GENERAL TECHNICAL OVERVIEW

Dec., 2016

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Company mission is to provide industry-leading protein engineering and biomanufacturing services

Biologics company focusing on providing integrated solutions

Founded in 2009 and based in San Francisco Bay Area

Named as an Inc. 5000 Fastest Growing Companies in 2015 and 2016

Named on San Francisco Business Times’ list of 100 Fastest Growing Private Companies in the Bay Area in 2016

Acquired Blue Sky BioServices (Worcester, MA) in March 2016

~100 employees, 30% have PhDs

LakePharma is the largest US-based biologics CRO, with most complete capabilities

Introduction

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3LakePharma Bay Area Sites

UCB

UCSF

Stanford

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3

1. Engineering SiteBelmont (15,000 sqft)

2. Development SiteSan Carlos (9,000 sqft)

3. Biomanufacturing Site Hayward (38,000 sqft)

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4LakePharma Worcester Site

Formerly Blue Sky BioServices

30+ employees

Clients include nearly every big pharma

Strong expertise in protein production in microbial and baculovirus expression systems

Major expansion of manufacturing operations planned for Massachusetts in 2018

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5Largest US Based Dedicated CRO Supporting Biologics R&D

Engineering Production Bioanalytical Bioactivity DevelopmentDiscovery

Molecular Engineering

BioExpression

BioProcessing

BioAnalytical

Protein Chemistry

BioFunction

Antibody Engineering

AntibodyDiscovery

Assay Services

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6Antibody Discovery

Custom immunogen preparation

UberCell™ immunizations for functional mAbs against

membrane targets displayed in native conformation

DNA based or rapid protein based RIMMS immunizations

Strategies for breaking tolerance enabling cross reactivity

and strong response to conserved targets

Proprietary myeloma line for high fusion efficiency

384 well screening of hybridomas

Incorporation of functional assays in screening cascade

Delivery of clonal, functional, purified mAbs along with V-

region sequences, hybridomas, and functional data

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7Antibody Engineering

High throughput gene synthesis and cloning

Antibody variable region cloning

Sequence liability analysis

Antibody reformatting

Custom library construction and screening

Immune library screening

Antibody humanization

Affinity maturation

Antibody affinity and functional assays

Thermostability engineering

de novo antibody sequencing

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8Molecular Engineering

Gene synthesis and molecular

cloning

High throughput cloning

DNA@lakepharma.com

Plasmid design & construction

Ligation cloning

PCR cloning

Site Mutagenesis

Gateway cloning

Custom cloning

DNA sequencing & analysis

Plasmid DNA production

Gene expression and copy

number analysis

Absolute and relative qPCR

SNP genotyping, genomic

sequencing

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9BioExpression

Multiple Expression Systems

Expression construct generation

Expression optimization

Endotoxin-free plasmid DNA scale up

Protein & Antibody production

Mammalian Expression

Baculovirus Expression

Yeast Expression

Bacterial Expression

Protein purification

Polishing and formulation Elution profile and CE-SDS

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10BioProcessing

Stable cell line generation

Process development

Optimization of cell culture and purification conditions

Scale up production

WAVE or single-use bioreactors

RCB@lakepharma.com

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11Protein Chemistry

Custom protein purification

Proteolytic cleavage and polishing

Biotinylation

Protein conjugation to beads

Protein conjugation to fluorophores

SDS-PAGE

kDa

190

15

115

25

80

30

50

70

10

NR R NR R

Un-cleaved Cleaved

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12BioFunction

Affinity measurement by Biacore

Affinity measurement by Octet

ELISA

Western (traditional and automated)

FACS

ADCC & CDC

Biochemical assays

Cell-based reporter gene assays

Cell proliferation assays

Octet

FACs

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13BioAnalytical

CE-SDS profiling

SEC-HPLC, RP-HPLC, IEX-HPLC profiling

Intact mass profiling

MS sequence confirmation and PTM analysis

de novo antibody sequencing

Glycosylation analysis

DLS, DSC & DSF

Stability analysis

Release assay development and validation

DSC

cIEF

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14Pharma Assay Development & Screening – East Coast

Cell-based Assays

Primary and Differentiated Cell Assays

High content screening

Small Molecule Cytotoxicity – HepG2

Cytokine Stimulation and Release

Flow Cytometry and FACS

Platforms

Meso Scale Discovery Sector S 600

BMG PHERAstar

Cellomics Cell Insight Reader

Standard data turnaround 5 days

Biochemical Assays

SPA-based Workflows

Radioligand binding

Fluorescence

FP, HTRF, FRET, TR-FRET

Luminescence

ELISA

qPCR

Fully Customized Assay Design and Development

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15LakePharma Provides Integrated Solutions

Our technical capabilities cover the entire spectrum of biologics development and analytics

We can take drug program from idea to lead to stable cell line to a formulated protein

construct optimization

Antibody engineering

Stable cell line generation

Cell killing assay

Affinity measurement

Cell culture process development

Purification process development

Research cell bank

Antigen engineering

FACS

Glyco-profling

Peptide map

Tm

SEC

Intact mass

Bispecific antibody

polishing

construct design

WAVE production

DNA cloning

cIEF

stability

formulation

AE AD

ME

PC

BEBF

BP

BA

Conjugation

Immunization

Hybridoma campaign

Transient production

ADCC, CDCReporter gene assay

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16Integrated Solutions Example

Bispecific antibody engineering program

Antibody engineering and production

Functional assays (cell binding, cell killing)

Biacore to observe dual binding

Stable cell line generation (RCB)

Bioanalytical characterization

Purification process development

Formulation and stability studies

Transfer to client or CMO

AE AD

ME

PC

BEBF

BP

BA

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17Track Records

Contributed to multiple IND filings

12 publications in peer-reviewed journals

>30,000 DNA plasmids constructed

>12,000 proteins produced

>500 CHO stable cell lines made

Our collaborators:

Harvard University Stanford UniversityU.S. Department of

Veterans Affairs

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18We take pride in our Client Services

Highlights

Integrated platforms support projects throughout the drug discovery process

Dedicated client services

Sophisticated software tracks and reports progress internally and externally

Clients are in control of their projects 24/7

Quality assurance and quality control steps in place

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19Our capabilities are YOUR capabilities. Our results are YOUR results.