Corporate Presentation November 2020...1.BeiGene is currently running a subset of combination studies of sitravatinib + tislelizumab (their anti-PD-1) in Asia for multiple solid tumor

1

NASDAQ: MRTX

Targeting the genetic and

immunological drivers of cancer

Corporate Presentation

November 2020

2

This presentation contains certain forward-looking statements regarding the business of Mirati Therapeutics, Inc. (“Mirati”). Any statement

describing Mirati’s goals, expectations, financial or other projections, intentions or beliefs, development plans and the commercial

potential of Mirati’s drug development pipeline, including without limitation MRTX849, sitravatinib and MRTX1133, is a forward-looking

statement and should be considered an at-risk statement. Such statements are subject to risks and uncertainties, particularly those

challenges inherent in the process of discovering, developing and commercialization of new drug products that are safe and effective for

use as human therapeutics, and in the endeavor of building a business around such drugs.

Mirati’s forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to

differ materially from those expressed or implied by such forward-looking statements. Although Mirati’s forward-looking statements reflect

the good faith judgment of its management, these statements are based only on facts and factors currently known by Mirati. As a result,

you are cautioned not to rely on these forward-looking statements. These and other risks concerning Mirati’s programs are described in

additional detail in Mirati’s quarterly reports on Form 10-Q and annual reports on Form 10-K, which are on file with the U.S. Securities and

Exchange Commission (the “SEC”) available at the SEC’s Internet site (www.sec.gov). Mirati assumes no obligation to update the

forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking

statements, except as required by law.

November 5, 2020

Safe Harbor Statement

3

Meaningful operational and

commercial synergies across our

portfolio, particularly in NSCLC

Continued progress and

advancement across our targeted

oncology research platform

$579.1 million in cash and cash

equivalents as of 9/30/20

Mirati is Taking a Bold Approach to Develop Novel Oncology Therapies, Including

Two Registration-Enabling Programs in Large NSCLC Patient Populations

IO Resistance

Adagrasib (MRTX849)

G12C selective inhibitor

KRAS Selective Inhibition

MRTX1133

G12D selective inhibitor

Preliminary P2 data in combo with PD-1 implies

doubling of median OS vs. SoC supporting

SAPPHIRE P3 approach in NSCLC*

Potential first-in-class G12D inhibitor

advancing through IND-enabling

studies

Compelling early efficacy and

favorable tolerability with broad development in

both monotherapy and combinations

Sitravatinib

Inhibitor of TAM and VEGFR2

NSCLC: non-small cell lung cancer; CRC: colorectal cancer; IO: immuno-oncology; IND: investigational new drug; OS: overall survival; SoC: standard of care

*As of the data cut-off of January 30, 2020 from P2 single-arm study: Preliminary median OS of 15.6 months for the Prior Clinical Benefit cohort (n=87). Preliminary median OS of 18.1 months for the subset of PCB patients (n = 73 of 87) who received the combination as either 2nd or 3rd line of therapy after progressing on treatment with a checkpoint inhibitor, which is a patient cohort consistent with the inclusion criteria for the ongoing SAPPHIRE Phase 3 clinical trial.

NSCLC Bladder NSCLC CRC Pancreatic CRC

Others Others Others

4

1. BeiGene is currently running a subset of combination studies of sitravatinib + tislelizumab (their anti-PD-1) in Asia for multiple solid tumor indications including NSCLC, HCC, RCC, ovarian and gastric cancers.

BeiGene has Asian commercialization rights (ex-Japan) for sitravatinib as part of our development and commercialization agreement (Jan. 2018) and is responsible for additional data disclosures. Additional data

is expected in 2021.

Phase 3Phase 1/1b Phase 2 Planned Near-Term CatalystsIndication

Sitravatinib

Multi Kinase

Inhibitor

PD-1

2/3L NSCLC

NSCLC, Bladder &

OtherAdditional data in 2021

P3 interim OS analysis by YE 2021

Monotherapy

2L+ NSCLC, CRC,

Pancreatic, Other

CDK4/6 & SOS1 initiations in 2021;

Initial combination data in 2021

POC combinations:

SHP2, pan-EGFR,

CDK4/6, SOS1

2L+ NSCLC & CRC

File NDA (2L+ NSCLC) by 2H:2021

Monotherapy Pancreatic, CRC,

NSCLC, OtherIND in 1H:2021

MRTX1133

KRAS G12D Inhibitor

POC P1/1b data in 2021;

P3 initiation in 2H:20212L CRCCetuximab (EGFR)

Adagrasib (MRTX849)

KRAS G12C Inhibitor

P2 initiation in Q1:2021

Development Approach

Synthetic Lethality Solid Tumors

Solid TumorsRAS Signaling Modifier

IND-enabling

Discovery Programs

Solid TumorsMutant KRAS Inhibitor

Lead

Optimization

Mirati-Sponsored Studies / ISTs / BeiGene (1)

SAPPHIRE (Checkpoint Refractory) – in combination with nivolumab

Randomized to FOLFIRI or FOLFOX

Proof of Concept (POC)

Robust Pipeline Spans Multiple Targets & Tumor Types with Near-Term Catalysts

P3 initiation in Q1:20212L NSCLC Randomized to Docetaxel

Pembrolizumab (PD-1) 1L NSCLCPOC P1/1b data in 2021;

P2 initiation in Q4:20202 Arms:

5

Adagrasib (MRTX849):

KRAS G12C Selective Inhibitor

5

6

KRAS is the Most Frequently Mutated Gene in Human Cancer

Adagrasib (MRTX849) KRAS G12C Inhibitor

KRAS Signaling Abnormal KRAS Signaling

Mutated KRAS activity is uncontrolledA key regulator of cell growth and survival

6

7

KRAS G12C Mutations Occur Frequently in Multiple Tumor Types

Prevalent in Tumors with High Unmet NeedKRAS G12C Mutational Frequencies1

NSCLCadenocarcinoma

14% ~ 44,000

Total US/EU

Pts (2)

3-4%

2%

~ 20,000

~ 4,000

Large Patient PopulationUS and EU Patients2

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

KRASG12C

ALK RET TRK

NSCLC CRC Pancreatic

~ 25,000

~ 13,000

~ 2,000

US

an

d E

U P

ati

en

ts ~ 70,000

Colorectal

Pancreatic

NSCLC: non-small cell lung cancer; CRC: colorectal cancer


1. Mirati frequency estimates based upon the following sources and underlying databases: Zehir A et al, Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med.

2017;23(6):703-713.; Campbell et al, Nature Genetics 2016 “Distinct patterns of somatic genome alterations in lung adenocarcinomas”; Bailey P et al, Nature 2016 “Genomic analyses identify molecular subtypes of pancreatic

cancer”; MSKCC Cancer Hot Spots database; NIH TCGA: The Cancer Genome Atlas

2. Mirati estimates based on epidemiology data reported in Globocan 2022 (accessed 2019) and frequencies by mutation; RET estimate does not include thyroid cancer. Rounded to the nearest 1,000.

8

Adagrasib (MRTX849) Is a Differentiated and Selective Inhibitor of KRASG12C

Presented at the 32nd EORTC-NCI-AACR Symposium, October 24-25, 2020

1. Zehir A, Benayed R, Shah RH, et al. Nat Med. 2017;23(6):703–713. 2. Schirripa M, Nappo F, Cremolini C, et al. Clin Colorectal Cancer. 2020; S1533-0028(20)30067-0. 3. NIH TCGA: The Cancer Genome Atlas. 4. Bos JL, Rehmann H, Wittinghofer A. Cell. 2007;129: 865-877. 5. Shukla S, Allam US, Ahsan A, et al. Neoplasia. 2014;16(2):115-128; 6. Hallin J, Engstrom LD, Hargis L, et al. Cancer Discov. 2020;10(1): 54-71.

Hypothesis: Maintaining continuous exposure of adagrasib above a target threshold enables inhibition of KRAS-

dependent signaling for the complete dose interval and maximizes depth and duration of antitumor activity


• KRAS G12C mutations act as oncogenic drivers and occur in approximately

14% of NSCLC (adenocarcinoma), 3-4% of CRC, and

1-2% of several other cancers1-3

• The KRAS protein cycles between GTP-On and GDP-Off states and has a

protein resynthesis half-life of ~24 h4,5

• Adagrasib is a covalent inhibitor of KRAS G12C that irreversibly and

selectively binds KRAS G12C in its inactive, GDP-bound state6

• Adagrasib was optimized for desired properties of a KRAS G12C inhibitor:

– Potent covalent inhibitor of KRAS G12C (cellular IC50: ~5 nM)

– High selectivity (>1000X) for the mutant KRAS G12C protein vs. wild-type KRAS

– Favorable PK properties, including oral bioavailability, long half-life (~24 h), and

extensive tissue distribution

Adagrasib Crystal Structure


9


KRAS G12C Selective Inhibitor-Clinical Results NSCLC

9

10

NSCLC: non-small cell lung cancer; BID: twice daily dosing

Data as of 30 August 2020.

Incidence of Treatment-Related Adverse Events

KRYSTAL-1: Adagrasib (MRTX849) KRAS G12C Inhibitor


• Grade 5 TRAEs included pneumonitis in a patient with recurrent pneumonitis (n=1) and cardiac failure (n=1)

• 4.5% of Treatment Related AEs led to discontinuation of treatment (7.3% of AEs led to discontinuation of treatment)

All Cohorts Pooled, 600 mg BIDa

(n=110)

TRAEsb,c, % Any grade Grades 3-4 Grade 5

Any TRAEs 85% 30% 2%

Most frequent TRAEsa,d, %

Nausea 54% 2% 0%

Diarrhea 51% 0% 0%

Vomiting 35% 2% 0%

Fatigue 32% 6% 0%

Increased ALT 20% 5% 0%

Increased AST 17% 5% 0%

Increased blood creatinine 15% 0% 0%

Decreased appetite 15% 0% 0%

QT prolongation 14% 3% 0%

Anemia 13% 2% 0%

aIncludes patients pooled from Phase 1/1b and Phase 2 NSCLC (n=79), and CRC and Phase 2 other tumor cohorts (n=31). bIncludes events reported between first dose and

30 August 2020. cThe most common treatment-related SAEs reported (2 patients each) reported were diarrhea (grade 1, grade 2) and hyponatremia (both grade 3). dOccurred in ≥10%.

11

Patient Demographics and Baseline Characteristics: NSCLC


aPhase 2 patients with NSCLC received prior treatment with platinum regimens.


Data as of 30 August 2020. Pooled includes NSCLC Phase 1/1b and Phase 2 600 mg BID.

KRYSTAL-1: Adagrasib (MRTX849) KRAS G12C Inhibitor in NSCLC

Phase 1/1b600 mg BID

(n=18)

Phase 1/1b and 2600 mg BID

(n=79)

Median age, y (range) 65 (40-76) 65 (25-85)

Female, n (%) 11 (61%) 45 (57%)

Race, n (%)

White 15 (83%) 67 (85%)

Black 3 (17%) 5 (6%)

Asian 0 (0%) 5 (6%)

Other 0 (0%) 2 (3%)

ECOG PS, n (%)

0 8 (44%) 17 (22%)

1 10 (56%) 62 (78%)

Current/former smokers 16 (89%) 75 (95%)

Nonsquamous histology, n (%) 18 (100%) 76 (96%)

Prior lines of anticancer therapya, median (range) 3 (1-9) 2 (1-9)

Prior anti-PD-1/L1 inhibitor, n (%) 16 (89%) 73 (92%)

12

Adagrasib in Patients With NSCLC: ORR in Pooled Dataset

Efficacy Outcomea, n (%)

Phase 1/1b, NSCLC

600 mg BID

(n=14)

Phase 1/1b and 2, NSCLC

600 mg BID

(n=51)

Objective Response Rate 6 (43%) 23 (45%)b

Best Overall Response

Complete Response (CR) 0 (0%) 0 (0%)

Partial Response (PR) 6 (43%) 23 (45%)

Stable Disease (SD) 8 (57%) 26 (51%)

Progressive Disease (PD) 0 (0%) 1 (2%)

Not Evaluable (NE) 0 (0%) 1 (2%)c

Disease control 14 (100%) 49 (96%)

aBased on investigator assessment of the clinically evaluable patients (measurable disease with ≥1 on-study scan); 14/18 patients (Phase 1/1b) and 51/79 patients (Phase 1/1b and 2 pooled) met these

criteria. bAt the time of the 30 August 2020 data cut off, 5 patients had unconfirmed PRs. All 5 were confirmed by scans that were performed after the 30 August 2020 data cut off. cOne patient had tumor

reimaging too early for response assessment.


NSCLC: non-small cell lung cancer; ORR: Overall response rate; BID: twice daily dosing



13

Adagrasib 600 mg BID in Patients With NSCLC: Best Tumor Change

From Baseline

• Clinical benefit (DCR) observed in 96% (49/51) of patients

• 70% (16/23) of responders had a best tumor response greater than 40% from baseline




aTwo timepoint assessments of CR were separated by recurrent disease associated with treatment interruption due to hypoxia; this patient remains on treatment and in two consecutive scans (1 after August 30 data

cutoff) demonstrated 100% tumor regression in target and non-target lesions after resuming treatment.

Best Tumor Change from BaselineStudy Phase

Phase 1/1b

Phase 2

Ma

xim

um

% C

ha

ng

e F

rom

Ba

se

lin

e

Evaluable Patients

40

20

0

-20

-40

-60

-80

-100

SD SD SD SDSD NE

SD

SDSD

SD SD SDSD SD SD SDSD SD

SD SD SD SD SD PR PR PR PR PR SD PR PRPD PR PR SD

PRPR

PRPR

PRSD PR PR PR PR

PRPR

PRPR

PRa

SD

NSCLC: non-small cell lung cancer; BID: twice daily dosing; DCR: disease control rate

14

Adagrasib 600 mg BID in Patients With NSCLC: Treatment Duration and

Change in Tumor Burden


As of 30 August 2020


Change in Tumor Burden Over Time, n=14

# Treatment ongoing

Time, months

0 2 4 6 8 10 12 14

40

20

50

-10

0

-50

-60

-90

--100

-80

-20

-70

-40

-30

10

30SD

SD

SDSD

SD

PR

SD

SD#SD# PR#

PR#

PR#

PR#

PR#

Duration of Treatment, months

Duration of Treatment, n=14

Eva

lua

ble

Pa

tie

nts

420 6 8 10 12 14

PR

PR

PR

PR

SD

PR

SD

SD

PR

SD

SD

SD

SD

SD

First response

Progression

Treatment ongoing

Death


as of August 30, 2020

Median (range) 8.2 (1.4, 13.1+)

• As of August 30, 2020, the median follow-up was 9.6 months

• Treatment ongoing >11 months in 4 responders

• As of October 16, 2020, 7 patients remain on treatment

• 5 of 6 responders remain on treatment; 4 remain in response%

Ch

an

ge

Fro

m B

as

eli

ne

15

0 2 4 6 8 10 12 14

Study Phase

Phase 1/1b

Phase 2

First response

Progression

Treatment ongoing

Death

Eva

lua

ble

Pa

tie

nts


PRPRPR

PRSD

PRSD

SDPRPR

SDPR

PRPRSDPR

SDPR

SDPR

PR

SDPR

SDPRPR

SDSD

PRPR

SDSDSD

SDSD

SDNESD

PDSD

SDSD

PRSD

PRSD

PRSD

SDSD

PR

Duration of Treatment

H O M E

• Median follow-up: 3.6 months

• Median time to response: 1.5 months

• 83% (19/23) of responders have not progressed and remain on study

• 65% (33/51) of patients remain on treatment


NSCLC: non-small cell lung cancer; BID: twice daily dosing; PR: partial response; SD: stable disease; PD: progressive disease; NE: not evaluablePresented at the 32nd EORTC-NCI-AACR Symposium, October 24-25, 2020

Duration of Treatment in Patients With NSCLC Treated With Adagrasib 600

mg BID in Pooled Dataset

16


KRAS G12C Selective Inhibitor-NSCLC CNS Metastases

16

17

Adagrasib Penetrates the Brain/CSF and Results in Tumor Regression in a Preclinical Modela


Vehicle

Adagrasib100 mg/kg BID

LU99Luc KRAS G12C Brain Metastases Model

• Adagrasib demonstrates dose-dependent brain and cerebrospinal fluid (CSF)

exposure in preclinical studies

• A single 100 mg/kg oral dose in mice results in brain concentrations exceeding the cellular IC50 of adagrasib

• Plasma levels achieved at 100 mg/kg BID in mice are comparable to levels achieved at a 600 mg BID human dose and

results in near complete tumor regression in LU99Luc KRAS G12C tumors

aData on file, Mirati Therapeutics, Inc.

1

10

100

1000

10000

1 8

Co

nc

en

tra

tio

n (

ng

/mL

)

Time, h

Mean Plasma

Mean Brain

Kp,uu = 0.4 (1 h)

Mean Plasma and Brain Concentrations of Adagrasib After a

Single 100 mg/kg Oral Dose in Mice

Cellular IC50


Mean plasma

Mean brain

Mean Plasma and Brain Concentrations of Adagrasib After a

Single 100 mg/kg Oral Dose in Mice

18

Patient Case: Patient With Brain Metastasis and KRAS G12C Mutation


Cycle 3, D1


C3D1C1D1

Baseline Adagrasib 600 mg BID, Cycle 7

PR, (-67%)

• 77-year-old female previous smoker

• NSCLC diagnosed, April 2019

• Only mutation identified by NGS panel: KRAS G12C

• Treatment history

– Carboplatin, pemetrexed, pembrolizumab, May-July 2019

– Pemetrexed maintenance, August-December 2019

– Left frontal brain met radiation, November 2019

– Pembrolizumab maintenance, January-February 2020

– Pemetrexed, March 2020

– Left and right cerebellar radiation, March 2020

• Patient started adagrasib 600 mg BID, May 2020

• Metastases were in the lung and liver, and an unirradiated

brain lesion in the right middle frontal gyrus

• TRAEs

– Grade 1 nausea, vomiting, diarrhea, dysphagia, anemia,

rash, and thigh discomfort

• Currently in cycle 7

Data as of 25 September 2020.

NSCLC: non-small cell lung cancer; BID: twice daily dosing; PR: partial response; NGS: next-generation sequencing; TRAEs: treatment-related adverse events

19


KRAS G12C Selective Inhibitor-NSCLC Co-Mutations

19

20

Co-mutations in KRAS and STK11 are Associated with Poor Prognosis

and Outcomes on Checkpoint Inhibitor Therapy in NSCLC

Ricciuti et al. Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019); Skouldis et al. Cancer Discov. 2018 Jul;8(7):822-835; Zehir et al. Nat Med. 2017 Aug 4;23(8):1004.

STK11 and KRAS mutations significantly co-occur and co-mutations comprise approximately 30% of KRAS G12C mutant NSCLC

Poor outcomes for KRAS and STK11 co-mutation positive patients on platinum-based chemotherapy regimens also evident


21

Preliminary Exploratory Correlative Analysis of Co-Mutations Including STK11 With

KRAS G12C and Response Rate in Patients with NSCLC Treated with Adagrasib

• 64% ORR in patients with tumors harboring STK11 and KRAS G12C mutations

• No apparent trend with KEAP1, TP53, or other common mutations and response rate

Data as of 30 August 2020. Based on unaudited data.



• STK11 and KRAS mutations co-mutations occur

in ~ 30% of KRAS G12C mutant NSCLC

• Patients with KRAS and STK11 mutations are

linked to poor outcomes to immunotherapy and

platinum-based chemotherapy regimens in

NSCLC

• Co-occurring KRAS and STK11 mutations may

cooperate to create an immune-suppressed

tumor microenvironment

NSCLC: non-small cell lung cancer; PR: partial response; SD: stable disease; ORR: overall response rate

Best Tumor Change From Baseline for

Patients Harboring KRAS G12C and STK11 Co-mutations

Evaluable Patients

Maxim

um

% F

rom

Baselin

e

-100

-80

-60

-40

-20

0

20

40

60

80

SD

SD

SD PRPD

PR PRPR

PR PRPR

PR

PR

SD

22


KRAS G12C Selective Inhibitor-Clinical Results CRC and Other

Tumor Types

22

23

Patient Demographics and Baseline Characteristics

CRC (Pooled),

600 mg BID (n=24)

“Other” Cohort,

600 mg BID (n=7)

Median age, y (range) 59 (37-79) 64 (25-80)

Female, n (%) 12 (50%) 2 (29%)

Race, n (%)

White 18 (75%) 5 (71%)

Black 4 (17%) 0 (0%)

Asian 2 (8%) 1 (14%)

Other 0 (0%) 1 (14%)

ECOG PS, n (%)

0 9 (38%) 0 (0%)

1 15 (63%) 7 (100%)

Tumor type, n (%)

CRC 24 (100%)

Pancreatic ductal adenocarcinoma 2 (29%)

Cholangiocarcinoma 1 (14%)

Endometrial cancer 1 (14%)

Ovarian cancer 1 (14%)

Appendiceal cancer 2 (29%)

Prior lines of anticancer therapy, median (range) 4 (1-9) 2 (1-5)

Data as of 30 August 2020. Pooled includes Phase 1/1b (n=2) and Phase 2 (n=22) 600 mg BID.Presented at the 32nd EORTC-NCI-AACR Symposium, October 24-25, 2020

KRYSTAL-1: Adagrasib (MRTX849) KRAS G12C Inhibitor in CRC and Other Solid Tumors

• 87% of CRC patients treated were at least 3rd line

CRC: colorectal cancer; BID: twice daily dosing

24

• Confirmed ORR 17% (3/18) of patients; SD 78% (14/18)

• Disease control observed in 94% (17/18) of patients

Best Tumor Change from Baselinea

Adagrasib in Patients With CRC: Best Overall Response and Disease Control Rate

aAll results based on investigator assessments.

Data as of 30 August 2020. Pooled includes Phase 1/1b and Phase 2 600 mg BID.

Change in Sum of Target Lesion Over Timea

# Treatment ongoing

% C

ha

ng

e F

rom

Ba

se

lin

e

Time, week

50

40

30

20

0

-10

-20

-40

-50

-30

10

0 7 13 19 25 31

Study Phase/Cohort

Phase 1/1b

Phase 2

PD

SD

SD#

SD#SD#

SD

SD#

PR#PR#

PR

SD#

SD#SD#

SD#SD# SD#

SD

Study Phase/Cohort

Phase 1/1b

Phase 2

SD# SD#SD SD SD# SD#

SD# SD# SD SD#PR# PR#

PR

PD

SD

Ma

xim

um

% C

ha

ng

e F

rom

Ba

se

lin

e

Evaluable Patients

80

60

40

20

0

-20

-40

-60

-80

-100

SD#

SD#

# Treatment ongoing



SD#

CRC: colorectal cancer; BID: twice daily dosing; ORR: overall response rate; PR: partial response; SD: stable disease

25

Adagrasib in Patients With Advanced CRC: Duration of Treatment

Data as of 30 August 2020. Pooled includes Phase 1/1b and Phase 2 600 mg BID.

Duration of TreatmentE

va

lua

ble

Pa

tie

nts

1050 15 20 25 30 35

SD

PR

SD

PR

SD

SD

PR

SD

SD

SD

SD

SD

SD

SD

SD

SD

SD

PD

Duration of Treatment, week

• Time to response in 3 patients with partial responses: 6.0, 12.9 and 19.3 weeks

• At time of analysis, 67% (12/18) of patients remain on treatment

• 55% (10/18) of patients have been on treatment for ≥4 months

Study Phase

Phase 1/1b

Phase 2

First response

Progression

Treatment ongoing

Death

45



CRC: colorectal cancer; PR: partial response; SD: stable disease; PD: progressive disease

26

Best Tumor Change From Baselinea

aAll results based on investigator assessments. bAt the time of the 30 August 2020 data cut off, the cholangiocarcinoma and ovarian cancer patients had unconfirmed PRs, which were

subsequently confirmed by scans that were performed after the 30 August 2020 data cut off.

Data as of 30 August 2020. All patients treated at 600 mg BID.

Ma

xim

um

% C

ha

ng

e F

rom

Ba

se

lin

e

Evaluable Patients

80

60

40

20

0

-20

-40

-60

-80

-100

SD

SD

PR PRb

PRb

PR

Adagrasib in Patients With Other Advanced Solid Tumors: Best Overall Response

Tumor Type

Mucinous appendiceal

Pancreatic

Ovarian

Endometrial

Cholangiocarcinoma



CRC: colorectal cancer; BID: twice daily dosing; ORR: overall response rate; PR: partial response; SD: stable disease

27

Duration of Treatment Change in Sum of Target Lesion Over Time

• All patients remain on treatment

Data as of 30 August 2020. All patients treated at 600 mg BID.

1050 15 20 25 30 35

Evalu

ab

le P

ati

en

ts

Duration of Treatment, week

SD

PR

PR

PR

PR

SD

% C

han

ge

Fro

m B

aselin

e

Time, week

40

20

50

-100

-50-60

-90-100

-80

-20

-70

-40

-30

10

30

0 7 13 19 25 31 37

# Treatment ongoing

SD#

SD#

PR# PR#

PR#PR#PR#

Adagrasib in Patients With Other Advanced Solid Tumors: Duration of Treatment

Tumor Type


Pancreatic

Ovarian

Endometrial

Cholangiocarcinoma

Tumor Type


Pancreatic

Ovarian

Endometrial

Cholangiocarcinoma



CRC: colorectal cancer; BID: twice daily dosing; PR: partial response; SD: stable disease

28


KRAS G12C Selective Inhibitor-Novel Combinations

28

29

MRTX849 Combination Development ApproachCombination therapy will be key to realizing the full value of KRAS G12C

NSCLC CRC

MRTX849 + PD-1

(pembrolizumab) MRTX849 + EGFR

(cetuximab)

MRTX849 + SHP2 Inhibitor

(TNO155 from Novartis)

NSCLC& CRC


Adagrasib (MRTX849) KRAS G12C Inhibitor in Novel Combinations

MRTX849 + SOS1

(BI 1701963 from

Boehringer Ingelheim)

MRTX849 + pan-EGFR

Inhibitor (afatinib)

MRTX849 + CDK 4/6

Inhibitor (palbociclib)

30

Patient Case: Response in Combination with Adagrasib + TNO155 (SHP2 inhibitor)*

Baseline

Post Cycle 3

PR, (-60%)

MRTX849 (600mg BID) + TNO155 (initial dose)

53-year-old male, smoker diagnosed with NSCLC

Treatment History

• Neoadjuvant Carbo/Pem x 4 (2017)

• Carbo/Pem/Bev > Pem/Bev maint (2017-2018)

• Atezo x 6 cycles (2018 - 2019)

• Pem + Pembro x 6 cycles (Mar – Oct 2019)

• KRAS G12Ci AMG510 x 4 cycles 11/19 - 2/20 (-

40%→ PD)

• SHP2i RMC4630 + Cobimetinib x 1 cycle (off for AE)

• FCN-437c (CDK4/6 inhibitor) (Mar – Jun 2020)

TRAEs: Gr 1 diarrhea

Disease Assessments

• Off O2 and wheelchair within days, neck mass

flattened within 1 week

– Currently in Cycle 4

Data as of August 24, 2020. * Study of combination of adagrasib and TNO155 in collaboration with Novartis. ClinicalTrials.gov. NCT04330664.


Adagrasib (MRTX849) KRAS G12C Inhibitor in Novel Combinations

31

Enrolled > 200 patients across tumor types

on adagrasib monotherapy at 600mg BID

Adagrasib Program Status: A Potential Best-in-Class G12C Inhibitor


Enrolled > 50 patients across three initial priority

combinations with adagrasib at 600mg BID

Other proof-of-concept combination studies either initiated or planned for 2021:

‒ Afatinib (pan-EGFR in 2nd/3rd line NSCLC) - Initiated

‒ Palbociclib (CDK4/6 in 2nd/3rd line NSCLC) - Planned

‒ BI 1701963 (SOS1 inhibitor in 2nd/3rd line NSCLC and CRC) - Planned

‒ Adagrasib shown to be well tolerated and

provides deep and durable benefit to patients with

KRAS G12C mutations

‒ Completed enrollment in Phase 2 registration-

enabling monotherapy 2/3L NSCLC cohort

‒ While early, all three combinations have all been well tolerated

‒ Pembrolizumab, in NSCLC, and cetuximab, in CRC, enrollment ongoing

‒ Cleared dose limiting toxicity evaluation period at the full dose of each

commercial agent

‒ TNO-155 (SHP2 inhibitor) in both NSCLC and CRC

‒ Initial dose expansion and dose escalation cohorts enrollment ongoing

NSCLC: non-small cell lung cancer; CRC: colorectal cancer; BID: twice daily dosing

32

MRTX1133:

KRAS G12D Selective Inhibitor

32

33

1. Mirati frequency estimates based upon the following sources and underlying databases: Zehir A et al, Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23(6):703-713.; Campbell et al, Nature

Genetics 2016 “Distinct patterns of somatic genome alterations in lung adenocarcinomas”; Bailey P et al, Nature 2016 “Genomic analyses identify molecular subtypes of pancreatic cancer”; MSKCC Cancer Hot Spots database; NIH TCGA: The Cancer Genome Atlas

2. Sources: Zehir, Ahmet et al. Nature Med 23 2017 “Mutational Landscape of Metastatic Cancer”; Krakstad et al. PLoS One 2012, “High-Throughput Mutation Profiling of Primary and Metastatic Endometrial Cancers”; NIH TCGA: The Cancer Genome Atlas;

cbioportal.org

3. Mirati estimates based on epidemiology data reported in Globocan 2022 (accessed 2019) and frequencies by mutation; Europe includes EU, Russia and 10 additional European countries; RET estimate does not include thyroid cancer. Rounded to the nearest 1,000.

Targeting KRAS G12D Mutations: Significant Opportunity with High Unmet Need

KRAS G12D2 Frequency: Large Patient PopulationUS and Europe Patients3

0

50,000

100,000

150,000

200,000

KRASG12D

KRASG12C

ALK RET TRK

Pancreatic CRC Endometrial NSCLC

US

an

d E

uro

pe P

ati

en

ts

ALK RET TRKKRAS

G12D

KRAS

G12C

Endometrial

~70,000

~180,000

MRTX1133 KRAS G12D Inhibitor

6%

~70,000

~80,000

~15,000

~13,000

Pancreatic36%

NSCLCadenocarcinoma

4%

Colorectal 12%


• KRAS G12D is a driver mutation

• KRAS G12D is sufficient to

induce pancreatic and lung

cancers in genetically

engineered mouse models

• KRAS G12D and KRAS G12C

are similarly potent oncogenes

in cell transformation assays

and functional genomics studies

34

MRTX1133: Potential First-in-Class G12D Selective Inhibitor

Assay Criteria MRTX1133

KRAS G12D cell activity 100-fold >1,000-fold

Predicted human half-life >24 hours ~50 hours

Low risk for hERG/off-target

pharmacology>10µM ✓

Drug-drug interaction (CYPs) Low risk ✓

• MRTX1133 is a small molecule that selectively & reversibly binds to & inhibits KRAS G12D in both active & inactive states

• MRTX1133 demonstrates selective inhibition of cell viability of KRAS G12D mutant, but not KRAS wild-type, tumor cells

• MRTX1133 demonstrates sustained dose-dependent inhibition of KRAS-dependent signaling in mouse tumor models


IC50 = 5 nM

0.01 0.1 1 10 100 1000 10000

0

25

50

75

100

Active KRAS G12D Assay

MRTX1133 (nM)

% A

cti

vit

y

Active GTP-Loaded KRAS G12D Assay

35

MRTX1133: Anti-Tumor Activity Observed in Pancreatic and CRC In-Vivo Models

AsPC-1

Pancreatic

AsPC-1

TGI-33

0 10 20 300

250

500

750

1000

1250

Vehicle

MRTX1133 3mg/kg BID

Study Day

Tu

mo

r vo

lum

e (

mm

3)

MRTX1133 10mg/kg BID


GP2D

TGI 200108-807

0 10 20 300

500

1000

1500

2000

Vehicle


Study Day

Tu

mo

r vo

lum

e (

mm

3)

MRTX1133 3mg/kg BID


Panc0403

TGI-26

0 10 20 30 400

500

1000

1500

2000

Vehicle

MRTX1133 3mg/kg BID

Study Day

Tu

mo

r vo

lum

e (

mm

3)



GP2D

Colorectal

Panc0403

Pancreatic


• MRTX1133 demonstrates dose-dependent inhibition of KRAS-dependent signaling, demonstrating tumor

regression in G12D mutant tumor models

BID: twice daily dosing

36

MRTX1133: Path to Clinical Development


MRTX1133 has a low predicted target plasma concentration (~25-100 ng/mL) required for near

complete sustained target inhibition and maximal antitumor activity based on its potency and high

unbound fraction

Both routes are commercially attractive and compatible with development as a monotherapy or in

combination with standard of care regimens

To ensure sustained therapeutic levels are achieved, we are pursuing both oral and parenteral

routes of administration in parallel into Phase 1

➢ Estimated fraction absorbed of 15% in preclinical studies

➢ Long predicted human half-life (~50 hrs), low target plasma concentration and high solubility

support both routes

➢ This will allow direct comparison and selection of the most promising path for further

development

37

MRTX1133: Initial Development Plan and Next Steps

▪ Multi-cohort Phase 1 monotherapy trial

comparable to adagrasib

‒ Rapid dose escalation strategies to define a

tolerated and active dose

▪ Multiple expansion cohorts for pancreatic,

colon, lung and other G12D patients

▪ Rational combination approaches are

similar to G12C and enabled in first-in-

human clinical trials


▪ Planned 1H:2021 IND filing

‒ Advancing through GLP toxicology studies

‒ GMP manufacturing is on track and not on

critical path

▪ Additional preclinical data to be

presented at a scientific conference in

2021

CLINICAL TRIAL DESIGN PRINCIPLES NEXT STEPS

IND: investigational new drug; GLP: good laboratory practice

38

Sitravatinib + Checkpoint Inhibitors

38

39

Sitravatinib Inhibits TAM (TYRO3, AXL and MER), VEGFR2, and KIT Receptors

and May Restore Immune Response


• Increase dendritic cell maturity & antigen

presentation capacity

• Increase NK cell response

• Increase T cell expansion & trafficking into

tumors

Rationale for Targeting TAM & Split RTKs to Enhance Immune Response to Checkpoint Inhibitors

• Targeting VEGFR2 reduces Tregs & MDSCs

• Targeting KIT also depletes MDSCs

• Releases brakes for expansion of CD8+ T cells

via PD-1 inhibition

Both TAM & Split RTKs cooperate to:

• Targeting MERTK & AXL shifts tumor

associated macrophage (TAM) type to M1

• M1 macrophages secrete cytokines that

enhance immune response (IL-12, TNF)

CD8+

CD4+

M1 TAM

M2 TAM

iDC

mDC

MDSC

Treg

Targeting TAM:

Targeting Split RTKs:

1. Pircher et al., Synergies of Targeting Tumor Angiogenesis and Immune Checkpoints. Int J Mol Sci, 2017. 18(11).

2. Garton et al., Anti-KIT Monoclonal Antibody Treatment Enhances the Antitumor Activity of Immune Checkpoint Inhibitors by Reversing Tumor-Induced Immunosuppression. Mol Cancer Ther, 2017. 16(4)

3. Akalu, Y.T., C.V. Rothlin, and S. Ghosh, TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy. Immunol Rev, 2017. 276(1)

4. Graham, D.K., D. DeRyckere, K.D. Davies, and H.S. Earp, The TAM family. Nat Rev Cancer, 2014. 14(12)

5. Du, W., Huang, H., Sorrelle, N., & Brekken, R. A. (2018). Sitravatinib potentiates immune checkpoint blockade in refractory cancer models. JCI Insight, 3(21).

40

▪ Encouraging updated Overall Survival (OS) data from

ongoing Phase 2 clinical trial 1

– Sitravatinib + nivolumab in checkpoint refractory NSCLC

▪ Preliminary median OS of 18.1 months1 in subset of Prior

Clinical Benefit (PCB) patients who received the combination

as either 2nd or 3rd line therapy after progressing on treatment

with checkpoint inhibitor

– Patient cohort consistent with the inclusion criteria for

the ongoing Phase 3 SAPPHIRE clinical trial

▪ Preliminary median OS of 15.6 months1 in full PCB cohort

▪ Potential to establish sitravatinib + nivolumab as new

standard of care after checkpoint inhibitor failure

– >2nd line NSCLC U.S. & EU Populations (circa 2020):

over 100,000 patients in total with ~70,000 being non-

squamous

Compelling Phase 2 Results Support and Inform SAPPHIRE

Phase 3 Trial Design

Historical Data Points for Advanced NSCLC

2nd Line or Subsequent Therapy2

OS: overall survival; NSCLC: non-small cell lung cancer

1. MRTX-500 Phase 2 trial: full Prior Benefit Cohort (PCB) (n=87), data cut-off 30 Jan-2020. Patients with PCB on a checkpoint inhibitor as

part of their last treatment regimen prior to enrollment. PCB is defined as either complete response, partial response or stable disease

for ≥12 weeks. Subset of PCB patients (n=73) who received the combination as either 2nd or 3rd line of therapy after progressing on

treatment with a checkpoint inhibitor.

9.4

18.1

8.5

15.6

9.6

0

2

4

6

8

10

12

14

16

18

20

docetaxel (Avg. OS fromCheckMate, KEYNOTE & OAK

Trials)

MRTX-500 preliminary medianOS in sitravatinib + nivolumab

4

1

1

5

MO

NT

HS

3

2. Data presented are from the CheckMate 057,KEYNOTE 010 and OAK studies and do not reflect results that

might have been obtained from head-to-head studies. Results from Mirati’s on-going Phase 3 SAPPHIRE trial

comparing sitravatinib + nivolumab to docetaxel may differ materially from prior studies presented.

3. Borghaei H, et al. N Engl J Med. 2015;373:1627-1639.

4. Herbst RS, et al. Lancet. 2016;387:1540-1550.

5. Rittmeyer A, et al. Lancet. 2017;389:255-265.


41

SAPPHIRE: Phase 3 Trial in 2nd / 3rd Line NSCLCPotential to establish sitravatinib + nivolumab as new standard of care after checkpoint inhibitor failure

Sitravatinib +

NivolumabN=266

DocetaxelN=266

Checkpoint

Refractory

NSCLC

2nd / 3rd Line Patients

after Checkpoint

Inhibitor Therapy

DocumentedTumor

Progression

* This has been amended to include both 2nd and 3rd line patients who have progressed following checkpoint inhibitor therapy and to add OS as an interim analysis endpoint

ORR: overall response rate; DOR: duration of response; OS: overall survival; PFS: progression-free survival; NSCLC: non-small cell lung cancer

RA

ND

OM

IZA

TIO

N 1

:1

Key Inclusion/Exclusion Criteria:

▪ Advanced, Non-Squamous NSCLC

▪ 2nd / 3rd line: progression on or following

PD-(L)1 inhibitor in combination or

following chemotherapy*

▪ Patients must have remained on prior PD-

(L)1 therapy for at least 4 months

▪ Excludes known driver mutations

Endpoints:

▪ Primary: OS

▪ Secondary: PFS, duration of response,

safety, tolerability

▪ Interim Analysis: OS (242 events)

Final OS Analysis

YE 2022

Potential for Full Approval

Based on Interim OS Analysis

YE 2021

N=532

1:1 randomization

Powered for 3.5-month OS benefit


42 POC: proof of concept; NSCLC: non-small cell lung cancer; RCC: renal cell cancer; HCC: hepatocellular carcinoma

Sitravatinib has Potential Across Multiple Tumor Types

Bladder

Phase 3Phase 1/1b Phase 2

HCC, RCC

and Ovarian

BeiGene

Additional

Data 2020

& 2021Bladder & RCC

NSCLC 2nd / 3rd line NSCLC (SAPPHIRE) checkpoint refractorysitravatinib + nivolumab vs. docetaxel

1st line HCC checkpoint naïve

sitravatinib + tislelizumab; sitravatinib alone

1st / 2nd line RCC checkpoint naïve & refractory

sitravatinib + tislelizumab

Ovarian cancer following platinum


2nd / 3rd line Gastric following chemotherapy


2nd / 3rd line Bladder checkpoint refractory

sitravatinib + nivolumab

Additional

Data 2021

Interim

Analysis

YE 2021

2nd / 3rd line RCC checkpoint naïve

sitravatinib + nivolumab

Milestones

1st line NSCLC checkpoint naïve & refractory



43

Financial Update

43

44

Select Company Financials

*This amount is comprised of cash, cash equivalents and short-term investments.

**Shares outstanding as of September 30, 2020 includes 44.8 million shares of common stock outstanding and pre-funded warrants to purchase a total of 9.1 million shares of common stock. The pre-funded warrants have a per

share exercise price of $0.001.

***Amount disclosed is calculated as Q3 2020 operating expenses ($100.1M) less Q3 2020 stock-based compensation expense ($21.8M).

NASDAQ MRTX

Cash as of September 30, 2020* $579.1M

Shares outstanding as of September 30, 2020** 53.9M

Q3 2020: Operating Expenses net of stock-based compensation*** $78.3M

Q3 2020: Operating Expenses $100.1M

Completed a follow-on offering in October 2020, resulting estimated net proceeds of $879.7M and 4.6M shares of common stock issued

45

1. BeiGene is currently running a subset of combination studies of sitravatinib + tislelizumab (their anti-PD-1) in Asia for multiple solid tumor indications including NSCLC, HCC, RCC, ovarian and gastric cancers.

BeiGene has Asian commercialization rights (ex-Japan) for sitravatinib as part of our development and commercialization agreement (Jan. 2018) and is responsible for additional data disclosures. Additional data

is expected in 2021.

Phase 3Phase 1/1b Phase 2 Planned Near-Term CatalystsIndication

Sitravatinib

Multi Kinase

Inhibitor

PD-1

2/3L NSCLC

NSCLC, Bladder &

OtherAdditional data in 2021

P3 interim OS analysis by YE 2021

Monotherapy

2L+ NSCLC, CRC,

Pancreatic, Other

CDK4/6 & SOS1 initiations in 2021;

Initial combination data in 2021

POC combinations:

SHP2, pan-EGFR,

CDK4/6, SOS1

2L+ NSCLC & CRC

File NDA (2L+ NSCLC) by 2H:2021

Monotherapy Pancreatic, CRC,

NSCLC, OtherIND in 1H:2021

MRTX1133

KRAS G12D Inhibitor

POC P1/1b data in 2021;

P3 initiation in 2H:20212L CRCCetuximab (EGFR)

Adagrasib (MRTX849)

KRAS G12C Inhibitor

P2 initiation in Q1:2021

Development Approach

Synthetic Lethality Solid Tumors

Solid TumorsRAS Signaling Modifier

IND-enabling

Discovery Programs

Solid TumorsMutant KRAS Inhibitor

Lead

Optimization

Mirati-Sponsored Studies / ISTs / BeiGene (1)

SAPPHIRE (Checkpoint Refractory) – in combination with nivolumab

Randomized to FOLFIRI or FOLFOX

Proof of Concept (POC)

Robust Pipeline Spans Multiple Targets & Tumor Types with Near-Term Catalysts

P3 initiation in Q1:20212L NSCLC Randomized to Docetaxel

Pembrolizumab (PD-1) 1L NSCLCPOC P1/1b data in 2021;

P2 initiation in Q4:20202 Arms:

46

NASDAQ: MRTX

Targeting the genetic and

immunological drivers of cancer

Corporate Presentation

November 2020

Documents

Corporate Presentation November 2020...1.BeiGene is currently running a subset of combination studies of sitravatinib + tislelizumab (their anti-PD-1) in Asia for multiple solid tumor