Targeting tumor suppressor lossto unmask vulnerabilities in cancer

for the next generation of precision medicines

Corporate overview

November 2021

Confidential | 2

Disclaimer and Safe Harbor Statement

Certain statements in this Presentation may be considered forward-looking statements. Forward-looking statements generally relate to future events, Tango’s future financial and operating performance, goals, expectations,

beliefs, development plans and development objectives for Tango’s product pipeline. In some cases, you can identify forward-looking statements by terminology such as “may”, “should”, “expect”, “intend”, “will”, “achievable”,

“milestones”, “goal”, “forecast”, “estimate”, “anticipate”, “believe”, “predict”, “potential” or “continue”, or the negatives of these terms or variations of them or similar terminology. For example, statements concerning the

following include or constitute forward-looking statements: Tango’s ability to identify, develop and commercialize drug candidates; the future anticipated benefits and future product candidates identified through the Tango

discovery platform; the expected timing of: (i) development candidate declaration for certain targets, (ii) initiating IND-enabling studies; (iii) filing INDs, (iv) clinical trial initiation and (v) the release of preliminary safety and

efficacy data and final safety and efficacy data from clinical trials; expected paths to clinical proof of concept for pipeline products; potential future product registrations for treatment of certain cancer tumor types; the initiation,

cost, timing, progress and results of research and development activities, preclinical and/or clinical trials with respect to PRMT5 and potential future drug candidates; TNG908 is a potentially first in class PRMT5 inhibitor that

is synthetic lethal with MTAP deletion; the various steps to be taken in Tango’s comprehensive development plan; the expected benefits and the timing of development and launch of the next generation PRMT5 inhibitors; in-

licensed and internal chemical matters provides what is expected to be an optimized IP position for USP1 pipeline product; recent improvements in crystal structure may drive future potency gains in USP1; the STK11

mutation enables the first potential genetic patient selection for an immuno-oncology clinical trial; estimates of Tango’s total addressable market and patient opportunity, future revenue, expenses, capital requirements and

the need for additional financing; Tango’s ability to advance TNG908/PRMT5 or other future product candidates into, and successfully complete, preclinical studies and clinical studies; the multiple key milestones identified in

this Presentation that are considered achievable; the projected milestones for TNG908/PRMT5 (including the completion of phase 1/2 trials, registrational studies start up and development of additional next generation

inhibitors); the projected milestones for the product pipeline; the discovery pipeline has the potential to deliver one new IND every 12 to 18 months; the TNG908 composition of matter patent application that has been filed

with patent offices will provide meaningful patent protection through at least 2041; and Tango has a cash balance that provides a runway into second half of 2024. Such forward-looking statements are subject to risks,

uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements. These forward-looking statements are based upon estimates and

assumptions that, while considered reasonable by Tango and its management are inherently uncertain. Drug development and commercialization involves a high degree of risk, and only a small number of research and

development programs result in commercialization of a product. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to

differ materially from current expectations include, but are not limited to: Tango has a limited operating history and has not generated any revenue to date from drug sales, and may never become profitable; Tango has

incurred significant operating losses and anticipates continued losses for the foreseeable future; we will need to raise capital in the future and if we are unable to raise capital when needed or on attractive terms, we would be

forced to delay, scale back or discontinue some of our development programs or future commercialization efforts; we may be unable to advance our preclinical development programs into and through the clinic for safety or

efficacy reasons or commercialize our product candidates or experience significant delays in doing so as a result of factors beyond Tango’s control; Tango’s approach to the discovery and development of product candidates

is novel and unproven, which makes it difficult to predict the time, cost of development, and likelihood of successfully developing any products; Tango may not identify or discover additional product candidates (including next

generation products) or may expend limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater

likelihood of success; delays or difficulties in the initiation or enrollment of patients in clinical trials could delay or prevent receipt of regulatory approvals; our products candidates may cause adverse or other undesirable side

effects that could, among other things, delay or prevent regulatory approval; even if we obtain regulatory approval to market a product, we will be subject to ongoing obligations and continued regulatory review, which may

result in significant expense; our dependence on third parties for conducting clinical trials and producing drug product; our ability to obtain and maintain patent and other intellectual property protection for our technology and

product candidates or the scope of intellectual property protection obtained is not sufficiently broad; and delays and other impacts on product development and clinical trials from the COVID-19 pandemic. Additional

information concerning risks, uncertainties and assumptions can be found in Tango’s filings with the SEC, including the risk factors referenced in Tango’s Quarterly Report on Form 10-Q for the quarter ended September 30,

2021 as filed with the SEC on November 9, 2021. You should not place undue reliance on forward-looking statements in this presentation, which speak only as of the date they are made and are qualified in their entirety by

reference to the cautionary statements herein. Tango specifically disclaims any duty to update these forward-looking statements.

Certain information contained in this Presentation relates to or is based on studies, publications, surveys and Tango’s own internal estimates and research. In addition, the market data included in this presentation involve a

number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while Tango believes its internal research is reliable, such research has not been verified

by any independent source.

Confidential | 3

COMPANY OVERVIEW

Confidential | 4

Tango summary

Precision oncology company based on synthetic lethality, combining discovery and clinical

development in the same genetic context

Expanding oncology target space into tumor suppressor gene loss with a productive,

state-of-the-art discovery platform

Sustainable pipeline of novel drug programs for cancers with specific tumor

suppressor gene loss and bringing precision medicine to immuno-oncology

TNG908 is a potentially first-in-class synthetic lethal PRMT5 inhibitor for MTAP-deleted

tumors with IND filing planned for 4Q 2021

Broad strategic collaboration with Gilead based on immune evasion effects of tumor

suppressor gene loss

Management team with deep expertise in cancer genetics, drug discovery, clinical development

and extensive pharmaceutical experience backed by top-tier investors

Confidential | 5

BOARD OF DIRECTORS

Reid Huber, PhD

Barbara Weber, MD

Malte Peters, MD

Mace Rothenberg, MD

Alexis Borisy

Chairman

Aaron Davis

Lesley Calhoun

Leaders in drug discovery, cancer biology, functional genomics and translational medicine

LEADERSHIP

John Maxwell, PhDChemistry

Barbara Weber, MDCEO

Alan Huang, PhDCSO

Daniella BeckmanCFO

Jannik Andersen, PhDBiology

Bill Mallender, PhDBiochemistry

Heather

DiBenedetto, MSDevelopment Operations

Charles Davis, PhDPharmaceutical Sciences

Doug BarryGeneral Counsel

Marc Rudoltz, MDCMO

Confidential | 6

José Baselga, MD PhDHead of Oncology R&D

AstraZeneca

Alan Ashworth, PhD FRSPresident

UCSF Cancer Center

Bill Kaelin, MD Professor, Dana Farber

Cancer Institute

Ulrich Elling, PhDInvestigator

Institute of Molecular Biotechnology, Vienna

Leaders in cancer genetics, synthetic lethality, CRISPR technology and immuno-oncology

Scientific advisors

In memoriam

1959-2021

John Doench, PhDInstitute Scientist

Broad Institute

Antoni Ribas, MD PhD Professor

UCLA

Confidential | 7

$125MUPFRONT

$6BMILESTONES

$410M/program

Up to $110M through

clinical POC

LOW

DOUBLE DIGIT

ROYALTIES

$20MEQUITY

15 TARGETSIMMUNE EVASION

50/50US PROFIT/LOSS

ON CO-CO

PROGRAMS

5 PROGRAMSCO-DEVELOP

AND CO-PROMOTE

TANGOFULL RIGHTS RETAINED

TO THREE LEAD

PROGRAMS

All new cell autonomous targets

TANGOTARGET VALIDATION

TO CLINICAL POC

GILEADMULTIPLE

TIMEPOINTS TO

LICENSE A

PROGRAM

Funded by milestone

payments during option

extension

GILEADLICENSE RIGHTS

All immune evasion

targets

SCOPERESEARCH AND DEVLOPMENT

RIGHTSSHARED

ECONOMICS DEAL TERMS

2 licensed,

2 option-extended

to date

A strong strategic partnership with Gilead

Confidential | 8

A sustainable precision oncology pipeline of novel targets

PROGRAMPATIENT

SELECTIONDISCOVERY

IND-ENABLING

CLINICAL TRIALSANTICIPATED MILESTONES

Phase 1 Phase 2 Phase 3

PRMT5

TNG908

MTAP-del

cancersIND filing 4Q 2021

USP1BRCA1-mut

cancersIND filing 2022

TARGET 3STK11-mut

lung cancerIND filing 2023

Multiple wholly owned targets in discovery phase

Gilead options and licensed targets not listed

Confidential | 9

SYNTHETIC LETHALITY FOR CANCER THERAPEUTICS

Confidential | 10

Most cancer targets are not drugged yet

SYNTHETIC LETHALITY

is currently the only way

to target tumor

suppressor gene loss

makes large scale

synthetic lethal

discovery efforts

feasible

CRISPR TECHNOLOGY

TUMOR SUPPRESSOR GENES

• Important drivers of cancer inactivated or deleted in almost all human cancers

• Not directly druggable

• Indirectly targeted with synthetic lethality

• PARP inhibitors are the first examples of synthetic lethal targeting

Confidential | 11

Synthetic lethality provides a path to targeting undruggable tumor suppressor gene loss

barglass

or

barglass

Tumor suppressor gene

Synthetic lethal

partner gene Inhibitor

No effect

Normal cell

Tumor suppressor gene

Synthetic lethal

partner geneInhibitor

Cell death

Cancer cell

X

Synthetic lethality was first described in fruit flies…

…and is now applied to cancer therapies

Confidential | 12

BRCA1/2 mutation and PARP inhibition are a synthetic lethal pair

PARP inhibitors are approved in

BRCA mutant breast, ovarian

and prostate cancer

Niraparib

Placebo

BRCA-mut

cancer cell

CELL

DEATH

+ PARPi

Normal

cell

NO

EFFECT

+ PARPi

• PARP inhibitors are clinical validation for synthetic lethal drug targeting

• Synthetic lethal drugs inherently have a wide therapeutic index

• Multiple analyses suggest hundreds of synthetic lethal pairs exist in human cancer

PARP is the first synthetic lethal drug target

Confidential | 13

A unique approach to target discovery and clinical development in the same genetic context

DISCOVERdrugs against

context-specific

target

IDENTIFYdrug targets dependent

on genetic context for

activity “context-specific”

DEVELOPdrugs in same genetic

context used for target

discovery

DISCOVERY AND

DEVELOPMENT

IN THE

SAME GENETIC

CONTEXT

SELECTcancer subtypes with

high unmet need

DEFINEgenetic alterations

in cancer subtype

“genetic context”

Confidential | 14

Cancer types with high unmet medical need

Genetic selection from the first patient dosed

Increased probability of meaningful clinical

resultsProprietary genetic

perturbation data from hundreds of CRISPR screens

Efficient screening,actionable hits

Leveraging massive public data sets from Broad, NIH

and Sanger Institute

Combinatorial, T cell co-culture and in vivo genetic screens

NOVEL TARGET DISCOVERYCOMPUTATIONAL

ANALYSISPRECISIONMEDICINE

Multiple, highly optimized CRISPR systems

Druggable genome, paralog and genome-wide CRISPR libraries

Cancer genetics Functional data

Sophisticated and proprietary

Linking large Tango and public datasets

Integrating target, genetic context &

functional data

TANDEM

Tango cancer dependency map

A robust discovery platform linked to a precision medicine approach

Confidential | 15

PRMT5 inhibition in MTAP-deleted cancers

Confidential | 16

Lead program is a potential first-in-class synthetic lethal PRMT5 inhibitor

TNG908

MTA-cooperative PRMT5 inhibitor that is synthetic lethal with MTAP deletion

DIFFERENTIATED MECHANISM

Novel MTA-cooperative mechanism targeting tumor cells with MTAP deletion enables

stronger target inhibition than non-selective PRMT5 inhibitors currently in clinical

development

LARGE PATIENT OPPORTUNITY

10-15% of all human cancers have MTAP deletion

NEAR TERM MILESTONES

Expected IND filing 4Q 2021, clinical trial initiation 1H 2022, preliminary safety and efficacy

data 1H 2023

MT

AP

Confidential | 17

MTAP DELETION

FREQUENCY

TCGA

PanCancer

Atlas

• MTAP co-deleted with tumor

suppressor gene CDKN2A

• Clear path to clinical POC in

MTAP-null solid tumors with

multiple histologies

• Potential for histology-

agnostic registration with

broad-based activity across

tumor types

10-15% of all human cancers are MTAP-null

Confidential | 18

MTAP-deleted cancer cell lines are sensitive to PRMT5 knockdown

Cell d

ea

th e

ffect s

ize

Mavrakis et al., Science 2016; Kryukov et al., Science 2016

Project DRIVE1

0.5

0

-0.5

-1

-1.5

-2

-2.5

MTAP-intact

MTAP-deleted

Cancer cell lines (n= 400)

MTAP is deleted in 10-15% of human cancers and leads to PRMT5 inhibition

MTA MTA

MTAMTA

SDMAPRMT5-specific

methyl mark

MTAP

PRMT5

SAMPRMT5 methyl donor

X

Chromosome 9p21 deletion

MTA accumulation

PRMT5inhibition

PRMT5 and MTAP are a synthetic lethal pair

Confidential | 19

Normal

cells

MTAP-null

cells

CELL DEATH

Existing PRMT5 inhibitors

CELL DEATH

TNG908

NO EFFECT CELL DEATH

PRMT5

MTAPMTAP

SAM

Substrate-Me

Degradation Degradation

MTA

MTA

MTA MTA

MTAMTA

MTA

MTA MTA

MTA

MTA

MTA

MTA

MTA

MTA

Multiple key

cellular functions

Substrate

PRMT5

SAM and MTA bind to the same pocket in PRMT5

X

X

• Work with MTA in the

active pocket

• Take advantage of

the high MTA levels

in MTAP-null tumor

cells

• Inhibit PRMT5 to

lethal threshold in

tumors at much

lower concentrations

than in normal cells

MTA-cooperative

PRMT5 inhibitors

Known PRMT5 inhibitors are not synthetic lethal with MTAP deletion

Confidential | 20

Known PRMT5 inhibitors are not synthetic lethal with MTAP deletion because of their mechanism of action

Cancer cells with no MTAP deletion

and normal cellsMTAP-deleted cancer cells MTAP-deleted cancer cells + TNG908

• PRMT5 catalyzes methyl group transfer from SAM to proteins

• GSK3326595 is substrate competitive

• Prelude, Pfizer and JNJ inhibitors are SAM competitive

• MTAP degrades MTA, which inhibits PRMT5

• MTAP deletion causes high intracellular MTA levels

• High MTA levels partially inhibit PRMT5 creating a vulnerability

• MTA-cooperative PRMT5 inhibitors require MTA in the pocket for PRMT5 binding

• TNG908 is an MTA-cooperative PRMT5 inhibitor

Cytotoxic epigenetic modifiers TNG908 is an MTA-cooperative PRMT5 inhibitor that is synthetic lethal with MTAP deletion

SAM Protein

substrate

PRMT5

MTA

PRMT5

Protein

substrate MTA

PRMT5

MeGSK

Prelude

JNJPfizer

Confidential | 21

Am

ax

at

1 µ

M

200 cancer cell lines representing multiple lineages

TNG908IC50 = 110 nM

15X selectivity for MTAP deletion

MTA-cooperative PRMT5 inhibitors are highly selective for MTAP-null cancer cell lines

MTAP WT

MTAP-null

7-day viability assay

All cell lines represented in both panelsA

max

at

1 µ

M

MTAP WT

MTAP-null

GSK3326595IC50 = 120 nM

No selectivity for MTAP deletion

Confidential | 22

TNG908IC50 = 110 nM

15X MTAP selectivity

GSK3326595IC50 = 120 nM

1X MTAP selectivity

Prelude*IC50 = 90 nM

1X MTAP selectivity

MTAP selectivity of TNG908 makes MTAP-deleted tumors 15X more sensitive than normal cells

Isogenic HAP1 cells (parental WT line)

TNG908 is 15X selective for MTAP-null cells

* Compound I from Patent WO2020168125, chemical structure of Prelude clinical molecules not disclosed

Confidential | 23

TNG908 IC50 110 nM, 15X selectivity for MTAP deletion

LN18(glioblastoma cancer cell line)

HAP1(haploid cell line)

Restoring MTAP in MTAP-null cells reverses TNG908 sensitivity

Confidential | 24

TNG908

MTA-cooperative PRMT5 inhibition is dose-dependent and MTAP-null selective

• SDMA measures PRMT5-specific methylation

• SDMA suppression in MTAP-null and WT cells

cannot be uncoupled by non-selective PRMT5

inhibitors

HCT116 colon cancer xenografts

IC90

IC90

IC90

IC90

HAP1 MTAP isogenic cell lines

150nM 550nM

Confidential | 25

TNG908 IC50 110 nM, 15X selectivity for MTAP deletion

HCT116 (colon)

TNG908 anti-tumor activity is dose and MTAP-deletion dependent

MTAP-null MTAP-WT

Confidential | 26

TNG908 drives tumor regression in MTAP-null xenograft models across lineages

NSCLC (adeno)

PDX

Bladder (TCC)

PDX

• Stasis or

regression in ~55%

of models (n=41)

• No obvious

histology restriction

• Stasis or regression

in ~60% of models

(n=52)

• No obvious histology

restriction

TNG908 IC50 110 nM, 15X selectivity for MTAP deletion

Cholangiocarcinoma

PDX

OCI-Ly19

DLBCL CDXU87MG

GBM CDX

Continuous treatment

Confidential | 27

2021 2022 2023

ADVANCED DRUG DISCOVERY PROGRAM

• Excellent drug-like properties

• Good pharmacokinetics in all pre-clinical species

• Dose-dependent, MTAP-null selective in vivo tumor regression

• In-life portion of rat and dog 28-day GLP tox studies complete, IND filing on track

• Composition of matter patent applications filed to provide meaningful patent protection through at least 2041

Development candidateselection

PHASE 1/2

TNG908 is a potentially first-in-class PRMT5 inhibitor that is synthetic lethal with MTAP deletion

IND-ENABLING

IND

filing1H study

start

1H early

clinical data

Confidential | 28

• Strong preclinical activity

in xenograft and patient-

derived models of

multiple histologies

• Expansion cohorts

provide optionality for

multiple registration

strategies

• Planned study start 1H

2022

Lung(squamous and non-squamous)

Mesothelioma

Cholangiocarcinoma

n ~ 20 each

15-70%

MTAP-null

Malignant peripheral nerve sheath

tumorsn ~ 20

30-50%

MTAP-nullAccelerated

approval option

Histology-agnostic “bucket”

(enriched for bladder,

pancreatic & unknown

primary)

n ~ 20

20-35%

MTAP-nullHistology-agnostic

approval option

Any solid tumor

with MTAP

deletion

DOSE

ESCALATION

Efficient trial design to evaluation efficacy in multiple histologiessupporting several registration strategies

CLINICAL RATIONALE

Confidential | 29

An

MTAP deletions occur in 10-15% of all human cancers

• Planning multiple rational

combination trials based on

strong pre-clinical synergy

data

• Extensive effort to define and

address resistance

mechanisms in a range of

genetic backgrounds

• Aggressive, structurally-

enabled medicinal chemistry

program of nextGen PRMT5

inhibitors with an experienced

team

• One of the largest genetically-defined

patient populations that may benefit

• Potential first-in-class PRMT5 inhibitor

that is 15X more potent in MTAP-null

cells than normal cells

• Multiple synergistic combination

partners in various cancer types

• A homozygous deletion that cannot

revert to wild-type as a resistance

mechanism

A very large and important opportunity A COMPREHENSIVEDEVELOPMENT PLAN

The most common

homozygous deletion

in human cancer

Confidential | 30

Nextgen PRMT5 exemplar compounds drive strong tumor regressions

Add

Exemplar IC50 4 nM, 20-fold selectivity for MTAP deletion

• Increased potency and MTAP-

deletion selectivity may

increase therapeutic index and

anti-tumor efficacy

• Multiple highly potent and

selective MTA-cooperative

PRMT5 inhibitors being profiled

• Next-generation compounds

follow TNG908 by ~ one year

Next-generation

PRMT5 inhibitors

LN18 (glioblastoma)

Confidential | 31

USP1 inhibition in BRCA1 mutant cancers

Confidential | 32

Control

(DMSO)

USP1i

(0.5 µM)

BR

CA

1 m

ut

BR

CA

1 W

T

UWB1.289

MDA-MB-436

HCC1954

AU565

• USP1 is a de-ubiquitinating

enzyme (DUB) that is

synthetic lethal with BRCA1

but not BRCA2

• Loss of USP1 results in

replication fork collapse in

BRCA1 mutant cells

• Some BRCA1 WT lung

cancer cell lines are sensitive

to USP1 inhibition, patient

selection marker being

evaluated

Fals

e d

iscovery

rate

Effect size Resistance markersPotential drug targets

Tango druggable genome CRISPR screen

in 13 cell line panel

USP1

USP1 and BRCA1 are a synthetic lethal pair

Confidential | 33

%

MDA-MB436 (mutant) vs HCC1954 (WT)

TNGXXX IC50 38 nM, > 200-fold selectivity for BRCA1 mutation

Lead series with good physiochemical properties and 200-fold selectivity for BRCA1 mutant cells

• Low nanomolar potency

• Highly selectivity for BRCA1

mutant vs. WT cells

• High oral bioavailability

• Moderate clearance

• Low hERG risk

Lead Series

Confidential | 34

Dose dependent in vivo anti-tumor activity with USP1 lead series exemplar

MDA-MB-436(BRCA1mut breast)

• Strong anti-tumor activity

in BRCA1 mutant

xenografts

• Recently solved inhibitor-

bound crystal structure

revealed novel allosteric

binding site

TNGXXX IC50 38 nM, >200 fold selectivity for BRCA1 mut vs. WT

Confidential | 35

SUM149PTBRCA1 mutant

SUM149PTBRCA1 WT (revertant)

• USP1i + PARPi is

synergistic in BRCA1

mutant cells but not in WT

• BRCA1 mutant selective

synergy confirmed in 16

cell line panel (6 BRCA1

mut, 10 WT)

• Synergy not seen in

BRCA2 mutant cell lines 0.001 0.01 0.1 1 10 100

0

50

100

150

SUM149PT(BRCA1m breast)

Olaparib concentration (M)

% c

ell v

iab

ilit

y r

ela

tive t

o D

MS

O

PARPi (olaparib)

PARPi + 0.12M USP1i

0.001 0.01 0.1 1 10 100

0

50

100

150

SUM149PT BRCA1 revertant

Olaparib concentration (M)

% c

ell v

iab

ilit

y r

ela

tive t

o D

MS

O

PARPi (olaparib)

PARPi + 0.12M USP1i

USP1i + PARPi is synergistic in BRCA1 mutant cells

20 fold IC50 shift

Confidential | 36

NOVEL TARGET

• Strong synthetic lethality with BRCA1

mutation

• Single agent activity and strong

PARP1 synergy in preclinical models

ADVANCED DRUG DISCOVERY

• In-licensed and internal chemical

matter provides optimized IP position,

multiple provisional patents submitted

• Lead series with low nanomolar in vivo

activity

• Recently solved inhibitor bound crystal

structure may drive further potency

gains

SIGNIFICANT PATIENT OPPORTUNITY

• ~15% ovarian, 5% breast, and 1%

prostate cancers are BRCA1 mutant,

~ half of PARP inhibitor market

• Selective dependency identified in a

subset of lung cancer cell lines, patient

selection markers being evaluated

USP1 development candidate anticipated 1H 2022

PROGRAMPATIENT

SELECTIONDISCOVERY

IND-ENABLING

CLINICAL TRIALSANTICIPATED MILESTONES

Phase 1/2 Phase 3

USP1BRCA1-mut

cancersIND filing 2022

Confidential | 37

Target 3 inhibition reverses immune evasion in SKT11 mutant cancers

Confidential | 38

The foundation of our collaboration with Gilead

Discovering drug targets that reverse immune evasion is a two-step process

Novel drug targets reverse

immune evasion in cancer cells

and enable immune cell killing

Context-specific

Immune evasion

Immune

destruction

Discover novel drug targets

that disable immune evasion

caused by specific tumor

suppressor gene loss

TARGET DISCOVERY SCREEN

2

Tumor suppressor gene loss is not directly druggable

Immune evasion driven by

tumor suppressor gene loss

CONTEXT DISCOVERY SCREEN

Identify tumor suppressor

genes that drive immune

evasion when deleted or

inactivated

1

X

Confidential | 39

Immuno-competent

+αPD1

Immuno-

competent

Immuno-

compromised

Immune evasion

contextsTumor suppressor

genes driving immune

evasion are enriched

CRISPR

tumor suppressor

gene library

Sequence tumorsgrowing under

increasing

immune pressure

Identifying tumor suppressor gene loss that drives immune evasion

Confidential | 40

Loss promotes

immune evasion

Loss promotes

immune-mediated killing

3-factor-comparison (exclude BL6)

adaptive+T

adaptive_PD1.beta

adaptive

_P

D1.f

dr

-1.00 -0.50 0.00 0.50 1.00 1.50 2.00 2.50 3.00

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

LKB1 KEAP1

Data table:

3LL-mageck4way- exclude_

Color by

Gene_type

Deleted_gene

Essential_gene

IO_positive_control

Other_gene

Tumor_suppressor

Filter settings

trends

- Gene: (Acvr1b)

masterTwoCondUsingNTC

- cond1_treatments: (nude)- cond2_treatments: (PD1_10mg)

False

discovery

rate

STK11AND KEAP1 MUTATIONS

are strongly associated

with clinical immune

evasion manifest as

checkpoint inhibitor

resistance

Nude mice vs. B6 mice + anti-PD1

Multiple tumor suppressor genes being

validated for immune evasion effect

Effect Size

STK11

Multiple tumor suppressor genes drive immune evasion when deleted

Confidential | 41

Control knockout

(MC38)

0 5 1 0 1 5

0

1 0 0 0

2 0 0 0

3 0 0 0

D a y s a f t e r t r e a t m e n t

Tu

mo

r V

olu

me

(m

m3

)

B A L B / c , P B S , I P , B I W x 2 , n = 1 8

C 5 7 B L / 6 , a n t i - I g G 2 a , 1 0 m g / k g , I P , B I W x 2 , n = 1 8

C 5 7 B L / 6 , a n t i - P D - 1 , 1 0 m g / k g , I P , B I W x 2 , n = 3 0

Immune deficient

Immune competent

Immune competent + PD1

STK11-DRIVEN IMMUNE EVASION

Unique model

validated for use in

target discovery

STK11 knockout

(MC38)

STK11 deletion drives immune evasion

0 5 10 150

500

1000

1500

Days after the start of treatment

Tum

or

volu

me

(mm

3)

Tum

or

volu

me

(mm

3)

0 5 10 150

500

1000

1500

C57BL/6 anti-PD1

Days post treatment initiation

Tu

mo

r V

olu

me (

mm

3)

NTC_nude

NTC_C57BL/6 + anti-IgG

NTC_C57BL/6 + anti-PD1

NTC+STK11_nude

NTC+STK11_C57BL/6 + anti-IgG

NTC+STK11_C57BL/6 + anti-PD1

0

500

1000

1500

0 5 10 15

Days after the start of treatment

Aggressive growth

in immune

competent mice

-PD1 resistant

0 5 10 150

500

1000

1500

C57BL/6 anti-PD1

Days post treatment initiation

Tu

mo

r V

olu

me (

mm

3)

NTC_nude

NTC_C57BL/6 + anti-IgG

NTC_C57BL/6 + anti-PD1

NTC+STK11_nude

NTC+STK11_C57BL/6 + anti-IgG

NTC+STK11_C57BL/6 + anti-PD1

-PD1 sensitive

Confidential | 42

Days

Lead series molecules with strong in vivo efficacy with anti-PD1

Biochemical IC50 6 nM

Cellular IC50 127 nM

Isoform selectivity 139

CYP3A4 IC50 >10 M

CL

(ml/min/kg)21

%F 27

Lead series exemplar

• CRISPR library of 850

immune response-related

druggable genes

• Target 3 inhibition reverses

immune evasion in STK11

mutant tumors

• Pharmacologic validation in

vivo with tool compound

Target 3 identified with in vivo CRISPR

screening• Good pharmacologic

properties with marked

isoform selectivity

Lead series

Days after treatment start

Tum

or

volu

me (

mm

3)

No detectable tumor in 10/10 mice at day 60

Treatment

stopped

Confidential | 43

STK11 and KEAP1 mutations drive clinical checkpoint inhibitor resistance

45%

33%29%

7%

Overall response rate in first line pembrolizumab + chemotherapy in non-small cell lung cancer

77% OF PATIENTS

with primary refractory

disease had STK11 and/or

KEAP1 mutations % PR/CR

as best

overall

response

ASCO 2019

Confidential | 44

NOVEL TARGET

• Multiple tumor suppressor genes play a

role in immune response to cancer

• In vivo target discovery leveraging

synthetic lethality identifies drug targets

that reverse immune evasion caused by

specific tumor suppressor gene loss

• Target 3 inhibition reverses checkpoint

inhibitor resistance in pre-clinical

STK11-mutant models

ADVANCED DRUG DISCOVERY

SIGNIFICANT PATIENT OPPORTUNITY

Target 3 IND-enabling studies planned for 2H 2022

PROGRAMPATIENT

SELECTIONDISCOVERY

IND-ENABLING

CLINICAL TRIALSANTICIPATED MILESTONES

Phase 1/2 Phase 3

TARGET 3STK11-mut

lung cancerIND filing 2023

• Multiple diverse lead series

• Structurally enabled to drive further lead

optimization

• Strong in vivo PD, in vivo efficacy with

lead series compound

• STK11 mutations occur in ~20% NSCLC

and are associated with checkpoint

inhibitor resistance

• STK11 mutation enables the first genetic

patient selection for an immuno-oncology

clinical trial

Confidential | 45

FINANCIAL HIGHLIGHTS AND MILESTONES

Confidential | 46

Cash balance Shares outstandingCash runway

a

88M common shares outstandingSufficient to fund operations into 2H 2024

$504M cash, cash equivalents and marketable securities

• Including net proceeds of $327M from SPAC/PIPE closing in August 2021

Q3 2021 financial highlights (Nasdaq: TNGX)

Confidential | 47

2021

2H2023

FY

2022

FY

IND filing for Target 3

Preliminary safety and efficacy data on TNG908 in 1H

Initiate TNG908 first-in-human clinical trial in 1H

Development candidate declaration for USP1

File IND for USP1

Development candidate declaration for Target 3

Full GLP toxicology profile for TNG908 (PRMT5)

IND filing for TNG908

Projected key milestones