Anil Singhal, President and CEO June 2019

Off-The-Shelf, Engineered Gamma Delta γδ T cell Therapy for Oncology

Adicet Bio: Two Compelling Platforms for Cell Therapy

2

• Founded in 2015 with $51M Series A funding - 60 employees

• Potent off-the-shelf, engineered γδ T cell therapy for oncology and other indications

• Proprietary intracellular tumor-selective targets from TCR-L platform for treatment of solid tumors

• IND for ADI-001 planned in Q4’19 for non-Hodgkin’s lymphoma and CLL

• Robust, cost-effective, cGMP-compliant manufacturing from healthy donors

• Strategic collaboration with Regeneron

• Experienced leadership team and top tier investors

Leading the Next Generation of CAR-T Therapies

Our Goal: Improve Cancer Immunotherapy

3

• Autologous CAR-T have demonstrated remarkable efficacies in heme malignancies, however..

• Cumbersome, high manufacturing cost of patient-specific therapies

• Current therapies are compromised by patient’s immune system dysfunction

• Existing cell therapies present challenging safety profiles

• Loss of target from current cell therapies leading to relapses

• Unsuccessful treatment of solid tumors due to lack of selective targets

Engineered γδ T Cells Solve Key Challenges of Current Cellular Therapies

Adicet Advantages

4

γδ T Cells: The Foundation of Superior ‘Off-The-Shelf’ T Cell Therapies

• Allogeneic without gene editing

• Bind tumor antigen without MHC complex

• Highly potent against solid and liquid tumors

• Provide both innate and adaptive immunity

• No risk of GvHD

• Actively traffic to solid tumors and tissues

• Potent γ-IFN production

• Able to redose on demand

NCRs

DNAM-1

NKG2D

Engineered TCR(defined specificity)

Engineered CAR (defined specificity)

γδ T cell

γδTCR

γδ T cells express multiple tumor-recognizing receptors

5

Godder et al. 2007 Meraviglia et al. 2017

Improved Disease Free ProgressionColorectal Cancer

γδ T cell hi

γδ T cell lo

γδ T cell hi

γδ T cell lo

γδ T cell lo / IFNγ lo

Pan-Cancer: Improved Overall Prognosis

Gentles et al. 2015

Post-HSCTImproved Survival

Overall Survival

Improving Cancer Immunotherapy

γδ T Cells Strongly Correlate with Positive Clinical Outcomes

Building a Broad Pipeline in Cancer

6

Program Indication Discovery Target Optimization

Preclinicalγδ cells

Manufacturing & IND-enabling

studies

InitiatePhase 1

CD20 NH Lymphoma IND filing 4Q’19 1Q’20

UT1 Melanoma

UT2 Solid Tumors

UT3 Multiple Myeloma

UT4 Solid Tumors

UT5 Prostate Cancer

UT6 Solid Tumors

ADI-001

UT: Undisclosed Targets Derived from TCR-L platform

ADI-001 Cells Potently Kill Multiple Lymphoma Cell Lines in vitro

7

• Innate and CAR-mediated activity of γδ T cells is superior to published results of competitor products

• CD20 CAR potentiates innate tumor recognition and killing

• Effective killing of HLA-Class 1 null (Daudi) cells

• Effective killing of cell lines expressing low CD20 levels

Raji*(~54,000 CD20 /cell)

Daudi*(>50,000 CD20 /cell)

Mino*(>90,000 CD20/cell)

WILL-2*(<1000 CD20 /cell)

CD20 CAR Vδ1 cells Un-engineered Vδ1 cells* Adicet Study

0.001 0.01 0.1 1 10 100

0

25

50

75

100

-25

0

25

50

75

100

Effector: Target Ratio

0.001 0.01 0.1 1 10 100

0

25

50

75

100

0

25

50

75

100

Effector: Target Ratio

0.001 0.01 0.1 1 10 100

0

25

50

75

100

0

25

50

75

100

Effector: Target Ratio

% C

ytot

oxic

ity

0.001 0.01 0.1 1 10 100

0

25

50

75

100

0

25

50

75

100

Effector: Target Ratio

y

y

-5 0 5 10 15 20 25 30 350

1×1010

2×1010

3×1010

4×1010

5×1010

6×1010

7×1010

Mea

nTo

tal F

lux

(p/s

) +/-

SE

M

ADI-001 Cells Effectively Control Aggressive Lymphoma Tumors in Mice

• γδ T cell treatment initiated* at T=0, s.c. tumor volume ≥ 200mm3

• 2nd generation CD20 CAR-modified γδ T cells effectively control multiple disseminated (iv) and localized (sc) tumors

-5 0 5 10 15 20 25 300

1000

2000

3000

4000

5000

Days Post Treatment

Mea

n Tu

mor

Vol

ume

(mm

3 ) +/

- S

EM

Subcutaneous Raji Tumor Growth*

* Adicet Study

Intravenous Granta Tumor Growth*

-5 0 5 10 15 20 25 30 35 400

1000

2000

3000

4000

()

Subcutaneous Mino Tumor Growth*

Mea

n Tu

mor

Vol

ume

(mm

3 ) +/-

SEM

-5 0 5 10 15 20 25 30 35 40 45105

106

107

108

109

1010

1011

1012

Days Post Treatment

Mea

n To

tal F

lux

(p/s

) +/-

SE

M

Intravenous Raji Tumor Growth*

**

* *

Subcutaneous Raji Tumor Growth*

ADI-001 Cells Effectively Control Secondary Challenge Tumors

• Control of secondary tumor challenge strongly indicates persistence, potency & lack of exhaustion

1o Tumor Challenge 2o Tumor Challenge

Mice with no / low tumor burden at Day 55-60 were rechallenged with tumor

* Adicet Study

0 20 40 60 80 1000

1000

2000

3000

4000

5000

6000

Days Post Treatment

Mea

n Tu

mor

Volu

me

(mm

3 ) +/-

SEM

CD20 CAR γδ T Cells Proliferate in Response to Activation in Tumors

10

Blood

Spleen

Liver

Bone marrow

Tumor

Cel

l Num

ber

T cell Proliferation

Day 2 Post-treatmentCAR-T γδ

Substantial target-mediated proliferation of CD20 CAR γδ T cells in localized lymphoma tumors at 6 days post treatment

CD20 CAR γδ T Cells Proliferate in Response to Activation in Tumors

11

Blood

Spleen

Liver

Bone marrow

Tumor

Cel

l Num

ber

T cell Proliferation

Day 2 Post-treatmentCAR-T γδ

Day 6 Post-treatment CAR-T γδ

Substantial target-mediated proliferation of CD20 CAR γδ T cells in localized lymphoma tumors at 6 days post treatment

T cell Proliferation

CD20 CAR γδ T Cells Proliferate in Response to Activation in Tumors

12

Blood

Spleen

Liver

Bone marrow

Tumor

Cel

l Num

ber

T cell Proliferation T cell Proliferation

Day 2 Post-treatmentCAR-T γδ

Day 6 Post-treatment CAR-T γδ

Day 6 Post-treatment CAR-T αβ

Substantial target-mediated proliferation of CD20 CAR γδ T cells in localized lymphoma tumors at 6 days post treatment

Blood

Spleen

Liver

Tumor

Bone marrow

T cell Proliferation

• No GvHD observed in mice treated with γδ cells

• No gene editing required to overcome GvHD

• Deaths in the αβ CAR T cell group due to GvHD

Intravenous Raji Tumor in SRG-15 Mice†*

Absence of GvHD with ADI-001 Cells

13

αβ CART cells CAR γδ T cellsTumor alone

Days Post Treatment Pe

rcen

tage

Sur

vivi

ng

0 2 0 4 0 6 0 8 00

2 5

5 0

7 5

1 0 0

†SRG-15 mice express human IL-15 transgene* Adicet study

• Robust activation using Adicet’s γδ TCR mAbs

• Viral transduction

+

Selection of Optimal Healthy Donors Manufacturing Process < 1 Month Batch Sizes of 2E11 Cells

• Large-scale closed-system perfusion bioreactor-based expansion

• Excellent post cryopreservation viability & function

14

~1000s of doses per batch

Able to selectively expand different γδ T cell subsets

Simplify for Robustness, Partner for Capability and Capacity

Adicet Advantages: Robust, Large-Scale Manufacture of γδ T Cells

Clinical Development of ADI-001

• Target product profile of ADI-001 (CD20 CAR γδ T cells derived from healthy donor)⎼ Highly effective (ORR, PFS/OS) in CD20 expressing NHL and CLL

⎼ No GvHD

⎼ Significantly lower CRS

• Phase 1 Study⎼ NHL, CLL patients relapsing from 2 or more prior lines of treatment

⎼ 2-3 cohorts for dose escalation/safety

⎼ Up to 30 patients at the selected dose

⎼ Single treatment with ADI-001

• Pivotal study likely in DLBCL and/or MCL

ADI-001 Timeline

GMP Manufacturing initiated: 4Q’18

Pre-IND meeting Q1’ 2019

• IND filing: 4Q’19

• Phase 1 initiation: 1Q’20

• Clinical data: 1H’21

16

TCR-Like monoclonal antibodies (TCRL)

17

Adicet Advantages: Unlocking the Intracellular Proteome

18

CHALLENGE

SOLUTION

• Lack of disease-specific cell surface targets in solid tumors (80% of proteins are intracellular)

• Ability to target disease-specific intracellular proteins highly expands the target pool

• Unlikely to express on normal cells• TCR-Like (TCR-L) antibodies are specific to

peptide-MHC complexes and have multiple applications– Mimic TCR specificity with mAb affinity– scFv for chimeric antigen receptors for cellular

therapy– Bispecific T-cell engaging antibodies

Tyrosinase TCR-Ls Effectively Control Melanoma Growth

19

• Tyr CAR γδ T cells effectively controls subcutaneous growth of melanoma cell line

• Tyr-CD3 bispecific antibodies effectively control subcutaneous growth of melanoma cell line

Mea

n Tu

mor

Vol

ume

(mm

3) +

/-SE

M

- 1 0 -5 0 5 1 0 1 5 2 0 2 5 3 00

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

2 5 0 0

Tyr CAR γδ T cells

Tumor alone

Day Post Treatment

WM266.4 Tumor Growth in NSG Mice*

* Adicet StudyM

ean

Tum

or V

olum

e (m

m3)

+/-

SEM

WM266.4 Tumor Growth in NSG Mice*

Tumor alone

Tumor alone + PBS

Tumor + Tyr-CD3 bispecific 1

Tumor + Tyr- CD3 bispecific 2

Tumor + irrelevant bispecific

2000

1500

1000

500

00 5 10 15 20 25 30

Day

Additional Opportunities for Adicet Platform Technologies

20

• Potential to treat severe infectious disease with γδ T cells

• Potential to eradicate autoreactive B-cells with CAR γδ T cells

• Growing portfolio of internally-validated tumor-specific TCR-like antibody targets

– Able to develop TCR-like antibodies as T cell engaging antibodies

Strong IP Portfolio: 11 Patent Families Worldwide

Patent portfolio on γδ T cell technologyComposition of matter for engineered γδ T cells

Selective expansion of γδ T cell populations and compositions thereof

Family of patents on TCRL technologyTCRL technology and use in cancer, viral infection, and autoimmune disease

Specific TCRL Antibodies and their targets

Class I major histocompatibility complexes

21

Key Terms of the Collaboration with Regeneron in Oncology

22

Structure of the agreement: • Multiple targets • REGN has option to license a defined number of product

candidates at IND̶ REGN optioned products: Adicet has option to co-

develop/co-commercialize OR receive royalties

• Adicet products: royalties to REGN

γδ T cells engineered with CARs and TCRs for oncologyGenerate a pipeline of liquid and solid tumor product candidates

Five year research collaboration; Initiated 7/2016

Adicet: Leader in CAR and TCR Engineered γδ T cells

Company γδ Subtype Engineering Partner Stage (engineered ACT)

Vδ1

Adicet δ1 CAR/TCR Regeneron FPI 1Q2020

Gamma Delta/Lymphact δ1 no Takeda preclinical

TC Biopharm δ1 not clear UDublin (2019) FPI 2H2019?

non-

Vδ1 Adicet δ2, δ3 CAR/TCR Regeneron FPI 2020

TC Biopharm δ2 CAR bluebird bio Ph 1Incysus δ2 TMZ-R UAlabama FPI 2H2019

Immatics δ2 TCR MDACC preclinical

• Other players, not directly competing with Adicet, include: Gadeta (αβT, autologous), Phosphogam (Vδ2), American Gene Technologies (viral activation of Vγ9Vδ2 cells), potentially Universal Cells/Adaptimmune

Experienced Team with Proven Track Record

24

Stewart Abbot, Ph.D.Chief Scientific and Operating Officer

Brian HoganChief Financial Officer

Anil Singhal, Ph.D.President and CEO

Investment Opportunity

25

• Potent off-the-shelf, engineered γδ T cell therapy for oncology and other indications

• Proprietary targets derived from TCR-L platform for treatment of solid and liquid tumors

• Robust, cost-effective, cGMP-compliant manufacturing from healthy donors

• IND for ADI-001 planned in Q4’19 for non-Hodgkin’s lymphoma and CLL

• Strategic collaboration with Regeneron

• Experienced leadership team and top tier investors

Leading the Next Generation of CAR-T Therapies

Back up

C o n f i d e n t i a l U s e O n l y26

Engineered γδ T Cell Product Development Timeline

27

Program Indication 2019 2020 2021 2022 2023 2024

ADI-001 NH Lymphoma

ADI-002 Oncology

ADI-003 Oncology

Phase 1

Phase 2 / Pivotal BLA filingIND

Preclinical

Phase 1IND

IND

Phase 1

Preclinical

Phase 2 / Pivotal