IMUGENE LIMITED — Investor Presentation 2021

May 17, 2021

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A S X : I M U

Imugene Licenses CD19 Oncolytic Virus to Turn CAR T Therapy Against Solid Tumours 18[th] May 2021

Disclaimer

1. The information in this presentation does not constitute personal investment advice. The presentation is not intended to be comprehensive or provide all information required by investors to make an informed decision on any investment in Imugene Limited (Company). In preparing this presentation, the Company did not take into account the investment objectives, financial situation and particular needs of any particular investor.

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Investment Highlights

Worldwide exclusive license to novel technology which provides Imugene’s CF33 oncolytic virus the ability to utilize CD19 CAR T therapies against solid tumours

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The four FDA approved CD19 CAR T drugs only work in blood cancers- solid tumours remain the holy grail

This technology makes the treatment of solid tumours by CAR T drugs viable

Offers Imugene numerous partnering or collaboration opportunities for both approved and in-development CAR Ts, bispecifics, ADC’s etc

Enhancement of our scientific team to spearhead clinical development of onCARlytics

Compelling pre-clinical activity

in TNBC, colorectal, pancreatic, prostate, ovarian, head and neck and glioma cancers when combining onCARlytics (CF33-CD19) with CD19 CAR T

Phase 1 CF33 oncolytic virus studies, commencing shortly will accelerate development of onCARlytics

Attractive industry standard licensing terms and royalty rates

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OnCARlytics Phase 1 study to commence in 2022

Robust intellectual property with long patent life

Four-year Sponsored Research Agreement with City of Hope Cancer Centre to further develop the technology

3

Introducing onCARlytics

OnCARlytics is a novel and effective combination immunotherapy utilizing its exclusively licensed CF33 oncolytic virus to deliver and present cell surface CD19 antigen (CF33-CD19) promoting CD19 CAR T cell anti-tumour responses against solid tumours

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“OnCARlytics makes
the treatment of
solid tumours by
CAR T drugs viable”
Dr Saul Priceman
Watch:
Combination CAR T
Oncolytic Virus
Immunotherapy Kills
Tumours
Dr’s Saul Priceman and Anthony Park
from the City of Hope Cancer Centre
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The CAR T Solid Tumour Challenge & Imugene’s Solution

Chimeric Antigen Receptor (CAR) T cell therapy has had limited activity in solid tumours, largely due to a lack of selectively and highly expressed surface antigens, such as the blood B cell antigen CD19.

CD19 CAR T Cells

CD19 Targeting domain

Solid Tumour

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N E W C O N C E P T

Utilise OV’s as a delivery vector to deliver CD19 antigen to solid tumour cells

Engineer Imugene’s CF33 to infect solid tumour cells and insert CD19 transgene to enable presentation of CD19 over the tumour cells during tumour cell infection, onCARlytics (CF33-CD19)

Combination use of autologous or allogeneic CD19 CAR Ts (eg. Novartis KYMRIAH®) with onCARlytics (CF33CD19) presents CD19 targets on solid tumours

OV generated CD19

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Mechanism of Action: How does it work?

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onCARlytics makes solid tumours “seen” by CD19 directed CAR T

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1
4
2
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1. OnCARlytics infects tumour cells

2. Virus replication and production of CF33-CD19 on the cell surface enabling CD19 CAR T cell targeting

3. Tumour cell lysis leads to viral particle release and the combination promotes endogenous immune cell recruitment to tumours

4. Released viral particles re-initiate virus infection of surrounding tumour cells.

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3
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onCARlytics Delivers CAR Targets to “ Targetless ” Solid Tumours

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a
J2R
Vaccinia Oncolytic VirusonCARlytics
CF33-(SE)hCD19tCF33-CD19 P SE Vaccinia Virus
hCD19t
CD19
b DAPI
A
MOI 0.025 MOI 1 MOI 0 CD19t
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• A. Immunofluorescence microscopy of MDAMB-468 cells infected for 24 hours with CF33-CD19 at multiplicity of infection (MOI) of 0.025 or 1, untransduced (MOI of 0), or cells transduced with lentivirus to stably express CD19t. Blue is DAPI, pink indicates CD19t, and green indicates vaccinia.

• B. Fluorescence-activated cell sorting (FACS) plots of MDA-MB-468 tumour cells positive for CD19t and vaccinia virus after 24 hours of CF33-CD19 infection at increasing MOIs. Percent indicates CD19t+, virus-positive population in the boxed region.

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c MOI 0 0.00625 0.0125 0.025 0.05 0.1 1
<1% 6.8% 11.5% 22.2% 37.8% 63.8% 98.0%
B
Vaccinia Virus
d 100 100 100 24h24h
80 80 80 48h48h
60 60 60 72h72h
C 40 40 40
20 20 20
0 0 0
7
Multiplicity of Infection
0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10 0.001 0.01 0.1 1 10
CD19
CD19t (%)
Vaccinia (%) Viability (%)
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B

• C. Quantification of percent CD19t+ (left), vaccinia+ (middle), and viable (right) MDA-MB-468 tumour cells after 24-, 48-, and 72-hour exposure to the indicated MOIs of CF33-CD19.

Park AK, Fong Y, Kim SI, Yang J, Murad JP, Lu J, Jeang B, Chang WC, Chen NG, Thomas SH, Forman SJ, Priceman SJ.Sci Transl Med. 2020 Sep 2;12(559): eaaz1863. doi: 10.1126/scitranslmed.aaz1863.PMID: 32878978

onCARlytics Drives CD19 CAR T cell Anti-Tumour Responses in Solid Tumours

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Antitumour efficacy of combination therapy of CF33-CD19 and CD19 CAR T cells in human xenograft tumour models.

MDA-MB-468 tumour–bearing mice treated with CF33-CD19 and CD19 CAR T cells. NSG mice were injected subcutaneously with MDA-MB-468 (5 × 106 cells) on day 0, and tumours were injected with CF33-CD19 (107 pfu, 10 M) on day 36. On day 46, tumours were injected with either untransduced T cells (mock) or CD19-CAR T cells (CAR; 5 × 106 cells).

Park AK, Fong Y, Kim SI, Yang J, Murad JP, Lu J, Jeang B, Chang WC, Chen NG, Thomas SH, Forman SJ, Priceman SJ.Sci Transl Med. 2020 Sep 2;12(559): eaaz1863. doi: 10.1126/scitranslmed.aaz1863.PMID: 32878 978

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Tumour injection CF33-CD19 CAR T cells
D0 D36 D46 Monitor tumour growth
i.t. 10M i.t. 5M Mock or
pfu CF33-CD19 CD19 CAR T cells No treatment Mock alone CAR alone
600 600 600
400 400 400
s.c.
MDA-MB-468
200 200 200
OV T cells
600 0 0 0
0 20 40 60 80 0 20 40 60 80 0 20 40 60 80
400
CF33-CD19 alone CF33-CD19 + Mock CF33-CD19 + CAR
200
600 6 0 0 600
p < 0.05
0
400 400 400
0 20 40 60 80
Days post tumor injection 200 2 0 0 200
No treatment OV19t aloneCF33-CD19 alone 0 0 0
Mock alone OV19t + MockCF33-CD19 + Mock 0 20 40 60 80 0 20 40 60 80 0 20 40 60 80
CAR alone OV19t + CARCF33-CD19 + CAR
Days post tumor injection
)
3
)
3
Tumor Volume (mm
Tumor Volume (mm
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Combination of CF33-CD19 and CD19 CAR T cells promotes tumour regression in xenograft m ~~ode~~ l of TNBC

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onCARlytics promotes endogenous & CAR T cell tumour infiltration

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Combination of CF33-CD19 and CD19 CAR T
CAR T cell tumour infiltration
CF33-CD19 + CF33-CD19 + p = 0.0003 cells promotes endogenous cytotoxic T cells,
Mock alone CAR alone Mock CAR CAR T cells & memory T cell responses
p = 0.08
1000
800 p = 0.01 1500
600
A B
400
200 1000
0
500
0
CF33-CD19
alone 0 10 20 30 40
p = 0.0013
3
Days post tumor rechallenge
2
C D E Treatment naive
CAR p = 0.11
1
alone Previously cured
0
A. Histology showing murine CD3+ and CD8+ T cells in subcutaneous MC38 tumours harvested from mice treated
intravenously with untransduced T cells (mock) alone, mCD19 CAR T cells alone, CF33-CD19 + mock T cells, and CF33-
CD19 + mCD19 CAR T cells. Tumours were harvested 4 days after T cell administration and 6 days after CF33-CD19
injection.
CF33-CD19
B. Quantification of immunohistochemical staining for murine CD8+ cells in tumours from mice treated as in (A).
+ CAR
Symbols indicate individual tumours from mice.
C. Representative flux imaging of mice 2 days after treatment with intratumoural CF33-CD19 alone (n = 4), intravenous
firefly luciferase–expressing mCD19 CAR T cells alone (n = 5), or CF33-CD19 + firefly luciferase–expressing mCD19
Mock aloneCF33-CD19 + MockOVm19t + MockCAR aloneCF33-CD19 + CAROVm19t + CAR
CF33-CD19 aloneOVm19t aloneCF33-CD19 + CARCAR aloneCAR aloneOVm19t + CAR
)
CD3 3
(cells/field)
+
CD8
CD8
) Tumor Volume (mm
6
Flux (photons/sec x 10
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A. Histology showing murine CD3+ and CD8+ T cells in subcutaneous MC38 tumours harvested from mice treated intravenously with untransduced T cells (mock) alone, mCD19 CAR T cells alone, CF33-CD19 + mock T cells, and CF33CD19 + mCD19 CAR T cells. Tumours were harvested 4 days after T cell administration and 6 days after CF33-CD19 injection.

C. Representative flux imaging of mice 2 days after treatment with intratumoural CF33-CD19 alone (n = 4), intravenous firefly luciferase–expressing mCD19 CAR T cells alone (n = 5), or CF33-CD19 + firefly luciferase–expressing mCD19 CAR T cells (n = 10).

Park AK, Fong Y, Kim SI, Yang J, Murad JP, Lu J, Jeang B, Chang WC, Chen NG, Thomas SH, Forman SJ, Priceman SJ. Sci Transl Med. 2020 Sep 2;12(559): eaaz1863. doi: 10.1126/scitranslmed.aaz1863.PMID: 32878978

D. Quantification of T cell flux from the regions of interest shown in (C).

E. Tumour volume in treatment-naïve or previously cured C57BL/6j mice rechallenged by subcutaneous injection of MC38 (5 × 105 ) cells. n = 7 for rechallenge group, n = 2 for treatment-naïve group. Individual tumours from mice are shown.

CD19 CAR T with onCARlytics Amplifies Intratumoural Virus Spread In Vivo

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p = 0.016
A
No treatment CF33-CD19 alone B p = 0.008
60 p = 0.056
40
20
Combining CD19 CAR T
0 with CF33-CD19
CF33-CD19 + Mock CF33-CD19 + CAR
p = 0.056 supercharges viral
p = 0.032 spread in solid tumours
40
30 p = 0.15
20
10
Histology showing vaccinia virus in MC38 tumors harvested from mice with no treatment 0 Park AK, Fong Y, Kim SI, Yang J, Murad
or treatment with CF33-CD19 alone, CF33-CD19 + mock T cells, and CF33-CD19+ mCD19- JP, Lu J, Jeang B, Chang WC, Chen NG,
CAR T cells. T cell treatment was 2 days after CF33-CD19 injection. Tumors were Thomas SH, Forman SJ, Priceman SJ.Sci
Transl Med. 2020 Sep 2;12(559):
harvested and stained for vaccinia virus (green) 4 days after CF33-CD19 alone or 2 days
eaaz1863. doi:
after T cell treatments.
10.1126/scitranslmed.aaz1863.PMID:
Quantification of percent cells positive for vaccinia and mCD19t in subcutaneous tumors
32878978
from mice receiving the indicated treatments. Mice were injected subcutaneously MC38
tumors (5 × 105 cells) on day 0. On days 14 and 16, mice were intratumorally injected with
OVm19t (5 × 107 pfu per mouse). On day 18, mice were treated intravenously with mock T
No treatmentMock aloneCF33-CD19 aloneCAR aloneOVm19t aloneCF33-CD19 + MockOVm19t + MockCF33-CD19 + CAROVm19t + CAR
DAPI Vaccinia (%)
/
Vaccinia
mCD19t (%)
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• A. Histology showing vaccinia virus in MC38 tumors harvested from mice with no treatment or treatment with CF33-CD19 alone, CF33-CD19 + mock T cells, and CF33-CD19+ mCD19CAR T cells. T cell treatment was 2 days after CF33-CD19 injection. Tumors were harvested and stained for vaccinia virus (green) 4 days after CF33-CD19 alone or 2 days after T cell treatments.

• B. Quantification of percent cells positive for vaccinia and mCD19t in subcutaneous tumors from mice receiving the indicated treatments. Mice were injected subcutaneously MC38 tumors (5 × 105 cells) on day 0. On days 14 and 16, mice were intratumorally injected with OVm19t (5 × 107 pfu per mouse). On day 18, mice were treated intravenously with mock T cells or mCD19-CAR T cells. Tumors were harvested 5 days after CF33-CD19 or 3 days after T cell treatments. Cells were analyzed by flow cytometry. n = 2 to 5 per group

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Published Front Cover of Science Translational Medicine Journal in 2020

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Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumours Park AK, Fong Y, Kim SI, Yang J, Murad JP, Lu J, Jeang B, Chang WC, Chen NG, Thomas SH, Forman SJ, Priceman SJ. Sci Transl Med. 2020 Sep 2;12(559): eaaz1863. doi: 10.1126/scitranslmed.aaz18 63.PMID: 32878978

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Milestones

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Next 12-24 months

Ø GMP manufacturing for pre-clinical toxicology & Phase 1 study

Ø FDA Pre-IND Meeting Ø GLP Toxicology Study

Ø FDA IND Clearance

• Ø 1[st] Patient Dosed Monotherapy

Ø 1[st] Patient Dosed Combination Therapy

Ø Recommended Phase 2 Dose Established & Expansion Opened

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Four FDA Approved CD19 CAR T’s

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Approved and in-development autologous or allogeneic CD19 CAR Ts can be partnered with Imugene’s onCARlylics for treating solid tumours:

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onCARlytics Management Team

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Leslie Chong MD & CEO Dr Yuman Fong Dr Saul Priceman Dr Anthony Park CAR T Cell Therapy Dr Nick Ede Dr Rita Laeufle Inventor Inventor Inventor Expert Chief Technology Officer Chief Medical Officer Chief Business Officer

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Intellectual Property

Intellectual Property
F O U N D A T I O N P A T E N	T ( 2 0 3 8 )
PCT	US2019/033030
Title	Oncolytic virus expressing a CAR T cell target and uses thereof
Inventors	Fong, Priceman, Forman, Chen & Park
Assignee	City of Hope
Primary Date	11 August 2017
International Publication	14 February 2019
Expiration Date	2038

PCT application filing date was 10/8/2018 and estimated expiration date is in late 2038. The patent application includes both composition of matter and method of use. It is currently pending with the opportunity to secure worldwide rights. International search report was favorable for composition of matter.

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Three Novel Technology Platforms

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onCARlytics
CF33 Oncolytic Virus B Cell Immunotherapy
CHECKvacc VAXINIA
CF33-CD19 CAR T Combination Therapy HER-Vaxx PD1-Vaxx
“Armed” Virus Parental Virus
B-Vaxx, PDL1-Vaxx, LAG3-Vaxx,
TIM3-Vaxx, VEGF-Vaxx, CTLA4-Vaxx etc
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Summary and Projections

WORLDWIDE EXCLUSIVE

license to novel technology which provides Imugene’s CF33 oncolytic virus the ability to utilise CD19 CAR T

THERAPIES AGAINST SOLID TUMOURS

COMPELLING PRE-CLINICAL ACTIVITY

in TNBC, colorectal, pancreatic, prostate, ovarian, head and neck and glioma cancers when combining onCARlytics (CF33-CD19) with CD19 CAR T

THE FOUR FDA APPROVED CD19 CAR T drugs only work in blood cancers…

solid tumours remain THE HOLY GRAIL

this technology makes the treatment of solid tumours by

CAR T DRUGS VIABLE

PHASE 1 CF33 ONCOLYTIC VIRUS STUDIES

commencing shortly, will accelerate development of the onCARlytics

OFFERS IMUGENE ~~NUMEROUS~~ PARTNERING OR COLLABORATION OPPORTUNITIES

for both approved and indevelopment CAR Ts onCARlytics makes the treatment of solid tumours by CAR T drugs viable

4yr SPONSORED

RESEARCH AGREEMENT

with City of Hope Cancer Centre to further develop the technology

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OnCARlytics Phase 1 study to commence in 2022

Robust intellectual property with long patent life

Enhancement of our scientific team to spearhead clinical development of onCARlytics

Attractive industry standard licensing terms and royalty rates

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Leslie Chong Managing Director & CEO leslie.chong@imugene.com +61 458 040 433