IMUGENE LIMITED — Investor Presentation 2021

Oct 4, 2021

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A S X : I M U

IMUGENE October, 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.

2. Further advice should be obtained from a professional investment adviser before taking any action on any information dealt with in the presentation. Those acting upon any information without advice do so entirely at their own risk.

3. Whilst this presentation is based on information from sources which are considered reliable, no representation or warranty, express or implied, is made or given by or on behalf of the Company, any of its directors, or any other person about the accuracy, completeness or fairness of the information or opinions contained in this presentation. No responsibility or liability is accepted by any of them for that information or those opinions or for any errors, omissions, misstatements (negligent or otherwise) or for any communication written or otherwise, contained or referred to in this presentation.

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1. Neither the Company nor any of its directors, officers, employees, advisers, associated persons or subsidiaries are liable for any direct, indirect or consequential loss or damage suffered by any person as a result of relying upon any statement in this presentation or any document supplied with this presentation, or by any future communications in connection with those documents and all of those losses and damages are expressly disclaimed.

2. Any opinions expressed reflect the Company’s position at the date of this presentation and are subject to change

3. International offer restrictions - This document does not constitute an offer to sell, or a solicitation of an offer to buy, securities in the United States or any other jurisdiction in which it would be unlawful. In particular, the New Shares have not been, and will not be, registered under the US Securities Act of 1933 and may not be offered or sold in the United States except in transactions exempt from, or not subject to, the registration requirements of the US Securities Act and applicable US state securities laws. The distribution of this presentation in jurisdictions outside Australia may be restricted by law and any such restrictions should be observed.

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Introduction to Imugene

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Imugene is a biotech company 2 0 1 8 S E P 2 0 2 1 headquartered in Australia and Licensed extensive B cell Entered the publicly traded on the Australian portfolio and platform from S&P/ASX 300 Securities Exchange (ASX:IMU) OSU and Mayo Clinic M A Y 2 0 2 1 Index comprising of PD1, HER1, Licensed onCARlytics HER2, HER3, VEGF, from City of Hope IGF-1R, CD28 invented by Dr Y Fong, Dr S Priceman & A U G 2 0 2 1 2 0 1 5 2 0 1 9 Dr A Park Strategic Partnership Leslie Chong with Celularity 2 0 1 3 Completed the from Genentech 2 0 1 7 acquisition of a prolific Paul Hopper built joined Imugene HER-Vaxx, our HER-2 oncolytic virus from Imugene around a technology that targeted B Cell City of Hope invented by originated from the Immunotherapy Dr Yuman Fong Medical University of entered the clinic Vienna

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Investment Highlights

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• Three novel technology platforms: Oncolytic virotherapies, onCARlytics in cellular therapy and B-Cell activating immunotherapies

• B-Cell Technologies: HER-Vaxx Phase 2 in gastric cancer and PD1-Vaxx in NSCLC

• CF33 Oncolytic Virotherapies: 2 (CHECKvacc and Vaxinia) Phase 1 Clinical Trials

• OnCARlytics: Pre-clinical Toxicology Trials and strategic partnership with Celularity

• Highly experienced team in oncolytic virus and cellular therapies

• Significant news flow with multiple near & medium term valuation inflections

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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 “Armed” PD-L1 HER-Vaxx PD1-Vaxx
Parental Virus
Virus
TIGIT-Vaxx, PDL1-Vaxx, LAG3-Vaxx,
TIM3-Vaxx, VEGF-Vaxx, CTLA4-Vaxx etc
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Imu ene’s Dee Pi eline g p p

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Technology	Program	CMC & Pre-Clinical			IND	Phase I			Phase II		Key Data / Results	Intellectual Property
onCARlytics	CF33-CD19										• Compelling pre-clinical activity in multiple cancers when combining onCARlytics (CF33-CD19) with CD19 CAR T • Combination of onCARlytics and CD19 CAR T cells promotes endogenous memory T cell responses • Research agreement with Celularity’s s allogeneic CAR T (CyCART-19)	Expiring 2038
VAXINIA (CF33- hNIS)	MAST (Solid tumours)										• CF33 has shown strong anti tumour responses in preclinical studies • Inhibition of tumour growth in nearly all NCI60 models in TNBC, Lung, Pancreatic etc. • Signs of increased tumour growth inhibition with CF33 + anti PD-L1	Expiring 2037
CHECKvacc (CF33-hNIS- aPD-L1)	COH TNBC IST (Breast Cancer)										• Potentially solves the industry problem of additive toxicity of combined checkpoint inhibitors if safety of CF33 is maintained in combination • FDA IND approval, Phase 1 IST Open	Expiring 2037
HER-Vaxx (HER-2)	HERIZON (First line Gastric Cancer)										• Two further company sponsored Phase 2 studies and one Investigator Sponsored Study with HER-Vaxx in early and late stage gastric cancer are in planning • Phase 2 Interim data: 0.418 HR (80% 2-sided CI: 0.186, 0.942); 14.2 months HER-Vaxx + chemo compared to 8.8 months chemo alone • Strong phase 1b results with no safety or toxicity issues, all patients had increased antibody response, 11/14 evaluable patients with encouraging clinical responses	Expiring 2036
	neoHERIZON (Neoadjuvant Gastric Cancer)
	NextHERIZON (Metastatic Gastric Cancer)
PD1-Vaxx (PD-1)	IMPRINTER (Lung Cancer)										• PD1-Vaxx has shown encouraging response in preclinical studies • Strong inhibition of tumour growth in mouse models of colorectal cancer (outperformed industry standard mouse PD-1 mAb) • Signs of increased tumour growth inhibition when co-administered with B-Vaxx • FDA IND approval, First patient dosed December 2020	~~6~~ Expiring 2037

International Leadership Team with Extensive Commercialisation Expertise in the Sector

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Imugene has a team with oncology drug development experience

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Leslie Chong

SYDNEY, AU

Managing Director & CEO

• 23+ years of oncology experience across Phase I – III clinical development programs

• Ex Senior Clinical Program Lead at Genentech, one of the world’s most successful biotech businesses which sold the best selling breast cancer drug Herceptin

• Also worked at global majors GSK and Exelixis

• Non-Executive Director of Cure Brain Cancer Foundation (CBCF) & Chimeric Therapeutics

Paul Hopper

SYDNEY, AU

Executive Chairman

• Founder and Chairman of Imugene

• Founder & Chairman of Chimeric Therapeutics

• Chairman of SUDA Pharmaceutical

• Former Chairman of Viralytics

• Founder & Director of Prescient

• Extensive international & ASX biotech capital markets experience particularly in immuno-oncology & vaccines

Dr Jens Eckstein

CAMBRIDGE, USA

Non-Executive Director

• Managing Partner of Apollo Ventures

• Former president of SR One Ltd., the VC arm of GSK

• 15+ years in VC experience funding early to clinical stage biopharmaceutical companies

• Extensive experience as chairman, board director and founder of several biotechnology and venture capital companies.

• Creator of OneStart, the world’s

• largest life science accelerator

Charles Walker

Dr Lesley Russell

Dr Axel Hoos

PHILADELPHIA, USA

PHILADELPHIA, USA

BRISBANE, AU

Non-Executive Director

Non-Executive Director

Non-Executive Director

• 25+ years of senior • CEO of Scorpion Therapeutics international operational and • Former Senior Vice President leadership experience having and Head of Oncology at GSK

• worked at Amgen, Eli Lilly, Teva, and Cephalon • Former Medical Lead for

• • Extensive knowledge and Yervoy, the first immunooncology treatment to improve

• experience with new drug first survival .

• Experienced listed biotech CEO and CFO (ASX:ACL and ASX:IMU)

• Extensive financial markets experience having executed 50+ cross border transactions

• Extensive knowledge and experience with new drug development

  • Clinical experience includes managing pipeline of drugs in all stages from discovery, through to Phase III to product launch

• Board of Director of TCR[2 ] Therapeutics in Boston

• Non-Executive Director of Enanta Pharmaceuticals.

• Chairman of the Sabin Vaccine Institute

• Co-Chair of the Cancer • CEO, Founder and NED of Immunotherapy Consortium RedEarth Energy Storage

• Think-Tank

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B-Cell Immunotherapies

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B Cell Based Antibodies Have Distinct Advantages To Existing Treatments

B cell Vaccines offer a unique opportunity to intervene at multiple points in the immune system and create immune memory which N A T U R A L B C E L L D E R I V E D enhances durability of response. A N T I B O D I E S Stimulates the immune system to produce Safety Abs, which may be potentially safer Polyclonal Ab response reduces risk of Efficacy resistance and potentially increases efficacy Antibodies continuously produced with Durability lasting immune response to potentially inhibit tumor recurrence Potentially low numbers of vaccinations Usability required per year

Low cost of production enables greater pricing flexibility facilitating combination

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M O N O C L O N A L A N T I B O D I E S

Synthetic Ab, with side effects (including ventricular dysfunction, CHF, anaphylaxis, immune mediation) Monoclonal Ab – may develop anti-drug antibodies Half life necessitates recurrent dosing Requires regular infusion

Expensive course of treatment >US$100K 9 per year

Cost

HER-Vaxx Phase 2 Recruitment Complete

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Trial

• Phase 2

• Open label

• Asia

• Eastern Europe

• India

Patients

• HER-2+++

• HER-2++ FISH/CISH +ve

• Advance or metastatic Gastric Cancer

• Stage IIIb/IV

• 36 patients in two arms

• Study Randomised

HER-Vaxx in combination

• with standard of care chemotherapy Or

Standard of care chemo: Cisplatin and 5FU or capecitabine or oxaliplatin

Primary Endpoints

• Overall survival

• Secondary Endpoints

• Progression-free survival

• Safety and Tolerability

• • Immune response

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First patient dosed March 2019/Last patient enrolled Jan 2021

Days	-21	0	14	21	35	42	63	77	84	105	126 +42	140 +63
IMU-131 administration
Chemotherapy Cycle		1		2		3	4		5	6

Max 6 cycles SOC chemo with progression assessment every 42 days

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AACR 2021 Presentation Poster

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Abstract No. CT107 A PHASE 1B/2 OPEN-LABEL STUDY WITH RANDOMIZATION IN PHASE 2 OF IMU-131 HER2/NEU PEPTIDE VACCINE PLUS STANDARD OF CARE CHEMOTHERAPY IN PATIENTS WITH HER2/NEU OVEREXPRESSING METASTATIC OR ADVANCED ADENOCARCINOMA OF THE STOMACH OR GASTROESOPHAGEAL JUNCTION Interim Analysis Results

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Marina Maglakelidze[1] , Dinara Ryspayenva[2] , Iurie Bulat[3] , Zoran Andric[4] , Ivan Nikolic[5] , Tanuj Chawla[6] , Rajnish Nagarkar[7] , Vaibhav Choudhary[8] , Giri Venkata[9] , Rajesh Kumar Singh[10] , Davorin Radosavljevic[11] , Zoran Petrovic[12] , Ursula Wiedermann[13 ] , Leslie Chong[14] , Rita Laeufle[1][4] Nicholas Ede[14] , Bonnie NIxon[14] , Anthony Good[14]

1ARENSIA Exploratory Medicine, Tbilitsi, Georgia, 2ARENSIA Exploratory Medicine, Kiev, Ukraine, 3ARENSIA Exploratory Medicine, Chisinau, Moldova, 4Republic of, Clinical Hospital Center Bezanijska Kosa, Belgrade, Serbia, 5Oncology Institute of Vojvodina, Sremska Kamenica, Serbia, 6Tata Medical Centre, Kolkata, India, 7HCG Manavata Cancer Centre, Nashik, India, 8HCG NCHRI Cancer Centre, Nagpur, India,[9] Victoria Hospital, Bangalore, India,[10] Regional Cancer Centre Indira Gandhi Institute of Medical Sciences, Patna, India,[11] Institute of Oncology and Radiology of Serbia, Belgrad,[12] Serbia, Military Medical Academy, Belgrad, Serbia,[13] Medical University, Vienna, Austria,[14] Imugene, Sydney, Australia,

INTRODUCTION

IMU-131 plus chemotherapy treated patients received 50ug dose of IMU-131 at Baseline/Day 0, Day 14, Day 35, Day 77 and then every 63 days until disease progression.

HER-Vaxx (IMU-131) is a B-cell activating immunotherapy consisting of three fused B-cell epitopes (p467) from the HER2/neu extracellular domain coupled to CRM197 and administered with the adjuvant Montanide.

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The Phase 2 part of the study hypothesizes that active immunization with HER-Vaxx (IMU-131) will replicate or improve efficacy and safety of the approved monoclonal antibodies that target HER2 in patients with confirmed Her2+ advanced or metastatic Gastric Cancer. In the Phase 1b dose finding part of the study tumor response of patients who received 50ug dose strongly correlated with antibody levels with 50ug selected as the Phase 2 dose (Wiedermann et. al., Annals of Oncology

Figure 2: IMU.ACS.001 Phase 2 Treatment Schedule

RESULTS

Here we report the safety and efficacy results from the 1[st] interim analysis (OS and PFS) in a total of 27 patients after 15 progression events.

(2019)). BACKGROUND

Within the ITT patient population, 8 of 27 patients have died on the control arm and 4 are deceased on the HER-Vaxx plus SOC chemotherapy arm. This translated into an overall survival HR of 0.418 (2 sided 80% CI: 0.186, 0.942) and a 1-sided p-value of 0.083. Progression free survival data of 27 patients was available, 9 patients progressed on the control arm and 6 patients on the HER-Vaxx plus SOC chemotherapy arm with a HR of 0.532 (2 sided 80% CI 0.267, 1.060) and a 1-sided p-value of 0.086.

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Figure 1: IMU.ACS.001 Study Design

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In part 2 of study IMU.ACS.001, patients are randomized into two arms of either HER-Vaxx plus standard chemotherapy or standard chemotherapy alone.

The study is conducted in countries with limited access to trastuzumab in Asia and Eastern Europe.

The primary endpoint is overall survival, with progression-free survival and safety as secondary endpoints. Immune related endpoints include values and changes from randomization in humoral and cellular immunogenicity data.

METHODS

IMU-131 plus chemotherapy treated patients received 50ug dose of IMU-131 at Baseline/Day 0, Day 14, Day 35, Day 77 and then every 63 days until disease progression.

Table 1: IMU.ACS.001 Phase 2 Overall Survival & Progression Free Survival

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Table 2: IMU.ACS.001: Safety Overview of Treatment Emergent Adverse Events (TEAE)

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Figure 3 : IMU.ACS.001 KM-Curve Overall Survival Primary Endpoint

Figure 5: IMU.ACS.001 PHASE 2 - HER2 Specific Antibodies

By week 6 HER2-AB were developed by the patient’s immune system as response to HER-Vaxx vaccinations and remained high during treatment with every 63 days maintenance vaccinations only. One patient on the chemo control arm progressed at week 24 and received trastuzumab containing treatment. The patient returned for one AB assessment that showed a similar level as HER-Vaxx (Figure 5). Further data on response and biomarker is awaited.

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CONCLUSIONS

These data demonstrate HER-Vaxx may provide treatment benefits consistent with traditional monoclonal antibodies with a corresponding adaptive immune response without toxicity. A study (neoHERIZON) in perioperative HER2+GC with HERVaxx in combination with FLOT +/- anti-PD-L1 is in planning.

Table 3: IMU.ACS.001 Grade 3 and Higher Non- Hematological AE

Figure 4: IMU.ACS.001 KM-Curve Progression Free Survival Secondary Endpoint

REFERENCES

There was no difference in safety between the two treatment arms, suggesting HER-Vaxx does not add toxicity to SOC chemotherapy (Table 2).Incidence of Grade 3 and higher non-hematological (Table 3) and hematological adverse events (Table 4) were low and Table 4: balanced between the treatment arms. IMU.ACS.001 Two patients on each treatment arm had an Grade 3 and DISCLOSURES asymptomatic LVEF drop, none of them below LVEF of Higher 50. Hematological AE

Wiedermann et al: 2019, Annals of Oncology Volume 30 P495-496: Results of P1b study with a HER2/neu B-cell vaccine administered with chemotherapy in patients with HER2/neu overexpressing advanced gastric cancer

Study is sponsored by Imugene Limited B-cell peptide vaccine (IMU-131) was developed at the Medical University of Vienna

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.

AACR Presentation

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Highlights

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PFS Endpoint Events met on 21st April 2021: Top Line Data expected July 2021

Treatment with HER-Vaxx clearly demonstrates that all patients develop high levels of HER2-specific antibodies early in the treatment protocol.

The constant and high HER2 antibody levels correlate with the early separation of the Kaplan Meier (KM) Curves for overall survival (OS) and progression free survival (PFS) clinical trial endpoints. The Kaplan Meier Curve provides a recognised statistical estimation of the survival function which visually represents the probability of an event occurring for each treatment arm at a respective time interval.

Analysis of the antibody data reveals high levels are maintained during the treatment and maintenance phases, with only minimal booster injections of HER-Vaxx required to maintain the high levels.

Overall, this interim data is suggestive that the treatment is effective and well tolerated with an overall survival benefit that is superior to chemotherapy alone.

Final tumour response, correlation of antibodies with tumour response, and final PFS and OS data is expected to read out in 2021.

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HER-Vaxx Phase 2: Interim Analysis

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E N D P O I N T O V E R A L L S U R V I V A L P R O G R E S S I O N F R E E S U R V I V A L
Intent to Treat (Primary) Intent to Treat (Secondary)
Her-Vaxx + Chemotherapy Her-Vaxx + Chemotherapy
Treatment
Chemotherapy Only Chemotherapy Only
All Patients N=27 14 13 14 13
Events 4 8 6 9
HR 0.418 0.532
2-sided 80%CI (0.186,0.942) (0.267,1.060)
Log-rank Test (1-sided p-value) * 0.083 [+] 0.086 [+]
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• Pre-specified alpha at 0.10 + Statistically Significant

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HER-Vaxx Phase 2: Interim Analysis

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HER-Vaxx Phase 2: Interim Analysis	HER-Vaxx Phase 2: Interim Analysis	HER-Vaxx Phase 2: Interim Analysis	HER-Vaxx Phase 2: Interim Analysis	HER-Vaxx Phase 2: Interim Analysis
T R E A T M E N T E M E R G E N T A D V E R S E E V E N T S
	H E R - V A X X + C H E M O T H E R A P Y ( N = 1 4 )		C H E M O T H E R A P Y O N LY ( N = 1 3 )
Patients with at least one TEAE	13 92.9%		12 92.3%
	n	%	n	%
Grade 1 / 2	7	50%	5	38.5 %
Grade> 3	6	42.9%	7	53.8%
Serious AE*	1	7.1%	5	38.5%
Fatal AE	0	0%	1	7.7%

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*SAEs are also included in the >3 AE. N = number of patients in the treatment arm at interim analysis. n = number of patients who experienced the event.

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PD1-Vaxx

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PD1-Vaxx Phase 1: Study Design

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Part 1: Monotherapy Dose Escalation Part 2: Combination Escalation & Dose Expansion (Planned)
PD1-Vaxx Monotherapy (MTD/OBD evaluation)
Cohort 1 Cohort 2 Cohort 3
10 µg 50 µg 100 µg
IMU-201 IMU-201 IMU-201
n = 3-6 n = 3-6 n = 3-6
IMU-201+SOC Expansion
PD1-Vaxx + SOC Combination (MTD/OBD evaluation) n = 12
Cohort X Cohort 4 Cohort 5
X µg X µg = mOBD-1 X µg
IMU-201 + SOC IMU-201 + SOC IMU-201 + SOC
n = 3-6 n = 3-6 n = 3-6
Phase Part 1: Monotherapy Dose Escalation Part 2: Combination Escalation & Expansion (Planned)
Indication Non-small cell lung cancer expressing PD-L1
Objectives Safety & Tolerability, Immunogenicity, OBD Monotherapy
No. of Patients Approx. 12-22 Approx. 12-30
Site Location Australia & USA
Combination OBD
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PD1-Vaxx Phase 1: Recruiting

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Current Status
1st Patient Dosed 1st Patient Dosed Cohort 3 Cleared,
Cohort 1 Cleared Cohort 2 Cleared 1st Patient Dosed
Cohort 1 Cohort 2 RP2D & Expansion
Jan 2021 April 2021 Cohort 3
30 Nov 2020 Feb 2021 Opened
Ohio State University
(open)
Hackensack University
(open)
Macquarie University (open)
Chris O'Brien Lifehouse (open)
Cabrini Malvern (open)
Mayo Clinic
(open)
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M I L E S T O N E S
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ESMO 2021 Presentation Poster

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IMPRINTER: An Open Label, Multi-Center, Dose Escalation/Expansion, Phase 1 Study of I M U-201 (P D1-Vaxx), Poster ID: 1367 TiP a B-Cell Immunothe r apy, in Adul t s with Non-Small Cell Lung Canc er

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John Jae Won Park[1] , Gary Richardson[2] , Martin Gutierrez[3] , David Carbone[4] , Michael Boyer[5] , Panayiotis Savvides[6] , Pravin Kaumaya[7] , Tanios Bekaii-Saab[6] , Tri Giang Phan[8] , Leslie Chong[9] , Rita Laeufle[9,] Nicholas Ede[9] , Bonnie NIxon[9] , Anthony J. Good[9]

1Macquarie University Hospital, Sydney, Australia; 2Cabrini Hospital Malvern, Melbourne, Australia; 3Hackensack University Medical Center, New Jersey, NY; 4The James Comprehensive Cancer Center, Columbus, OH; 5Chris O'Brien Lifehouse Hospital, Sydney, Australia; 6Mayo Clinic, Phoenix/Scottsdale, AZ;[7] Ohio State University, Columbus, OH;[8] St Vincent's Clinical School, UNSW, Sydney, Australia;[9] Imugene, Sydney, Australia,

Background

Study Design

Patient Selection

Study Status

Therapies with monoclonal antibodies targeting PD-1 and its ligands are associated with remarkable outcomes in various cancers and, together with antibodies targeting CTLA-4, have revolutionized cancer treatment (Honey 2017). Some patients treated with PD-1/PD-L1 blockade may develop a “primary or secondary resistance” to therapy (Sharma, Hu-Lieskovan et al. 2017). The hypothesis is that a polyclonal induced B-cell antibody response will be more effective or as effective with improved safety over current monoclonal antibody therapy.

IMU-201 is being developed using an active immunization approach to treat cancers that overexpress programmed cell death ligand 1 (PD-L1) by inducing the production of anti-PD-1 antibodies through immunization of patients with a peptide epitope designed to stimulate polyclonal antibodies against PD-1 (Kaumaya et al. 2020).

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Figure 1, MOA of PD1-Vaxx

Study Description

The IMPRINTER study is an open-label dose escalation/dose expansion study of IMU-201 as monotherapy treatment for PD-L1 expressing lung cancer, to evaluate safety, tolerability, and immunogenicity and assess the optimum biological dose (OBD) of IMU-201 to be used for further clinical development . All patients enrolled in the study must have previously received an immune checkpoint inhibitor for their underlying cancer and experienced disease progression.

The study will continue into combination therapy that includes combination with SOC which may include a monoclonal AB (such as anti-PD-L1)

Figure 2, Study Design

Participating Countries and Sites

info@imugene.com

Figure 3 Map participating countries and sites

Treatment Regimen

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Figure 4, Vaccination schedule

The study has fully enrolled into the third dose cohort, each cohort includes 3 patients. Treatment comprises 3 primary injections (days, 1, 15 and 29), a day 64 vaccination and from there a maintenance treatment every 2 months (see Figure 4). No dose limiting toxicity, or any significant vaccination related adverse event have been reported. Minor, grade 1 injection site reaction were reported with a duration of 1 day.

Histologically confirmed non-small-cell lung cancer (NSCLC) tumor stage IIIb or IV (3 major types of NSCLC are acceptable including squamous, adenocarcinoma, and large cell carcinoma);

Progressed on an approved PD-1 inhibitor or an approved PD-L1 inhibitor

Overall, the treatment is well tolerated, and the study will therefore move into the expansion cohort enrolling 10 patients into the optimal biological dose, to confirm safety response and the development of PD1-antibody in correlation to response.

Tumor PD-L1 overexpression with Tumor Proportion Score (TPS) ≥50%. Patients with PD-L1 TPS ≥1% expression may be included with agreement of Imugene Limited;

In planning is the combination with SOC therapy in the same patient population. This may include monoclonal AB such as a PD-L1 inhibitor or other immunotherapy agents. Patients may have either progressed on their previous therapy or lack of response to their SOC and are at high risk of progression .

Objectives and primary Enpoints

Primary Objectives

Other tumor indication eligible for the treatment with immunotherapy are currently under evaluation.

• To evaluate safety/tolerability and immunogenicity of IMU-201 as monotherapy following treatment with PD-1 inhibitor or PD-L1 inhibitor therapy in patients with advanced NSCLC tumors that are positive for PD-L1.

REFERENCES

• To identify the Optimal Biological Dose (OBD) of IMU-201 as monotherapy (mOBD), in patients with advanced NSCLC tumors that are positive for PD-L1.

• SecondaryObjectives

• Honey, K. (2017). "FDA Approves Fourth Immune Checkpoint Inhibitor for Bladder Cancer." Cancer Research Catalyst. The Offical Blof of the American Association for Cancer Research.

• To evaluate the efficacy of IMU-201 as monotherapy following treatment with SOC including monoclonal PD-1 inhibitor or PD-L1 inhibitor therapy in patients with advanced NSCLC tumors that are positive for PD-L1.

• Sharma, P., S. Hu-Lieskovan, J. A. Wargo and A. Ribas (2017 ). "Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy." Cell 168 (4): 707-723.

Exploratory Objectives

• Pravin T. P. Kaumaya, Linlin Guo, Jay Overholser, Manuel L. Penichet & Tanios Bekaii-Saab (2020) Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse

To evaluate changes in immunological, biomarker and additional radiological markers of tumor progression in patients treated with IMU-201 as monotherapy.

Primary Endpoints:

model, OncoImmunology, 9:1, DOI: 10.1080/2162402X.2020.1818437

• Frequency of patients experiencing adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Sponsor and Contact

• Frequency of patients discontinuing study treatment due to AEs.

• The OBD of IMU-201 evaluated by safety/tolerability and immunogenicity data Imugene Ltd, Australia, Contact via: info@imugene.com (IMU-201 and PD-1 specific antibody (IgG) titers).

.

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Oncolytic Virus CF33

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CF33 Mechanism of Action

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HOW A VIRUS KILLS A CELL
Step 1: Step 2: Step 3:
Virus enters cell Virus duplicates itself Cell explodes,
releasing thousands of
brand new virus particles
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• Direct infection, replication within and cancer cell killing

• Viral infection increases local check point targets (PD-1, PD-L1, CTLA4 etc)

• Cell death is immunogenic [surface expression of calreticulin, release of adenosine triphosphate (ATP) and release of high mobility group box 1 (HMGB1)]

• Local anti-PD-L1 expression may allow enhancement of anti-cancer immunotherapy

• Human sodium iodine symporter (hNIS) expression allows additional use of[131] Iodine or[188] Rhenium killing of infected cells and adjacent cells

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CHECKvacc Phase 1 TNBC Study CF33+hNIS+aPD-L1 (“Armed” Virus)

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FDA IND Cleared

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COHORT | 3-6 PATIENTS
Identify:
COHORT | 3-6 PATIENTS Recommended Phase 2
Dose (RP2D)
RP2D Expansion
Metastatic Triple Negative COHORT | 3-6 PATIENTS
Based on:
Breast Cancer
12 Patients
COHORT | 3-6 PATIENTS • Safety
• Immunogenicity
COHORT | 3-6 PATIENTS • Tumour Response
Disease of need Potential target for Treatment responses to Potential for registration
Indication TNBC
immunotherapy Atezolizumab (JAMA in well-designed,
• 8-13 month survival Oncology, 5:74, 2019) randomised P2 study
for metastatic disease • Expresses PD1, FDA IND CHECKvacc: CF33-hNIS-aPDL1
with few treatments PD-L1 • 1st line: 24%;
2nd line: 6% N Part 1=18-24 ; Part 2=12
• Approved by FDA
8 March 2019 Location Single Center: COH
Admin Route Intratumoral (IT)
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VAXINIA Phase 1 MAST Study (Metastatic Advanced Solid Tumours)

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Dose Admin Part 1: VAXINIA Monotherapy Part 2: VAXINIA + SOC IO []
Dose Escalation Combination Dose Escalation
IT
IT IV Identify IT IV Identify
IT Administration
Monotherapy Combination
Head & Neck,
Advanced COHORT COHORT Maximum Feasible COHORT COHORT DLT [#] cleared VAXINIA
Melanoma, TNBC 3-6 PATIENTS 3-6 PATIENTS Dose (MFD), 3-6 PATIENTS 3-6 PATIENTS monotherapy dose
based on: combined with IO [] in
IV COHORT COHORT • Safety COHORT COHORT dose escalation cohorts.
3-6 PATIENTS 3-6 PATIENTS • Immunogenicity 3-6 PATIENTS 3-6 PATIENTS Select IO [ ] Combination
IV Administration • Tumour Response for recommended phase
Head & Neck, COHORT COHORT COHORT COHORT 2 dose (RP2D) based on:
Advanced Melanoma, 3-6 PATIENTS 3-6 PATIENTS 3-6 PATIENTS 3-6 PATIENTS • Safety
TNBC, NSCLC, • Immunogenicity
Bladder, Gastric, •
COHORT COHORT Tumour Response
Colorectal, RCC
3-6 PATIENTS 3-6 PATIENTS
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No. of Patients: Approx. 60-120

Site Location: USA

*IO: Immunotherapy #DLT: Dose Limiting Toxicity

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 with onCARlytics (CF33-CD19) presents CD19 targets on solid tumours

OV generated CD19

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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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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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J2R
Vacci ni a O ncol yti c Virus
CF33-(SE)hCD19t P SE Vaccin ia Vir us
hCD19t
CD19
DAPI
MOI 0.025 MOI 1 MOI 0 CD19t
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onCARlytics (CF33-CD19) infects a wide array of solid tumour cell lines, with dose-dependent CD19 cell surface expression

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100
Capan-1 (pancreas)
80
DU145 (prostate)
60
OV90 (ovarian)
40
Pan c -1 (pancrea s)
20
UM- SCC -1 (head and neck)
0
UM-S CC -47 (head and neck)
U25 1 T ( glioma)
Multiplicity if infection
0.001 0.01 0.1 1 10
CD19t (%)
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Combination of onCARlytics (CF33-CD19) and ~~CD19~~ -CAR T cells promotes tumour regression in ~~xenog~~ raft model of TNBC

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i.t.10M i.t. 5M Mock or
pfu OV19t CD19-CAR T cells
s.c.
MDA-MB-468
OV T cells
600
400
200
p < 0.05
0
0 20 40 60 80
Days post tumor injection
No treatment OV19t alone
Mock alone OV19t + Mock
CAR alone OV19t + CAR
)
3
Tumor Volume (mm
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26

Park et al. Science Translational Medicine 2020

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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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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28

Milestones

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estones
Technology	Milestone
onCARlytics	1st Patient Dosed
onCARlytics	FDA IND Clearance
PD1-Vaxx	Combination RP2D	Next 12-24 months
onCARlytics	GLP Toxicology Study
VAXINIA	1st Patient Dosed
onCARlytics	FDA Pre-IND Meeting
onCARlytics	GMP manufacturing for pre-clinical toxicology & Phase 1 study
VAXINIA	FDA IND Clearance
HER-Vaxx	Neo and Next HERIZON studies
PD1-Vaxx	Maximum Feasible Dose Identified
HER-Vaxx	OS Primary Endpoint
CHECKvacc	TNBC IST 1st Patient Dosed
HER-Vaxx	PFS analysis data
onCARlytics	Strategic partnership with Celularity on CD19 CART
CHECKvacc	FDA IND Clearance

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Financial Summary

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Public Market Overview		Share Price Performance(last 6 months)
Share Price1	A$0.415
52 week range	0.052 - 0.515
Market Capitalisation2	A$2.43B
Cash equivalents (30 Jun 21)3	A$29.5M
Enterprise Value	A$2.538B
Top 5 Shareholders(as at September 2021)
Citicorp Nominees Pty Limited	5.96%
Richard Mann and Assoc.	5.35%
Paul Hopper	5.34%
HSBC Custody Nominees (Australia)	3.35%
Dr Nicholas Smith	2.16%

Note:

1. As of 22 Sep 2021

2. Market capitalisation calculations based on ordinary shares (5.46 bn) only and excludes the dilutive impact of options outstanding (0.64 bn)

3. Does not include 95m from capital raise and SPP

30

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A S X : I M U

IMUGENE LIMITED www.imugene.com info@imugene.com