biacore 8K

Analysis of
oligonucleotide
drug evaluation
PKDK &
Metabolites
Immunogenicity
Evaluation
Immunotoxicity
Evaluation
Pk Analysis
PK/TK
ADA
 Molecular hybridization-enzyme assay (H-ELISA)
 Molecular hybridization-electrochemiluminescence analysis (H-ECL)
 Reverse transcription fluorescence quantitative PCR (RT-qPCR)
 Quantitative PCR (qPCR)
 Digital Microdrop (ddPCR)
 LC-MS/MS Platform
PK/TK Analysis
 Total Anti-Drug Antibody (ADA) Assay: MSD
 Neutralizing antibody (Nab) analysis: CLBA or Cell-based Assay
Immunogenicity analysis
 Singleplex (based on various LBA technologies)
 Multiplex (Luminex, MSD, FACS CBA technologies)
 FACS
PD or TOX-related cytokines and biomarkers
(Cytokine & Biomarker)

Medicilon started ADC drug non-clinical studies in 2014 and has
contributed to the clinical approval of several ADC drugs
In 2022, Medicilon has ADC studies approved by NMPA and/or FDA
Nb. Disease Target Payload
Payload
(LLOQ)
Total Ab/ADC
(LLOQ)
Status Date
1 Anti-tumor HER2 Cys-L-4AA-MDC 2.5 ng/mL 6.25 ng/mL
NMPA Approved
FDA Approved
2016-10-11
2021
2 Anti-tumor HER2 Tub114-Cys 2 ng/mL 1.25 ng/mL
NMPA Approved
FDA Approved
2019-1-21
2021
3 Anti-tumor Trop-2 Tub196-Cys 1 ng/mL 1.188 ng/mL NMPA Approved 2020-7-20
4 Anti-tumor HER2 MMAE 0.05 ng/mL 0.625 ng/mL FDA Approved 2018-2-6
5 Anti-tumor HER2 MMAE 0.05 ng/mL 0.625 ng/mL NMPA Approved 2019-7-26
6 Anti-tumor HER2 Cys-L-4AA-MDC 2.5 ng/mL 6.25 ng/mL NMPA Approved 2019-3-7
7 Anti-tumor Muc1 Tub201-Cys 1 ng/mL 0.781 ng/mL NMPA Approved 2021-6-28
8 Anti-tumor Not public Tub255-Cys 0.5 ng/mL 0.781 ng/mL NMPA Approved 2021-12-28
9 Anti-tumor Folate receptor (FRα) Exatecan 0.1 ng/mL 0.781 ng/mL NMPA Approved 2022-3-8
10 Anti-tumor xxx xxx 0.02 ng/mL 1.95 ng/mL Ongoing
11 Anti-tumor xxx xxx 0.05 ng/mL 3.125 ng/mL
Ongoing
12 Anti-tumor xxx xxx 0.01 ng/mL Ongoing
Ongoing
13 Anti-tumor xxx xxx 0.05 ng/mL 2 ng/mL
Ongoing
*Data as of 2022.12

Metabolite Identification, MetID plays an important role in the field of new drug discovery. During the Lead Optimization phase,
Metabolite Identification can help locate metabolic Soft Spots for targeted structural modifications by medicinal chemists to
improve pharmacokinetic properties. According to NMPA and FDA guidelines, in vitro metabolite identification and comparison is
an important basis for the selection of experimental animal species for the IND-Enabling phase. In addition, Reactive Metabolite
can covalently bind to biomolecules in vivo, leading to toxic reactions. Therefore, early screening for reactive metabolites, such
as GSH Trapping, can help reduce the risk of late development
In vitro incubation metabolite identification:
 Liver microsomes/S9/hepatocytes/tumor cell metabolite
identification
 Plasma stability metabolite identification
 Compounds: small molecules, peptides, ADCs, PDCs
Reactive metabolite identification：
 GSH trapping
In vivo metabolite identification:
 Plasma, urine, feces, bile, PK and TK samples from preclinical
animals
 Compounds: small molecules, peptides, ADC, PDC
MetID studies to support new drug discovery and filing UHPLC-UV-QE HF-X System

MSD electrochemiluminescence
analyzer
Bio-Plex 200 Suspension Chip
System
GE Biacore 8K Intermolecular
Interaction Analysis Platform
Molecule Devices SpectraMax iD5
Multifunctional Enzyme Labeler
Molecule Devices SpectraM4/M5
Gyrolab xPlore
Fully automated nano-scale
immunoassay workstation
Molecular Devices Enzyme Labeler Applied Biosystems 7500
Real-Time Fluorescence PCR
Instrument

CTL enzyme-linked immunospot
(ELISOPT) analyzer
CytoFlex S Flow Analyzer BECKMAN Vi-CELL XR Cell
Counter
Molecule Devices SpectraMax iD5
MSD SQ120
Electrochemiluminescence Analyzer
KingFisher Nucleic Acid Automated
Extractor
Covaris E220 Non-Contact
Ultrasonic Disintegrator
KingFisher Apex Nucleic Acid
Automated Extractor

Drug Type Name
Monoclonal
Antibodies
adalimumab(TNF-alpha)
Avastin (VEGF)
Herceptin (Her2)
Anti-CD47 mAb
Evolocumab(PCSK9)
Ipilimumab(CTLA4)
Secukinumab(IL-17A)
Pembrolizumab(PD1)
Cetuximab (EGFR)
infliximab( TNF-alpha)
Anti IL-6 mAb
Anti PDL-1 mAb
Anti CD20 mAb
Anti-TIGIT mAb
Anti-Trop2 mAb
Anti-Muc1 mAb
Anti-IL-12/IL-23 mAb
Anti-IL-4RA mAb
Anti-MCP-1 mAb
Anti-IgE mAb
Anti-Covid19 RBD mAb
Anti-TGF beta mAb
Anti-SIRP alpha mAb
Anti-IF2 mAb
Anti-TIGIT mAb
Anti-IL-6RA mAb
Anti-Galectin-3 mAb
Anti ALK-1 mAb
Drug Type Name
Bispecific/
multi-
specific
therapeutic
proteins
Bispecific antibody(PD-1 and CTLA4)
Bispecific antibody(PDL-1 and CD47)
Bispecific antibody(PDL-1 and 4-1BB)
Bispecific antibody(OX40 and TNF-alpha)
Bispecific antibody(hPD-L1and hTGF-betaRII)
Bispecific antibody(PD-1 and TGF-beta)
Bispecific antibody(hPD-L1 and hCD47)
Bispecific antibody(PD-L1 and TIGIT)
Bispecific antibody(PD-1and TIGIT)
Bispecific antibody(PD-1and VEGF)
Bispecific antibody(claudin 18.2 and CD3)
Bispecific antibody(VEGF and CD47)
Bispecific antibody(Claudin and CD3)
Bispecific antibody(CD20 and CD47)
Bispecific antibody(hPD-L1 and hCD47)
Trispecific antibody(CD28 and CD3 and CD19)
Biofunctional four domain TGFRII & TF& IL-15& IL-15Rα
Peptide
PEG-Tα1
Exendin 4
GNP
Active GLP-1
rh Insulin
Insulin Asprin
Liraglutide
PTH
Calcitonin
Drug Type Name
Protein or
Enzyme
VEGFR ECD-Fc
SIRPα-Fc
rh EPO
rh NGF
rPI-T1
rh Midkine
FXA(Factor X Activator)
FSH
Recombinant Human Growth Hormone(rhGH)
Pegaspargase
HSA-Exendin 4
rhLeptin
Pegaspargase
MFG-E8
rhIFN α-2b
ADC
Herceptin-MMAE Conjugate
Herceptin-DM1 Conjugate
Herceptin-Tub114 Conjugate
Trop2 Mab-Tub196 Conjugate
Muc1 Mab-Tub201 Conjugate
Pertuzumab-MMAE Conjugate
Anti-FRα-mAb exatecan derivant
CD33 Mab-Tub255 Conjugate
Trop2 Mab-MMAE Conjugate
CD22 Mab-PE38 Conjugate
CD79b Mab-MMAE Conjugate
Claudin18.2 Mab-MMAE Conjugate
Vaccines
Covid-19 Vaccine (Protein),
Norovirus vaccine, HPV vaccine
CGT
5T4 CAR-NK, Full hIgG mRNA, VSV-based
Oncolytic virus, NDV-based Oncolytic virus
*Data as of 2023.02

Histopathology Studies Clinical Pathology Studies
• Single/multiple dose toxicity studies
• Reproductive toxicity studies
• Genotoxicity studies
• Toxicokinetic studies
• HE staining
• Special staining
• Immunohistochemistry (IHC)
• Tissue Cross-Reaction Test (TCR)
• Hematology Analysis
• Urinalysis
• Clinical Biochemistry Analysis
• Hemocoagulation Analysis
• Lymphocyte typing
• Safety Pharmacology Research
• Immunogenicity studies
• Local toxicity studies
• Carcinogenicity studies
GLP & Non-GLP
Internationally recognized pathology support
Ophthalmology
Safety Assessment
Inhalation Formulation
Safety Assessment

HEKA Elektronik EPC10 USB
DOUBLE Diaphragm Clamp
System
Oral and nasal exposure
system-detail view
Sciex Triple Quad 6500 Waters
ACQUITY UPLC
Monitoring Room
Animal housing room - Dog Animal housing room -
Monkey
Animal housing room -
Rodent room
Sample storage room

Beckman Coulter AU5800
Fully Automated Biochemistry
Analyzer
Sysmex Coagulometer Sysmex Fully Automated
Urine Analyzer
Sysmex Hematology Analyzer
Thermo freezing centrifuge Leica Peloris 3 Automatic
Dehydrator
Epredia Embedding
Machine
Leica Microtome

“ years experience to
advance your new drug R&D“

Preclinical
Research
Package
IND Filing
Enabling Package
CMC & BE
Package
API &
Formulation
Package
Druggability
Evaluation
Package
From Target to
PCC Package

Preclinical studies
and IND filings for
candidate
compounds
12 ~ 15 Mths
Identification of
candidate
compounds
~ 3 Mths
Optimization of
lead compounds
6 ~ 9 Mths
Discovery of
lead compounds
4 ~ 6 Mths
 Cooperation Model: Risk-sharing
− Medicilon is responsible for the overall progress of the project (chemistry, biology,
pharmacodynamics, DMPK, CMC, preclinical studies, filings).
− Payment by milestone
− Medicilon does two projects at the same time, one official and one as backup; to ensure
the completion of at least one project.

• Medicinal chemistry：lead compound
screening and optimization
• Efficiency：0.9
compounds/week/experimentalist, total
of ~2000 compounds synthesized
• Process development & Scale-up
synthesis：Synthesis of 1 Kg
compounds to support non-GLP and
US GLP toxicology studies
Chemistry
• Gene vector construction：
• 3 assays, 3 lentiviral vectors, 8
adenoviral vectors, 2 stable cell lines
• Analysis of 1 novel crystal structure,
8 co-crystalline structures with
ligands
• Production of 20-30 mg protein for
testing
Biology
• PK testing of 65 compounds
• In vivo activity studies of 9
compounds
• Non-GLP toxicity screening of 9
compounds
Preclinical
Cooperation
Type:
Project Background:
Clients: US-based biopharmaceutical company
Project Team：38 FTEs (32-24 chemical researchers + 6-14 biological researchers) + preclinical
researchers
Starting Point：2-3 novel targets in metabolic diseases, starting with HTS lead compounds
Results： 5 preclinical candidates over ~2 years, 1 of which is in clinical testing

Pharmacy Study
API process development
research
• Customization of starting
materials
• Synthesis process studies
• Quality studies
• Stability studies
• Crystalline screening and
crystalline process
development
• Preparation and writing of
application materials
Formulation Studies
• Pre-prescription studies
• Prescription process
studies
• Formulation analytical
method development and
validation
• Pilot scale up
• Formulation quality study
• Stability testing of pilot
batch 3 (declared batch)
• Preparation and writing of
filing materials
PD Study
• In vitro cell line screening
assay, repeated once
• Toxicity test in non-GLP
nude mice administered
for 5 consecutive days
• In vivo assay
• PK/PD studies
• Mechanistic studies
PK Study
• Formulation analytical
method establishment
and validation
• Establishment and
validation of bio-analytical
methods
• Pharmacokinetic pre-test
and formal test
• Tissue distribution test in
SD rats
• Pre-test and formal
excretion test in SD rats
• CYP inhibition and
induction assay
• Plasma protein binding
assay
• In vitro metabolic stability
test
• In vitro and in vivo
metabolite identification
assays
• Caco-2 study
Safety Evaluation
• Safety Pharmacology
Studies
• Single dose toxicity pre-
tests and formal tests
• Dose range exploration
studies
• Repeated 4-week dosing
and recovery 4-week
toxicity test
• Genotoxicity tests (three,
standard design
Filing Information
• NMPA filing information
writing
• FDA filing preparation
• SEND conversion of
general toxicology data

In-depth understanding of China and US regulatory environment and its requirements
for drug application, able to provide IND/ANDA application services for NMPA and US
FDA for domestic and foreign clients
 With professional IND and ANDA research team, we can provide one-stop
research, full project management and filing services
 With rich resources of NMPA and FDA review experts, we can provide targeted
technical, regulatory and application strategy advice
 Medicilon’s IND filing service platform can provide customers with customized
registration strategies, avoid potential registration risks, ensure timely and
accurate submission of filings, and track the progress of reviews, so as to help
customers complete the registration review process quickly
MEDICILON

FZ016, neurological drug
Clinical phase I in progress
HG381, anti-tumor drug
First clinical STING agonist in
China
OB1440, B-cell lymphoma drug
Clinical approval
Pyrrolitinib maleate tablets.
Antitumor drug, NDA phase
CYH33, anti-tumor drug
TBN, acute ischemic stroke
Clinical phase II in progress
SY009, type II diabetes drug
Clinical phase I completed
RX108, anti-tumor drug
LH021, osteoarthritis drug
Clinical approval
HS270, anti-tumor drug
Clinical approval
KX02, anti-tumor drug
Chinese clinical phase I
in progress
AMX3009, anti-tumor drug
Clinical approval

IMM01 for injection, Antitumor,
Monoclonal Antibody,
Clinical phase II
LQ036, the world's first inhaled
nanobody drug for moderate to
severe asthma
JYB1904 Injection
Clinical approval
ZT002, Semaglutide Injection.
China (accepted), US, Australia
(clinical phase I) three filed
Muc1, anti-tumor
The first domestic MUC1 ADC
BAT1308 PD-1
Monoclonal antibody injection
DP303c, antitumor, ADC HB002.1T, anti-tumor
Novel recombinant fusion
protein
Recombinant Human
Papillomavirus IX Prophylactic
Vaccine (Yeast)
V-01, recombinant novel
coronavirus fusion protein
vaccine
- Lyophilized human rabies vaccine
(MRC-5 cells)
- Quadrivalent Influenza Virus Lysate
Vaccine
GT90008, antitumor.
PD-L1/TGF- β Dual Target
Antibody

Azithromycin Tablets
Ibuprofen Tablets
Amlodipine Benzoate Tablets
Isoniazid Tablets
Lamivudine Tablets
Promethazine Hydrochloride
Tablets
Montelukast Sodium Tablets
Mosapride Citrate Granules
Cephalexin Capsules
Pyrazinamide Tablets
Atracurium benzoate injection
Pantoprazole sodium for
injection
Cefoxitin sodium for injection
Terdizolamide phosphate for
injection
Compound Sulfamethoxazole
Tablets
Ranitidine Hydrochloride Capsules
Mometasone Furoate Nasal Spray
Tacrolimus Ointment
Amantadine for Injection
Meropenem for Injection
Omeprazole Sodium for Injection
Moxifloxacin Hydrochloride Eye Drops
Erythromycin Injection
Domperidone dry mix suspension
Ambroxol Hydrochloride Capsules
Lenatinib Maleate Tablets
Sodium potassium polyethylene glycol
dispersion
Sevelamer Carbonate Tablets
Minoxidil Tincture
Scopolamine Hydrochloride Injection
Vitamin B1 Tablets
Dextromethorphan Hydrobromide
Tablets
Hexyl aminoglutarate hydrochloride for
injection
Metformin Hydrochloride Tablets
Troglitazone Succinate Tablets
Sitagliptin phosphate tablets
Cefoperazone sodium sulbactam for
injection
Cysteine solution for inhalation
Oxycodone Naloxone Hydrochloride
Extended Release Tablets
Sodium creatine phosphate for injection
* Products in blue part have been approved

Shanghai Medicilon Inc.
No. 585, Chuanda Road, Pudong,
Shanghai, 201299, China
www.medicilon.com
MEDICILON

Medicilon Introduction-Preclinical CRO

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