ENGINEERING PRECISION EXOSOMES DEVELOPING …

ENGINEERING PRECISION EXOSOMESDEVELOPING REVOLUTIONARY MEDICINES

A p r i l 2 0 2 1

Forward-Looking Statements and Disclaimers

2PROPRIETARY INFORMATION OF CODIAK BIOSCIENCES |

These slides and the accompanying presentation contain forward-looking statements and

information. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,”

“anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and

other similar expressions are intended to identify forward-looking statements. All forward-looking

statements are based on estimates and assumptions by our management that, although we

believe to be reasonable, are inherently uncertain. All forward-looking statements are subject to

risks and uncertainties that may cause actual results to differ materially from those that we

expected, including those risks and uncertainties that are described under the heading “Risk

Factors” in our Annual Report on Form 10-K for the year ended December 31, 2020, as well as

discussions of potential risks, uncertainties and other important factors in our subsequent filings

with the Securities and Exchange Commission. Any forward-looking statement speaks only as of

the date on which it was made. We undertake no obligation to publicly update or revise any

forward-looking statement, whether as a result of new information, future events or otherwise,

except as required by law.

“Nature’s Evolved Macromolecule Delivery System”

CHARACTERISTICS OF AN IDEAL

DRUG DELIVERY PLATFORM?

✓ Immune silent for repeat dosing

✓ Broad delivery potential for multiple

macromolecules

✓ Tropism for targeted delivery

✓ Access to all body compartments

3

Codiak: Harnessing Nature’s “Drug Delivery” System

PROPRIETARY INFORMATION OF CODIAK BIOSCIENCES |

The body’s “FedEx”

4

Pioneering the Development of Targeted, Precision Exosome Therapeutics

INNOVATIVEEngineering

INDUSTRIALIZEDManufacturing

engEx™ Platform


DESIGN THE PACKAGEDiverse Functionality and Payloads


engExCELL-ENGINEERING & EXOSOME LOADING

MEMBRANE

Exterior

Lumen

BASP-1

PTGFRN

PTGFRN/

BASP-1

Expression target(e.g. IL12,

antigen)

Targeted integration

MEMBRANE

Exterior

Lumen

Antigen

IL-12

Surface Cargo

• Antibodies, scFab, scFv

• Cytokines

• Ligands, Receptors

• Co-stimulatory molecules

• Peptides

• Antigens

Lumen Cargo

• Antigens

• AAV

• RNA binding proteins

• Peptides

• Nucleases

• Enzymes

engExEXOGENOUS EXOSOME LOADING

DESIGN THE PACKAGE Diverse Functionality and Payloads


= STING CDN

agonist

= linker-conjugated

ASO

EXOGENOUS LOADING

• STING agonist

• Small molecules

• ASO

• Peptides

• Adjuvants

• Proteins

ADDRESS THE PACKAGECustomized Cellular Tropism for Optimizing Exosome Uptake


ENGINEERED MACROPHAGE (MF) TROPISMS ENGINEERED CELL-SPECIFIC TROPISM

engExEXOSOME-TROPISM

Schwann Cell Targeting Peptide

No Targeting Peptide

Motor Neuron Targeting Peptide

No Targeting Peptide

Sc

hw

an

n c

ells

Ne

uro

2A

ce

lls

Glial or Neuronal Tropism

11b+ Ly6C

+

11b+ Ly6G

+

T, NK, B

cDC2

pDCcDC

1

0

5

10

FC o

ver c

on

tro

l

Monocyt

ic

Gra

nulocyt

ic

B cells

NK cells

CD8+ T

cells

CD4+ T

cells0

5

10

15

20

Primary human

MΦ

0 5 10 15 20

0

10

20

30

Time (hr)

% in

tern

aliza

tio

n

CD47-PTGFRN

PTGFRN

Myeloid Cells for Innate Immunity

T and B Cells for Adaptive Immunity

SOURCE: INTERNAL PRECLINICAL DATA

DELIVER THE PACKAGE Selective Targeting of Specific Cells / Tissues via Various Routes

HISTOLOGICAL BIODISTRIBUTION (MOUSE)

Intravenous Intraperitoneal Intrathecal

COMPARTMENTAL DOSING

DOSING ROUTE BIODISTRIBUTION EXAMPLES OF 89ZR-EXOSOMES

8PROPRIETARY INFORMATION OF CODIAK BIOSCIENCES | 8

Liver (IV)

Spleen (IV)

Liver Tumor (ITu)

Intra-tumor

Intravenous

Neurons (Intravitreal)

Intestine (PO)

Muscle (IM)

Neurons (Intracranial)

Lung (inhalation)

Lymph node (IP)

Exosomes = Red

Compartmental


Our Proprietary, Scalable engEx Manufacturing Technology Has Multiple Advantages

9

Cell Source Cell Culture Purified ProductPurification

1 GMP

Production

Run

CODIAK

GMP cell bank, well characterized human cell line

2,000L fed-batch or 500L perfusion, suspended culture, very high cell

density, chemically defined media

Large volume GMP lots, high purity and reproducibility,

closed processing

High productivity, advanced chromatography & filtration

technology, scalable

>2,000

Centrifugation

Runs

Primary human cellsLow density, adherent cell

culture, serum, low productivity Manual product collection,

open processing

Multiple centrifugation steps,low productivity, low purity,

high complexity

TRADITIONAL METHOD


EXPAND THERAPEUTIC

INDEX BY

engEx Exosomes Engineered Cell-Specific Delivery to “Drug the Undruggable”

10

OPTIMIZE delivery and

target engagement

in/on the right cell

MINIMIZE exposure

to non-target cells

Therapeutic Index =

CELLULAR TROPISM

ADMINISTRATION ROUTE(Compartmental Dosing)

TISSUE RETENTION AND ACCUMULATION


Codiak Today: a Clinical-Stage Company Pioneering Development of Exosome-Based Therapeutics

11

Preclinical program with anticipated 2H 2021 IND/CTA filing

Partnering in diverse TAs; incl. Jazz, Sarepta, Ragon Institute, WUSTL, OSU

Anticipating multiple clinical data events; readouts mid-2021 and by year-end 2021


Two engEx candidates entered clinic in September 2020

Successful CMC efforts to industrialize manufacturing

Proprietary engExTM Platform for generating targeted therapeutic candidates

Positive exoIL-12 Phase 1 data in HV; favorable safety profile and proof of principle

Expanding Pipeline of Proprietary Exosome Therapeutic Candidates


Candidate PayloadDoseRoute Indication Discovery Preclinical Phase 1 Phase 2 Phase 3

Worldwide Rights

Oncology

exoIL-12™ Biologic ITu CTCL, Melanoma, TNBC, MCC, Kaposi & GBM

exoSTING™ Sm. Mol.

ITuSolid Tumors

(i.e., HNSCC, TNBC, cSCC & ATC)

ITu / ITh GBM & Leptomeningeal Cancer

exoASO™ – STAT6 ASO IVMyeloid-rich Cancers

(i.e., HCC, PDAC, CRC & Ovarian)

exoASO™ – NRAS* ASO TBD Hematologic Cancers / Solid Tumors

Oncogene Targets* TBD TBD Hematologic Cancers / Solid Tumors

Neurology

exoASO™ – NLRP3 ASO ITh Neuroinflammation

exoASO™ – NLRP3 ASO ITh Neuropathy

Gene Targets**Genetic

ModulationTBD Neuromuscular Diseases

Vaccines

exoVACC™*** Vaccine TBDCancers /Neurodegeneration/Viral Diseases

(i.e., HIV, SARS-CoV2)

Topline data expected: mid-2021

Topline data expected: by year-end 2021

Submit IND:2H 2021

*Jazz Pharmaceuticals Collaboration Programs – Focused on use of exosomes to develop therapeutic candidates directed at NRAS and other oncogene targets. Codiak has opt-in rights for two Jazz candidates.

** Sarepta Therapeutics Collaboration Programs – Focused on use of exosomes for non-viral delivery of AAV, gene-editing and RNA therapeutics to address gene targets associated with neuromuscular diseases.

*** Includes Scientific Collaboration Programs with The Ragon Institute to develop exoVACC candidates for (i) HIV using HIV epitopes identified by Ragon and (ii) SARS-CoV-2 using T cell epitopes identified by Ragon.

Definitions: iTu = Intratumoral; iTh = Intrathecal; IV = Intravenous; IM = Intramusuclar


exoIL-12

exoIL-12: Enhancing Therapeutic Index of exoIL-12


IL-12 displayed on the surface

via PTGRFN

Best in Class Profile

✓ Tissue retention, prolonged PD

✓ Undetectable systemic exposure to IL-12

✓ Enhanced therapeutic index

✓ Consistent with preclinical data

Mechanism of Action

IT Injection

T cells and NK cells

via IL-12 receptor

Interferon-gamma-

induced protein-10

(IP-10)

Manuscript published online 12/21/20

• rIL-12 validated as single agent in CTCL studies with 56 – 74% ORR

• Up to 22% CR

exoIL-12 Phase 1 Trial Design and Data Flow


PART A – HEALTHY VOLUNTEERS –SAD

Screening

DLT

SafetyPK

BiomarkersPD

Dosing

Labs

Biopsy

Dosing

PART B – CTCL STAGE IA-IIB –MAD, “3+3” DESIGN

EXPANSION

INDICATIONS INCIDENCE (US)

CTCL12000 currentStage IA/IIB cases

3,000/y

TNBC 27,000/y

Melanoma 95,000/y

GBM 10,000/y

MCC 2,000/y

Kaposi 2,000/y

Screening

DLT

SafetyPK

BiomarkersPD

Dosing

Labs

Biopsy

Dosing

ClinicalActivity CT Scan

Cycle 3+Cycle 2Cycle 1

Initial safety, tolerability and systemic exposure/ pharmacokinetics and pharmacodynamics data

SAFETY AND PK DATA 12/30/20; PD DATA 02/04/21

Biomarker, safety and preliminary pharmacodynamics and efficacy data in CTCL patients

EXPECTED DATA READOUT BY YEAR-END 2021:

exoIL-12 Phase 1 Trial – Part A Design



Screening

DLT

SafetyPK

BiomarkersPD

Dosing

Labs

Biopsy

Dosing

• Objectives:

• Confirm TPP and identify optimal dose for Part B

• Study design:

• Randomized controlled single ascending dose trial

• 25 healthy volunteers (randomized 3:2 between exoIL-

12 and placebo)

• A total of 5 dose cohorts were completed: 0.3, 1.0,

3.0, 6.0 and 12.0 μg


1

10

100

0 10 20 30 40

IL-1

2 [

pg

/mL]

Time [hours]

Plasma IL-12 following exoIL-12

exoIL-12 0.3, 1.0, 3.0, 6.0 and 12 mcg

(all BLQ)

Limit of quantification: 8 pg/mL

TolerabilityTolerability

- SC SAD of exoIL-12 from 0.3 – 12 μg

- No treatment-related AEs

Codiak BioSciences, 2020

Plasma IL-12 following rIL-12

Gokhale et al, 2014

- SC SAD of rIL-12 from 2 – 12 μg

- Dose dependent treatment related AE:

- Chills

- Fatigue

- Myalgia

- Back pain

- Fever

- Dizziness

- Headache

rIL-

12

ex

oIL

-12

Plasma IL-12 following rIL-12

Improved Systemic PK / Tolerability Compared with rIL-12

Sample Timepoints, Skin Punch Biopsy Procedure & PD


D1 -1H D1 6H D2 24H D3 36H D8 D15 D22 D29

Skin

Biopsy core ( ) taken using Stiefel Biopsy Punch - 3mm and scalpel.

Penetrating epidermis, dermis and reaching upper sub-cutaneous tissue.

Pre-treatment

3mm Area reserved for observation

for injection site reaction

24hr

30mm

D8D15

: Injection site of exoIL-12 (variable dose, fixed volume of 2ml)

D3 48H

T cells and NK cells

via IL-12 receptor

Interferon-gamma-

induced protein-10

(IP-10)

exoIL-12

Plasma

Potent, Durable IP-10 Effects in Injected Skin Following exoIL-12


Skin

0 100 200 300 400

1

10

100

1000

10000

Time [hrs]

Skin

IP

-10

[p

g/m

L]

Placebo

exoIL-12 0.3 mcg

exoIL-12 1.0 mcg

exoIL-12 3.0 mcg

exoIL-12 6.0 mcg

exoIL-12 12.0 mcg

24 hrs, D8, D15

No Plasma IP-10 Generation of exoIL-12 at 0.3 to 6.0 μg


Plasma

0 200 400 600 800

10

100

1000

Time [hrs]

Pla

sm

a IP

-10 [

pg

/mL

]

Placebo

exoIL-12 0.3 mcg

exoIL-12 1.0 mcg

exoIL-12 3.0 mcg

exoIL-12 6.0 mcg

exoIL-12 12.0 mcg

The 6.0 μg Dose is Optimal and Meets all Pre-Specified Criteria


Plasma

0 200 400 600 800

10

100

1000

Time [hrs]

IP-1

0 [

pg

/mL

]

PlaceboexoIL-12 6.0 mcg

-200 0 200 400 600 800

1

10

100

Time [hrs]

IL-1

2 [

pg

/mL

PlaceboexoIL-12 6.0 mcg

Skin

0 100 200 300 400

1

10

100

1000

10000

Time [hrs]

IP-1

0 [

pg

/mL

]

Placebo

exoIL-12 6.0 mcg

0 100 200 300 400

10

100

1000

Time [hrs]

IL-1

2 [

pg

/mL

]

Placebo

exoIL-12 6.0 mcg

Data Confirm Distinctive Profile of exoIL-12


No systemic exposure of IL-12 – direct contrast with comparable dosages of rIL-12

exoIL-12 was well tolerated at SADs from 0.3 to 12.0 μg in healthy volunteers

Data support Part B starting dose of 6.0 μg every other week

exoIL-12 detectable in skin at 6 μg – data supportive of retention at injection site

exoIL-12 at 1.0 to 12.0 μg showed potent skin IP-10 with highest levels at 6.0 μg

Slight increase in plasma IP-10 12.0 μg on Day 3

Provides validation of engEx Platform for engineering exosome therapeutic candidates

• rIL-12 validated as single agent in CTCL studies with 56 – 74% ORR

• Up to 22% CR

exoIL-12 Phase 1 Trial Design and Data Flow



Screening

DLT

SafetyPK

BiomarkersPD

Dosing

Labs

Biopsy

Dosing

PART B – CTCL STAGE IA-IIB –MAD, “3+3” DESIGN

EXPANSION

INDICATIONS INCIDENCE (US)

CTCL12000 currentStage IA/IIB cases

3,000/y

TNBC 27,000/y

Melanoma 95,000/y

GBM 10,000/y

MCC 2,000/y

Kaposi 2,000/y

Screening

DLT

SafetyPK

BiomarkersPD

Dosing

Labs

Biopsy

Dosing

ClinicalActivity CT Scan

Cycle 3+Cycle 2Cycle 1

Initial safety, tolerability and systemic exposure/ pharmacokinetics and pharmacodynamics data

SAFETY AND PK DATA 12/30/20; PD DATA 02/04/21

Biomarker, safety and preliminary pharmacodynamics and efficacy data in CTCL patients

EXPECTED DATA READOUT BY YEAR-END 2021:


exoSTING

exoSTING: Precise Targeting Creates a Differentiated Therapeutic Candidate



✓ Local STING Activation

✓ Limited Systemic Exposure

✓ Enhanced Therapeutic Index

• Selective delivery to M2 Macrophages, CDC through known cognate

• Recapitulates natural immune surveillance

• T cell avoidance due to engineered tropism

Mechanism of Action

IT Injection

PTGFRN Internalizing

Cognate

• Prolonged TME retention, prolonged tumor localized pharmacology

• Precedent: local dosing (Aldara™, BCG, IMLYGIC®)

Engineered to express high

levels of PTGFRN

Loaded with proprietary CDN

STING Agonist

KEY DESIGN

ELEMENTS/OBSERVATIONS

Data Anticipated Mid-2021

exoSTING Prevents Non-Specific Intratumoral Immune Ablation


Dose 2 – 4 h Dose 2 – 24 h

FSA

exo

STI

NG

F4

/80

CD

8D

AP

I

• Anticipated results from serial tumor biopsies

• T cell expansion and preservation

• Reduced off target toxicity


27

exoSTING Phase 1/2 Trial Design and Data Flow


Safety and preliminary pharmacodynamics and efficacy data in patients with solid tumors

Screening

DLT

SafetyPK

BiomarkersPD

Dosing

Labs

Biopsy

CT Scan

Dosing

ClinicalActivity

Cycle 3+Cycle 1 Cycle 2

PART A – MULTIPLE DOSE ESCALATION, “3+3” DESIGN PART B – EXPANSION COHORTS

Target Indications Incidence (Us)

HNSCC 53,000/y

TNBC 27,000/y

cSCC 10,000/y

ATC 450/y

Add On Indications

Leptomeningeal 110,000/y

GBM 10,000/y

EXPECTED FIRST DATA

READOUT MID-2021:


Preclinical

Programs

exoASO-STAT6: Selective Knockdown of STAT-6 Transcription Factor Repolarizes M2 Macrophages in the TME


• Selective delivery to M2 macrophages

• Single-agent complete anti-tumor response in preclinical models

• Broad therapeutic index with multiple routes of administration (IV, IP, ITu, intrathecal)


✓ Cell selective transcription factor

regulation

✓ Enhanced therapeutic index

✓ TME selective delivery

Mechanism of Action

IT/Systemic Injection

M2 macrophage selective

uptake M2 to M1

Repolarization

STAT-6 ASO

Engineered to express high levels

of PTGFRN

Source: AACR 2019

KEY DESIGN

ELEMENTS/OBSERVATIONS

IND filing anticipated H2 2021

exoASO-STAT6: Displays in vivo STAT-6 Knockdown, TAM Reprograming, and Single Agent Activity


MONOTHERAPY ACTIVITY


M2 TO M1 MACROPHAGE REPROGRAMMING

Colon Carcinoma (CT-26)Intra-tumor Dosing

Tum

or

CD

11

b+

ce

lls

Hepatocellular Carcinoma (Hepa1-6)Intravenous Dosing

8 10 12 14 16 18 20 22 24 26 28 30 32 34 36

0

250

500

750

1000

1250

1500

1750

2000

2250

Days Post Tumor Implantation

Tu

mo

r V

olu

me (

mm

3)

(Geo

Mea

n)

PBS

Free STAT6 ASO

exoASO-STAT6

anti-PD1

exoASO-Scramble

anti-CSF1R

Exosom

es O

nly

exoASO

Scra

mble

anti PD

1

exoASO

STAT6

exoASO

STAT6+aP

D1

anti CSF1R

0

50

100

150

% Scored lesions in Liver

%

Sco

red

lesio

ns

(tu

mo

r in

vasio

n)

***

*****

CR:4/8

CR:5/8

CR:1/8

CR:0/8

M1 Marker NOS2

M2 marker CSF1RColon Carcinoma (CT-26)

Intra-tumor Dosing

Near-Term Opportunities:Neuro-Oncology and Neuro-Inflammation


INTRATHECAL EXOSOMES TARGET CNS MACROPHAGES

exoSTING exoIL-12 exoASO-STAT6/exoASO-NLRP3

Neuro-Oncology Indications for ExistingPipeline

• Leptomeningeal cancer disease

• Glioblastoma multiforme

Neuro-Inflammatory Indications

• Progressive multiple sclerosis

• Neuropathies and Radiculopathies

• Neurodegenerative diseases

COMPARTMENTAL DOSING

ExosomeM2 macrophages

Exosome (PrX)

ExosomeLymphatics

Meningeal IHC Intracranial dosing

Intrathecal dosing

Intrathecal Tropism of Exosomes for Nervous System Immune Cells

PRECLINICAL PROGRAM

exoVACC: A Precision Engineered Vaccine Platform


A Modular Platform for Constructing Vaccines

• Luminal antigen to protect from neutralizing antibodies

• Diverse adjuvant and co-stimulators to tailor response

• Robust adaptive and innate immune responses

• Strong mucosal CD8+ T cell immune response

Co-stimulators(e.g. CD40L) Antigens

Luminal & Surface

TropismTargeting mAb

(e.g. anti-Clec9A)

Adjuvants(e.g. CDN, TLR9)

33

Modular exoVACC Vaccine Platform Enables Tailored Immune Response for Addressing a Broad Range of Diseases

Engineered Immune

ResponseDisease Antigen Collaboration

Humoral and T-cellPan-SARS RBD &

T-cell epitopes

Ragon Institute

(G Gaiha & B Walker)

T-cell HIVHIV T-cell

epitopes

Ragon Institute

(G Gaiha & B Walker)

T-cell CancerCancer cell neo-

antigens

Wash U

(K Sheehan & B Schreiber)

T-cell EBV - PTLDEBV T-cell

epitopes

Ohio State Univ

(Rob Baiocchi)

Multiple collaborations with leading scientists


engEx-AAVTM: Seeking a Solution for Non-Viral Delivery of Gene Therapy


• Improved intrinsic AAV activity

• Manufacturing advantages / COGS

• Neutralizing anti-AAV antibodies (nAbs)

• Inadequate or fading gene expression

• Limited tropism of effective AAV-vectors

• High dose AAV associated with toxicity

CHALLENGES

High Dose of AAVAssociated with Toxicity

Free AAV25nm

engEx-AAV SOLUTION

Targeted, Repeat Dosing Regardless of AAV Exposure

Exosome shieldedAAV

Compartmentaldosing

Engineered exosome cellular tropism

Ocular engEx-AAV Gene Expressionwithin Retinal Cells

High efficiency, neutralization-resistant gene expression

Engineering enhancedengEx-AAV loading

0

10

20

30

40

50

60

70

80

WT engEx-1 engEx-2 engEx-3

fold

en

ric

hm

en

t v

s W

T

engEx-AAV25nm


PBS exoAAV9101

102

103

104

na

no

Lu

c

(RL

U/

mg

of

pro

tein

)


Corporate

Snapshot

Doug Williams, Ph.D.President and CEO

Linda BainCFO

Nicole BarnaSVP, Head of Human Resources

Richard BrudnickCBO, Head of Strategy

Yalonda HowzeEVP, Chief Legal Officer

Konstantin Konstantinov, Ph.D.EVP, Manufacturing and Process Sciences

Benny Sorensen, M.D., Ph.D.SVP, Head of Clinical Development

Experienced Leadership, Continued Execution

36

BOARD OF DIRECTORS

Steven Gillis, Ph.D.

Chairman

Karen Bernstein, Ph.D.

Director

Charles L. Cooney, Ph.D.

Director

Jason Haddock

Director

Theo Melas-Kyriazi

Director

Douglas E. Williams, Ph.D.

President, CEO

EXECUTIVE TEAM


Expanding Global IP Portfolio*


Codiak has additional acquired and in-licensed patent families, including

20+ issued patents and 60+ pending applications

PRODUCT CANDIDATES10+ Families

1 issued US patent

METHOD OF TREATMENT5+ Families

engEx PLATFORM20+ Families

2 issued US patents

PROCESSES10+ Families

50+Patent Families

* AS OF 8/31/2020

Financial Summary

38

Unaudited cash, cash

equivalents and

restricted cash of

$88.9 MILLION

at December 31, 2020


Cash and follow-on

proceeds to fund

operations

through 2022

Runway to potentially

deliver meaningful

value inflections over

multiple programs

Multiple Near-Term Catalysts Anticipated

PROPRIETARY INFORMATION OF CODIAK BIOSCIENCES | 39

exoSTING topline data (mid-2021)

exoIL-12 healthy volunteer pharmacodynamic (PD) data (02/04/21)

exoIL-12 topline data (by year-end 2021)

exoASO-STAT6 IND (H2:21)

Continue progressing partner programs

Broaden focus to neuro-oncology, neurology and vaccines

Potential additional strategic partnerships to enhance engEx Platform capabilities


Documents

ENGINEERING PRECISION EXOSOMES DEVELOPING …