NEXT GENERATION

Natural Killer Cells

Engineered to Beat Cancer

MARCH 2022 1
Forward looking statements
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Pioneering the next
revolution in cell therapy
OX40
costimulatory domain
Next generation NK cell platform built for Targeting receptor
CD3ζ signaling moiety
Blood cancers and solid tumors

Allogeneic and off-the-shelf

CAR
Industrialized manufacturing

Outpatient administration

membrane
Two Clinical Data Updates Expected in 2022 bound IL-15
CAR-NK Cell
NKX101 Phase 1 dose finding – 1H 2022
NKG2D

NKX019 Phase 1 dose finding – FY 2022

CD19
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 Which allows for:

Donor selection Potential for universal

for desired cell donors and master
Next gen features cell banks
platform
Efficient
enlists natural, Process starts with
manufacturing
highly active,
healthy human cytotoxic, NK cells enables rapid,
NK immune large-scale production
cells for Multiplex gene
optimal engineering to
enhance immune
Well defined, high
quality, consistent
product cell performance product

Predictable Potential for flexible

pharmacokinetics multi-dose and multi-
with low risk of cycle treatment, and
CRS and outpatient
neurotoxicity administration 4
 Global Collaboration to
Develop Gene Edited Cell Therapies

GENOME ENGINEERING CAPABILITY

Best-in-class, clinically validated CRISPR gene editing

Ability to deploy up to 5 CRISPR/Cas9 gene edits in unlimited number

of Nkarta product candidates

Cell therapy
leaders EXPERIENCED CLINICAL DEVELOPMENT PARTNER
Co-development and co-commercialization of CD70 CAR NK,
Complementary CAR NK + CAR T, and option for a third early-pipeline target program
expertise
Leverage CD70 and allogeneic T cell expertise of CRISPR Therapeutics

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 ü Armored cells with membrane-bound IL-15 for persistence

ü Multiplexed CRISPR/Cas9 genome engineering

Staying Ahead
of the Curve: ü Enhanced expansion, persistence and TME resistance via
gene edits, including CISH deletion
A Platform That
Incorporates ü Cytokine activation using IL-12, -15 and -18 to enhance
Multiple Next anti-tumor activity persistence and memory-like properties
Generation
Enhancements ü Clinical trial designs include multi-doses and multi-cycles of
treatment

ü No requirement for cytokine support

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Evolving body of clinical data validates NK approach

NKG2D and non-engineered NK cells – AML CD19 – advanced B cell malignancies

Multiple clinical studies show tolerability
~30 clinical studies and activity of engineered NK cells
Well tolerated and no GvHD
(non-transplant)
MD Anderson study with CD19 CAR-NK cells
New England Journal of Medicine, Feb 2020

PRE-TREATMENT DAY 30 POST CAR-NK

~600 ~330 ~100

R/R AML
patients AML/MDS patients No reported
treated patients (non-transplant) CRS, GvHD or
~19% true CR rate
~34% aggregate CR rate
neurotoxicity
(MFLS, CRi, CRp, CR)

Bachier 2020; Nkarta systematic literature review. CR: Complete remission. K. Rezvani, et al., N Engl J Med 2020, 382:545-553. DOI: 10.1056/NEJMoa1910607. Takeda Investor Day 2019.
CRS: Cytokine release syndrome. GvHD: Graft versus host disease.
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 Platform-driven pipeline with multiple upcoming milestones

2021 2022 2023

Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 H1 H2

NKX101 Potential
Ph1 dose finding: Heme Dose expansion
(NKG2D heme) pivotal trials

NKX101 IND Ph1 dose finding:

(NKG2D solid tumor) Amend Solid Tumors

NKX019 Ph1 dose finding: Potential

Dose expansion pivotal trials
(CD19) B cell malignancies

CD70 Research-development with CRISPR Therapeutics

(solid tumor & heme)

NK + T Research-development with CRISPR Therapeutics

IND
(not disclosed)
Pivotal / Commercial GMP In-House
Manufacturing
Design Build Qualification
Facility

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Platform

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 Expansion Persistence
Donor NK cells are NK cells are engineered
co-cultured with proprietary for expression of
K562 stimulatory cell line to proprietary membrane
achieve high cell numbers bound IL-15 to enhance
time in circulation

Proprietary
technologies
in place
for a Cryopreservation Targeting
best-in-class Freezing process
maintains NK cell
NK cells are engineered
for expression of
NK cell platform viability and potency optimized CARs
to enable true
off-the-shelf
cell product

Gene Editing
NK cells are gene edited to enhance
cytotoxicity and improve resistance to
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suppression by tumor microenvironment
 Persistence and targeting to maximize anti-tumor activity
NKG2D-CAR
Control GFP-expressing NKG2D-CAR + mbIL-15
(PBS) NK cells NK cells NK cells
1.2×10 10
Control
Day 7 GFP-expressing NKs
NKG2D-CAR NKs
1×10 10
NKG2D-CAR + mbIL-15 NKs
Day 14

BLI (photon/sec)
8×10 9
Post tumor

Day 21

6×10 9
Day 28

4×10 9
Day 35

2×10 9
Day 49

0
Day 63 7 14 21 28 35 49 63
Time (days)
Source: Nkarta. U2OS osteosarcoma model; 3 x 106 NK cells administered on
D7. Graphical data at right are average BLI of mice above.

NK cells demonstrate enhanced tumor killing when engineered for targeting and mbIL-15
expression

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Our cryopreserved products are highly cytotoxic
NON-
CONTROL ENGINEERED NKX019 NKX019 6x109
(PBS) NK CELLS (FRESH) (CRYO)

DAY 2 5x109

4x109
DAY 7

3x109
DAY 12

2x109
DAY 23

1x109
DAY 30

DAY 56

Nalm-6 lymphoma model. 107 cells administered one day post tumor. Graphical data above
are an average of mouse luminescence at left. “Cryo” denotes cryopreserved then thawed NKX019.
DAY 65

NKX019 production under optimized conditions allows

DAY 69
cryopreservation with retention of in vivo activity

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Manufacturing

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 A powerful and efficient process for off-the-shelf products

1 Collect & Isolate 2 Activate 3 Engineer 4 Expand 5 Cryopreserve 6 Thaw & Administer

NK cell

Proprietary K562
stimulatory g-retrovirus
cell line

NK cells collected from NK cell expansion using Expanded NK cells are Continued expansion Harvesting and NK product candidate
healthy donors by proprietary stimulatory transduced to express driven by mbIL-15. cryopreservation of is thawed for off-the-
leukapheresis. cells. mbIL-15 and CAR and final cell product. shelf administration
may be gene edited using to patients.
CRISPR.

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 Proprietary expansion and engineering enable industrial-scale manufacturing

Current process supporting dose escalation Potential future scalability could

trials: >3 thousand-fold expansion achieve >2 billion-fold expansion

10,000 10,000,000,000

3,404
100,000,000

Fold Expansion
Fold Expansion

1,000

1,000,000
Donor 1
100
Donor 2
41 10,000
Donor 3

10
100

1 1
0 6 14 0 1 2 3 4 5 6 7 8

Days of Expansion Time

Data are from NKX019 expansions at current manufacturing scale for clinical supply. Data presented at SITC 2021: Potentiating the Large-Scale Expansion and Engineering of
Peripheral Blood-Derived CAR NK Cells for Off-the-Shelf Application, J. Trager, Abstract 151.

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 Clinical GMP Facility South San Francisco, CA

In-house manufacturing to control process and production

CLINICAL GMP FACILITY FUTURE COMMERCIAL-SCALE FACILITY
Multi-product facility 88,000 sq ft facility in South San Francisco

Combined manufacturing hub and company

Support early clinical trials and research
headquarters

Manufacturing NKX019 for Phase 1 clinical Expected to supply pivotal trials and early
trial commercial

Design and engineering process initiated

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Pipeline
NKX101:
CAR-NK targeting
NKG2D ligands OX40
costimulatory domain

CD3ζ signaling moiety

NKG2D activating receptor
NKG2D receptor is primary
driver of NK cell activation and
tumor killing

>10x increase in NKG2D

expression vs. non-engineered CAR
NK cells

OX40 selected based on

superiority vs. other
costimulatory domains

Targets of NKG2D are membrane

selectively over-expressed bound IL-15
in cancer cells CAR-NK Cell

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NKG2D: ligands in multiple tumors, responses in AML

NKG2D ligand expression in multiple tumor types
Clinical responses observed in r/r AML
• Non-engineered allogeneic NK cells
• Heterogeneous patient population
• Single center academic studies
• 19% true CR rate (aggregate)

TUMOR TYPE REFERENCE STUDY Response

AML, ALL, CML, CLL Hilpert, J Immunol 2012 Bachanova, Crit Rev Oncog 2014,
9 / 42 (21%)
MULTIPLE MYELOMA Carbone, Blood 2005 A+B cohorts

HCC Kamimura, J Hep 2012 Bachanova, Crit Rev Oncog 2014,

8 / 15 (53%)
C cohort
BREAST de Kruijf, BMC Can 2012
Curti, Blood 2011 1 / 5 (20%)
OVARIAN McGilvray, Int J Can 2010
Kottaridis, PLOS One 2015 1 / 1 (100%)
LUNG Okita, Can Imm Immunother 2016
Miller, Blood 2005 5 / 19 (26%)
COLON McGilvray, CCR 2009
MELANOMA Vetter, J Inv Derm 2002 Romee, Sci Transl Med 2016 5 / 9 (56%)

OSTEOSARCOMA Lu, Neoplasma 2008 Rubnitz, Pediatr Blood Cancer 2015 6 / 12 (50%)

GLIOMA Weiss, CCR 2018 OVERALL 35 / 103 (34%)*

*AML responses in patients with morphologic disease at baseline as

reported in individual trials, patients with CR at study entry excluded from
summary. The 35 responses include 20 CR, 12 CRi, 2 CRp and 1 MLFS.
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 NKX101:
Rationale in GFP-expressing NKX101 NKX101 NKX101

acute myeloid
NK cells (5 x 106 cells) (1 x 107 cells) (2 x 107 cells)

leukemia (AML) Day 6

NKG2D TARGETS Day 12

ARE OVER-EXPRESSED
in AML blasts
Day 18

Post tumor
CLINICAL ACTIVITY
with non-engineered NKs
Day 24

UNMET NEED:
• AML US incidence: ~21K / yr Day 30
• No approved therapy for
patients with r/r AML
Day 36
• 12 to 18% CR rate in r/r AML
population with recycle
THP-1 xenograft model treated with a single dose of NK cells (i.v.)
chemotherapy 2 days after tumor injection
Sources: SEER database; Veluchamy, Front Immunol 2017;
Brayer ASH 2018; Hilpert, J Immunol, 2012: Roboz et al, JCO
2014; Faderl et al, JCO 2012; Ravandi et al, Lancet 2015.

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 NKX101 Two-part Phase 1 study evaluating safety and efficacy
Trial Design of NKX101 in r/r AML and higher-risk MDS patients
• Multi-cycle
• Multi-dosing per cycle
• 3 dose levels of CAR NK cells* Lymphodepletion NKX101 multi-dosing cycle
Cyclophosphamide and Two dosing regimens: 2 or 3 doses per cycle
- Regimen A: 3 doses per cycle
Fludarabine daily for 3 days
- 100 M dose x 3
- 300 M dose x 3
- 1.0 B dose x 3

- Regimen B: 2 doses per cycle

- 150 M dose x 2
- 450 M dose x 2 Day 28
- 1.5 B dose x 2 Day 0 Day 7 Day 14
• Modified 3+3 design Reg A: Dose 1 Reg A: Dose 2 Reg A: Dose 3

• Dose finding followed by

multiple dose expansion
cohorts Day 0 Day 7
Reg B: Dose 1 Reg B: Dose 2
ClinicalTrials.gov: NCT04623944

AML: acute myeloid leukemia

*Protocol amendment includes option for Up to 5 treatment cycles
MDS: myelodysplastic syndrome 21
increased dosing of NKX101
NKX101 demonstrates
anti-tumor activity
in solid tumors NKX101 activity in NSG mice
LIVER & BILE CANCER US PBS CONTROL GFP-EXPRESSING NKS NKX101

INCIDENCE: ~42K / YR
5-year survival rate ~18% DAY 7

NKG2D TARGETS OVER-EXPRESSED DAY 14

on HCC and CRC cells

Post tumor
NK CELLS ARE IMPORTANT IN LIVER DAY 21

immunity and tumor surveillance

DAY 28
ACTIVITY OF NON-ENGINEERED NK
cells in HCC/ICC: 3/16 PRs
DAY 35

PLANNED PHASE 1: LOCOREGIONAL

delivery using SOC technique in 1° liver SNU449 HCC xenograft model
cancer or liver metastases 3 x 106 NK cells injected at day 7 post-tumor

HCC: Hepatocellular carcinoma. CRC: Colorectal cancer. Sources: SEER database; Sun Act Pharm Sin 2015;
Kamimura, J Hepatology, 2012; Kamiya et. al, Cancer Immunol Res 2016; Qin 2017
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 NKX019: OX40
CD19 targeted CAR-NK costimulatory domain
Proprietary CD19 binder
CD3ζ signaling moiety

CD19 is a CLINICALLY VALIDATED TARGET

• 32% to 54% CR (complete response) rate
in relapsed/refractory large B cell lymphoma patients
who received approved CD19 CAR-T therapy
CAR
UNMET NEED REMAINS DUE to SAFETY,
SPEED, ACCESS of APPROVED CD19 CAR-T
THERAPIES
• Gr3+ CRS: 13% to 49%; Gr3+ neurotoxicity: 18% to 31%
• Limited number of specialized sites can treat
• 9% to 34% of patients in pivotal trials did not receive membrane
bound IL-15
cells (primarily due to mfg. challenges)
CAR-NK Cell
IL-12 and IL-18 EXPANSION ENHANCES IN VITRO
and IN VIVO CYTOTOXICITY and PERSISTENCE
• In combination with Nkarta’s NKSTIM feeder NK
expansion platform
Sources: Breyanzi®, Kymriah® and Yescarta® package inserts; Rezvani NEJM 2020. Per NEJM
publication, CR/SD patient achieved a CR for Richter’s transformation and SD for underlying CLL.
Trager SITC 2019. 23
NKX019 kills tumors with high or low levels of CD19 expression

High CD19 Expressing Cells Low CD19 Expressing Cells

NKX019 NKX019
CD19 CAR-T

CD19 CAR-T

Effector : Target Effector : Target

NKX019 can achieve high levels of cytotoxicity even when tumor cells express low levels
of CD19 antigen, whereas CD19-targeted T cells are not as efficacious

Nalm6 cells engineered to express varying levels of CD19 were obtained from R. Majzner, Stanford
CD19 CAR-T cells: express construct used in Kymriah®
Effector : Target is the ratio of NK or T cells to tumor cells 24
NKX019 Two-part Phase 1 study evaluating safety and efficacy
Trial Design of NKX019 in patients with r/r B cell malignancies
• Multi-cycle
• Multi-dosing per cycle
- 3 doses per cycle
• 2 dose levels of CAR NK cells*
Lymphodepletion NKX019 dosing cycle Efficacy assessment
- 300 M dose x 3 Cyclophosphamide and
Fludarabine daily for 3 days
- 1 B dose x 3
• Modified 3+3 design
• Dose finding followed by
multiple dose expansion
cohorts Day 0 Day 7 Day 14 Day 28
Dose 1 Dose 2 Dose 3

ClinicalTrials.gov: NCT05020678
Up to 5 treatment cycles
*Protocol amendment includes option for
increased dosing of NKX019 25
Corporate

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 Platform-driven pipeline with multiple upcoming milestones

2021 2022 2023

Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 H1 H2

NKX101 Potential
Ph1 dose finding: Heme Dose expansion
(NKG2D heme) pivotal trials

NKX101 IND Ph1 dose finding:

(NKG2D solid tumor) Amend Solid Tumors

NKX019 Ph1 dose finding: Potential

Dose expansion pivotal trials
(CD19) B cell malignancies

CD70 Research-development with CRISPR Therapeutics

(solid tumor & heme)

NK + T Research-development with CRISPR Therapeutics

IND
(not disclosed)
Pivotal / Commercial GMP In-House
Manufacturing
Design Build Qualification
Facility

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Pioneering the Next Revolution in Cell Therapy

NKX101 Phase 1 dose finding – 1H 22

Two clinical NKG2D
updates in 2022 NKX019 Phase 1 dose finding – FY 22
CD19

Strong balance
$240.2 M as of 31 December 2021
sheet

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Thank you!

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