CHTEOBIDIMAMembrane Proteins andMonoclonal Antibodies

DIMA's products and services for your drug target research

Dedicate on immuno-oncology，Perfect with recombinant mAb development

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DIMA Biotechnology LTD

DIMA's Mission

DIMA harnesses cutting-edge technologies to provide a fully integrated solution for theDIMA's VisionCH

preclinical research and development of antibody drugs and membrane proteins.

antibody drug discovery.

About DIMA

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Empowering our customers to accelerate their preclinical research and development inO

DIMA Biotechnology Ltd. is a biotech company offering products and services for BioPharmacompanies for their preclinical research need. Different from other traditional CRO companies,BI

we provide on-shelf pre-stocked and validated hit-to-lead stage antibody molecules for
BioPharma companies.

Currently we have over 5000 on-shelf lead antibody molecules for around 300 drug targets withverified sequences and validation data. In the next couple of years, we plan to develop leadDIMA

antibody molecules for all druggable targets. Our purpose is to help BioPharma companies
speed up their antibody-based drug discovery process.

Over the years, DIMA Biotech has been deeply engaged in developing and optimizing various

technology platforms for antibody-based drug development. Here is a summary of ourtechnology platforms:

1. DiMProTM membrane protein production platform: We use mammalian cell expression system

to prepare and purify various membrane proteins including single and multi-pass membraneproteins. Right now, we are offering over 1000 on-shelf functional validated druggable target

proteins. For multi-transmembrane proteins, such as GPCRs and ion channels, we havesuccessfully utilized five different technology solutions, i.e., Membrane Nanoparticle (MNP),
Virus-Like Particle (VLP), Exosome (EXO), Detergent and Nanodisc, to produce and purify active

full length membrane proteins. As of now, we have made more than 50 multi-transmembranefull-length proteins in Nanodisc format, all of which can be shipped by the next day.

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2. DimAb® single B-cell lead antibody molecule discovery platform: Using this platform, DIMA

Biotech has completed hit-to-lead discovery for around 300 druggable targets and obtained
over 5000 antibody molecules with IgG sequence information. Our DimAb® B cell libraryplatform can help customers easily obtain more than 10,000 positive hits in as short as aCH

month's time.

3. DiLibraryTM mammalian display based antibody engineering platform: DIMA developed its

proprietary mammalian display platform for antibody engineering. DiLibraryTM mammaliandisplay platform can be utilized for antibody humanization, affinity maturation or otherTE

antibody engineering applications. As opposed to phage or yeast display platforms, thedevelopability of molecules engineered from our system could be much better since we use amammalian cell-based system during development.

Our products and services are widely recognized. A number of top-tier BioPharma companiesOalready in-licensed DimAb® lead antibody molecules from DIMA Biotech. We offer flexible

DIMABI

partnership models tailored to your needs.

SuzhouWuhan

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DIMA Biotechnology LTD

Technology Platform
DiMProTM platform for functional membrane protein preparationCH

One of the key requirements for antibody development is to utilize protein immunogens that best
mimic native state of target protein. Most druggable targets for antibody-based therapy aremembrane proteins, which are notoriously hard to express. DIMA biotech has created multiple

solutions for membrane protein production. Human proteins are produced using HEK293 secretion
expression system, so that they can have a good chance to keep their native conformation andTEmodifications. To find the best production strategy, we individually study and design the expression
construct for every membrane protein target.

For single transmembrane protein, we use the well-designed ECD to mimic its functional domain.

For full length multi-transmembrane proteins, such as GPCR and Claudin series proteins, we invested

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heavily on new expression and extraction technologies, and developed 5 different solutions to extract

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different targets, e.g. VLP, Exosome, MNP, Detergent and Synthetic Nanodisc.

Key advantagesl Mammalian cell expression system with authentic post-translational modifications
l Serum free medium culturing system to minimize host cell contaminationl Function validated proteinsl Custom protein and large batch production available

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Key applicationsl Native immunogens for therapeutic antibody drug developmentl Native ligand and receptor identificationl In Vitro protein functional testl Cell based assays

Extra Cellular Domain (ECD) Protein
druggable targets

l Over 1000 on-shelf ECD-Fc fusion
proteins

5 different platforms in 2 categories:l Multi-transmembrane proteins in native

membranous vesicles: Membrane

Nanoparticles (MNPs), exosome (EXO)
and Virus-like particles (VLPs).

l Purified proteins: Detergent andO

l HEK293 mammalian expression system

Nanodisc platforms.

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Multi-pass Transmembrane Protein (MTP)

TEl Ideal for the single transmembrane

CHl Therapeutic drug In Vitro functional test

DimAb® single B-cell lead antibody discovery

DIMA

DimAb® recombinant monoclonal antibody development platform is considered as a technology
revolution for monoclonal antibody development. Compared with traditional hybridoma based
monoclonal antibody development platform, this new technology platform can directly obtain IgG

gene sequences from immunoreactive B cells without the need of hybridoma fusion. From our data,
we can easily isolate more than 10,000 immunoreactive B cell clones from a single immunized animal.

The success rate for downstream application is far higher than the traditional hybridoma platform.

Therefore, we have a good chance to find monoclonal antibodies with high specificity and high affinity.
With IgG sequence available, we can directly edit, optimize and identify antibodies for downstream
applications, such as humanization, affinity maturation, CAR-T , etc.

Since DimAb® preparation process no longer depends on the availability of myeloma fusion partner, it
is possible for us to use this platform to develop monoclonal antibodies from different species.

Therefore, DimAb® offers a unique solution for the antigens with high homology and weak

immunogenicity by using different hosts for immunization. At present, we have optimized the highthroughput development process on rabbit and mouse derived recombinant monoclonal antibodies.

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Platform Workflow

Comparison Between DimAb® Platform and Hybridoma Platform
COMPARISON ITEMSHYBRIDOMA PLATFORM
Hybridoma cells: high cost for
preservation, difficult to store
and transfer

High（80-90%）

Storage mode

Digital information; easy to store
and transferLow（50%）

Screening efficiency

HighLow

Antibody quality

Recombinant antibody with DNA
sequence available

Hybridoma cells are unstable,
which may lead to the loss ofantibody genes

Preparation procedure

Fast and antibody genes can beobtained directly

slow

Animal ethics

No need to kill animals

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Success Rate

DIMAB® ANTIBODY PREPARATION
PLATFORM

Host species

Various animal species

Mostly mouse mAb

Need to sacrifice animal to obtainsplenocytes

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DiLibraryTM mammalian display platform for antibody engineering

Antibody humanization is important for therapeutic antibody development, especially for thecandidate antibodies derived from animal sources. DIMA Biotech has developed a proprietary

mammalian display platform for antibody humanization and affinity maturation, DiLibraryTM antibody
engineering platform. With this platform, we can deliver a panel of humanized variants with improvedCHaffinity than its parental antibody. In addition to improved affinity, the engineered clones also exhibit
improved developability for downstream development, such as high expression level and low
aggregation tendency. Therefore, DiLibraryTM system is a superior antibody engineering platform tohelp us optimize antibody molecules with better developability.

Advantages:

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Experiment orientedscreeningAntibody yieldassessment

At least 3x increase inaffinity

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Mammalian cell display

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PowerfulFlexible

Custom designedBIOne-step process forhumanization, optimization

mAb library for& developability assessment

your needs

Complete

Risk Free

discovery , optimization tohumanization

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One stop shop from antibodyfunctional evaluation.

Platform Workflow5TE1

Guarantee affinity after

Human IgG germline FR libraryFinish in 48 days

Fast

Deliver humanizedmAb sequences anddata in 48 days.

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DIMA Biotechnology LTD

Case Studies：Humanization of Anti-BCMA rabbit mAb
By using DiLibraryTM display platform, we have successfully obtained humanized antibodies withincreased binding affinity (Hu-BCMA3 shows around 18-fold increase).
Ka(1/Ms)

Rabbit BCMA

4.3884E+4

Hu-BCMA22.8604E+4

Hu-BCMA1

3.1023E+4
6.4527E+4

Hu-BCMA43.3508+4

Rmax (RU)

4.3530E-6

0.14

105.2

0.015

81.3

1.1750E-5
4.5480E-6
1.0250E-6

0.267
0.159

1.9060E-60.056

Variant 1

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WT

KD (nM)

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Variant 2

Variant 4

65.3
78.9

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Hu-BCMA3

Kd(1/s)CHAnalyte

Variant 3

92.1

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All Druggable Targets (ADT) lead discovery program
To help Biopharma accelerate its pace on pre-clinical antibody drug lead selection and optimization,

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DIMA, equipped with its proprietary single B cell discovery platform, launched an “All DruggableTargets (ADT)” lead discovery program. The goal is to provide on-shelf pre-stocked and pre-validated
hit-to-lead stage antibody molecules for all druggable targets. Currently, we have completed around300 druggable targets and obtained over 5000 antibody molecules with IgG sequence information andantibody validation data. The complete list of our available targets can be found on our website

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(www.dimabio.com/lead-antibody-molecule).

Contact us for the complete list of targets!

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DIMA Biotechnology LTD

Products for Drug Target Research
DIMA Biotech has developed many on-shelf high-quality bioreagents including ECD membraneproteins, Full length membrane proteins, DimAb monoclonal antibodies and Biosimilar antibodies toCH

support the discovery and development of drug targets.

Drug target research is crucial in mechanism-based drug discovery and development. Currently, we

have over 2000 on-shelf products covering almost 900 drug targets, including many G protein-coupled

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new therapeutic targets.

TEreceptors (GPCRs), CD markers, receptors, and enzymes et al. Please contact us for your R&D needs on

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10Custom Services for Pre-clinical Research
Empowered by the cutting-edge technologies in proteins and antibodies, DIMA biotech can easilyCHdeliver many mAb molecules for your druggable targets. We offer multiple on-shelf mAb molecules foreach target protein (On-shelf Lead mAbs Service), and pre-validated B cell libraries for further

screening of good candidates. We also provide a comprehensive services from antigen preparation

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TE(Custom Protein Production) to Lead mAbs Discovery Service and Antibody Engineering Service.

DIMA Biotechnology LTDDIMA

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Dedicate on immuno-oncology，Perfect with recombinant mAb development

DIMA Biotechnology LTDFuchunjiang Rd No. 188, Gaoxin District, Suzhou+001-86-15307149771

Wuhan institute of Biotechnology B7, No.666 Gaoxin Road, Wuhan

info@dimabio.com

www.dimabio.com