PRECISION EXOSOMES REVOLUTIONARY MEDICINES

PRECISION EXOSOMESREVOLUTIONARY MEDICINES

S e p t e m b e r 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 within the meaning of the Private Securities Litigation Reform Act of 1995. 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 current expectations of future events, estimates and assumptions by our management that,

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

are subject to a number of risks and uncertainties that may cause actual results to differ

materially and adversely from those set forth in or implied by such forward-looking statements,

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.

Codiak BioSciences – Advancing a New Therapeutic Category

3

The Leader in

Exosome

Therapeutics:

A New Category

of Biologic

Candidates

Proprietary

engEx™ Platform → Precision

Engineered

Exosomes

Clinical-stage

Biotechnology

Company with

Rich Diversified

Pipeline

PROPRIETARY INFORMATION OF CODIAK BIOSCIENCES |

Accelerating Momentum in 2020 and 2021

4

exoIL-12TM and exoSTINGTM clinical studies initiated


Sarepta collaboration expands BD initiatives (incl. Jazz, Ragon Institute, WUSTL, OSU)

exoIL-12 dose selection completed with advancement into CTCL

Successful IPO (10/20) and follow-on offering (2/21) completed

Peer-review publications on engExTM Platform, exoIL-12 and exoSTING

Clinical Manufacturing Facility on-line

Anticipated 2021 milestones:

- exoSTING top-line data in Q4:21

- exoIL-12 CTCL data by YE 2021

- exoASOTM-STAT6 IND filing 2H 2021

Exosomes: Nature’s Highly EvolvedMacromolecule Delivery System

✓ Immune silent for tolerability and

repeat dosing

✓ Broad delivery potential for multiple

drug-like molecules

✓ Tropism for targeted cell delivery

✓ Access and retention in all body

compartments

5

Codiak: Co-opting Nature’s Drug Delivery System


The body’s “FedEx”

Peer-Reviewed Scientific Excellence


engEx™ Platform: Creating the “tool kit” for precise exosome engineering.

exoIL-12™: Preclinical confirmation of the unique target product profile (TPP). Potent activity without toxicity.

Late-Breaking Abstract:Presentation of positive randomized control Phase 1 clinical data of exoIL-12.

exoSTING™: Preclinical confirmation of the unique TPP. Targeted CDN delivery and abscopal tumor immunity.

Presented April 10, 2021

Published online April 22, 2021

Published online Jan 20, 2021In print May 5, 2021 issue

Published online Dec 21, 2020In print March 2021 issue

The Leading Platform for Engineered Exosome Therapeutics

7

Drug Creation

Functionalizing Exosomes via Modular Engineering

Multiple Drug Modalities, Directed Tropism

Drug Production

Versatile and Scalable Manufacturing

Integrated Clinical Manufacturing Facility


Codiak’sengEx™Platform

Precision Exosome

Engineering

engEx™│Designing Drug Candidates with Preferential Cell Tropism


MEMBRANE

Exterior

Lumen

Surface Cargo

• Antibodies, scFab, scFv

• Cytokines

• Receptors

• Enzymes

• Peptides

• Tropism Modifiers

Luminal Cargo

• Antigens

• AAV

• Peptides

• Nucleases

• Enzymes

PTGFRN

BASP-1

Luminal Cargo

Surface cargo

Cell Line Engineering Post-purification Loading

Secreted Exosomes

Surface Cargo

• ASO

• siRNA

• miRNA

• Small molecules

• Proteins/Peptides

Luminal Cargo

• Small molecules

Selective Targeting│engEx™ & Compartmental Dosing

Exosome BiodistributionCommercial Rationale for

Compartmental Dosing

COMMERCIAL VALIDATION

99

Compartmental Dosing

Engineered Tropism

Tissue Retention & Accumulation

Expanded Therapeutic Index

Spleen

Macrophages (F4/80+)Exosomes

Lymph node Lung


IV ITh

Fed Batch or Continuous Bioprocessing Technologies Established

10

Suspension, high cell density,

chemically defined media

Advanced analytics for

characterization and QC release

Advanced chromatography &

filtration: scalable


• Broad IP filings

• Scalable

• MHRA and FDA reviewed

• Proprietary analytics

Bioreactor Purification AnalyticsCell Banking

• High purity, product quality, stability

• Highly intensified processing

• Proprietary exosome drug-loading

• Multiple scales with multiple constructs

GMP cell banks, human cell line

Clinical Mfg

Codiak’s Clinical

Manufacturing Facility

Expanding Pipeline of Proprietary Exosome Therapeutic Candidates


Candidate Payload

Dose

Route Indication Discovery Preclinical Phase 1 Phase 2 Phase 3

Worldwide

Rights

Oncology

exoIL-12™ Biologic ITu CTCL

exoSTING™ Sm. Mol.ITu

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

ITu / ITh 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

exoASO™ – NLRP3 ASO ITh Chemotherapy Induced Neuropathy

Neuromuscular

Gene TargetsGenetic

ModulationTBD Neuromuscular Diseases

Vaccines and Tolerance

exoVACC™Vaccines

ToleranceTBD Cancer /Viral Diseases/Viral Vectors

Topline data expected: Q4 2021

Topline data expected: by year-end 2021

Submit IND:2H 2021

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


Target Profile Confirmed Through HV Data:

• Tumor retained pharmacology

• Absence of systemic IL-12 exposure

• Lack of cytokine related AEs

• Local administration, systemic immunity

exoIL-12™

Preclinical DataPeer ReviewedDecember 2020

PTGFRN

IL-12 displayed on the surface

via PTGRFN

Phase 1 Trial Provides Human Clinical Validation of exoIL-12™Profile as a Single Agent


From Part A of Phase 1 Trial (HV):

✓ Complete tissue retention of IL-12

✓ Lack of systemic exposure to IL-12

✓ Lack of treatment-related AEs

✓ Local, potent, prolonged PD effect

✓ Confirmed 6 μg Q2wk for Part B

✓ Validates engEx Platform

0 200 400 600 800

1

10

100

Time [hrs]

PL

AS

MA

IL-1

2 [

pg

/mL

PlaceboexoIL-12 6.0 mcg

0 100 200 300 400

10

100

1000

Time [hrs]

SK

IN

IL-1

2 [

pg

/mL

]

Placebo

exoIL-12 6.0 mcg

KEY PK & PD RESULTSFIRST & BEST IN CLASS IL-12 PROFILE

0 100 200 300 400

1

10

100

1000

10000

Time [hrs]

IP-1

0 [

pg

/mL

]

Placebo

exoIL-12 6.0 mcg

LATE BREAKING ABSTRACT

StudyDesign

exoIL-12™ Phase 1 Trial in CTCL: Data Expected By Year-End 2021

Dose Escalation

Expansion

exoIL-12 monotherapy

3+3 and adaptive cohort

enrichment

Expected Data

Endpoint Measures

14

PK PLASMA IL-12 Plasma levels low/absent

PLASMA BIOMARKERSIFN-γ

NanostringLack of systemic immune activation

TISSUE BIOMARKERS(2 & 6 weeks after dosing)

IL-12

IP-10CD8

CD56

Ki67

Nanostring

Local IL-12 retention

Lesional IL-12R activation

Local Immune cell influx, proliferation, activation

RESPONSE ASSESSMENT(4-week intervals)

CAILS injected

CAILS noninjected

mSWAT

CAILS Response Rate >40%FDA approved registrational endpoints


Target Population: CTCL Stage IA/IIB

- Plaques

- Patches

- Tumors

Desired Outcome

CAILS - Composite Assessment of Index Lesion Severity

Phase 1 Optional Extension CTCL IA-IIB

(N=12-18)

exoIL-12 ™ │Projected Clinical Development Plan


Phase 1 Part ARCT, Healthy volunteers

(N=25)

Phase 1 Part B3+3, CTCL IA-IIB

(N=6-9)

Phase 2/3 Pivotal*CTCL IA-IIB

(N=75-150)

2021 2022 2023

End of Year 2021 Data Readout

(ongoing)

(completed)

*Pending Regulatory confirmation


Target Profile for Clinical Confirmation:

• Selective CDN delivery to tumor APC

• T-Cell avoidance

• Lack of systemic CDN exposure

• Systemic anti-tumor immune response

exoSTING™

Preclinical DataPublishedMay 2021

= CDN: STING agonist

Loaded with proprietary CDN

Engineered to express high levels

of PTGFRN

exoSTING™ Preliminary Data Readout (Q4)


Early assessment of exoSTING™

safety & differentiated

pharmacologic activity in active

dose cohorts

Initial Top-lineData

Safety, PK, and available PD data from Cohorts 1-3.Confirmation of

TPP

Q4 Readout

Ongoing assessment for

ORR. Up to 42 patients. Final Part A data

expected H1 2022

Complete Part A Data

exoSTING

F4/80 CD8 DAPI

StudyDesign

exoSTING™ Phase 1/2 Trial and Data

Dose Escalation

Expansion

exoSTING™monotherapy

3+3 and adaptive cohort

enrichment

Expected Data

18

PK STING (CDN) Plasma levels low/absent

PLASMA BIOMARKERSCytokines

Nanostring

Low levels of systemic inflammatory cytokines

TISSUE BIOMARKERS(2 & 6 weeks after dosing)

IFNβCD8

CD163

CXCL9/10

TCF7

Nanostring

Local STING pathway activation

Adaptive immune response signals in tumor samples

CD8 T cell infiltration/activation

RESPONSE ASSESSMENT(8 weeks intervals)

CT scans (RECIST 1.1, iRECIST, itRECIST)

Single agent objective response (as part of complete Part A data)

Optimized IT dosing

Injectable solid tumors

(HNSCC, ATC, cSCC, TNBC)


Endpoint Measures Desired Outcome

The Next Wave of Innovation and Value Creation


engEx™

First-in-Class Engineered Exosome Therapeutic Candidates


engEx-AAV™exoASO™-STAT6 exoVACC/Tolerance™

• Selective transcription factor

targeting candidate

• Best in Class TAM repolarization

with single agent activity

• 2H 2021 IND filing

• Tunable, modular vaccines with

potent T- and/or B cell immune

response

• Tissue directed immunity or

tolerance

• Next generation biologic

delivery vehicle for AAV

• Targeted delivery and immune

evasion may enable repeat

dosing


Target Profile for Clinical Confirmation:

• Cell selective transcription factor regulation

• Enhanced therapeutic index

• TAM selective delivery

• Primary and metastatic hepatic malignancies

exoASO™-STAT6

STAT-6 ASO

Engineered to express high levels

of PTGFRN

ASGCT 2021: Poster presentation

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

22PROPRIETARY INFORMATION OF CODIAK BIOSCIENCES |PRECLINICAL DATA

M2 TO M1 MACROPHAGE REPROGRAMMING

Colon Carcinoma (CT-26)Intra-tumor Dosing

Tum

or

CD

11

b+

ce

lls

M1 Marker NOS2

M2 marker CSF1R

exoASO STAT6exoASO Scramble

Retnla (Fizz-1) (M2)

Nos2 (M1)

exoASO STAT6exoASO Scramble

Colon Carcinoma (CT-26)Single Cell Sequencing

Hepatocellular Carcinoma (Hepa1-6)Intravenous Dosing

Exoso

mes

Only

exoA

SO S

cram

ble

exoA

SO S

TAT6

0

10

20

30

40

LW/BW ratio

% L

iver

weig

ht/

Bo

dy w

eig

ht ****

****

Untr

eate

d

aCSF1R

aPD-1

0

10

20

30

40

LW/BW ratio

Exosomes Only exoASO Scramble exoASO STAT6

MONOTHERAPY ACTIVITY

• First macrophage-targeting agent to show single agent activity

• Compelling macrophage repolarization data in vivo

• First ASO targeting a transcription factor delivered via exosome

• First systemically delivered engineered exosome therapeutic candidate

• IND filing anticipated 2H 2021

• Focus on M2 macrophage-rich solid tumors- advanced primary liver cancer such as hepatocellular carcinoma or secondary liver metastases from pancreatic

cancer, breast cancer, colorectal cancer

23

exoASO-STAT6: Codiak’s Third Clinical Candidate


Diverse adjuvant & immunomodulator combinationsSmall molecules, co-stimulatory proteins, nucleic acids

Enhanced pharmacological activity

Flexible antigen displaySurface and luminal expression of antigenRapid “Clip-on” attachment of peptides and proteins to the surface

24

exoVACCTM: A Versatile Exosome-based Vaccine Platform

Enhanced cell-specific tropismNatural tropism for antigen presenting cells (APCs)Tropism modified with surface engineered antibodies & proteins



Agonists

Tailoring Immune Responses via Antigen Orientation and Route of Administration


Turonova et al Science 2020

SARS CoV2120 RBD/virion

exoRBD~ 300 RBD/exo

exoRBD (PrX)SARS CoV2 RBD on Surface

exoRBDSARS CoV2 RBD on Surface

8 μg

exo

RBD

2.6 μg

exo

RBD

1.3 μg

exo

RBD

20 μ

g rR

BD +

STIN

G

8 μg

rRBD +

exo

exo

0

5000

10000

15000

Anti-RBD IgGUnadjuvanted

RB

D IgG

(ng/m

l)

ControlFree RBD

ExoRBD

Luminal Display Enables Robust CD8 T-cell Immunity

Robust IgG Response to SARS-CoV2 RBD

AdjuvantSTING Agonist

AntigenOva

Loaded in

Lumen

exoOVA (Lum)-CDN

OVA

exoO

VA (L

um)

exoO

VA (L

um) +

CDN

OVA

+poly I:

C

exoO

VA (L

um) +

poly I:

C

0

10

20

30

40

50

lung OVA+ CD8 TRM

% O

VA

+ C

D8 T

EM

ce

lls

*** **

Lung Tissue Resident CD8 T-cell Effector Memory Response

PRECLINICAL DATA


Targeted Profile:

• Exosomes with luminal AAV capsids

• Resistance to neutralizing antibodies

• Potential for repeat dosing

• Proprietary scaffolds enhance capsid loading

• Altered tropism via surface engineering

engEx-AAV™

Luminal loaded AAV particles

Potential for tropism modification



engEx-AAVTM: Seeking to Solve Delivery Challenges in Gene Therapy

• High efficiency • Neutralization-resistant gene expression

Free AAVStochastic exoAAV*

0.1 1 10 10

0

1,00

0

10,0

00

0

1000

2000

3000

200000

250000

300000

350000

400000

IVIG (mg/mL)

Lu

c (

RL

U)

exoAAV free AAV

PBS exoAAV10

100

1000

10000

na

no

Lu

c

(RL

U/

mg

of

pro

tein

)

• Ocular exoAAV Gene Expressionwithin Retinal Cells

WT engEx-AAV

0

5

10

15

20

% o

f A

AV

in e

xosom

es (

qP

CR

)

WTengEx-

AAV

~60X

VP1

VP2

VP3

anti-capsid western blot

*stochastic loading

Promise of Exosomes in Gene Therapy Advancing Codiak’s Proprietary engEx-AAV

• engEx™ engineering yield 60-fold increased AAV loading

• Precise and predictable exosome loading of AAV

MEMBRANE

Lumen

PRECLINICAL DATA

engEx™

engExTM Exosomes – Broad Applications in Multiple Therapeutic Areas


NEUROLOGIC DISEASE

FIBROTIC DISEASE

METABOLIC DISEASE

IMMUNO-ONCOLOGY,

HEMATOLOGY/ONCOLOGY

REGENERATIVE MEDICINE

AUTOIMMUNE/INFLAMMATORY

DISEASE

Doug Williams, Ph.D.President and CEO

Linda BainChief Financial Officer

Nicole BarnaSVP, Head of Human Resources

Richard BrudnickCBO, Head of Strategy

Yalonda HowzeEVP, Chief Legal & Compliance Officer

Konstantin Konstantinov, Ph.D.Chief Technology Officer

Sriram Sathyanarayanan, Ph.D.Chief Scientific Officer

Jennifer Wheler, M.D.Chief Medical Officer

Experienced Leadership, Continued Execution

29

BOARD OF DIRECTORS

Steven Gillis, Ph.D.

Chairman

Karen Bernstein, Ph.D.

Director

Charles L. Cooney, Ph.D.Director

Anne-Virginie EggimannDirector

Jason HaddockDirector

Theo Melas-KyriaziDirector

Lini Pandite, MBChBDirector

Douglas E. Williams, Ph.D.President, CEO

EXECUTIVE TEAM


Multiple Anticipated Near-Term Catalysts For Value Creation

PROPRIETARY INFORMATION OF CODIAK BIOSCIENCES | 30

exoASO-STAT6 IND (H2:21)

exoSTING preliminary topline data (Q4)

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

Continued progress on partner programs

Continued visibility at scientific meetings, peer-reviewed publications

Potential strategic partnerships to further unlock engExTM

Platform value


Documents

PRECISION EXOSOMES REVOLUTIONARY MEDICINES